<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02967510</url>
  </required_header>
  <id_info>
    <org_study_id>ITFE-2092-C1</org_study_id>
    <secondary_id>2015-005787-42</secondary_id>
    <nct_id>NCT02967510</nct_id>
  </id_info>
  <brief_title>Study Evaluating the Efficacy and Safety of Three Formulations of Ultra-low Dose Estriol Vaginal Gel (0.005%, 0.002%, 0.0008% Estriol Vaginal Gel) for the Treatment of Vaginal Dryness in Postmenopausal Women With Vulvovaginal Atrophy</brief_title>
  <official_title>A Phase 2, Dose-ranging, 12-week Randomized, Double-blind, Placebo Controlled, Parallel-group Study Evaluating the Efficacy and Safety of Three Formulations of Ultra-low Dose Estriol Vaginal Gel (0.005% Estriol Vaginal Gel, 0.002% Estriol Vaginal Gel, 0.0008% Estriol Vaginal Gel) for the Treatment of Vaginal Dryness in Postmenopausal Women With Vulvovaginal Atrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ITF Research Pharma, S.L.U.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ITF Research Pharma, S.L.U.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase 2, Dose-ranging, 12-week Randomized, Double-blind, Placebo controlled, Parallel-group&#xD;
      Study Evaluating the Efficacy and Safety of Three Formulations of Ultra-low Dose Estriol&#xD;
      Vaginal Gel (0.005% Estriol Vaginal Gel, 0.002% Estriol Vaginal Gel, 0.0008% Estriol Vaginal&#xD;
      Gel) for the Treatment of Vaginal Dryness in Postmenopausal Women with Vulvovaginal Atrophy.&#xD;
&#xD;
      Vulvovaginal atrophy is a natural consequence of the progressive estrogen deficiency that&#xD;
      occurs in menopause. Epidemiological data have indicated that about 50% of otherwise healthy&#xD;
      women over 60 years of age experience symptoms related to urogenital atrophy such as vaginal&#xD;
      dryness, dyspareunia, burning, itching, as well as urinary complaints or infections of the&#xD;
      lower urinary tract. As these alterations frequently affect the quality of life of&#xD;
      postmenopausal women, it is important for doctors to detect their presence and offer&#xD;
      treatment options. Estrogen therapy is the most effective treatment of moderate to severe&#xD;
      symptoms of vulvar and vaginal atrophy. One advantage of local treatment with estrogen is&#xD;
      avoidance of first-pass liver metabolism, making it possible to use lower doses of estrogen&#xD;
      compared with oral therapy; the local route also minimize systemic adverse effects. The&#xD;
      search for therapeutic alternatives which may present improvements in relation to the current&#xD;
      products has been encouraged.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2016</start_date>
  <completion_date type="Actual">May 2018</completion_date>
  <primary_completion_date type="Actual">May 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Vaginal Dryness</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>Percentage of Subjects with change from baseline to week 12 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline to Week 12 in Vaginal pH</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Change from Baseline to Week 12 in Vaginal pH was reported. A decrease in pH compare to Baseline represents a positive outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Change from Baseline to week 12 in the proportion of superficial cells of the vaginal epithelium was reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Change from Baseline to Week 12 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to Baseline represents a positive outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Dyspareunia</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Percentage of subjects with change from baseline to week 12 in the severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Pruritus or Itching</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Percentage of subjects with cvhange from Baseline to Week 12 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Burning</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 12 in the severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Dysuria</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 12 in the severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Global Symptom Score 1</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 12/ET visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Global Symptom Score 2</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Change from Baseline to Week 12 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Pallor.</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 12 in the severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Friability</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 12 in the severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Thinning or Flattening of Folds</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 12 in the severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Petechiae</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 12 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Severity of Dry Mucosa</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 12 in the severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Vaginal Dryness</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Dyspareunia</measure>
    <time_frame>From baseline to week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Pruritus or Itching</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Burning</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Dysuria</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Global Symptom Score 1</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 3 visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Global Symptom Score 2</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Change from Baseline to Week 3 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Pallor</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Friability</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Thinning or Flattening of Folds</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Presence of Petechiae</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Severity of Dry Mucosa</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Percentage of subjects with change from Baseline to Week 3 in severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in Vaginal pH</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Change from Baseline to Week 3 in vaginal pH was reported. A decrease in pH compared to Baseline represents a positive outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Proportion of Superficial Cells of the Vaginal Epithelium</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Change from baseline to week 3 in the proportion of superficial cells of the vaginal epithelium was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 3 in the Proportion of Parabasal Cells of the Vaginal Epithelium</measure>
    <time_frame>Baseline to Week 3</time_frame>
    <description>Change from Baseline to Week 3 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to baseline represents a positive outcome.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">283</enrollment>
  <condition>Vaginal Atrophy</condition>
  <arm_group>
    <arm_group_label>0.005% estriol vaginal gel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.002% estriol vaginal gel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.0008% estriol vaginal gel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>estriol vaginal gel</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estriol</intervention_name>
    <arm_group_label>0.0008% estriol vaginal gel</arm_group_label>
    <arm_group_label>0.002% estriol vaginal gel</arm_group_label>
    <arm_group_label>0.005% estriol vaginal gel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>estriol vaginal gel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Capable of understanding the written informed consent, provides signed and witnessed&#xD;
