<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/NCT03240081</url>
  </required_header>
  <id_info>
    <org_study_id>OHSU IRB 16770</org_study_id>
    <nct_id>NCT03240081</nct_id>
  </id_info>
  <brief_title>Treating Postmenopausal Dyspareunia Where it Hurts</brief_title>
  <official_title>Treating Where it Hurts: A Randomized Blinded Clinical Trial of Local Estrogen to the Vulvar Vestibule for Dyspareunia in Postmenopausal Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oregon Health and Science University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the effectiveness of two low doses of estrogen cream&#xD;
      applied to a new location for the treatment of moderate or severe pain during sexual&#xD;
      intercourse in postmenopausal women.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Estrogen cream is FDA-approved for vaginal use for the treatment of sexual pain, but its use&#xD;
      in a new location is experimental. Pain with sex is a common problem experienced by women&#xD;
      after menopause and the relationship of pain to sexual difficulties is well established. The&#xD;
      cause has been assumed to be atrophy and the location has been assumed to be the vagina.&#xD;
      Recent focused studies have shown that the location of pain is the vulvar vestibule and&#xD;
      usually not the vagina. This study will look at pain before and after therapy with estrogen&#xD;
      when only the vulvar entryway area is treated. This will be a study focused on sexual&#xD;
      dysfunction in postmenopausal women.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 20, 2017</start_date>
  <completion_date type="Actual">November 21, 2019</completion_date>
  <primary_completion_date type="Actual">November 21, 2019</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Median Dyspareunia Pain Scores After 4 Weeks Using Study Drug</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>Change in median dyspareunia pain scores between baseline and 4 weeks of use of nightly use of study medication. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Median Pain Scores for Intercourse After 12 Weeks Using Study Drug</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Difference in median dyspareunia pain scores between arms for intercourse at 12 weeks after use of nightly study medication for 90d. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Dyspareunia</condition>
  <arm_group>
    <arm_group_label>50mcg estradiol cream</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects randomized to 50mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100mcg estradiol cream</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects randomized to 100mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>50mcg estradiol cream</intervention_name>
    <description>Use of study drug nightly applied to vulvar vestibule</description>
    <arm_group_label>50mcg estradiol cream</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>100mcg estradiol cream</intervention_name>
    <description>Use of study drug nightly</description>
    <arm_group_label>100mcg estradiol cream</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Postmenopausal women aged 40 to 70 years old.&#xD;
&#xD;
          2. Postmenopausal, demonstrated by at least one of the following:&#xD;
&#xD;
             i. Cessation of menses for ≥1 years if age is &gt;50 ii. Bilateral oophorectomy iii. A&#xD;
             history of climacteric symptoms if below age 50, having an ovary and scarred or absent&#xD;
             uterus.&#xD;
&#xD;
          3. Onset of dyspareunia after menopause.*&#xD;
&#xD;
          4. Stable heterosexual partnership ≥2 years (or by investigator discretion if less than 2&#xD;
             years) and both partners want to have more satisfying penetrative intimacy.&#xD;
&#xD;
          5. No estrogen product use, local or systemic, for 6 months.*&#xD;
&#xD;
          6. More than 6 months of consistent insertional pain with intercourse (may have stopped&#xD;
             having intercourse due to this consistent experience of pain).*&#xD;
&#xD;
          7. Willingness to enter a study where she will receive low-dose local estrogen.*&#xD;
&#xD;
          8. Willingness to enter a study that requires application of cream on a frequent schedule&#xD;
             for 3 months. *&#xD;
&#xD;
          9. Willingness to evaluate the progress of therapies by use of the Tampon Test as many as&#xD;
             2 times per week, and willingness to attempt intercourse if the Tampon Test indicates&#xD;
             tolerable penetrative pain.*&#xD;
&#xD;
               -  n/a for reference group&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Consistently has pain in the pelvis or low abdomen during or after intercourse (deep&#xD;
             dyspareunia).&#xD;
&#xD;
          2. Negative cotton-swab touch test in the vulvar vestibule or vestibular tenderness that&#xD;
             is not extinguishable by application of lidocaine 4% topical solution applied for 3&#xD;
             minutes.&#xD;
&#xD;
          3. Partner with sexual dysfunction limiting his performance or making it inconsistent.&#xD;
             (The use of male therapy for erectile dysfunction is acceptable.)&#xD;
&#xD;
          4. Diagnosis by a physical therapist or clinician of significant pelvic floor muscle&#xD;
             tension causing pain (pelvic floor myalgia) or has been found on screening examination&#xD;
             to have pelvic floor tenderness or bladder tenderness.&#xD;
&#xD;
          5. Constant burning pain localized to the vulva.&#xD;
&#xD;
          6. Allergy to local estrogen products or lidocaine numbing agents.&#xD;
&#xD;
          7. Previous estrogen receptor positive breast cancer or endometrial cancer.&#xD;
&#xD;
          8. Endometrial thickness ≥5mm on screening via transvaginal ultrasound.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martha Goetsch, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oregon Health &amp; Science University, Portland, OR</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oregon Health &amp; Science Univerity</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2017</study_first_posted>
