<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/NCT02253173</url>
  </required_header>
  <id_info>
    <org_study_id>TXV14-01</org_study_id>
    <nct_id>NCT02253173</nct_id>
  </id_info>
  <brief_title>Estradiol Vaginal Softgel Capsules in Treating Symptoms of Vulvar and Vaginal Atrophy in Postmenopausal Women</brief_title>
  <acronym>REJOICE</acronym>
  <official_title>A Phase 3, Randomized, Double-blind, Placebo-controlled, Multi-center Trial to Evaluate the Safety and Efficacy of TX-004HR in Postmenopausal Women With Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TherapeuticsMD</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>TherapeuticsMD</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess the safety and efficacy of a new formulation of vaginal estradiol for&#xD;
      the treatment of symptoms of vulvar and vaginal atrophy in postmenopausal women.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <phase>Phase 3</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, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Co-Primary Efficacy Endpoint - Vaginal Superficial Cells</measure>
    <time_frame>Baseline and 12 Weeks</time_frame>
    <description>• Change from Baseline to Week 12 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Co-Primary Efficacy Endpoint - Vaginal Parabasal Cells</measure>
    <time_frame>Baseline and 12 Weeks</time_frame>
    <description>• Change from Baseline to Week 12 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Co-Primary Efficacy Endpoint - Vaginal pH</measure>
    <time_frame>Baseline and 12 Weeks</time_frame>
    <description>• Change from Baseline to Week 12 in vaginal pH as compared to placebo</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Co-Primary Efficacy Endpoint - Severity of Most Bothersome Symptom (Dyspareunia)</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>• Change from Baseline to Week 12 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 12</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Superficial Cells</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>• Change from Baseline to Week 2 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints- Vaginal Superficial Cells</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>Change from Baseline to Week 6 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Superficial Cells</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Change from Baseline to Week 8 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Parabasal Cells</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>Change from Baseline to Week 2 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Parabasal Cells</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>Change from Baseline to Week 6 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Parabasal Cells</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Change from Baseline to Week 8 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal pH</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>Change from Baseline to Week 2 in vaginal pH as compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal pH</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>Change from Baseline to Week 6 in vaginal pH as compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal pH</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Change from Baseline to Week 8 in vaginal pH as compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>Change from Baseline to Week 2 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>Change from Baseline to Week 6 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Change from Baseline to Week 8 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>Change from Baseline to Week 2 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>Change from Baseline to Week 6 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Change from Baseline to Week 8 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>Change from Baseline to Week 2 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>Change from Baseline to Week 6 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Change from Baseline to Week 8 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>Change from Baseline to Week 2 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</measure>
    <time_frame>Baseline to Week 6</time_frame>
    <description>Change from Baseline to Week 6 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</measure>
    <time_frame>Baseline to Week 8</time_frame>
    <description>Change from Baseline to Week 8 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>Change from Baseline to Week 2 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>Change from Baseline to Week 6 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Change from Baseline to Week 8 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>Change from Baseline to Week 2 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>Change from Baseline to Week 6 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Change from Baseline to Week 8 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</measure>
    <time_frame>Baseline and Week 2</time_frame>
    <description>Change from Baseline to Week 2 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>Change from Baseline to Week 6 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Change from Baseline to Week 8 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) - Total Score</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in FSFI Total Score as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Arousal</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in FSFI Domain Score (Arousal) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Desire</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in FSFI Domain Score (Desire) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Lubrication</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in FSFI Domain Score (Lubrication) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Orgasm</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in FSFI Domain Score (Orgasm) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Pain</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in FSFI Domain Score (Pain) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Satisfaction</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>Change from Baseline to Week 12 in FSFI Domain Score (Satisfaction) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>PK Substudy - Hormone Concentration Assessments (Serum Estradiol, Estrone and Estrone Conjugates; SHBG)</measure>
    <time_frame>Pre-treatment, Day 2, Weeks 2 and 12</time_frame>
    <description>Blood samples will be obtained from a subset of subjects at pre-selected sites to characterize PK parameters (AUC, tmax, Cmin, Cmax, Cavg) and to measure SHBG</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">764</enrollment>
  <condition>Vulvovaginal Atrophy</condition>
  <condition>Menopause</condition>
  <condition>Dyspareunia</condition>
  <condition>Painful Intercourse</condition>
  <arm_group>
    <arm_group_label>Estradiol 4mcg Vaginal Softgel Capsule</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Estradiol 4mcg Vaginal Softgel Capsule</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Estradiol 10mcg Vaginal Softgel Capsule</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Estradiol 10mcg Vaginal Softgel Capsule</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Estradiol 25mcg Vaginal Softgel Capsule</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Estradiol 25mcg Vaginal Softgel Capsule</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Vaginal Softgel Capsule</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Vaginal Softgel Capsule</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estradiol</intervention_name>
    <arm_group_label>Estradiol 10mcg Vaginal Softgel Capsule</arm_group_label>
    <arm_group_label>Estradiol 25mcg Vaginal Softgel Capsule</arm_group_label>
    <arm_group_label>Estradiol 4mcg Vaginal Softgel Capsule</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo Vaginal Softgel Capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Postmenopausal female subjects between the ages of 40 and 75 years (at the time of&#xD;
             randomization) with at least:&#xD;
&#xD;
               -  12 months of spontaneous amenorrhea (women &lt;55 years of age with a history of&#xD;
                  hysterectomy without bilateral oophorectomy prior to natural menopause must have&#xD;
                  follicle stimulating hormone (FSH) levels &gt; 40 mIU/mL), OR&#xD;
&#xD;
               -  6 months of spontaneous amenorrhea with follicle stimulating hormone (FSH) levels&#xD;
                  &gt; 40mlU/mL OR&#xD;
&#xD;
               -  At least 6 weeks postsurgical bilateral oophorectomy.&#xD;
&#xD;
          2. ≤5% superficial cells on vaginal cytological smear&#xD;
&#xD;
          3. Vaginal pH &gt; 5.0&#xD;
&#xD;
          4. Moderate to severe symptom of vaginal pain associated with sexual activity considered&#xD;
             the most bothersome vaginal symptom by the subject at screening visit 1A.&#xD;
&#xD;
          5. Moderate to severe symptom of vaginal pain associated with sexual activity at&#xD;
             screening visit 1B.&#xD;
&#xD;
          6. Onset of moderate to severe dyspareunia in the postmenopausal years.&#xD;
&#xD;
          7. Subjects should be sexually active (i.e. have sexual activity with vaginal penetration&#xD;
             within approximately 1 month of screening visit 1A).&#xD;
&#xD;
          8. Subjects should anticipate having sexual activity (with vaginal penetration) during&#xD;
             the conduct of the trial.&#xD;
&#xD;
          9. For subjects with an intact uterus: Subjects must have an acceptable result from an&#xD;
             evaluable screening endometrial biopsy.&#xD;
&#xD;
         10. Subjects who have a Body Mass Index (BMI) less than or equal to 38 kg/m2. BMI values&#xD;
             should be rounded to the nearest integer (ex. 32.4 rounds down to 32, while 26.5&#xD;
             rounds up to 27).&#xD;
&#xD;
         11. In the opinion of the investigator, the subject will comply with the protocol and has&#xD;
             a high probability of completing the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of the following:&#xD;
&#xD;
               1. Oral estrogen-, progestin-, androgen-, or SERM-containing drug products within 8&#xD;
                  weeks before screening visit 1A (can enter washout);&#xD;
&#xD;
               2. Use of transdermal hormone products within 4 weeks before screening visit 1A (can&#xD;
                  enter washout);&#xD;
&#xD;
               3. Use of vaginal hormone products (rings, creams, gels) within 4 weeks before&#xD;
                  screening visit1A (can enter washout);&#xD;
&#xD;
               4. Use of intrauterine progestins within 8 weeks before screening visit 1A (can&#xD;
                  enter washout);&#xD;
&#xD;
               5. Use of progestin implants/injectables or estrogen pellets/injectables within 6&#xD;
                  months before screening visit 1A (cannot enter washout);&#xD;
&#xD;
               6. Use of vaginal lubricants or moisturizers within 7 days before the screening&#xD;
                  visit 1B vaginal pH assessment.&#xD;
&#xD;
          2. A history or active presence of clinically important medical disease that might&#xD;
             confound the study or be detrimental to the subject, examples include:&#xD;
&#xD;
               1. Hypersensitivity to estrogens;&#xD;
&#xD;
               2. Endometrial hyperplasia;&#xD;
&#xD;
               3. Undiagnosed vaginal bleeding;&#xD;
&#xD;
               4. Have a history of a chronic liver or kidney dysfunction/disorder (e.g., Hepatitis&#xD;
                  C or chronic renal failure);&#xD;
&#xD;
               5. Thrombophlebitis, thrombosis or thromboembolic disorders;&#xD;
