<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/NCT02214550</url>
  </required_header>
  <id_info>
    <org_study_id>EH13-094</org_study_id>
    <secondary_id>1R01DK100368-01</secondary_id>
    <nct_id>NCT02214550</nct_id>
  </id_info>
  <brief_title>Chronic Pain Risk Associated With Menstrual Period Pain</brief_title>
  <acronym>CRAMPP</acronym>
  <official_title>Deciphering the Hormonal and Nociceptive Mechanisms Underlying Bladder Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NorthShore University HealthSystem</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>NorthShore University HealthSystem</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if some women with dysmenorrhea (painful periods)&#xD;
      are at higher future risk of developing chronic pelvic pain (CPP) and if oral contraceptives&#xD;
      (OC) can be used to reverse this chronic pain risk.&#xD;
&#xD;
      Investigators will examine whether dysmenorrhea produces CPP via repetitive cross organ&#xD;
      sensitization (COS) episodes. The use of cyclical OCs to eliminate dysmenorrhea is expected&#xD;
      to reduce COS and decrease the risk of developing CPP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Endometrial shedding during the menstrual cycle elicits profound changes in neuronal activity&#xD;
      and cytokine concentrations producing moderate to severe pelvic pain in more than 20% of&#xD;
      reproductive-age women. One out of every five of those women in turn will develop chronic&#xD;
      pelvic pain (CPP), yet women without dysmenorrhea rarely report CPP. CPP disorders such as&#xD;
      irritable bowel syndrome (IBS) and painful bladder syndrome (PBS) can cause severe,&#xD;
      unrelenting pain due to a lack of effective treatments.&#xD;
&#xD;
      This study consists of 2 aims.&#xD;
&#xD;
      Aim #1: To determine if dysmenorrhea with concomitant bladder pain sensitivity exhibits&#xD;
      neurophysiological features consistent with established CPP. Women with chronic pain or&#xD;
      dysmenorrhea without COS will be used as controls. Quantitative sensory testing (QST) and a&#xD;
      noninvasive bladder pain test that investigators validated previously be used to determine&#xD;
      whether impairments in descending inhibition and pelvic sensitivity are responsible for&#xD;
      vulnerability to COS in women with dysmenorrhea. EEG will be recorded to look for differences&#xD;
      in brain activity in response to sensory stimulation between participants cohorts.&#xD;
&#xD;
      Aim #2: To differentiate the individual contributions of circulating sex hormones and&#xD;
      repeated sensitizing events (painful menses) on descending and peripheral mechanisms of&#xD;
      bladder pain. The same QST/bladder pain measures studied in Aim #1 will be retested within&#xD;
      the dysmenorrhea+COS group following a one-year randomized trial of cyclical OCs vs.&#xD;
      continuous OCs vs. no treatment. An observational arm of PBS participants will receive&#xD;
      continuous OCs and serve as controls.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">January 2021</completion_date>
  <primary_completion_date type="Actual">November 2020</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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Participant Bladder Pain Sensitivity From Baseline.</measure>
    <time_frame>0 (baseline), 6 month, and 12 month visits</time_frame>
    <description>Score on a scale. Specifically, we used a Visual Analog Scale- 0 through 100 scale with 0 being no pain and 100 worst pain imaginable. Results from the visual analog scale (VAS) of the bladder filling test at the initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in pain. Bladder pain ratings at first urge will be used at the outcome measure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline</measure>
    <time_frame>0 (baseline), 6 months and 12 months</time_frame>
    <description>Results from the QST testing performed at initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in sensitivity from baseline. Specifically, measure reported is the pressure pain threshold in newtons observed at the transition from pressure to pain transvaginally at the 12 o'clock position (anteriorly against the bladder). Lower values (pressure) indicate greater sensitivity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in EEG Recorded Cortical Activity Among Participants</measure>
    <time_frame>Baseline, 6 months and 12 months</time_frame>
    <description>We obtained the peak alpha frequency at the right and left parietal occipital electrodes and averages of the two sides were assessed at Baseline, 6 month, and 12 Month to determine whether differences in resting state brain activity at parieto-occipital electrode sites are affected by oral contraceptives</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">353</enrollment>
  <condition>Cystitis, Interstitial</condition>
  <condition>Dysmenorrhea</condition>
  <condition>Migraine Disorders</condition>
  <condition>Pelvic Pain</condition>
  <condition>Endometriosis</condition>
  <condition>Visceral Pain</condition>
  <condition>Chronic Pain</condition>
  <arm_group>
    <arm_group_label>D+COS-no OC</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Ten participants in the Dysmenorrhea + COS group will not receive an OC intervention. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D+COS-cyclic microgestin 1/20</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>26 participants in the Dysmenorrhea + COS group will receive cyclic OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D+COS-continuous microgestin 1/20</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>26 participants in the Dysmenorrhea + COS group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PBS-continuous microgestin 1/20</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>26 participants in the Painful Bladder Syndrome group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Intervention: Pain Discovery Aim</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>255 Reproductive-age women (18-45) will be identified and divided into 5 groups&#xD;
Healthy Controls Chronic Pain (Positive Controls) Dysmenorrhea (D) Dysmenorrhea with Cross Organ Sensitization (D+COS) Painful bladder syndrome (PBS)/interstitial cystitis (IC) After a screening, dysmenorrhea with COS and PBS participants will be compared with controls. Daily Diaries will be completed for 1-3 months. During the luteal phase of the participants' menstrual cycle or a predetermined time, participants will complete aim #1 testing consisting of a battery of questionnaires, bladder sensitivity testing, quantitative sensory testing (QST), a blood draw and EEG testing. All participants will also complete a yearly follow-up questionnaire for 5 years.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cyclic microgestin 1/20</intervention_name>
    <description>Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat</description>
    <arm_group_label>D+COS-cyclic microgestin 1/20</arm_group_label>
    <other_name>loestrin 1/20</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>continuous microgestin 1/20</intervention_name>
    <description>Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