  <results_first_submitted>November 20, 2020</results_first_submitted>
  <results_first_submitted_qc>December 27, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 20, 2021</results_first_posted>
  <last_update_submitted>May 18, 2023</last_update_submitted>
  <last_update_submitted_qc>May 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oregon Health and Science University</investigator_affiliation>
    <investigator_full_name>Jeffrey Jensen</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Post-menopause dyspareunia</keyword>
  <keyword>Vulvar vestibular pain</keyword>
  <keyword>Genitourinary syndrome of menopause</keyword>
  <keyword>Sexual pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyspareunia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estradiol 17 beta-cypionate</mesh_term>
    <mesh_term>Estradiol 3-benzoate</mesh_term>
    <mesh_term>Estradiol</mesh_term>
    <mesh_term>Polyestradiol phosphate</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 13, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/81/NCT03240081/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>50mcg Estradiol Cream</title>
          <description>Subjects randomized to 50mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
50mcg estradiol cream: Use of study drug nightly</description>
        </group>
        <group group_id="P2">
          <title>100mcg Estradiol Cream</title>
          <description>Subjects randomized to 100mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
100mcg estradiol cream: Use of study drug nightly</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>50mcg Estradiol Cream</title>
          <description>Subjects randomized to 50mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
50mcg estradiol cream: Use of study drug nightly</description>
        </group>
        <group group_id="B2">
          <title>100mcg Estradiol Cream</title>
          <description>Subjects randomized to 100mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
100mcg estradiol cream: Use of study drug nightly</description>
        </group>
        <group group_id="B3">
          <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="25"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="50"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="25"/>
                    <count group_id="B3" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="25"/>
                    <count group_id="B3" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.24" spread="6.16"/>
                    <measurement group_id="B2" value="60.17" spread="7.7"/>
                    <measurement group_id="B3" value="59.69" spread="6.90"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="25"/>
                    <count group_id="B3" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="25"/>
                    <count group_id="B3" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="25"/>
                    <count group_id="B3" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="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>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="25"/>
                    <count group_id="B3" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <population>One was not analyzed because she was found to have a disqualifying diagnosis after the trial had commenced 1 mo.</population>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="25"/>
                    <count group_id="B2" value="24"/>
                    <count group_id="B3" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.59" spread="4.04"/>
                    <measurement group_id="B2" value="25.91" spread="7.7"/>
                    <measurement group_id="B3" value="25.23" spread="4.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Median Dyspareunia Pain Scores After 4 Weeks Using Study Drug</title>
        <description>Change in median dyspareunia pain scores between baseline and 4 weeks of use of nightly use of study medication. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.</description>
        <time_frame>Baseline to 4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>50mcg Estradiol Cream</title>
            <description>Subjects randomized to 50mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
50mcg estradiol cream: Use of study drug nightly</description>
          </group>
          <group group_id="O2">
            <title>100mcg Estradiol Cream</title>
            <description>Subjects randomized to 100mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
100mcg estradiol cream: Use of study drug nightly</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Median Dyspareunia Pain Scores After 4 Weeks Using Study Drug</title>
          <description>Change in median dyspareunia pain scores between baseline and 4 weeks of use of nightly use of study medication. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" lower_limit="-2" upper_limit="-1"/>
                    <measurement group_id="O2" value="-3" lower_limit="-5" upper_limit="-2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>We set 2 points (20%) as the margin of difference when defining and evaluating non-inferiority in comparing the 2 arms at 4 weeks.</non_inferiority_desc>
            <p_value>0.08</p_value>
            <p_value_desc>Threshold for significance &lt; 0.05</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>2</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Median Pain Scores for Intercourse After 12 Weeks Using Study Drug</title>
        <description>Difference in median dyspareunia pain scores between arms for intercourse at 12 weeks after use of nightly study medication for 90d. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.</description>
        <time_frame>Baseline and 12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>50mcg Estradiol Cream</title>
            <description>Subjects randomized to 50mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
50mcg estradiol cream: Use of study drug nightly</description>
          </group>
          <group group_id="O2">
            <title>100mcg Estradiol Cream</title>
            <description>Subjects randomized to 100mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