&#xD;
               6. Cerebrovascular accident, stroke, or transient ischemic attack;&#xD;
&#xD;
               7. Myocardial infarction or ischemic heart disease;&#xD;
&#xD;
               8. Malignancy or treatment for malignancy, within the previous 5 years, with the&#xD;
                  exception of basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
                  skin. A history of estrogen dependent neoplasia, breast cancer, melanoma or any&#xD;
                  gynecologic cancer, at any time, excludes the subject;&#xD;
&#xD;
               9. Endocrine disease (except for controlled hypothyroidism or controlled non-insulin&#xD;
                  dependent diabetes mellitus).&#xD;
&#xD;
          3. Recent history of known alcohol or drug abuse.&#xD;
&#xD;
          4. History of sexual abuse or spousal abuse that, in the opinion of the PI, may interfere&#xD;
             with the subject's assessment of vaginal pain with sexual activity.&#xD;
&#xD;
          5. Current history of Heavy smoking (more than 15 cigarettes per day) or use of&#xD;
             e-cigarettes.&#xD;
&#xD;
          6. Use of an intrauterine device within 12 weeks before screening visit 1A.&#xD;
&#xD;
          7. Use of an investigational drug within 60 days before screening visit 1A.&#xD;
&#xD;
          8. Any clinically important abnormalities on screening physical exam, assessments, ECG,&#xD;
             or laboratory tests, such as:&#xD;
&#xD;
               1. Unresolved cervical cytologic smear report of atypical glandular cells of&#xD;
                  undetermined significance (AGUS) or atypical squamous cells of undetermined&#xD;
                  significance (ASCUS).&#xD;
&#xD;
                  Cervical cytologic smear report of low-grade squamous intraepithelial lesion&#xD;
                  (SIL) or greater, CIN1 or greater, or any reported dysplasia; Subjects with ASCUS&#xD;
                  are eligible only if high risk human papilloma virus (HPV) result is negative.&#xD;
&#xD;
               2. Unresolved findings suspicious for malignancy on the breast exam; incomplete&#xD;
                  mammogram result (BI-RADS 0) or unresolved findings suggestive of malignant&#xD;
                  changes or findings requiring short interval follow-up on the prestudy mammogram&#xD;
                  (subjects must have mammography result of BI-RADS 1 or 2 to enroll.) Mammogram&#xD;
                  may be performed within 9 months prior to Visit 2 (randomization) with&#xD;
                  documentation available. (The site must obtain a copy of the official report for&#xD;
                  the subject's study file, and it must be verified that the mammogram itself is&#xD;
                  available if needed for additional assessment);&#xD;
&#xD;
               3. In subjects with intact uterus: have a screening endometrial biopsy sample that&#xD;
                  is found by both primary pathologists to have endometrial tissue insufficient for&#xD;
                  diagnosis, no endometrium identified, or no tissue identified. (With the approval&#xD;
                  of the Medical Monitor, the screening endometrial biopsy may be repeated once);&#xD;
&#xD;
               4. In subjects with intact uterus: an endometrial biopsy report by one central&#xD;
                  pathologist at screening with one of the following:&#xD;
&#xD;
                    -  Endometrial hyperplasia endometrial cancer, proliferative endometrium,&#xD;
                       weakly proliferative endometrium, disordered proliferative pattern; OR&#xD;
&#xD;
                    -  Endometrial polyps with hyperplasia, glandular atypia of any degree (e.g.,&#xD;
                       atypical nuclei) or cancer;&#xD;
&#xD;
               5. Vulvar or vaginal inflammatory condition such as a contact or allergic&#xD;
                  dermatitis, lichen sclerosis or other pathological findings;&#xD;
&#xD;
               6. Presence of suspicious vulvar or vaginal lesions for dysplasia, malignancy or&#xD;
                  other pathology other than atrophy;&#xD;
&#xD;
               7. Painful genital warts or localized areas of ulceration;&#xD;
&#xD;
               8. A history of active, chronic pelvic pain;&#xD;
&#xD;
               9. Interstitial cystitis;&#xD;
&#xD;
              10. Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST)&#xD;
                  greater than 1.5 times the upper limit of normal for the laboratory used;&#xD;
&#xD;
              11. Fasting total cholesterol greater than 300 mg/dL (7.77 mmol/L) or triglycerides&#xD;
                  greater than 300 mg/dL (3.39 mmol/L);&#xD;
&#xD;
              12. Fasting blood glucose greater than 125 mg/dL (6.94 mmol/L) with a hemoglobin A1C&#xD;
                  of greater than or equal to 6.5%;&#xD;
&#xD;
              13. Uncontrolled hypertension; subjects with elevated sitting blood pressure, greater&#xD;
                  than 140 mm Hg systolic or greater than 90 mm Hg diastolic and may not be using&#xD;
                  more than 2 antihypertensive medications for the treatment of hypertension;&#xD;
&#xD;
              14. Clinically significant abnormal 12-lead ECG (such as myocardial infarction or&#xD;
                  other findings suggestive of ischemia)&#xD;
&#xD;
          9. Be known to be pregnant or have a positive urine pregnancy test. (Note: A pregnancy&#xD;
             test is not required for subjects who have had bilateral tubal ligation, bilateral&#xD;
             oophorectomy, hysterectomy, or are 55 years old or greater and have experienced&#xD;
             cessation of menses for at least 1 year.&#xD;
&#xD;
         10. Current use of marijuana.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Medical Affiliated Research Center</name>
      <address>
        <city>Huntsville</city>
        <state>Alabama</state>
        <zip>35801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montogomery Women's Health</name>
      <address>
        <city>Montgomery</city>
        <state>Alabama</state>
        <zip>36117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cactus Clinical Research</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Wellness Center for Women</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiant Research</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85251</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Visions Clinical Research - Tucson</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter East Bay Medical Foundation</name>
      <address>
        <city>Berkeley</city>
        <state>California</state>
        <zip>94705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torrance Clinical Research Institute Inc</name>
      <address>
        <city>Lomita</city>
        <state>California</state>
        <zip>90717</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Futura Research</name>
      <address>
        <city>Norwalk</city>
        <state>California</state>
        <zip>90650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern California Research</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95821</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center for Clinical Research</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Diego Sexual Medicine</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Health Care Research Corp.</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lynn Institute of the Rockies</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Downtown Women's Health Care</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Horizons Clinical Research Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Red Rocks OB/Gyn</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Consulting</name>
      <address>
        <city>Milford</city>
        <state>Connecticut</state>
        <zip>06460</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coastal Connecticut Research, LLC</name>
      <address>
        <city>New London</city>
        <state>Connecticut</state>
        <zip>06320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James A. Simon, Women's Health &amp; Research Consultants</name>
      <address>
        <city>Washington, D.C.</city>
        <state>District of Columbia</state>
        <zip>20036</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Florida Medical Research</name>
      <address>
        <city>Aventura</city>
        <state>Florida</state>
        <zip>33180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nature Coast Clinical Research</name>
      <address>
        <city>Crystal River</city>
        <state>Florida</state>
        <zip>34429</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avail Clinical Research</name>
      <address>
        <city>DeLand</city>
        <state>Florida</state>
        <zip>32720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Physiology Associates</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33916</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF Health Physicians Women's &amp; REI Springhill</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF College of Medicine-Jacksonville, Dept. of Obstetrics and Gynecology</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jacksonville Center for Clinical Research</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Florida Wellness &amp; Clinical Research Institute</name>
      <address>
        <city>Margate</city>
        <state>Florida</state>
        <zip>33063</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Age Medical Research Corporation</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33186</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Suncoast Clinical Research, Inc.</name>
      <address>
        <city>New Port Richey</city>
        <state>Florida</state>
        <zip>34652</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ideal Clinical Research</name>
      <address>
        <city>North Miami Beach</city>
        <state>Florida</state>
        <zip>33162</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Healthcare Clinical Data</name>
      <address>
        <city>North Miami</city>
        <state>Florida</state>
        <zip>33161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiant Research</name>
      <address>
        <city>Pinellas Park</city>
        <state>Florida</state>
        <zip>33781</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>All Women's Healthcare of West Broward</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Physician Care Clinical Research</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Clinical Trials</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Health Associates</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Masters of Clinical Research, Inc.</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Soapstone Center for Clinical Research</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>WR-Mount Vernon Clinical Research</name>
      <address>
        <city>Sandy Springs</city>
        <state>Georgia</state>
        <zip>30328</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fellows Research Alliance, Inc.</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Clinical Research</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Healthcare Associates P.A.</name>
      <address>
        <city>Idaho Falls</city>
        <state>Idaho</state>
        <zip>83404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiant Research</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60654</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Health Network of Indiana, LLC</name>
      <address>
        <city>Avon</city>
        <state>Indiana</state>
        <zip>46123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lafayette Clinical Research Group</name>
      <address>
        <city>Lafayette</city>
        <state>Indiana</state>