             written informed consent, and agrees to comply with the protocol procedures and&#xD;
             assessments&#xD;
&#xD;
          2. Age &gt;40 and &lt;80 years&#xD;
&#xD;
          3. Postmenopausal (≥12 months since last spontaneous menstrual period, or having 6 months&#xD;
             of spontaneous amenorrhea with serum FSH levels &gt;40 IU/L, or ≥6 weeks since bilateral&#xD;
             oophorectomy with or without hysterectomy)&#xD;
&#xD;
          4. BMI ≤36 kg/m2&#xD;
&#xD;
          5. Vaginal Maturation Index ≤ 5% superficial cells on a vaginal smear&#xD;
&#xD;
          6. Vaginal pH &gt;5&#xD;
&#xD;
          7. Moderate to severe vaginal dryness currently reported as the most bothersome symptom&#xD;
             of vaginal atrophy.&#xD;
&#xD;
          8. Documented negative mammogram within 9 months prior to randomization, with normal&#xD;
             breast examination at screening.&#xD;
&#xD;
          9. Negative Papanicolau test at screening (in women with cervix).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with contraindications for hormone therapy with estrogens such as those&#xD;
             diagnosed or history of: malignant and premalignant lesions of the breast and/or&#xD;
             endometrium, malignancy of the colon, malignant melanoma, hepatic tumor, venous&#xD;
             thromboembolic conditions (including deep vein thrombosis or pulmonary embolism),&#xD;
             arterial thromboembolic conditions (including angina pectoris, myocardial infarction,&#xD;
             or cerebrovascular accident), coagulopathies, vaginal bleeding of unknown etiology,&#xD;
             acute liver disease or a history of liver disease as long as liver function tests have&#xD;
             failed to return to normal, or porphyria.&#xD;
&#xD;
          2. Subjects who have abnormal laboratory values at screening that the investigator&#xD;
             considers clinically relevant for the purposes of the study.&#xD;
&#xD;
          3. Subjects with any medical-surgical pathology which is not controlled at the time of&#xD;
             inclusion in the study&#xD;
&#xD;
          4. Subjects with any acute or chronic condition whose management or progression may&#xD;
             interfere with the subject´s participation in the study.&#xD;
&#xD;
          5. Subject with uncontrolled hypertension (&gt;140 mmHg systolic blood pressure and/or ≥90&#xD;
             mmHg diastolic blood pressure).&#xD;
&#xD;
          6. Subjects with Grade II or higher utero-vaginal prolapse.&#xD;
&#xD;
          7. Subjects with uterine polyps.&#xD;
&#xD;
          8. Subjects with symptomatic and/or large uterine fibroids (&gt;3 cm) and/or palpable&#xD;
             fibroids at gynecological examination.&#xD;
&#xD;
          9. Subjects who have had urogenital surgery within 3 months of baseline visit.&#xD;
&#xD;
         10. Subjects with signs and symptoms suggestive of infection of the genital or urinary&#xD;
             tract requiring treatment at the start of the study.&#xD;
&#xD;
         11. In women who have a uterus, evidence of hyperplasia, cancer or other endometrial&#xD;
             pathology in endometrial biopsy.&#xD;
&#xD;
         12. Subjects who have received the following treatments within the specified time periods&#xD;
             prior to screening procedures: any type of non-hormonal vulvovaginal treatment in the&#xD;
             7 days (including cosmetics expected to have an impact on vaginal pH such as special&#xD;
             feminine wash gels); phytoestrogens by any route within 1 month; vaginal hormone&#xD;
             therapy within 1 month; hormone therapy (estrogen alone, progestin alone or&#xD;
             estrogen/progestin combination) by oral, intrauterine or transdermal route within 2&#xD;
             months; progestational implants, estrogen, or estrogen/progestational injectable&#xD;
             within 3 months; estrogen pellet therapy or progestin injectable drug therapy within 6&#xD;
             months; percutaneous estrogen lotions or gels within 1 month; testosterone or&#xD;
             testosterone derivatives, DHEA, tibolone, or SERMs by any route within 2 months;&#xD;
&#xD;
         13. Subjects receiving antiepileptic drugs (barbiturates, hydantoins, carbamazepine),&#xD;
             certain antibiotics and other antiinfective medicinal products; phenylbutazone;&#xD;
             preparations based on medicinal plants that contain St. John's Wort.&#xD;
&#xD;
         14. Subjects who are allergic to any of the components of the medication under study.&#xD;
&#xD;
         15. Subjects who are currently participating or have participated in the experimental&#xD;
             evaluation of any product within 8 weeks of the start of the study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U</name>
      <address>
        <city>Brno</city>
        <zip>602 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Ceske Budejovice</city>
        <zip>370 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Olomouc</city>
        <zip>779 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Olomouc</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Pisek</city>
        <zip>397 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Prague</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Vsetin</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U</name>
      <address>
        <city>Szeged</city>
        <zip>6725</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U</name>
      <address>
        <city>Szekesfehervar</city>
        <zip>8000</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Szentes</city>
        <zip>6725</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Tatabanya</city>
        <zip>2800</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Catania</city>
        <zip>95123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Catanzaro</city>
        <zip>88100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Modena</city>
        <zip>41124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Siena</city>
        <zip>53100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Barcelona</city>
        <zip>80022</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Murcia</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Santander</city>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Huddinge</city>
        <zip>141 86</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Kungsbacka</city>
        <zip>434 30</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>For additional information regarding investigative sites for this trial, contact ITF Research Pharma S.L.U.</name>
      <address>
        <city>Stockholm</city>
        <zip>171 76</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>Sweden</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <results_first_submitted>May 10, 2019</results_first_submitted>
  <results_first_submitted_qc>August 22, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">September 25, 2019</results_first_posted>
  <last_update_submitted>August 22, 2019</last_update_submitted>
  <last_update_submitted_qc>August 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 22, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT02967510/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT02967510/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Estriol 0.005%</title>
          <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="P2">
          <title>Estriol 0.002%</title>
          <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="P3">
          <title>Estriol 0.0008%</title>
          <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="P4">
          <title>Placebo</title>
          <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="70"/>
                <participants group_id="P2" count="70"/>
                <participants group_id="P3" count="72"/>
                <participants group_id="P4" count="71"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="67"/>