    <arm_group_label>D+COS-continuous microgestin 1/20</arm_group_label>
    <arm_group_label>PBS-continuous microgestin 1/20</arm_group_label>
    <other_name>loestrin 1/20</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All&#xD;
&#xD;
          -  Reproductive age women (18-45)&#xD;
&#xD;
        For dysmenorrhea and D+COS group only:&#xD;
&#xD;
          -  Participants must have had regular (22-45 day) menstrual cycles over at least a two&#xD;
             month period preceding testing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        All&#xD;
&#xD;
          -  presence of active pelvic or abdominal malignancies (primary or metastatic)&#xD;
&#xD;
          -  active genitourinary infection in the last four weeks&#xD;
&#xD;
          -  unable to read or comprehend the informed consent in English&#xD;
&#xD;
          -  unwilling to undergo pelvic examination/testing&#xD;
&#xD;
          -  presence of hypertension or risk for developing hypertension, and&#xD;
&#xD;
        For dysmenorrhea and D+COS group only:&#xD;
&#xD;
          -  absence of regular menses (including current pregnancy, recent pregnancy, or active&#xD;
             breast feeding) unwilling to take either cyclic or combined OCs&#xD;
&#xD;
          -  unwilling to withdraw from OCs for two months prior to the sensory testing study&#xD;
             visit.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frank Tu, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>NorthShore University HealthSystem</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NorthShore University Health System</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://bit.ly/WeJRsW</url>
    <description>Click here for more information about this study: CRAMPP</description>
  </link>
  <reference>
    <citation>Tu FF, Epstein AE, Pozolo KE, Sexton DL, Melnyk AI, Hellman KM. A noninvasive bladder sensory test supports a role for dysmenorrhea increasing bladder noxious mechanosensitivity. Clin J Pain. 2013 Oct;29(10):883-90. doi: 10.1097/AJP.0b013e31827a71a3.</citation>
    <PMID>23370073</PMID>
  </reference>
  <reference>
    <citation>Tu FF, Fitzgerald CM, Kuiken T, Farrell T, Norman Harden R. Vaginal pressure-pain thresholds: initial validation and reliability assessment in healthy women. Clin J Pain. 2008 Jan;24(1):45-50. doi: 10.1097/AJP.0b013e318156db13.</citation>
    <PMID>18180636</PMID>
  </reference>
  <reference>
    <citation>Zondervan KT, Yudkin PL, Vessey MP, Jenkinson CP, Dawes MG, Barlow DH, Kennedy SH. Chronic pelvic pain in the community--symptoms, investigations, and diagnoses. Am J Obstet Gynecol. 2001 May;184(6):1149-55. doi: 10.1067/mob.2001.112904.</citation>
    <PMID>11349181</PMID>
  </reference>
  <reference>
    <citation>Westling AM, Tu FF, Griffith JW, Hellman KM. The association of dysmenorrhea with noncyclic pelvic pain accounting for psychological factors. Am J Obstet Gynecol. 2013 Nov;209(5):422.e1-422.e10. doi: 10.1016/j.ajog.2013.08.020. Epub 2013 Aug 22.</citation>
    <PMID>23973396</PMID>
  </reference>
  <reference>
    <citation>Brotzner CP, Klimesch W, Doppelmayr M, Zauner A, Kerschbaum HH. Resting state alpha frequency is associated with menstrual cycle phase, estradiol and use of oral contraceptives. Brain Res. 2014 Aug 19;1577(100):36-44. doi: 10.1016/j.brainres.2014.06.034. Epub 2014 Jul 7.</citation>
    <PMID>25010817</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 8, 2014</study_first_submitted>
  <study_first_submitted_qc>August 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <results_first_submitted>July 20, 2022</results_first_submitted>
  <results_first_submitted_qc>May 17, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 18, 2023</results_first_posted>
  <disposition_first_submitted>September 1, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>December 21, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">December 28, 2021</disposition_first_posted>
  <last_update_submitted>May 17, 2023</last_update_submitted>
  <last_update_submitted_qc>May 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>NorthShore University HealthSystem</investigator_affiliation>
    <investigator_full_name>Frank Tu</investigator_full_name>
    <investigator_title>Division Director, Gynecological Pain and Minimally Invasive Surgery, Department of Obstetrics and Gynecology</investigator_title>
  </responsible_party>
  <keyword>Cystitis, Interstitial</keyword>
  <keyword>Dysmenorrhea</keyword>
  <keyword>Migraine Disorders</keyword>
  <keyword>Cross Organ Sensitization</keyword>
  <keyword>Pelvic Pain</keyword>
  <keyword>Endometriosis</keyword>
  <keyword>Contraceptives, Oral</keyword>
  <keyword>Birth Control Pills</keyword>
  <keyword>Painful Bladder Syndrome</keyword>
  <keyword>Visceral Pain</keyword>
  <keyword>Chronic Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
    <mesh_term>Endometriosis</mesh_term>
    <mesh_term>Cystitis</mesh_term>
    <mesh_term>Cystitis, Interstitial</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
    <mesh_term>Pelvic Pain</mesh_term>
    <mesh_term>Dysmenorrhea</mesh_term>
    <mesh_term>Visceral Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination</mesh_term>
    <mesh_term>Norinyl</mesh_term>
    <mesh_term>Mestranol</mesh_term>
    <mesh_term>Norethindrone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>February 3, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT02214550/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Patients were drawn from a separate cross-sectional, observational study that included women who mostly had moderate-to-severe dysmenorrhea, but also included some healthy controls, and patients with other chronic pain conditions who served as positive controls for that study. Those with D+COS and PBS in the four intervention arms first participated in the strictly observational study, yielding all baseline data. The Intervention arm participants are NOT included in the &quot;no intervention' arms.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>D+COS-no OC</title>
          <description>10 participants in the Dysmenorrhea + COS group will not receive an OC intervention. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.</description>
        </group>
        <group group_id="P2">
          <title>D+COS-cyclic Microgestin 1/20</title>
          <description>26 participants in the Dysmenorrhea + COS group will receive cyclic OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
cyclic microgestin 1/20: Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat</description>
        </group>
        <group group_id="P3">
          <title>D+COS-continuous Microgestin 1/20</title>
          <description>26 participants in the Dysmenorrhea + COS group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
        </group>
        <group group_id="P4">
          <title>PBS-continuous Microgestin 1/20</title>
          <description>26 participants in the Painful Bladder Syndrome group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
        </group>
        <group group_id="P5">
          <title>No Intervention: Healthy Controls</title>
          <description>Healthy control cases will have average pain ≤ 3/10 with menses or with withdrawal uterine bleeding from cyclical OCs and b) &lt; 2 migraines per year will be recruiting preferentially.</description>