        <zip>47905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cypress Medical Research Center</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Kentucky Research Associates, Inc.</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bluegrass Clinical Research, Inc.</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40291</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Horizon Research Group of Opelousas</name>
      <address>
        <city>Eunice</city>
        <state>Louisiana</state>
        <zip>70535</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital Women's Care</name>
      <address>
        <city>Frederick</city>
        <state>Maryland</state>
        <zip>21702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Center for Sexual Health</name>
      <address>
        <city>Lutherville</city>
        <state>Maryland</state>
        <zip>21093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ClinSite, LLC</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beyer Research</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saginaw Valley Medical Research Group, L.L.C.</name>
      <address>
        <city>Saginaw</city>
        <state>Michigan</state>
        <zip>48604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montana Health</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Clinic of Lincoln</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Office of Edmond E. Pack, MD</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Office of R. Garn Mabey, MD</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lawrence OB-GYN Clinical Research, LLC</name>
      <address>
        <city>Lawrenceville</city>
        <state>New Jersey</state>
        <zip>08648</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers-Robert Wood Johnson Medical School</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Health Research Center</name>
      <address>
        <city>Plainsboro</city>
        <state>New Jersey</state>
        <zip>08536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bosque Women's Care</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Clinical Research</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Suffolk OB/GYN</name>
      <address>
        <city>Port Jefferson</city>
        <state>New York</state>
        <zip>08536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Wellness Clinic</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pinewest OB-GYN, Inc.</name>
      <address>
        <city>High Point</city>
        <state>North Carolina</state>
        <zip>27262</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Research Associates</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hawthorne Research</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lyndhurst Clinical Research</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lillestol Research</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radiant Research</name>
      <address>
        <city>Akron</city>
        <state>Ohio</state>
        <zip>44311</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Physicians Company</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267-0457</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rapid Medical Research</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbus Center for Women's Health Research</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HWC Women's Research Center</name>
      <address>
        <city>Englewood</city>
        <state>Ohio</state>
        <zip>45322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Landerbrook Health Center</name>
      <address>
        <city>Mayfield Heights</city>
        <state>Ohio</state>
        <zip>44124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunstone Medical Research</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <zip>97504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Clinical Trial Center</name>
      <address>
        <city>Jenkintown</city>
        <state>Pennsylvania</state>
        <zip>19046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials Research Services</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fellows Research Alliance, Inc.</name>
      <address>
        <city>Bluffton</city>
        <state>South Carolina</state>
        <zip>29910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vista Clinical Research</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coastal Carolina Research Center</name>
      <address>
        <city>Mount Pleasant</city>
        <state>South Carolina</state>
        <zip>29464</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chattanooga Medical Research</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Research Associates</name>
      <address>
        <city>Corpus Christi</city>
        <state>Texas</state>
        <zip>78414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Across America</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advances in Health</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hwca, Pllc</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TMC Life Research</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stone Oak, LLC dba Discovery Clinical Trials</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Clinical Research-Norfolk</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Center, EVMS</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Women's Center, Inc.</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Clinical Research-Richmond, Inc</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tidewater Clinical Research</name>
      <address>
        <city>Virginia Beach</city>
        <state>Virginia</state>
        <zip>23456</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Women's Health, Research, and Gynecology</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Spokane Women's Health</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Diex Research Montreal Inc.</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4N 3C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Diex Research Sherbrooke Inc.</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 1Z1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manna Research Inc</name>
      <address>
        <city>St-Romuald</city>
        <state>Quebec</state>
        <zip>G6W 5M6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique RSF Inc.</name>
      <address>
        <city>Quebec</city>
        <zip>G1S 2L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Research Saint-Louis</name>
      <address>
        <city>Quebec</city>
        <zip>G1W4R4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <results_first_submitted>August 8, 2016</results_first_submitted>
  <results_first_submitted_qc>April 20, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 25, 2017</results_first_posted>
  <last_update_submitted>April 20, 2017</last_update_submitted>
  <last_update_submitted_qc>April 20, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>VVA</keyword>
  <keyword>Painful Sex</keyword>
  <keyword>Postmenopausal</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyspareunia</mesh_term>
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estradiol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
          <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
        </group>
        <group group_id="P2">
          <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
          <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
        </group>
        <group group_id="P3">
          <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
          <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
        </group>
        <group group_id="P4">
          <title>Placebo Vaginal Softgel Capsule</title>
          <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="191"/>
                <participants group_id="P2" count="191"/>
                <participants group_id="P3" count="190"/>
                <participants group_id="P4" count="192"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="175"/>
                <participants group_id="P2" count="174"/>
                <participants group_id="P3" count="177"/>
                <participants group_id="P4" count="178"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="13"/>
                <participants group_id="P4" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The modified intent to treat (MITT) population was the primary efficacy population, defined as all ITT subjects who received the treatment to which they were randomized, had baseline values for all co-primary variables, and had at least one post-baseline value for any of the four co-primary variables at any visit.</population>
      <group_list>
        <group group_id="B1">
          <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
          <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
        </group>
        <group group_id="B2">
          <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
          <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
        </group>
        <group group_id="B3">
          <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
          <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
        </group>
        <group group_id="B4">
          <title>Placebo Vaginal Softgel Capsule</title>
          <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</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="191"/>
            <count group_id="B2" value="191"/>
            <count group_id="B3" value="190"/>
            <count group_id="B4" value="192"/>
            <count group_id="B5" value="764"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="148"/>
                    <measurement group_id="B2" value="162"/>
                    <measurement group_id="B3" value="156"/>
                    <measurement group_id="B4" value="151"/>
                    <measurement group_id="B5" value="617"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="34"/>
                    <measurement group_id="B4" value="41"/>
                    <measurement group_id="B5" value="147"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="59.8" spread="5.90"/>
                    <measurement group_id="B2" value="58.5" spread="6.29"/>
                    <measurement group_id="B3" value="58.9" spread="6.26"/>
                    <measurement group_id="B4" value="59.3" spread="6.07"/>
                    <measurement group_id="B5" value="59.1" spread="6.14"/>
                  </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="191"/>
                    <measurement group_id="B2" value="191"/>
                    <measurement group_id="B3" value="190"/>
                    <measurement group_id="B4" value="192"/>
                    <measurement group_id="B5" value="764"/>
                  </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>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="178"/>
                    <measurement group_id="B2" value="181"/>
                    <measurement group_id="B3" value="175"/>
                    <measurement group_id="B4" value="180"/>
                    <measurement group_id="B5" value="714"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="162.7" spread="6.86"/>
                    <measurement group_id="B2" value="162.9" spread="6.93"/>
                    <measurement group_id="B3" value="162.3" spread="6.37"/>
                    <measurement group_id="B4" value="162.2" spread="6.30"/>
                    <measurement group_id="B5" value="162.5" spread="6.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.4" spread="14.26"/>
                    <measurement group_id="B2" value="71.1" spread="13.49"/>
                    <measurement group_id="B3" value="70.6" spread="13.7"/>
                    <measurement group_id="B4" value="70.4" spread="13.6"/>
                    <measurement group_id="B5" value="70.6" spread="13.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.5" spread="4.87"/>