                <participants group_id="P3" count="65"/>
                <participants group_id="P4" count="63"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Estriol 0.005%</title>
          <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="B2">
          <title>Estriol 0.002%</title>
          <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="B3">
          <title>Estriol 0.0008%</title>
          <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="B4">
          <title>Placebo</title>
          <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="70"/>
            <count group_id="B2" value="70"/>
            <count group_id="B3" value="72"/>
            <count group_id="B4" value="71"/>
            <count group_id="B5" value="283"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.5" spread="7.43"/>
                    <measurement group_id="B2" value="61.9" spread="6.87"/>
                    <measurement group_id="B3" value="62.2" spread="7.05"/>
                    <measurement group_id="B4" value="62.3" spread="7.24"/>
                    <measurement group_id="B5" value="62.0" spread="7.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="72"/>
                    <measurement group_id="B4" value="71"/>
                    <measurement group_id="B5" value="283"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="71"/>
                    <measurement group_id="B4" value="71"/>
                    <measurement group_id="B5" value="282"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Week 12 in the Severity of Vaginal Dryness</title>
        <description>Percentage of Subjects with change from baseline to week 12 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
        <time_frame>From baseline to week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Vaginal Dryness</title>
          <description>Percentage of Subjects with change from baseline to week 12 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="13"/>
                    <measurement group_id="O4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="33"/>
                    <measurement group_id="O3" value="26"/>
                    <measurement group_id="O4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="16"/>
                    <measurement group_id="O3" value="20"/>
                    <measurement group_id="O4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.304</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.109</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.119</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Week 12 in Vaginal pH</title>
        <description>Change from Baseline to Week 12 in Vaginal pH was reported. A decrease in pH compare to Baseline represents a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in Vaginal pH</title>
          <description>Change from Baseline to Week 12 in Vaginal pH was reported. A decrease in pH compare to Baseline represents a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>pH</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.03" spread="0.106"/>
                    <measurement group_id="O2" value="-1.04" spread="0.108"/>
                    <measurement group_id="O3" value="-0.95" spread="0.107"/>
                    <measurement group_id="O4" value="-0.29" spread="0.108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.031</ci_lower_limit>
            <ci_upper_limit>-0.444</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.75</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.051</ci_lower_limit>
            <ci_upper_limit>-0.458</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.66</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.951</ci_lower_limit>
            <ci_upper_limit>-0.369</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.</title>
        <description>Change from Baseline to week 12 in the proportion of superficial cells of the vaginal epithelium was reported.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.</title>
          <description>Change from Baseline to week 12 in the proportion of superficial cells of the vaginal epithelium was reported.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>ratio</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="64"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.24" spread="0.023"/>
                    <measurement group_id="O2" value="0.17" spread="0.024"/>
                    <measurement group_id="O3" value="0.19" spread="0.023"/>
                    <measurement group_id="O4" value="0.02" spread="0.024"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.147</ci_lower_limit>
            <ci_upper_limit>0.278</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.15</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.078</ci_lower_limit>
            <ci_upper_limit>0.213</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.16</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.097</ci_lower_limit>
            <ci_upper_limit>0.226</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.</title>
        <description>Change from Baseline to Week 12 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to Baseline represents a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.</title>
          <description>Change from Baseline to Week 12 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to Baseline represents a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>ratio</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="64"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.54" spread="0.036"/>
                    <measurement group_id="O2" value="-0.51" spread="0.037"/>
                    <measurement group_id="O3" value="-0.47" spread="0.036"/>
                    <measurement group_id="O4" value="-0.04" spread="0.038"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.603</ci_lower_limit>
            <ci_upper_limit>-0.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.47</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.572</ci_lower_limit>
            <ci_upper_limit>-0.365</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.43</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.531</ci_lower_limit>
            <ci_upper_limit>-0.331</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Severity of Dyspareunia</title>
        <description>Percentage of subjects with change from baseline to week 12 in the severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Dyspareunia</title>
          <description>Percentage of subjects with change from baseline to week 12 in the severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="41"/>
                <count group_id="O4" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="16"/>
                    <measurement group_id="O4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="12"/>
                    <measurement group_id="O4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.47</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.448</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <other_analysis_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.451</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Severity of Pruritus or Itching</title>
        <description>Percentage of subjects with cvhange from Baseline to Week 12 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Pruritus or Itching</title>
          <description>Percentage of subjects with cvhange from Baseline to Week 12 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="15"/>
                    <measurement group_id="O4" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="20"/>
                    <measurement group_id="O4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="22"/>
                    <measurement group_id="O3" value="28"/>
                    <measurement group_id="O4" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.329</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.348</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.266</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Severity of Burning</title>