        </group>
        <group group_id="P6">
          <title>No Intervention Chronic Pain (Positive Controls)</title>
          <description>Chronic Pain (Positive Controls) will have a diagnosed, documented (reviewed by PI) chronic pain disorder greater than six months' duration, which has required at least 2 different prescription treatments and/or surgical management. They must report an average pain of at least 5/10 in the last month. We will accept participants with any type of chronic pain (except for individuals with bilateral knee and hand pain) but anticipate many of our chronic pain participants to suffer from fibromyalgia, lower back pain, and chronic pelvic pain (including irritable bowel syndrome).</description>
        </group>
        <group group_id="P7">
          <title>No Intervention: Dysmenorrhea (D)</title>
          <description>Dysmenorrhea cases will have: a) average menstrual pain ≥ 5/10 (0=no pain and 10=the worst imaginable pain) with menses or withdrawal uterine bleeding from cyclic OCs without painkillers, b) menstrual pain in the region between the umbilicus and the perineum, above the level of the inguinal ligament and c) indication the participant has attempted to resolve pain by medical means (including NSAIDs and/or OCs). Dysmenorrhea ONLY cases will have &lt;16 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
        </group>
        <group group_id="P8">
          <title>No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS)</title>
          <description>will meet criteria for Dysmenorrhea cases, with &gt;15 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
        </group>
        <group group_id="P9">
          <title>No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC)</title>
          <description>Diagnosis of PBS participants will be confirmed by medical records indicating chronic (&gt;3 months) pelvic pain (average intensity ≥ 3/10), pressure, or discomfort related to the bladder accompanied by at least one other urinary symptom such as persistent urge to void or frequency.34 PBS participants will also have records review to confirm the exclusion of other conditions by clinical examination or cystoscopy if necessary. PBS participants can have other chronic pain conditions.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="15"/>
                <participants group_id="P5" count="45"/>
                <participants group_id="P6" count="39"/>
                <participants group_id="P7" count="187"/>
                <participants group_id="P8" count="35"/>
                <participants group_id="P9" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Baseline</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="14"/>
                <participants group_id="P5" count="37"/>
                <participants group_id="P6" count="31"/>
                <participants group_id="P7" count="102"/>
                <participants group_id="P8" count="34"/>
                <participants group_id="P9" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Month 6</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="8"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
                <participants group_id="P9" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="37"/>
                <participants group_id="P6" count="31"/>
                <participants group_id="P7" count="102"/>
                <participants group_id="P8" count="34"/>
                <participants group_id="P9" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="9"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="8"/>
                <participants group_id="P7" count="85"/>
                <participants group_id="P8" count="1"/>
                <participants group_id="P9" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>For PBS-continuous microgestin 1/20, one of the 15 participants who signed consent and came for a screening visit, changed her mind about taking microgestin and did not come for a baseline visit, so the final sample size for that subgroup is n=14</population>
      <group_list>
        <group group_id="B1">
          <title>D+COS-no OC</title>
          <description>10 participants in the Dysmenorrhea + COS group will not receive an OC intervention. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.</description>
        </group>
        <group group_id="B2">
          <title>D+COS-cyclic Microgestin 1/20</title>
          <description>26 participants in the Dysmenorrhea + COS group will receive cyclic OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
cyclic microgestin 1/20: Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat</description>
        </group>
        <group group_id="B3">
          <title>D+COS-continuous Microgestin 1/20</title>
          <description>26 participants in the Dysmenorrhea + COS group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
        </group>
        <group group_id="B4">
          <title>PBS-continuous Microgestin 1/20</title>
          <description>26 participants in the Painful Bladder Syndrome group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
        </group>
        <group group_id="B5">
          <title>No Intervention: Healthy Controls</title>
          <description>Healthy control cases will have average pain ≤ 3/10 with menses or with withdrawal uterine bleeding from cyclical OCs and b) &lt; 2 migraines per year will be recruited preferentially.</description>
        </group>
        <group group_id="B6">
          <title>No Intervention Chronic Pain (Positive Controls)</title>
          <description>Chronic Pain (Positive Controls) will have a diagnosed, documented (reviewed by PI) chronic pain disorder greater than six months' duration, which has required at least 2 different prescription treatments and/or surgical management. They must report an average pain of at least 5/10 in the last month. We will accept participants with any type of chronic pain (except for individuals with bilateral knee and hand pain) but anticipate many of our chronic pain participants to suffer from fibromyalgia, lower back pain, and chronic pelvic pain (including irritable bowel syndrome).</description>
        </group>
        <group group_id="B7">
          <title>No Intervention: Dysmenorrhea (D)</title>
          <description>Dysmenorrhea cases will have: a) average menstrual pain ≥ 5/10 (0=no pain and 10=the worst imaginable pain) with menses or withdrawal uterine bleeding from cyclic OCs without painkillers, b) menstrual pain in the region between the umbilicus and the perineum, above the level of the inguinal ligament and c) indication the participant has attempted to resolve pain by medical means (including NSAIDs and/or OCs). Dysmenorrhea ONLY cases will have &lt;16 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
        </group>
        <group group_id="B8">
          <title>No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS)</title>
          <description>will meet criteria for Dysmenorrhea cases, with &gt;15 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
        </group>
        <group group_id="B9">
          <title>No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC)</title>