                    <measurement group_id="B2" value="26.8" spread="4.68"/>
                    <measurement group_id="B3" value="26.7" spread="4.79"/>
                    <measurement group_id="B4" value="26.7" spread="4.59"/>
                    <measurement group_id="B5" value="26.7" spread="4.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Co-Primary Efficacy Endpoint - Vaginal Superficial Cells</title>
        <description>• Change from Baseline to Week 12 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
        <time_frame>Baseline and 12 Weeks</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Co-Primary Efficacy Endpoint - Vaginal Superficial Cells</title>
          <description>• Change from Baseline to Week 12 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>percentage of vaginal superficial cells</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="170"/>
                <count group_id="O2" value="171"/>
                <count group_id="O3" value="174"/>
                <count group_id="O4" value="172"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.50" spread="1.542"/>
                    <measurement group_id="O2" value="16.72" spread="1.540"/>
                    <measurement group_id="O3" value="23.20" spread="1.529"/>
                    <measurement group_id="O4" value="5.63" spread="1.537"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Co-Primary Efficacy Endpoint - Vaginal Parabasal Cells</title>
        <description>• Change from Baseline to Week 12 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
        <time_frame>Baseline and 12 Weeks</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Co-Primary Efficacy Endpoint - Vaginal Parabasal Cells</title>
          <description>• Change from Baseline to Week 12 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>percentage of vaginal parabasal cells</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="170"/>
                <count group_id="O2" value="171"/>
                <count group_id="O3" value="174"/>
                <count group_id="O4" value="172"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-40.63" spread="1.755"/>
                    <measurement group_id="O2" value="-44.07" spread="1.751"/>
                    <measurement group_id="O3" value="-45.55" spread="1.745"/>
                    <measurement group_id="O4" value="-6.73" spread="1.750"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Co-Primary Efficacy Endpoint - Vaginal pH</title>
        <description>• Change from Baseline to Week 12 in vaginal pH as compared to placebo</description>
        <time_frame>Baseline and 12 Weeks</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Co-Primary Efficacy Endpoint - Vaginal pH</title>
          <description>• Change from Baseline to Week 12 in vaginal pH as compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>pH units</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="170"/>
                <count group_id="O2" value="171"/>
                <count group_id="O3" value="174"/>
                <count group_id="O4" value="174"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.32" spread="0.066"/>
                    <measurement group_id="O2" value="-1.42" spread="0.066"/>
                    <measurement group_id="O3" value="-1.34" spread="0.066"/>
                    <measurement group_id="O4" value="-0.28" spread="0.066"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Co-Primary Efficacy Endpoint - Severity of Most Bothersome Symptom (Dyspareunia)</title>
        <description>• Change from Baseline to Week 12 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 12</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Co-Primary Efficacy Endpoint - Severity of Most Bothersome Symptom (Dyspareunia)</title>
          <description>• Change from Baseline to Week 12 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 12</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="151"/>
                <count group_id="O2" value="154"/>
                <count group_id="O3" value="159"/>
                <count group_id="O4" value="163"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.52" spread="0.071"/>
                    <measurement group_id="O2" value="-1.69" spread="0.071"/>
                    <measurement group_id="O3" value="-1.69" spread="0.071"/>
                    <measurement group_id="O4" value="-1.28" spread="0.070"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0149</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Superficial Cells</title>
        <description>• Change from Baseline to Week 2 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Superficial Cells</title>
          <description>• Change from Baseline to Week 2 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>percentage of vaginal superficial cells</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="186"/>
                <count group_id="O2" value="188"/>
                <count group_id="O3" value="184"/>
                <count group_id="O4" value="185"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.35" spread="1.496"/>
                    <measurement group_id="O2" value="31.93" spread="1.488"/>
                    <measurement group_id="O3" value="38.85" spread="1.500"/>
                    <measurement group_id="O4" value="6.05" spread="1.498"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints- Vaginal Superficial Cells</title>
        <description>Change from Baseline to Week 6 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints- Vaginal Superficial Cells</title>
          <description>Change from Baseline to Week 6 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>percentage of vaginal superficial cells</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="172"/>
                <count group_id="O2" value="170"/>
                <count group_id="O3" value="173"/>
                <count group_id="O4" value="176"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.41" spread="1.536"/>
                    <measurement group_id="O2" value="16.88" spread="1.543"/>
                    <measurement group_id="O3" value="22.65" spread="1.532"/>
                    <measurement group_id="O4" value="5.43" spread="1.525"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Superficial Cells</title>
        <description>Change from Baseline to Week 8 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Superficial Cells</title>
          <description>Change from Baseline to Week 8 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>percentage of vaginal superficial cells</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="164"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="166"/>
                <count group_id="O4" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.04" spread="1.561"/>
                    <measurement group_id="O2" value="17.41" spread="1.558"/>
                    <measurement group_id="O3" value="23.88" spread="1.554"/>
                    <measurement group_id="O4" value="5.98" spread="1.551"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Parabasal Cells</title>
        <description>Change from Baseline to Week 2 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Parabasal Cells</title>
          <description>Change from Baseline to Week 2 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>percentage of vaginal parabasal cells</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="186"/>
                <count group_id="O2" value="188"/>
                <count group_id="O3" value="184"/>
                <count group_id="O4" value="185"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-40.23" spread="1.720"/>
                    <measurement group_id="O2" value="-44.42" spread="1.710"/>
                    <measurement group_id="O3" value="-45.60" spread="1.723"/>
                    <measurement group_id="O4" value="-7.00" spread="1.720"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Parabasal Cells</title>
        <description>Change from Baseline to Week 6 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Parabasal Cells</title>
          <description>Change from Baseline to Week 6 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>percentage of vaginal parabasal cells</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="172"/>
                <count group_id="O2" value="170"/>
                <count group_id="O3" value="173"/>
                <count group_id="O4" value="176"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-39.36" spread="1.750"/>
                    <measurement group_id="O2" value="-43.55" spread="1.752"/>
                    <measurement group_id="O3" value="-45.61" spread="1.746"/>
                    <measurement group_id="O4" value="-9.23" spread="1.741"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Parabasal Cells</title>
        <description>Change from Baseline to Week 8 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Parabasal Cells</title>
          <description>Change from Baseline to Week 8 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>percentage of vaginal parabasal cells</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="164"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="166"/>
                <count group_id="O4" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-41.87" spread="1.768"/>
                    <measurement group_id="O2" value="-43.78" spread="1.764"/>
                    <measurement group_id="O3" value="-45.08" spread="1.762"/>
                    <measurement group_id="O4" value="-7.86" spread="1.760"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal pH</title>
        <description>Change from Baseline to Week 2 in vaginal pH as compared to placebo</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal pH</title>
          <description>Change from Baseline to Week 2 in vaginal pH as compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>pH units</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="186"/>
                <count group_id="O2" value="188"/>
                <count group_id="O3" value="184"/>
                <count group_id="O4" value="186"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.23" spread="0.064"/>
                    <measurement group_id="O2" value="-1.37" spread="0.064"/>
                    <measurement group_id="O3" value="-1.30" spread="0.065"/>
                    <measurement group_id="O4" value="-0.28" spread="0.064"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal pH</title>
        <description>Change from Baseline to Week 6 in vaginal pH as compared to placebo</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal pH</title>
          <description>Change from Baseline to Week 6 in vaginal pH as compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>pH units</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="172"/>
                <count group_id="O2" value="170"/>
                <count group_id="O3" value="173"/>
                <count group_id="O4" value="176"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.32" spread="0.066"/>
                    <measurement group_id="O2" value="-1.40" spread="0.066"/>
                    <measurement group_id="O3" value="-1.48" spread="0.066"/>
                    <measurement group_id="O4" value="-0.30" spread="0.065"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal pH</title>
        <description>Change from Baseline to Week 8 in vaginal pH as compared to placebo</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal pH</title>
          <description>Change from Baseline to Week 8 in vaginal pH as compared to placebo</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>pH units</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="164"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="166"/>