        <description>Percentage of subjects with change from Baseline to Week 12 in the severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Burning</title>
          <description>Percentage of subjects with change from Baseline to Week 12 in the severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="21"/>
                    <measurement group_id="O3" value="18"/>
                    <measurement group_id="O4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="17"/>
                    <measurement group_id="O3" value="18"/>
                    <measurement group_id="O4" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="24"/>
                    <measurement group_id="O3" value="26"/>
                    <measurement group_id="O4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.122</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.188</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.222</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Severity of Dysuria</title>
        <description>Percentage of subjects with change from Baseline to Week 12 in the severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Dysuria</title>
          <description>Percentage of subjects with change from Baseline to Week 12 in the severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="17"/>
                    <measurement group_id="O4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43"/>
                    <measurement group_id="O2" value="39"/>
                    <measurement group_id="O3" value="40"/>
                    <measurement group_id="O4" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.393</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.221</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.432</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Global Symptom Score 1</title>
        <description>Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 12/ET visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Global Symptom Score 1</title>
          <description>Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 12/ET visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="41"/>
                <count group_id="O4" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.30" spread="0.425"/>
                    <measurement group_id="O2" value="-4.78" spread="0.478"/>
                    <measurement group_id="O3" value="-4.51" spread="0.412"/>
                    <measurement group_id="O4" value="-4.54" spread="0.467"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.65</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.24</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>1.487</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.361</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.24</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.568</ci_lower_limit>
            <ci_upper_limit>1.09</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.522</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.188</ci_lower_limit>
            <ci_upper_limit>1.257</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Global Symptom Score 2</title>
        <description>Change from Baseline to Week 12 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Global Symptom Score 2</title>
          <description>Change from Baseline to Week 12 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.83" spread="0.231"/>
                    <measurement group_id="O2" value="-3.78" spread="0.234"/>
                    <measurement group_id="O3" value="-3.74" spread="0.233"/>
                    <measurement group_id="O4" value="-3.27" spread="0.237"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.043</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.56</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.204</ci_lower_limit>
            <ci_upper_limit>0.079</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.061</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.51</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.158</ci_lower_limit>
            <ci_upper_limit>0.137</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.071</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.48</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.111</ci_lower_limit>
            <ci_upper_limit>0.16</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Severity of Pallor.</title>
        <description>Percentage of subjects with change from Baseline to Week 12 in the severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Pallor.</title>
          <description>Percentage of subjects with change from Baseline to Week 12 in the severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="16"/>
                    <measurement group_id="O3" value="25"/>
                    <measurement group_id="O4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="31"/>
                    <measurement group_id="O3" value="25"/>
                    <measurement group_id="O4" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="16"/>
                    <measurement group_id="O3" value="17"/>
                    <measurement group_id="O4" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.012</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.007</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Severity of Friability</title>
        <description>Percentage of subjects with change from Baseline to Week 12 in the severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Friability</title>
          <description>Percentage of subjects with change from Baseline to Week 12 in the severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="21"/>
                    <measurement group_id="O3" value="18"/>
                    <measurement group_id="O4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="22"/>
                    <measurement group_id="O3" value="31"/>
                    <measurement group_id="O4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="22"/>
                    <measurement group_id="O3" value="16"/>
                    <measurement group_id="O4" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.438</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.388</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.259</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Severity of Thinning or Flattening of Folds</title>
        <description>Percentage of subjects with change from Baseline to Week 12 in the severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Thinning or Flattening of Folds</title>
          <description>Percentage of subjects with change from Baseline to Week 12 in the severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="23"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="33"/>
                    <measurement group_id="O3" value="24"/>
                    <measurement group_id="O4" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="19"/>
                    <measurement group_id="O4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.022</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.02</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.003</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Severity of Petechiae</title>
        <description>Percentage of subjects with change from Baseline to Week 12 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Petechiae</title>
          <description>Percentage of subjects with change from Baseline to Week 12 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="23"/>
                    <measurement group_id="O3" value="23"/>
                    <measurement group_id="O4" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="35"/>
                    <measurement group_id="O3" value="35"/>
                    <measurement group_id="O4" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.002</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.331</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.043</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Severity of Dry Mucosa</title>