          <description>Diagnosis of PBS participants will be confirmed by medical records indicating chronic (&gt;3 months) pelvic pain (average intensity ≥ 3/10), pressure, or discomfort related to the bladder accompanied by at least one other urinary symptom such as persistent urge to void or frequency.34 PBS participants will also have records review to confirm the exclusion of other conditions by clinical examination or cystoscopy if necessary. PBS participants can have other chronic pain conditions.</description>
        </group>
        <group group_id="B10">
          <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="6"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="15"/>
            <count group_id="B5" value="37"/>
            <count group_id="B6" value="31"/>
            <count group_id="B7" value="102"/>
            <count group_id="B8" value="34"/>
            <count group_id="B9" value="10"/>
            <count group_id="B10" value="247"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="6"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="8"/>
                    <count group_id="B4" value="15"/>
                    <count group_id="B5" value="37"/>
                    <count group_id="B6" value="31"/>
                    <count group_id="B7" value="102"/>
                    <count group_id="B8" value="34"/>
                    <count group_id="B9" value="10"/>
                    <count group_id="B10" value="247"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.7" spread="5.5"/>
                    <measurement group_id="B2" value="20.00" spread="1.41"/>
                    <measurement group_id="B3" value="22.2" spread="4.06"/>
                    <measurement group_id="B4" value="30.4" spread="5.93"/>
                    <measurement group_id="B5" value="23.9" spread="7.1"/>
                    <measurement group_id="B6" value="27.5" spread="6.2"/>
                    <measurement group_id="B7" value="24.1" spread="6.7"/>
                    <measurement group_id="B8" value="24.7" spread="6.5"/>
                    <measurement group_id="B9" value="26.8" spread="5.5"/>
                    <measurement group_id="B10" value="26.1" spread="6.43"/>
                  </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="6"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="8"/>
                    <count group_id="B4" value="15"/>
                    <count group_id="B5" value="37"/>
                    <count group_id="B6" value="31"/>
                    <count group_id="B7" value="102"/>
                    <count group_id="B8" value="34"/>
                    <count group_id="B9" value="10"/>
                    <count group_id="B10" value="247"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="37"/>
                    <measurement group_id="B6" value="31"/>
                    <measurement group_id="B7" value="102"/>
                    <measurement group_id="B8" value="34"/>
                    <measurement group_id="B9" value="10"/>
                    <measurement group_id="B10" value="247"/>
                  </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 group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" 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="6"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="8"/>
                    <count group_id="B4" value="15"/>
                    <count group_id="B5" value="37"/>
                    <count group_id="B6" value="31"/>
                    <count group_id="B7" value="102"/>
                    <count group_id="B8" value="34"/>
                    <count group_id="B9" value="10"/>
                    <count group_id="B10" value="247"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="29"/>
                    <measurement group_id="B7" value="15"/>
                    <measurement group_id="B8" value="7"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="34"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="87"/>
                    <measurement group_id="B8" value="27"/>
                    <measurement group_id="B9" value="10"/>
                    <measurement group_id="B10" value="192"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" 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="6"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="8"/>
                    <count group_id="B4" value="15"/>
                    <count group_id="B5" value="37"/>
                    <count group_id="B6" value="31"/>
                    <count group_id="B7" value="102"/>
                    <count group_id="B8" value="34"/>
                    <count group_id="B9" value="10"/>
                    <count group_id="B10" value="247"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="9"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="15"/>
                    <measurement group_id="B8" value="7"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" 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="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="21"/>
                    <measurement group_id="B8" value="6"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="12"/>
                    <measurement group_id="B5" value="21"/>
                    <measurement group_id="B6" value="28"/>
                    <measurement group_id="B7" value="53"/>
                    <measurement group_id="B8" value="20"/>
                    <measurement group_id="B9" value="8"/>
                    <measurement group_id="B10" value="151"/>
                  </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="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="13"/>
                    <measurement group_id="B8" value="1"/>
                    <measurement group_id="B9" value="2"/>
                    <measurement group_id="B10" value="20"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                    <measurement group_id="B9" value="0"/>
                    <measurement group_id="B10" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Bladder Pain Sensitivity</title>
          <description>Visual Analog Scale is a 0 through 100 scale with 0 being no pain and 100 worst pain imaginable.&#xD;
Results from the visual analog scale (VAS) of the bladder filling test will be compared to determine if participants in each of the treatment groups had a reduction in pain. Bladder pain ratings at first urge will be used at the outcome measure.</description>
          <population>Participant did not report a pain rating for first urge during the bladder test.</population>
          <units>Visual Analog Scale</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="6"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="8"/>
                    <count group_id="B4" value="14"/>
                    <count group_id="B5" value="37"/>
                    <count group_id="B6" value="31"/>
                    <count group_id="B7" value="102"/>
                    <count group_id="B8" value="33"/>
                    <count group_id="B9" value="10"/>
                    <count group_id="B10" value="245"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.2" spread="13.5"/>
                    <measurement group_id="B2" value="37.0" spread="10.7"/>
                    <measurement group_id="B3" value="41.2" spread="16.9"/>