                <count group_id="O4" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.35" spread="0.067"/>
                    <measurement group_id="O2" value="-1.46" spread="0.067"/>
                    <measurement group_id="O3" value="-1.45" spread="0.066"/>
                    <measurement group_id="O4" value="-0.38" spread="0.066"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)</title>
        <description>Change from Baseline to Week 2 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 2</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)</title>
          <description>Change from Baseline to Week 2 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 2</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="145"/>
                <count group_id="O2" value="147"/>
                <count group_id="O3" value="140"/>
                <count group_id="O4" value="141"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.99" spread="0.072"/>
                    <measurement group_id="O2" value="-1.08" spread="0.072"/>
                    <measurement group_id="O3" value="-1.02" spread="0.073"/>
                    <measurement group_id="O4" value="-0.76" spread="0.072"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0260</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0019</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0105</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)</title>
        <description>Change from Baseline to Week 6 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 6</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)</title>
          <description>Change from Baseline to Week 6 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 6</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="148"/>
                <count group_id="O2" value="150"/>
                <count group_id="O3" value="150"/>
                <count group_id="O4" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.30" spread="0.072"/>
                    <measurement group_id="O2" value="-1.37" spread="0.072"/>
                    <measurement group_id="O3" value="-1.48" spread="0.072"/>
                    <measurement group_id="O4" value="-1.03" spread="0.070"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0069</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0009</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)</title>
        <description>Change from Baseline to Week 8 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 8</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)</title>
          <description>Change from Baseline to Week 8 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 8</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="140"/>
                <count group_id="O2" value="136"/>
                <count group_id="O3" value="129"/>
                <count group_id="O4" value="143"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.52" spread="0.073"/>
                    <measurement group_id="O2" value="-1.64" spread="0.074"/>
                    <measurement group_id="O3" value="-1.62" spread="0.075"/>
                    <measurement group_id="O4" value="-1.15" spread="0.072"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0003</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</title>
        <description>Change from Baseline to Week 2 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 2</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</title>
          <description>Change from Baseline to Week 2 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 2</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="186"/>
                <count group_id="O2" value="188"/>
                <count group_id="O3" value="184"/>
                <count group_id="O4" value="185"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.86" spread="0.066"/>
                    <measurement group_id="O2" value="-1.01" spread="0.065"/>
                    <measurement group_id="O3" value="-0.96" spread="0.066"/>
                    <measurement group_id="O4" value="-0.72" spread="0.066"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.1269</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0019</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0082</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</title>
        <description>Change from Baseline to Week 6 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 6</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</title>
          <description>Change from Baseline to Week 6 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 6</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="172"/>
                <count group_id="O2" value="170"/>
                <count group_id="O3" value="172"/>
                <count group_id="O4" value="176"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.14" spread="0.067"/>
                    <measurement group_id="O2" value="-1.27" spread="0.068"/>
                    <measurement group_id="O3" value="-1.23" spread="0.067"/>
                    <measurement group_id="O4" value="-0.90" spread="0.067"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0094</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0005</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</title>
        <description>Change from Baseline to Week 8 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 8</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</title>
          <description>Change from Baseline to Week 8 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 8</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="163"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="165"/>
                <count group_id="O4" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.25" spread="0.069"/>
                    <measurement group_id="O2" value="-1.44" spread="0.068"/>
                    <measurement group_id="O3" value="-1.34" spread="0.068"/>
                    <measurement group_id="O4" value="-1.01" spread="0.068"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0128</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0008</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</title>
        <description>Change from Baseline to Week 12 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 12</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)</title>
          <description>Change from Baseline to Week 12 on the severity of vaginal dryness associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 12</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="171"/>
                <count group_id="O2" value="173"/>
                <count group_id="O3" value="176"/>
                <count group_id="O4" value="174"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.27" spread="0.068"/>
                    <measurement group_id="O2" value="-1.47" spread="0.067"/>
                    <measurement group_id="O3" value="-1.47" spread="0.067"/>
                    <measurement group_id="O4" value="-0.97" spread="0.067"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0014</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</title>
        <description>Change from Baseline to Week 2 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 2</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</title>
          <description>Change from Baseline to Week 2 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 2</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="186"/>
                <count group_id="O2" value="188"/>
                <count group_id="O3" value="184"/>
                <count group_id="O4" value="185"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.47" spread="0.054"/>
                    <measurement group_id="O2" value="-0.56" spread="0.053"/>
                    <measurement group_id="O3" value="-0.51" spread="0.054"/>
                    <measurement group_id="O4" value="-0.47" spread="0.054"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.9616</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2439</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.6518</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</title>
        <description>Change from Baseline to Week 6 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 6</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</title>
          <description>Change from Baseline to Week 6 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 6</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="172"/>
                <count group_id="O2" value="170"/>
                <count group_id="O3" value="172"/>
                <count group_id="O4" value="176"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.57" spread="0.055"/>
                    <measurement group_id="O2" value="-0.64" spread="0.055"/>
                    <measurement group_id="O3" value="-0.61" spread="0.055"/>
                    <measurement group_id="O4" value="-0.55" spread="0.055"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.7829</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2328</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4118</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</title>
        <description>Change from Baseline to Week 8 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 8</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</title>
          <description>Change from Baseline to Week 8 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 8</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="163"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="165"/>
                <count group_id="O4" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.74" spread="0.056"/>
                    <measurement group_id="O2" value="-0.76" spread="0.056"/>
                    <measurement group_id="O3" value="-0.73" spread="0.056"/>
                    <measurement group_id="O4" value="-0.59" spread="0.056"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0639</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0356</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0914</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</title>
        <description>Change from Baseline to Week 12 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 12</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)</title>
          <description>Change from Baseline to Week 12 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo&#xD;
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.&#xD;
Subjects assessed severity at Baseline and Week 12</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="171"/>
                <count group_id="O2" value="173"/>
                <count group_id="O3" value="176"/>
                <count group_id="O4" value="174"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.75" spread="0.055"/>
                    <measurement group_id="O2" value="-0.81" spread="0.055"/>
                    <measurement group_id="O3" value="-0.77" spread="0.055"/>
                    <measurement group_id="O4" value="-0.60" spread="0.055"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0503</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0055</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0263</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</title>
        <description>Change from Baseline to Week 2 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 2</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</title>
          <description>Change from Baseline to Week 2 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 2</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="185"/>
                <count group_id="O2" value="187"/>
                <count group_id="O3" value="184"/>
                <count group_id="O4" value="187"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.69" spread="0.048"/>
                    <measurement group_id="O2" value="-0.77" spread="0.047"/>