        <description>Percentage of subjects with change from Baseline to Week 12 in the severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Severity of Dry Mucosa</title>
          <description>Percentage of subjects with change from Baseline to Week 12 in the severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="68"/>
                <count group_id="O3" value="70"/>
                <count group_id="O4" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="14"/>
                    <measurement group_id="O4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39"/>
                    <measurement group_id="O2" value="29"/>
                    <measurement group_id="O3" value="26"/>
                    <measurement group_id="O4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="23"/>
                    <measurement group_id="O4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.022</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.032</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.001</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Vaginal Dryness</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Vaginal Dryness</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="66"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="22"/>
                    <measurement group_id="O4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="33"/>
                    <measurement group_id="O3" value="26"/>
                    <measurement group_id="O4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="12"/>
                    <measurement group_id="O3" value="11"/>
                    <measurement group_id="O4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.176</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.358</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.21</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Dyspareunia</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>From baseline to week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Dyspareunia</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="10"/>
                    <measurement group_id="O4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="11"/>
                    <measurement group_id="O3" value="14"/>
                    <measurement group_id="O4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="8"/>
                    <measurement group_id="O4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.106</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>1</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.229</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>1</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.345</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Pruritus or Itching</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Pruritus or Itching</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="30"/>
                    <measurement group_id="O4" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35"/>
                    <measurement group_id="O2" value="27"/>
                    <measurement group_id="O3" value="27"/>
                    <measurement group_id="O4" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.026</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.424</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.414</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Burning</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Burning</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="17"/>
                    <measurement group_id="O3" value="14"/>
                    <measurement group_id="O4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="20"/>
                    <measurement group_id="O4" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="28"/>
                    <measurement group_id="O3" value="29"/>
                    <measurement group_id="O4" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.36</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.12</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.266</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Dysuria</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Dysuria</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="16"/>
                    <measurement group_id="O3" value="14"/>
                    <measurement group_id="O4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                    <measurement group_id="O2" value="39"/>
                    <measurement group_id="O3" value="48"/>
                    <measurement group_id="O4" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.47</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.137</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.133</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Global Symptom Score 1</title>
        <description>Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 3 visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Global Symptom Score 1</title>
          <description>Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 3 visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="37"/>
                <count group_id="O4" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.99" spread="0.483"/>
                    <measurement group_id="O2" value="-2.86" spread="0.520"/>
                    <measurement group_id="O3" value="-4.37" spread="0.454"/>
                    <measurement group_id="O4" value="-3.73" spread="0.527"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.85</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.74</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.669</ci_lower_limit>
            <ci_upper_limit>2.153</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.877</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.87</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.611</ci_lower_limit>
            <ci_upper_limit>2.361</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.178</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.64</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.009</ci_lower_limit>
            <ci_upper_limit>0.728</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Global Symptom Score 2</title>
        <description>Change from Baseline to Week 3 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Global Symptom Score 2</title>
          <description>Change from Baseline to Week 3 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="66"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.76" spread="0.251"/>
                    <measurement group_id="O2" value="-2.82" spread="0.254"/>
                    <measurement group_id="O3" value="-3.20" spread="0.253"/>
                    <measurement group_id="O4" value="-2.60" spread="0.255"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.323</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.16</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.854</ci_lower_limit>
            <ci_upper_limit>0.531</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.272</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.22</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.917</ci_lower_limit>
            <ci_upper_limit>0.484</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.043</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.29</ci_lower_limit>
            <ci_upper_limit>0.084</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Pallor</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Pallor</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="14"/>
                    <measurement group_id="O4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="24"/>
                    <measurement group_id="O4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="30"/>
                    <measurement group_id="O3" value="29"/>