                    <measurement group_id="B4" value="47.9" spread="12.9"/>
                    <measurement group_id="B5" value="2.2" spread="2.8"/>
                    <measurement group_id="B6" value="17.3" spread="17.3"/>
                    <measurement group_id="B7" value="4.1" spread="4.2"/>
                    <measurement group_id="B8" value="33" spread="13.9"/>
                    <measurement group_id="B9" value="49.0" spread="26.4"/>
                    <measurement group_id="B10" value="43.0" spread="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Quantitative Sensory Testing (QST) parameters regarding pelvic hyperalgesia</title>
          <description>Amount of pressure applied to the pelvic floor in newtons (0-30) before the first threshold for pain.</description>
          <population>Malfunctioning digital algometer or pelvic pain testing was too painful for participants to complete testing.</population>
          <units>Newtons</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="5"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="8"/>
                    <count group_id="B4" value="14"/>
                    <count group_id="B5" value="37"/>
                    <count group_id="B6" value="31"/>
                    <count group_id="B7" value="102"/>
                    <count group_id="B8" value="34"/>
                    <count group_id="B9" value="10"/>
                    <count group_id="B10" value="245"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.95" spread="3.96"/>
                    <measurement group_id="B2" value="9.38" spread="6.56"/>
                    <measurement group_id="B3" value="13.8" spread="11.9"/>
                    <measurement group_id="B4" value="8.21" spread="6.04"/>
                    <measurement group_id="B5" value="11.6" spread="6.4"/>
                    <measurement group_id="B6" value="6.9" spread="4.5"/>
                    <measurement group_id="B7" value="8.9" spread="5.6"/>
                    <measurement group_id="B8" value="7.2" spread="5.2"/>
                    <measurement group_id="B9" value="6.9" spread="3.2"/>
                    <measurement group_id="B10" value="9.43" spread="7.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Participant Bladder Pain Sensitivity From Baseline.</title>
        <description>Score on a scale. Specifically, we used a Visual Analog Scale- 0 through 100 scale with 0 being no pain and 100 worst pain imaginable. Results from the visual analog scale (VAS) of the bladder filling test at the initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in pain. Bladder pain ratings at first urge will be used at the outcome measure.</description>
        <time_frame>0 (baseline), 6 month, and 12 month visits</time_frame>
        <population>Some participant data were missing due to task error or attrition.</population>
        <group_list>
          <group group_id="O1">
            <title>D+COS-no OC</title>
            <description>10 participants in the Dysmenorrhea + COS group will not receive an OC intervention. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.</description>
          </group>
          <group group_id="O2">
            <title>D+COS-cyclic Microgestin 1/20</title>
            <description>26 participants in the Dysmenorrhea + COS group will receive cyclic OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
cyclic microgestin 1/20: Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat</description>
          </group>
          <group group_id="O3">
            <title>D+COS-continuous Microgestin 1/20</title>
            <description>26 participants in the Dysmenorrhea + COS group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
          </group>
          <group group_id="O4">
            <title>PBS-continuous Microgestin 1/20</title>
            <description>26 participants in the Painful Bladder Syndrome group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
          </group>
          <group group_id="O5">
            <title>No Intervention: Healthy Controls</title>
            <description>Healthy control cases will have average pain ≤ 3/10 with menses or with withdrawal uterine bleeding from cyclical OCs and b) &lt; 2 migraines per year will be recruiting preferentially.</description>
          </group>
          <group group_id="O6">
            <title>No Intervention Chronic Pain (Positive Controls)</title>
            <description>Chronic Pain (Positive Controls) will have a diagnosed, documented (reviewed by PI) chronic pain disorder greater than six months' duration, which has required at least 2 different prescription treatments and/or surgical management. They must report an average pain of at least 5/10 in the last month. We will accept participants with any type of chronic pain (except for individuals with bilateral knee and hand pain) but anticipate many of our chronic pain participants to suffer from fibromyalgia, lower back pain, and chronic pelvic pain (including irritable bowel syndrome).</description>
          </group>
          <group group_id="O7">
            <title>No Intervention: Dysmenorrhea (D)</title>
            <description>Dysmenorrhea cases will have: a) average menstrual pain ≥ 5/10 (0=no pain and 10=the worst imaginable pain) with menses or withdrawal uterine bleeding from cyclic OCs without painkillers, b) menstrual pain in the region between the umbilicus and the perineum, above the level of the inguinal ligament and c) indication the participant has attempted to resolve pain by medical means (including NSAIDs and/or OCs). Dysmenorrhea ONLY cases will have &lt;16 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
          </group>
          <group group_id="O8">
            <title>No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS)</title>
            <description>will meet criteria for Dysmenorrhea cases, with &gt;15 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
          </group>
          <group group_id="O9">
            <title>No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC)</title>
            <description>Diagnosis of PBS participants will be confirmed by medical records indicating chronic (&gt;3 months) pelvic pain (average intensity ≥ 3/10), pressure, or discomfort related to the bladder accompanied by at least one other urinary symptom such as persistent urge to void or frequency.34 PBS participants will also have records review to confirm the exclusion of other conditions by clinical examination or cystoscopy if necessary. PBS participants can have other chronic pain conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Participant Bladder Pain Sensitivity From Baseline.</title>
          <description>Score on a scale. Specifically, we used a Visual Analog Scale- 0 through 100 scale with 0 being no pain and 100 worst pain imaginable. Results from the visual analog scale (VAS) of the bladder filling test at the initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in pain. Bladder pain ratings at first urge will be used at the outcome measure.</description>
          <population>Some participant data were missing due to task error or attrition.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="14"/>
                <count group_id="O5" value="37"/>
                <count group_id="O6" value="31"/>