                    <measurement group_id="O3" value="-0.78" spread="0.048"/>
                    <measurement group_id="O4" value="-0.40" spread="0.047"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</title>
        <description>Change from Baseline to Week 6 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 6</description>
        <time_frame>Baseline to Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</title>
          <description>Change from Baseline to Week 6 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 6</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="172"/>
                <count group_id="O2" value="170"/>
                <count group_id="O3" value="173"/>
                <count group_id="O4" value="176"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.82" spread="0.049"/>
                    <measurement group_id="O2" value="-0.93" spread="0.049"/>
                    <measurement group_id="O3" value="-0.89" spread="0.049"/>
                    <measurement group_id="O4" value="-0.50" spread="0.048"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</title>
        <description>Change from Baseline to Week 8 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 8</description>
        <time_frame>Baseline to Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</title>
          <description>Change from Baseline to Week 8 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 8</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="164"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="166"/>
                <count group_id="O4" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.98" spread="0.050"/>
                    <measurement group_id="O2" value="-1.04" spread="0.050"/>
                    <measurement group_id="O3" value="-0.99" spread="0.049"/>
                    <measurement group_id="O4" value="-0.50" spread="0.049"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</title>
        <description>Change from Baseline to Week 12 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 12</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)</title>
          <description>Change from Baseline to Week 12 in Vaginal Color as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 12</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="171"/>
                <count group_id="O2" value="173"/>
                <count group_id="O3" value="175"/>
                <count group_id="O4" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.97" spread="0.049"/>
                    <measurement group_id="O2" value="-1.06" spread="0.049"/>
                    <measurement group_id="O3" value="-0.96" spread="0.049"/>
                    <measurement group_id="O4" value="-0.60" spread="0.049"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</title>
        <description>Change from Baseline to Week 2 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 2</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</title>
          <description>Change from Baseline to Week 2 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 2</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="185"/>
                <count group_id="O2" value="187"/>
                <count group_id="O3" value="184"/>
                <count group_id="O4" value="186"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.85" spread="0.049"/>
                    <measurement group_id="O2" value="-0.87" spread="0.049"/>
                    <measurement group_id="O3" value="-0.93" spread="0.049"/>
                    <measurement group_id="O4" value="-0.53" spread="0.049"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</title>
        <description>Change from Baseline to Week 6 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 6</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</title>
          <description>Change from Baseline to Week 6 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 6</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="172"/>
                <count group_id="O2" value="170"/>
                <count group_id="O3" value="173"/>
                <count group_id="O4" value="176"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.97" spread="0.051"/>
                    <measurement group_id="O2" value="-1.02" spread="0.051"/>
                    <measurement group_id="O3" value="-1.01" spread="0.051"/>
                    <measurement group_id="O4" value="-0.61" spread="0.050"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</title>
        <description>Change from Baseline to Week 8 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 8</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</title>
          <description>Change from Baseline to Week 8 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 8</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="164"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="166"/>
                <count group_id="O4" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.03" spread="0.052"/>
                    <measurement group_id="O2" value="-1.08" spread="0.051"/>
                    <measurement group_id="O3" value="-1.08" spread="0.051"/>
                    <measurement group_id="O4" value="-0.66" spread="0.051"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</title>
        <description>Change from Baseline to Week 12 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 12</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)</title>
          <description>Change from Baseline to Week 12 in Vaginal Epithelial Integrity as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 12</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline</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="171"/>
                <count group_id="O2" value="173"/>
                <count group_id="O3" value="175"/>
                <count group_id="O4" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.97" spread="0.051"/>
                    <measurement group_id="O2" value="-1.07" spread="0.051"/>
                    <measurement group_id="O3" value="-1.01" spread="0.050"/>
                    <measurement group_id="O4" value="-0.60" spread="0.050"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</title>
        <description>Change from Baseline to Week 2 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 2</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</title>
          <description>Change from Baseline to Week 2 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 2</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="185"/>
                <count group_id="O2" value="187"/>
                <count group_id="O3" value="184"/>
                <count group_id="O4" value="186"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.76" spread="0.049"/>
                    <measurement group_id="O2" value="-0.76" spread="0.049"/>
                    <measurement group_id="O3" value="-0.76" spread="0.049"/>
                    <measurement group_id="O4" value="-0.40" spread="0.049"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</title>
        <description>Change from Baseline to Week 6 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 6</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</title>
          <description>Change from Baseline to Week 6 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 6</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline</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="172"/>
                <count group_id="O2" value="170"/>
                <count group_id="O3" value="173"/>
                <count group_id="O4" value="176"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.85" spread="0.051"/>
                    <measurement group_id="O2" value="-0.93" spread="0.051"/>
                    <measurement group_id="O3" value="-0.90" spread="0.050"/>
                    <measurement group_id="O4" value="-0.53" spread="0.050"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</title>
        <description>Change from Baseline to Week 8 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 8</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</title>
          <description>Change from Baseline to Week 8 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 8</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="164"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="166"/>
                <count group_id="O4" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.96" spread="0.051"/>
                    <measurement group_id="O2" value="-1.04" spread="0.051"/>
                    <measurement group_id="O3" value="-0.99" spread="0.051"/>
                    <measurement group_id="O4" value="-0.59" spread="0.051"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</title>
        <description>Change from Baseline to Week 12 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 12</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)</title>
          <description>Change from Baseline to Week 12 in Vaginal Epithelial Surface Thickness as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 12</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline</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="171"/>
                <count group_id="O2" value="173"/>
                <count group_id="O3" value="175"/>
                <count group_id="O4" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.98" spread="0.051"/>
                    <measurement group_id="O2" value="-1.03" spread="0.051"/>
                    <measurement group_id="O3" value="-0.94" spread="0.050"/>
                    <measurement group_id="O4" value="-0.61" spread="0.050"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</title>
        <description>Change from Baseline to Week 2 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 2</description>
        <time_frame>Baseline and Week 2</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</title>
          <description>Change from Baseline to Week 2 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain) = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 2</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="185"/>
                <count group_id="O2" value="187"/>
                <count group_id="O3" value="184"/>
                <count group_id="O4" value="186"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.79" spread="0.050"/>
                    <measurement group_id="O2" value="-0.83" spread="0.050"/>
                    <measurement group_id="O3" value="-0.86" spread="0.050"/>
                    <measurement group_id="O4" value="-0.54" spread="0.050"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0004</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</title>
        <description>Change from Baseline to Week 6 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 6</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</title>
          <description>Change from Baseline to Week 6 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 6</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="172"/>
                <count group_id="O2" value="170"/>
                <count group_id="O3" value="173"/>
                <count group_id="O4" value="176"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.90" spread="0.051"/>
                    <measurement group_id="O2" value="-0.95" spread="0.051"/>
                    <measurement group_id="O3" value="-0.97" spread="0.051"/>
                    <measurement group_id="O4" value="-0.60" spread="0.051"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</title>
        <description>Change from Baseline to Week 8 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 8</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</title>
          <description>Change from Baseline to Week 8 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 8</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="164"/>