100mcg estradiol cream: Use of study drug nightly</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Median Pain Scores for Intercourse After 12 Weeks Using Study Drug</title>
          <description>Difference in median dyspareunia pain scores between arms for intercourse at 12 weeks after use of nightly study medication for 90d. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4" lower_limit="-6" upper_limit="-3"/>
                    <measurement group_id="O2" value="-5.5" lower_limit="-6" upper_limit="-4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>We set 2 points (20%) as the margin of difference when evaluating non-inferiority in comparing the 2 arms at 4 weeks.</non_inferiority_desc>
            <p_value>0.95</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>2</param_value>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 months</time_frame>
      <desc>We assessed certain symptoms that could be potentially related to the intervention by including relevant questions on a questionnaire administered repeatedly through the intervention period.</desc>
      <group_list>
        <group group_id="E1">
          <title>50mcg Estradiol Cream</title>
          <description>Subjects randomized to 50mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
50mcg estradiol cream: Use of study drug nightly</description>
        </group>
        <group group_id="E2">
          <title>100mcg Estradiol Cream</title>
          <description>Subjects randomized to 100mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump&#xD;
100mcg estradiol cream: Use of study drug nightly</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>increased hot flashes</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="25"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>fatigue</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>increased headaches</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>mastalgia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>postcoital spotting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Candida vaginitis</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>URI</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>Cold</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>local skin irritation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The design did not include a placebo arm. Therefore the various minor &quot;adverse events&quot; or side effects that were tabulated cannot be compared to the same complaints in a placebo arm. &quot;Adverse events&quot; includes specific possible estrogen side effects which were queried in repeating questionnaires rather than being volunteered by participants.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Martha Goetsch</name_or_title>
      <organization>OHSU</organization>
      <phone>503-494-3666</phone>
      <email>goetsch@ohsu.edu</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/NCT03240081
org study id: OHSU IRB 16770
nct id: NCT03240081
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to compare the effectiveness of two low doses of estrogen cream
      applied to a new location for the treatment of moderate or severe pain during sexual
      intercourse in postmenopausal women.
Estrogen cream is FDA-approved for vaginal use for the treatment of sexual pain, but its use
      in a new location is experimental. Pain with sex is a common problem experienced by women
      after menopause and the relationship of pain to sexual difficulties is well established. The
      cause has been assumed to be atrophy and the location has been assumed to be the vagina.
      Recent focused studies have shown that the location of pain is the vulvar vestibule and
      usually not the vagina. This study will look at pain before and after therapy with estrogen
      when only the vulvar entryway area is treated. This will be a study focused on sexual
      dysfunction in postmenopausal women.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double Blind
measure: Change in Median Dyspareunia Pain Scores After 4 Weeks Using Study Drug
time frame: Baseline to 4 weeks
description: Change in median dyspareunia pain scores between baseline and 4 weeks of use of nightly use of study medication. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.
measure: Change in Median Pain Scores for Intercourse After 12 Weeks Using Study Drug
time frame: Baseline and 12 weeks
description: Difference in median dyspareunia pain scores between arms for intercourse at 12 weeks after use of nightly study medication for 90d. Pain will be assessed using 11-point Numerical Rating Scale (NRS) where 0 = no pain and 10 = worst possible pain.
arm group label: 50mcg estradiol cream
arm group type: Active Comparator
description: Subjects randomized to 50mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump
arm group label: 100mcg estradiol cream
arm group type: Active Comparator
description: Subjects randomized to 100mcg of study medication will be issued a pump that will dispense 0.5gm of cream with each pump
intervention type: Drug
intervention name: 50mcg estradiol cream
description: Use of study drug nightly applied to vulvar vestibule
arm group label: 50mcg estradiol cream
intervention type: Drug
intervention name: 100mcg estradiol cream
description: Use of study drug nightly
arm group label: 100mcg estradiol cream
criteria: 
gender: Female
minimum age: 40 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Martha Goetsch, MD, MPH
role: Principal Investigator
affiliation: Oregon Health & Science University, Portland, OR
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Oregon Health and Science University
investigator full name: Jeffrey Jensen
investigator title: Principal Investigator
mesh term: Dyspareunia
mesh term: Estradiol 17 beta-cypionate
mesh term: Estradiol 3-benzoate
mesh term: Estradiol
mesh term: Polyestradiol phosphate
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The design did not include a placebo arm. Therefore the various minor "adverse events" or side effects that were tabulated cannot be compared to the same complaints in a placebo arm. "Adverse events" includes specific possible estrogen side effects which were queried in repeating questionnaires rather than being volunteered by participants.
point of contact: 