                    <measurement group_id="O4" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.009</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.025</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Friability</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Friability</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="11"/>
                    <measurement group_id="O3" value="13"/>
                    <measurement group_id="O4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="25"/>
                    <measurement group_id="O3" value="25"/>
                    <measurement group_id="O4" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="25"/>
                    <measurement group_id="O3" value="27"/>
                    <measurement group_id="O4" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.04</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.259</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.104</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Thinning or Flattening of Folds</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Thinning or Flattening of Folds</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="10"/>
                    <measurement group_id="O4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                    <measurement group_id="O2" value="35"/>
                    <measurement group_id="O3" value="31"/>
                    <measurement group_id="O4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="21"/>
                    <measurement group_id="O3" value="26"/>
                    <measurement group_id="O4" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Presence of Petechiae</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Presence of Petechiae</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="18"/>
                    <measurement group_id="O3" value="22"/>
                    <measurement group_id="O4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="41"/>
                    <measurement group_id="O3" value="38"/>
                    <measurement group_id="O4" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.054</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Severity of Dry Mucosa</title>
        <description>Percentage of subjects with change from Baseline to Week 3 in severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Severity of Dry Mucosa</title>
          <description>Percentage of subjects with change from Baseline to Week 3 in severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline: -3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="26"/>
                    <measurement group_id="O4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: -1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="30"/>
                    <measurement group_id="O3" value="21"/>
                    <measurement group_id="O4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="15"/>
                    <measurement group_id="O4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline: 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.008</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.01</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.001</p_value>
            <p_value_desc>Hodges-Lehmann estimate (HLE) of median difference between treatments was calculated. Medians were not calculated per SAP as might cause confusion since the HLE of treatment difference is not identical to the difference between 2 treatment medians</p_value_desc>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1</ci_lower_limit>
            <ci_upper_limit>0</ci_upper_limit>
            <estimate_desc>Hodges-Lehmann estimate of location shift and corresponding asymptotic Confidence Interval</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in Vaginal pH</title>
        <description>Change from Baseline to Week 3 in vaginal pH was reported. A decrease in pH compared to Baseline represents a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in Vaginal pH</title>
          <description>Change from Baseline to Week 3 in vaginal pH was reported. A decrease in pH compared to Baseline represents a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>pH</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="68"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.03" spread="0.095"/>
                    <measurement group_id="O2" value="-0.97" spread="0.096"/>
                    <measurement group_id="O3" value="-0.88" spread="0.095"/>
                    <measurement group_id="O4" value="-0.22" spread="0.096"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.81</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.071</ci_lower_limit>
            <ci_upper_limit>-0.548</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.75</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.013</ci_lower_limit>
            <ci_upper_limit>-0.484</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.66</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.916</ci_lower_limit>
            <ci_upper_limit>-0.397</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Proportion of Superficial Cells of the Vaginal Epithelium</title>
        <description>Change from baseline to week 3 in the proportion of superficial cells of the vaginal epithelium was reported.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Proportion of Superficial Cells of the Vaginal Epithelium</title>
          <description>Change from baseline to week 3 in the proportion of superficial cells of the vaginal epithelium was reported.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>ratio</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="61"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.48" spread="0.035"/>
                    <measurement group_id="O2" value="0.43" spread="0.036"/>
                    <measurement group_id="O3" value="0.38" spread="0.035"/>
                    <measurement group_id="O4" value="0.04" spread="0.037"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.44</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.337</ci_lower_limit>
            <ci_upper_limit>0.535</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.39</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.291</ci_lower_limit>
            <ci_upper_limit>0.494</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.34</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.245</ci_lower_limit>
            <ci_upper_limit>0.439</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 3 in the Proportion of Parabasal Cells of the Vaginal Epithelium</title>
        <description>Change from Baseline to Week 3 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to baseline represents a positive outcome.</description>
        <time_frame>Baseline to Week 3</time_frame>
        <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Estriol 0.005%</title>
            <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O2">
            <title>Estriol 0.002%</title>
            <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O3">
            <title>Estriol 0.0008%</title>
            <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 3 in the Proportion of Parabasal Cells of the Vaginal Epithelium</title>
          <description>Change from Baseline to Week 3 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to baseline represents a positive outcome.</description>
          <population>The ITT population defined as all randomized subjects. The number of subjects analyzed defined as number of subjects evaluable for this endpoint.</population>
          <units>ratio</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="65"/>
                <count group_id="O2" value="61"/>
                <count group_id="O3" value="68"/>
                <count group_id="O4" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.55" spread="0.037"/>
                    <measurement group_id="O2" value="-0.57" spread="0.037"/>
                    <measurement group_id="O3" value="-0.48" spread="0.036"/>