                <count group_id="O2" value="165"/>
                <count group_id="O3" value="166"/>
                <count group_id="O4" value="167"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.00" spread="0.052"/>
                    <measurement group_id="O2" value="-1.04" spread="0.052"/>
                    <measurement group_id="O3" value="-1.06" spread="0.052"/>
                    <measurement group_id="O4" value="-0.63" spread="0.052"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</title>
        <description>Change from Baseline to Week 12 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 12</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)</title>
          <description>Change from Baseline to Week 12 in Vaginal Secretions as compared to placebo&#xD;
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3&#xD;
Severity was assessed by the Investigator at Baseline and Week 12</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</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="171"/>
                <count group_id="O2" value="173"/>
                <count group_id="O3" value="175"/>
                <count group_id="O4" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.01" spread="0.051"/>
                    <measurement group_id="O2" value="-1.06" spread="0.051"/>
                    <measurement group_id="O3" value="-1.04" spread="0.051"/>
                    <measurement group_id="O4" value="-0.64" spread="0.051"/>
                  </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 or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) - Total Score</title>
        <description>Change from Baseline to Week 12 in FSFI Total Score as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) - Total Score</title>
          <description>Change from Baseline to Week 12 in FSFI Total Score as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="156"/>
                <count group_id="O4" value="158"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.909" lower_limit="6.748" upper_limit="9.070"/>
                    <measurement group_id="O2" value="9.431" lower_limit="8.261" upper_limit="10.601"/>
                    <measurement group_id="O3" value="10.283" lower_limit="9.133" upper_limit="11.434"/>
                    <measurement group_id="O4" value="7.458" lower_limit="6.315" upper_limit="8.602"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.9075</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0492</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0019</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Arousal</title>
        <description>Change from Baseline to Week 12 in FSFI Domain Score (Arousal) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Arousal</title>
          <description>Change from Baseline to Week 12 in FSFI Domain Score (Arousal) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="154"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="157"/>
                <count group_id="O4" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.875" lower_limit="0.657" upper_limit="1.093"/>
                    <measurement group_id="O2" value="1.287" lower_limit="1.066" upper_limit="1.507"/>
                    <measurement group_id="O3" value="1.392" lower_limit="1.176" upper_limit="1.608"/>
                    <measurement group_id="O4" value="0.93" lower_limit="0.715" upper_limit="1.145"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.9719</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0614</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0085</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Desire</title>
        <description>Change from Baseline to Week 12 in FSFI Domain Score (Desire) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Desire</title>
          <description>Change from Baseline to Week 12 in FSFI Domain Score (Desire) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="154"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="157"/>
                <count group_id="O4" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.625" lower_limit="0.471" upper_limit="0.779"/>
                    <measurement group_id="O2" value="0.800" lower_limit="0.646" upper_limit="0.955"/>
                    <measurement group_id="O3" value="0.848" lower_limit="0.695" upper_limit="1.000"/>
                    <measurement group_id="O4" value="0.630" lower_limit="0.479" upper_limit="0.782"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.9999</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2855</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1189</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Lubrication</title>
        <description>Change from Baseline to Week 12 in FSFI Domain Score (Lubrication) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Lubrication</title>
          <description>Change from Baseline to Week 12 in FSFI Domain Score (Lubrication) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="156"/>
                <count group_id="O4" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.834" lower_limit="1.578" upper_limit="2.090"/>
                    <measurement group_id="O2" value="2.242" lower_limit="1.984" upper_limit="2.500"/>
                    <measurement group_id="O3" value="2.299" lower_limit="2.045" upper_limit="2.553"/>
                    <measurement group_id="O4" value="1.595" lower_limit="1.343" upper_limit="1.846"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.4162</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0013</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0003</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Orgasm</title>
        <description>Change from Baseline to Week 12 in FSFI Domain Score (Orgasm) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Orgasm</title>
          <description>Change from Baseline to Week 12 in FSFI Domain Score (Orgasm) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="153"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="156"/>
                <count group_id="O4" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.162" lower_limit="0.903" upper_limit="1.421"/>
                    <measurement group_id="O2" value="1.274" lower_limit="1.013" upper_limit="1.535"/>
                    <measurement group_id="O3" value="1.591" lower_limit="1.334" upper_limit="1.847"/>
                    <measurement group_id="O4" value="1.202" lower_limit="0.948" upper_limit="1.457"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.9929</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.9634</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0898</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Pain</title>
        <description>Change from Baseline to Week 12 in FSFI Domain Score (Pain) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Pain</title>
          <description>Change from Baseline to Week 12 in FSFI Domain Score (Pain) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="154"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="156"/>
                <count group_id="O4" value="159"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.173" lower_limit="1.879" upper_limit="2.467"/>
                    <measurement group_id="O2" value="2.548" lower_limit="2.251" upper_limit="2.844"/>
                    <measurement group_id="O3" value="2.514" lower_limit="2.222" upper_limit="2.805"/>
                    <measurement group_id="O4" value="1.930" lower_limit="1.641" upper_limit="2.219"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.5146</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0099</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0150</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Satisfaction</title>
        <description>Change from Baseline to Week 12 in FSFI Domain Score (Satisfaction) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
        <time_frame>Baseline and Week 12</time_frame>
        <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 4mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O2">
            <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 10mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O3">
            <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
            <description>Estradiol 25mcg Vaginal Softgel Capsule&#xD;
Estradiol</description>
          </group>
          <group group_id="O4">
            <title>Placebo Vaginal Softgel Capsule</title>
            <description>Placebo Vaginal Softgel Capsule&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Satisfaction</title>
          <description>Change from Baseline to Week 12 in FSFI Domain Score (Satisfaction) as compared to placebo&#xD;
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.</description>
          <population>For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="154"/>
                <count group_id="O2" value="152"/>
                <count group_id="O3" value="157"/>
                <count group_id="O4" value="158"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.257" lower_limit="1.046" upper_limit="1.469"/>
                    <measurement group_id="O2" value="1.384" lower_limit="1.170" upper_limit="1.597"/>
                    <measurement group_id="O3" value="1.629" lower_limit="1.420" upper_limit="1.839"/>
                    <measurement group_id="O4" value="1.174" lower_limit="0.965" upper_limit="1.383"/>
                  </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 or Other</non_inferiority_type>
            <p_value>0.9039</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.3751</p_value>
            <method>ANCOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0073</p_value>
            <method>ANCOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>PK Substudy - Hormone Concentration Assessments (Serum Estradiol, Estrone and Estrone Conjugates; SHBG)</title>
        <description>Blood samples will be obtained from a subset of subjects at pre-selected sites to characterize PK parameters (AUC, tmax, Cmin, Cmax, Cavg) and to measure SHBG</description>
        <time_frame>Pre-treatment, Day 2, Weeks 2 and 12</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Estradiol 4mcg Vaginal Softgel Capsule</title>
          <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Estradiol 10mcg Vaginal Softgel Capsule</title>
          <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Estradiol 25mcg Vaginal Softgel Capsule</title>
          <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="192"/>
              </event>
              <event>
                <sub_title>Sinus node dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Endophthalmitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant melanoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cervical myelopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="45" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="66" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="192"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="192"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="15" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal discharge</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="192"/>
              </event>
              <event>
                <sub_title>Vulvovaginal pruritus</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="192"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="191"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="191"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="190"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="192"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Sebastian Mirkin, MD, Chief Medical Officer</name_or_title>
      <organization>TherapeuticsMD</organization>
      <phone>561-961-1900 ext 1952</phone>