                <count group_id="O7" value="102"/>
                <count group_id="O8" value="33"/>
                <count group_id="O9" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="14"/>
                    <count group_id="O5" value="37"/>
                    <count group_id="O6" value="31"/>
                    <count group_id="O7" value="102"/>
                    <count group_id="O8" value="33"/>
                    <count group_id="O9" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.2" spread="13.5"/>
                    <measurement group_id="O2" value="37.0" spread="10.7"/>
                    <measurement group_id="O3" value="41.2" spread="16.9"/>
                    <measurement group_id="O4" value="47.9" spread="12.9"/>
                    <measurement group_id="O5" value="2.2" spread="2.8"/>
                    <measurement group_id="O6" value="17.3" spread="17.3"/>
                    <measurement group_id="O7" value="4.1" spread="4.2"/>
                    <measurement group_id="O8" value="33" spread="13.9"/>
                    <measurement group_id="O9" value="49.0" spread="26.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="8"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.5" spread="18.5"/>
                    <measurement group_id="O2" value="32.0" spread="21.2"/>
                    <measurement group_id="O3" value="18.6" spread="14.7"/>
                    <measurement group_id="O4" value="41.4" spread="21.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.0" spread="17.3"/>
                    <measurement group_id="O2" value="34.0" spread="23.5"/>
                    <measurement group_id="O3" value="8.6" spread="10.0"/>
                    <measurement group_id="O4" value="38.8" spread="21.1"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A linear mixed-effects model was estimated predicting bladder pain at first urge ratings (0-100 visual analog scale) as a function of time (0, 6, 12 month visits), group, and their interaction. Random intercepts were estimated for each participant. The following three orthogonal contrasts were estimated: 1) OCP vs. No OCP, 2) cyclic vs. continuous microgestin, and 3) PBS-continuous microgestin vs. D+COS-continuous microgestin.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.02</p_value>
            <p_value_desc>The a priori threshold for statistical significance was .05 and p-values were not adjusted for multiple comparisons given a priori orthogonal contrasts.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>-1.96</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.69</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Parameter reported indicates time x group interaction (OCP vs. No OCP). PBS participants are included in the OCP group</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A linear mixed-effects model was estimated predicting bladder pain at first urge ratings (0-100 visual analog scale) as a function of time (0, 6, 12 month visits), group, and their interaction. Random intercepts were estimated for each participant. The following three orthogonal contrasts were estimated: 1) OCP vs. No OCP, 2) cyclic vs. continuous microgestin, and 3) PBS-continuous microgestin vs. D+COS-continuous microgestin.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.08</p_value>
            <p_value_desc>The a priori threshold for statistical significance was .05 and p-values were not adjusted for multiple comparisons given a priori orthogonal contrasts.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>-1.4597</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.8245</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Parameter estimated indicates the time x group (Continuous vs. Cyclic OCP) interaction. PBS participants are included in the continuous OCP group.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A linear mixed-effects model was estimated predicting bladder pain at first urge ratings (0-100 visual analog scale) as a function of time (0, 6, 12 month visits), group, and their interaction. Random intercepts were estimated for each participant. The following three orthogonal contrasts were estimated: 1) OCP vs. No OCP, 2) cyclic vs. continuous microgestin, and 3) PBS-continuous microgestin vs. D+COS-continuous microgestin.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.023</p_value>
            <p_value_desc>The a priori threshold for statistical significance was .05 and p-values were not adjusted for multiple comparisons given a priori orthogonal contrasts.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>1.9186</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.8121</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Parameter reported indicates a time x group interaction (D+COS-continuous microgestin vs. PBS-continuous microgestin).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline</title>
        <description>Results from the QST testing performed at initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in sensitivity from baseline. Specifically, measure reported is the pressure pain threshold in newtons observed at the transition from pressure to pain transvaginally at the 12 o'clock position (anteriorly against the bladder). Lower values (pressure) indicate greater sensitivity.</description>
        <time_frame>0 (baseline), 6 months and 12 months</time_frame>
        <population>Some participants have missing data due to equipment malfunction or reported pain testing as too painful.</population>
        <group_list>
          <group group_id="O1">
            <title>D+COS-no OC</title>
            <description>10 participants in the Dysmenorrhea + COS group will not receive an OC intervention. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.</description>
          </group>
          <group group_id="O2">
            <title>D+COS-cyclic Microgestin 1/20</title>
            <description>26 participants in the Dysmenorrhea + COS group will receive cyclic OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
cyclic microgestin 1/20: Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat</description>
          </group>
          <group group_id="O3">
            <title>D+COS-continuous Microgestin 1/20</title>
            <description>26 participants in the Dysmenorrhea + COS group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
          </group>
          <group group_id="O4">
            <title>PBS-continuous Microgestin 1/20</title>
            <description>26 participants in the Painful Bladder Syndrome group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
          </group>
          <group group_id="O5">
            <title>No Intervention: Healthy Controls</title>
            <description>Healthy control cases will have average pain ≤ 3/10 with menses or with withdrawal uterine bleeding from cyclical OCs and b) &lt; 2 migraines per year will be recruited preferentially.</description>
          </group>
          <group group_id="O6">
            <title>No Intervention Chronic Pain (Positive Controls)</title>