                    <measurement group_id="O4" value="-0.08" spread="0.038"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.47</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.575</ci_lower_limit>
            <ci_upper_limit>-0.371</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.49</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.592</ci_lower_limit>
            <ci_upper_limit>-0.383</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.5</ci_lower_limit>
            <ci_upper_limit>-0.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were assessed from the time the subject signed the ICF until exit from the study, aproximately 20 weeks</time_frame>
      <desc>The safety population included all randomized subjects who received at least 1 dose of study treatment. Data for treatment-emergent adverse events is presented here. Subjects were questioned and observed for evidence of AEs. For any preexisting condition or abnormal laboratory finding that changed in severity after dosing, the change was to be recorded as an AE. New abnormal laboratory findings that were considered clinically significant by the Investigator were considered AEs.</desc>
      <group_list>
        <group group_id="E1">
          <title>Estriol 0.005%</title>
          <description>Subjects received 1 gram of Estriol 0.005% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="E2">
          <title>Estriol 0.002%</title>
          <description>Subjects received 1 gram of Estriol 0.002% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="E3">
          <title>Estriol 0.0008%</title>
          <description>Subjects received 1 gram of Estriol 0.0008% vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>Subjects received 1 gram of matching placebo vaginal gel administered daily for Weeks 1-3. After 21 days of daily administration, treatment continued with twice-weekly administration up to Week 12</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Non-Hodgkin´s lymphoma</sub_title>
                <description>The event started 7 months after the subject completed the study</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="70"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="69"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="72"/>
                <counts group_id="E4" subjects_affected="20" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Hyperchlorhydria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Loose tooth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacterial vaginosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="72"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="72"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Vulval abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accidental overdose</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="70"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="69"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="72"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Animal bite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Neck injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Radius fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthritis reactive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Leukocyturia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Ovarian cyst</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Vulvovaginal burning sensation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Vulvovaginal pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="71"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Javier Suárez Almarza</name_or_title>
      <organization>ITF Research Pharma SLU</organization>
      <phone>+34 916572323</phone>
      <email>jsuarez@itfsp.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02967510
org study id: ITFE-2092-C1
secondary id: 2015-005787-42
nct id: NCT02967510
lead sponsor: 
has dmc: No
A Phase 2, Dose-ranging, 12-week Randomized, Double-blind, Placebo controlled, Parallel-group
      Study Evaluating the Efficacy and Safety of Three Formulations of Ultra-low Dose Estriol
      Vaginal Gel (0.005% Estriol Vaginal Gel, 0.002% Estriol Vaginal Gel, 0.0008% Estriol Vaginal
      Gel) for the Treatment of Vaginal Dryness in Postmenopausal Women with Vulvovaginal Atrophy.

      Vulvovaginal atrophy is a natural consequence of the progressive estrogen deficiency that
      occurs in menopause. Epidemiological data have indicated that about 50% of otherwise healthy
      women over 60 years of age experience symptoms related to urogenital atrophy such as vaginal
      dryness, dyspareunia, burning, itching, as well as urinary complaints or infections of the
      lower urinary tract. As these alterations frequently affect the quality of life of
      postmenopausal women, it is important for doctors to detect their presence and offer
      treatment options. Estrogen therapy is the most effective treatment of moderate to severe
      symptoms of vulvar and vaginal atrophy. One advantage of local treatment with estrogen is
      avoidance of first-pass liver metabolism, making it possible to use lower doses of estrogen
      compared with oral therapy; the local route also minimize systemic adverse effects. The
      search for therapeutic alternatives which may present improvements in relation to the current
      products has been encouraged.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change From Baseline to Week 12 in the Severity of Vaginal Dryness
time frame: From baseline to week 12
description: Percentage of Subjects with change from baseline to week 12 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.
measure: Change From Baseline to Week 12 in Vaginal pH
time frame: Baseline to Week 12
description: Change from Baseline to Week 12 in Vaginal pH was reported. A decrease in pH compare to Baseline represents a positive outcome.
measure: Change From Baseline to Week 12 in the Proportion of Superficial Cells of the Vaginal Epithelium.
time frame: Baseline to Week 12
description: Change from Baseline to week 12 in the proportion of superficial cells of the vaginal epithelium was reported.
measure: Change From Baseline to Week 12 in the Proportion of Parabasal Cells of the Vaginal Epithelium.
time frame: Baseline to Week 12
description: Change from Baseline to Week 12 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to Baseline represents a positive outcome.
measure: Change From Baseline to Week 12 in the Severity of Dyspareunia
time frame: Baseline to Week 12
description: Percentage of subjects with change from baseline to week 12 in the severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.
measure: Change From Baseline to Week 12 in the Severity of Pruritus or Itching
time frame: Baseline to Week 12
description: Percentage of subjects with cvhange from Baseline to Week 12 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.
measure: Change From Baseline to Week 12 in the Severity of Burning
time frame: Baseline to Week 12
description: Percentage of subjects with change from Baseline to Week 12 in the severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to Baseline represented a positive outcome.
measure: Change From Baseline to Week 12 in the Severity of Dysuria
time frame: Baseline to Week 12
description: Percentage of subjects with change from Baseline to Week 12 in the severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.
measure: Change From Baseline to Week 12 in the Global Symptom Score 1
time frame: Baseline to Week 12
description: Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 12/ET visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.
measure: Change From Baseline to Week 12 in the Global Symptom Score 2
time frame: Baseline to Week 12
description: Change from Baseline to Week 12 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 12 in the Severity of Pallor.
time frame: Baseline to Week 12
description: Percentage of subjects with change from Baseline to Week 12 in the severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive putcome.