      <email>sebastian.mirkin@therapeuticsmd.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/NCT02253173
org study id: TXV14-01
nct id: NCT02253173
lead sponsor: 
has dmc: No
This study will assess the safety and efficacy of a new formulation of vaginal estradiol for
      the treatment of symptoms of vulvar and vaginal atrophy in postmenopausal women.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Co-Primary Efficacy Endpoint - Vaginal Superficial Cells
time frame: Baseline and 12 Weeks
description: • Change from Baseline to Week 12 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
measure: Co-Primary Efficacy Endpoint - Vaginal Parabasal Cells
time frame: Baseline and 12 Weeks
description: • Change from Baseline to Week 12 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
measure: Co-Primary Efficacy Endpoint - Vaginal pH
time frame: Baseline and 12 Weeks
description: • Change from Baseline to Week 12 in vaginal pH as compared to placebo
measure: Co-Primary Efficacy Endpoint - Severity of Most Bothersome Symptom (Dyspareunia)
time frame: Baseline and Week 12
description: • Change from Baseline to Week 12 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 12
measure: Secondary Efficacy Endpoints - Vaginal Superficial Cells
time frame: Baseline and Week 2
description: • Change from Baseline to Week 2 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
measure: Secondary Efficacy Endpoints- Vaginal Superficial Cells
time frame: Baseline and Week 6
description: Change from Baseline to Week 6 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
measure: Secondary Efficacy Endpoints - Vaginal Superficial Cells
time frame: Baseline and Week 8
description: Change from Baseline to Week 8 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
measure: Secondary Efficacy Endpoints - Vaginal Parabasal Cells
time frame: Baseline and Week 2
description: Change from Baseline to Week 2 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
measure: Secondary Efficacy Endpoints - Vaginal Parabasal Cells
time frame: Baseline and Week 6
description: Change from Baseline to Week 6 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
measure: Secondary Efficacy Endpoints - Vaginal Parabasal Cells
time frame: Baseline and Week 8
description: Change from Baseline to Week 8 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
measure: Secondary Efficacy Endpoints - Vaginal pH
time frame: Baseline and Week 2
description: Change from Baseline to Week 2 in vaginal pH as compared to placebo
measure: Secondary Efficacy Endpoints - Vaginal pH
time frame: Baseline and Week 6
description: Change from Baseline to Week 6 in vaginal pH as compared to placebo
measure: Secondary Efficacy Endpoints - Vaginal pH
time frame: Baseline and Week 8
description: Change from Baseline to Week 8 in vaginal pH as compared to placebo
measure: Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)
time frame: Baseline and Week 2
description: Change from Baseline to Week 2 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 2
measure: Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)
time frame: Baseline and Week 6
description: Change from Baseline to Week 6 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 6
measure: Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)
time frame: Baseline and Week 8
description: Change from Baseline to Week 8 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 8
measure: Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)
time frame: Baseline and Week 2
description: Change from Baseline to Week 2 on the severity of vaginal dryness associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 2
measure: Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)
time frame: Baseline and Week 6
description: Change from Baseline to Week 6 on the severity of vaginal dryness associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 6
measure: Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)
time frame: Baseline and Week 8
description: Change from Baseline to Week 8 on the severity of vaginal dryness associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 8
measure: Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 on the severity of vaginal dryness associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 12
measure: Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)
time frame: Baseline and Week 2
description: Change from Baseline to Week 2 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 2
measure: Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)
time frame: Baseline and Week 6
description: Change from Baseline to Week 6 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 6
measure: Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)
time frame: Baseline and Week 8
description: Change from Baseline to Week 8 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 8
measure: Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo
VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.
Subjects assessed severity at Baseline and Week 12
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)
time frame: Baseline and Week 2
description: Change from Baseline to Week 2 in Vaginal Color as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 2
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)
time frame: Baseline to Week 6
description: Change from Baseline to Week 6 in Vaginal Color as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 6
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)
time frame: Baseline to Week 8
description: Change from Baseline to Week 8 in Vaginal Color as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 8
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in Vaginal Color as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 12
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)
time frame: Baseline and Week 2
description: Change from Baseline to Week 2 in Vaginal Epithelial Integrity as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3
Severity was assessed by the Investigator at Baseline and Week 2
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)
time frame: Baseline and Week 6
description: Change from Baseline to Week 6 in Vaginal Epithelial Integrity as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3
Severity was assessed by the Investigator at Baseline and Week 6
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)
time frame: Baseline and Week 8
description: Change from Baseline to Week 8 in Vaginal Epithelial Integrity as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3
Severity was assessed by the Investigator at Baseline and Week 8
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in Vaginal Epithelial Integrity as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3
Severity was assessed by the Investigator at Baseline and Week 12
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)
time frame: Baseline and Week 2
description: Change from Baseline to Week 2 in Vaginal Epithelial Surface Thickness as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3
Severity was assessed by the Investigator at Baseline and Week 2
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)
time frame: Baseline and Week 6
description: Change from Baseline to Week 6 in Vaginal Epithelial Surface Thickness as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3
Severity was assessed by the Investigator at Baseline and Week 6
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)
time frame: Baseline and Week 8
description: Change from Baseline to Week 8 in Vaginal Epithelial Surface Thickness as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3
Severity was assessed by the Investigator at Baseline and Week 8
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in Vaginal Epithelial Surface Thickness as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3
Severity was assessed by the Investigator at Baseline and Week 12
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)
time frame: Baseline and Week 2
description: Change from Baseline to Week 2 in Vaginal Secretions as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain) = 3
Severity was assessed by the Investigator at Baseline and Week 2
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)
time frame: Baseline and Week 6
description: Change from Baseline to Week 6 in Vaginal Secretions as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3
Severity was assessed by the Investigator at Baseline and Week 6
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)
time frame: Baseline and Week 8
description: Change from Baseline to Week 8 in Vaginal Secretions as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3
Severity was assessed by the Investigator at Baseline and Week 8
measure: Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in Vaginal Secretions as compared to placebo
Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3
Severity was assessed by the Investigator at Baseline and Week 12
measure: Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) - Total Score
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in FSFI Total Score as compared to placebo
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.
measure: Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Arousal
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in FSFI Domain Score (Arousal) as compared to placebo
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.
measure: Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Desire
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in FSFI Domain Score (Desire) as compared to placebo
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.
measure: Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Lubrication
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in FSFI Domain Score (Lubrication) as compared to placebo
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.
measure: Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Orgasm
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in FSFI Domain Score (Orgasm) as compared to placebo
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.
measure: Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Pain
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in FSFI Domain Score (Pain) as compared to placebo
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.
measure: Secondary Efficacy Endpoints - Female Sexual Function Index (FSFI) Domain Score - Satisfaction
time frame: Baseline and Week 12
description: Change from Baseline to Week 12 in FSFI Domain Score (Satisfaction) as compared to placebo
The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.
measure: PK Substudy - Hormone Concentration Assessments (Serum Estradiol, Estrone and Estrone Conjugates; SHBG)
time frame: Pre-treatment, Day 2, Weeks 2 and 12
description: Blood samples will be obtained from a subset of subjects at pre-selected sites to characterize PK parameters (AUC, tmax, Cmin, Cmax, Cavg) and to measure SHBG
arm group label: Estradiol 4mcg Vaginal Softgel Capsule
arm group type: Experimental
description: Estradiol 4mcg Vaginal Softgel Capsule
arm group label: Estradiol 10mcg Vaginal Softgel Capsule
arm group type: Experimental
description: Estradiol 10mcg Vaginal Softgel Capsule
arm group label: Estradiol 25mcg Vaginal Softgel Capsule
arm group type: Experimental
description: Estradiol 25mcg Vaginal Softgel Capsule
arm group label: Placebo Vaginal Softgel Capsule
arm group type: Placebo Comparator
description: Placebo Vaginal Softgel Capsule
intervention type: Drug
intervention name: Estradiol
arm group label: Estradiol 10mcg Vaginal Softgel Capsule
arm group label: Estradiol 25mcg Vaginal Softgel Capsule
arm group label: Estradiol 4mcg Vaginal Softgel Capsule
intervention type: Drug
intervention name: Placebo
arm group label: Placebo Vaginal Softgel Capsule
criteria: 
gender: Female
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Dyspareunia
mesh term: Atrophy
mesh term: Estradiol
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