            <description>Chronic Pain (Positive Controls) will have a diagnosed, documented (reviewed by PI) chronic pain disorder greater than six months' duration, which has required at least 2 different prescription treatments and/or surgical management. They must report an average pain of at least 5/10 in the last month. We will accept participants with any type of chronic pain (except for individuals with bilateral knee and hand pain) but anticipate many of our chronic pain participants to suffer from fibromyalgia, lower back pain, and chronic pelvic pain (including irritable bowel syndrome).</description>
          </group>
          <group group_id="O7">
            <title>No Intervention: Dysmenorrhea (D)</title>
            <description>Dysmenorrhea cases will have: a) average menstrual pain ≥ 5/10 (0=no pain and 10=the worst imaginable pain) with menses or withdrawal uterine bleeding from cyclic OCs without painkillers, b) menstrual pain in the region between the umbilicus and the perineum, above the level of the inguinal ligament and c) indication the participant has attempted to resolve pain by medical means (including NSAIDs and/or OCs). Dysmenorrhea ONLY cases will have &lt;16 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
          </group>
          <group group_id="O8">
            <title>No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS)</title>
            <description>will meet criteria for Dysmenorrhea cases, with &gt;15 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
          </group>
          <group group_id="O9">
            <title>No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC)</title>
            <description>Diagnosis of PBS participants will be confirmed by medical records indicating chronic (&gt;3 months) pelvic pain (average intensity ≥ 3/10), pressure, or discomfort related to the bladder accompanied by at least one other urinary symptom such as persistent urge to void or frequency.34 PBS participants will also have records review to confirm the exclusion of other conditions by clinical examination or cystoscopy if necessary. PBS participants can have other chronic pain conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline</title>
          <description>Results from the QST testing performed at initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in sensitivity from baseline. Specifically, measure reported is the pressure pain threshold in newtons observed at the transition from pressure to pain transvaginally at the 12 o'clock position (anteriorly against the bladder). Lower values (pressure) indicate greater sensitivity.</description>
          <population>Some participants have missing data due to equipment malfunction or reported pain testing as too painful.</population>
          <units>Newtons</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="14"/>
                <count group_id="O5" value="37"/>
                <count group_id="O6" value="31"/>
                <count group_id="O7" value="102"/>
                <count group_id="O8" value="34"/>
                <count group_id="O9" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="14"/>
                    <count group_id="O5" value="37"/>
                    <count group_id="O6" value="31"/>
                    <count group_id="O7" value="102"/>
                    <count group_id="O8" value="34"/>
                    <count group_id="O9" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.95" spread="3.96"/>
                    <measurement group_id="O2" value="9.38" spread="6.56"/>
                    <measurement group_id="O3" value="13.8" spread="11.9"/>
                    <measurement group_id="O4" value="8.21" spread="6.04"/>
                    <measurement group_id="O5" value="11.6" spread="6.4"/>
                    <measurement group_id="O6" value="6.9" spread="4.5"/>
                    <measurement group_id="O7" value="8.9" spread="5.6"/>
                    <measurement group_id="O8" value="7.2" spread="5.2"/>
                    <measurement group_id="O9" value="6.9" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.40" spread="5.71"/>
                    <measurement group_id="O2" value="13.9" spread="12.9"/>
                    <measurement group_id="O3" value="12.3" spread="10.1"/>
                    <measurement group_id="O4" value="3.39" spread="1.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="5"/>
                    <count group_id="O4" value="5"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.36" spread="8.67"/>
                    <measurement group_id="O2" value="7.74" spread="6.13"/>
                    <measurement group_id="O3" value="9.94" spread="6.80"/>
                    <measurement group_id="O4" value="5.59" spread="1.85"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A linear mixed-effects model was estimated predicting pressure pain thresholds (in Newtons of force transvaginally measured anteriorly against the bladder) as a function of time (0, 6, 12 month visits), group, and their interaction. Random intercepts were estimated for each participant. The following three orthogonal contrasts were estimated: 1) OCP vs. No OCP, 2) cyclic vs. continuous microgestin, and 3) PBS-continuous microgestin vs. D+COS-continuous microgestin.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2315</p_value>
            <p_value_desc>The a priori threshold for statistical significance was .05 and p-values were not adjusted for multiple comparisons given a priori orthogonal contrasts.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>0.3716</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.3056</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Parameter reported indicates time*group interaction (OCP vs. No OCP). PBS participants are included in the OCP group</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A linear mixed-effects model was estimated predicting pressure pain thresholds (in Newtons of force transvaginally measured anteriorly against the bladder) as a function of time (0, 6, 12 month visits), group, and their interaction. Random intercepts were estimated for each participant. The following three orthogonal contrasts were estimated: 1) OCP vs. No OCP, 2) cyclic vs. continuous microgestin, and 3) PBS-continuous microgestin vs. D+COS-continuous microgestin.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4097</p_value>
            <p_value_desc>The a priori threshold for statistical significance was .05 and p-values were not adjusted for multiple comparisons given a priori orthogonal contrasts.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>0.2703</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.3244</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Parameter estimated indicates the time x group (Continuous vs. Cyclic OCP) interaction. PBS participants are included in the continuous OCP group.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A linear mixed-effects model was estimated predicting pressure pain thresholds (in Newtons of force transvaginally measured anteriorly against the bladder) as a function of time (0, 6, 12 month visits), group, and their interaction. Random intercepts were estimated for each participant. The following three orthogonal contrasts were estimated: 1) OCP vs. No OCP, 2) cyclic vs. continuous microgestin, and 3) PBS-continuous microgestin vs. D+COS-continuous microgestin.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6341</p_value>