measure: Change From Baseline to Week 12 in the Severity of Friability
time frame: Baseline to Week 12
description: Percentage of subjects with change from Baseline to Week 12 in the severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 12 in the Severity of Thinning or Flattening of Folds
time frame: Baseline to Week 12
description: Percentage of subjects with change from Baseline to Week 12 in the severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 12 in the Severity of Petechiae
time frame: Baseline to Week 12
description: Percentage of subjects with change from Baseline to Week 12 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 12 in the Severity of Dry Mucosa
time frame: Baseline to Week 12
description: Percentage of subjects with change from Baseline to Week 12 in the severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Vaginal Dryness
time frame: Baseline to Week 3
description: Percentage of subjects with change from Baseline to Week 3 in the severity of vaginal dryness was reported. Severity was defined as: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Dyspareunia
time frame: From baseline to week 3
description: Percentage of subjects with change from Baseline to Week 3 in severity of dyspareunia was reported. Dyspareunia was only applicable in subjects who had experienced sexual activity with penetration since the previous study visit. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Pruritus or Itching
time frame: Baseline to Week 3
description: Percentage of subjects with change from Baseline to Week 3 in the severity of pruritus or itching was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Burning
time frame: Baseline to Week 3
description: Percentage of subjects with change from Baseline to Week 3 in severity of burning was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Dysuria
time frame: Baseline to Week 3
description: Percentage of subjects with change from Baseline to Week 3 in severity of dysuria was reported. Symptom scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Global Symptom Score 1
time frame: Baseline to Week 3
description: Global Symptom Score 1 was defined as the sum of all 5 individual symptom scores at a given visit, and was calculated only when all 5 symptom scores had a response available. the Global Symptom Score 1 ranged at Screening/Baseline between 2 (at least moderate vaginal dryness -per inclusion criteria) to 15 (all 5 studied symptoms severe in intensity). At Week 3 visit, the Global Symptom Score ranged between 0 (no symptoms) and 15 (all symptoms severe in intensity). A decrease in score compared to Baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Global Symptom Score 2
time frame: Baseline to Week 3
description: Change from Baseline to Week 3 in the Global Symptom Score 2 was reported. Global Symptom Score 2 was defined as the sum of all 4 individual symptoms excluding dyspareunia (vaginal dryness, pruritus or itching, burning, and dysuria) for each subject at each time point: Screening/Baseline, Week 3 and Week 12/ET., and was calculated only when all 4 symptom scores had a response available. The maximum score possible to be obtained at a visit with the Global Symptom Score 2 was 12 (all symptoms severe in intensity). A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Pallor
time frame: Baseline to Week 3
description: Percentage of subjects with change from Baseline to Week 3 in severity of pallor was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Friability
time frame: Baseline to Week 3
description: Percentage of subjects with change from Baseline to Week 3 in severity of friability was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Thinning or Flattening of Folds
time frame: Baseline to Week 3
description: Percentage of subjects with change from Baseline to Week 3 in severity of thinning or flattening of folds was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Presence of Petechiae
time frame: Baseline to Week 3
description: Percentage of subjects with change from Baseline to Week 3 in the severity of presence of petechiae was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in the Severity of Dry Mucosa
time frame: Baseline to Week 3
description: Percentage of subjects with change from Baseline to Week 3 in severity of dry mucosa was reported. Sign scores at each visit: 0= Absent, 1= Mild, 2= Moderate, 3= Severe. A decrease in score compared to baseline represented a positive outcome.
measure: Change From Baseline to Week 3 in Vaginal pH
time frame: Baseline to Week 3
description: Change from Baseline to Week 3 in vaginal pH was reported. A decrease in pH compared to Baseline represents a positive outcome.
measure: Change From Baseline to Week 3 in the Proportion of Superficial Cells of the Vaginal Epithelium
time frame: Baseline to Week 3
description: Change from baseline to week 3 in the proportion of superficial cells of the vaginal epithelium was reported.
measure: Change From Baseline to Week 3 in the Proportion of Parabasal Cells of the Vaginal Epithelium
time frame: Baseline to Week 3
description: Change from Baseline to Week 3 in the proportion of parabasal cells of the vaginal epithelium was reported. A decrease in proportion of parabasal cells compared to baseline represents a positive outcome.
arm group label: 0.005% estriol vaginal gel
arm group type: Experimental
description: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration
arm group label: 0.002% estriol vaginal gel
arm group type: Experimental
description: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration
arm group label: 0.0008% estriol vaginal gel
arm group type: Experimental
description: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration
arm group label: estriol vaginal gel
arm group type: Placebo Comparator
description: Vaginal. Administration by an applicator inserted deep inside the vagina Dose: 1 g of gel, containing 50 Mcg of estriol Dosage schedule: Weeks 1-3: single daily application Weeks 4-12: twice weekly administration
intervention type: Drug
intervention name: Estriol
arm group label: 0.0008% estriol vaginal gel
arm group label: 0.002% estriol vaginal gel
arm group label: 0.005% estriol vaginal gel
intervention type: Drug
intervention name: Placebo
arm group label: estriol vaginal gel
criteria: 
gender: Female
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
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country: Czechia
country: Hungary
country: Italy
country: Spain
country: Sweden
country: Czech Republic
responsible party type: Sponsor
mesh term: Atrophy
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provided document: 
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reported events: 
certain agreements: 
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