            <p_value_desc>The a priori threshold for statistical significance was .05 and p-values were not adjusted for multiple comparisons given a priori orthogonal contrasts.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>-0.1574</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.3283</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Parameter estimated indicates the time x group (continuous microgestin: D+COS-vs. PBS) interaction.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Differences in EEG Recorded Cortical Activity Among Participants</title>
        <description>We obtained the peak alpha frequency at the right and left parietal occipital electrodes and averages of the two sides were assessed at Baseline, 6 month, and 12 Month to determine whether differences in resting state brain activity at parieto-occipital electrode sites are affected by oral contraceptives</description>
        <time_frame>Baseline, 6 months and 12 months</time_frame>
        <population>Some participant data were missing due to attrition, or lack of available equipment on day of study</population>
        <group_list>
          <group group_id="O1">
            <title>D+COS-no OC</title>
            <description>Ten participants in the Dysmenorrhea + COS group will not receive an OC intervention. EEG's done at baseline will be repeated at 6 months and 12 months.</description>
          </group>
          <group group_id="O2">
            <title>D+COS-cyclic Microgestin 1/20</title>
            <description>26 participants in the Dysmenorrhea + COS group will receive cyclic OC. EEG's done at baseline will be repeated at 6 months and 12 months.&#xD;
cyclic microgestin 1/20: Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat</description>
          </group>
          <group group_id="O3">
            <title>D+COS-continuous Microgestin 1/20</title>
            <description>26 participants in the Dysmenorrhea + COS group will receive continuous OC. EEG's done at baseline will be repeated at 6 months and 12 months.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
          </group>
          <group group_id="O4">
            <title>PBS-continuous Microgestin 1/20</title>
            <description>26 participants in the Painful Bladder Syndrome group will receive continuous OC. EEG's done at baseline will be repeated at 6 months and 12 months.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
          </group>
          <group group_id="O5">
            <title>No Intervention: Healthy Controls</title>
            <description>Healthy control cases will have average pain ≤ 3/10 with menses or with withdrawal uterine bleeding from cyclical OCs and b) &lt; 2 migraines per year will be recruited preferentially.</description>
          </group>
          <group group_id="O6">
            <title>No Intervention Chronic Pain (Positive Controls)</title>
            <description>Chronic Pain (Positive Controls) will have a diagnosed, documented (reviewed by PI) chronic pain disorder greater than six months' duration, which has required at least 2 different prescription treatments and/or surgical management. They must report an average pain of at least 5/10 in the last month. We will accept participants with any type of chronic pain (except for individuals with bilateral knee and hand pain) but anticipate many of our chronic pain participants to suffer from fibromyalgia, lower back pain, and chronic pelvic pain (including irritable bowel syndrome).</description>
          </group>
          <group group_id="O7">
            <title>No Intervention: Dysmenorrhea (D)</title>
            <description>Dysmenorrhea cases will have: a) average menstrual pain ≥ 5/10 (0=no pain and 10=the worst imaginable pain) with menses or withdrawal uterine bleeding from cyclic OCs without painkillers, b) menstrual pain in the region between the umbilicus and the perineum, above the level of the inguinal ligament and c) indication the participant has attempted to resolve pain by medical means (including NSAIDs and/or OCs). Dysmenorrhea ONLY cases will have &lt;16 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
          </group>
          <group group_id="O8">
            <title>No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS)</title>
            <description>will meet criteria for Dysmenorrhea cases, with &gt;15 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1.</description>
          </group>
          <group group_id="O9">
            <title>No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC)</title>
            <description>Diagnosis of PBS participants will be confirmed by medical records indicating chronic (&gt;3 months) pelvic pain (average intensity ≥ 3/10), pressure, or discomfort related to the bladder accompanied by at least one other urinary symptom such as persistent urge to void or frequency.34 PBS participants will also have records review to confirm the exclusion of other conditions by clinical examination or cystoscopy if necessary. PBS participants can have other chronic pain conditions.</description>
          </group>
        </group_list>
        <measure>
          <title>Differences in EEG Recorded Cortical Activity Among Participants</title>
          <description>We obtained the peak alpha frequency at the right and left parietal occipital electrodes and averages of the two sides were assessed at Baseline, 6 month, and 12 Month to determine whether differences in resting state brain activity at parieto-occipital electrode sites are affected by oral contraceptives</description>
          <population>Some participant data were missing due to attrition, or lack of available equipment on day of study</population>
          <units>Hertz</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="10"/>
                <count group_id="O5" value="31"/>
                <count group_id="O6" value="31"/>
                <count group_id="O7" value="92"/>
                <count group_id="O8" value="29"/>
                <count group_id="O9" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="6"/>
                    <count group_id="O4" value="10"/>
                    <count group_id="O5" value="31"/>
                    <count group_id="O6" value="31"/>
                    <count group_id="O7" value="92"/>
                    <count group_id="O8" value="29"/>
                    <count group_id="O9" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.03" spread="0.26"/>
                    <measurement group_id="O2" value="10.0" spread="0.59"/>
                    <measurement group_id="O3" value="10.05" spread="0.07"/>
                    <measurement group_id="O4" value="10.13" spread="0.08"/>
                    <measurement group_id="O5" value="10.03" spread="0.06"/>
                    <measurement group_id="O6" value="10.15" spread="0.07"/>
                    <measurement group_id="O7" value="10.12" spread="0.04"/>
                    <measurement group_id="O8" value="9.96" spread="0.06"/>
                    <measurement group_id="O9" value="10.0" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="2"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.10" spread="0.24"/>
                    <measurement group_id="O2" value="10.01" spread="0.1"/>
                    <measurement group_id="O3" value="10.19" spread="0.26"/>
                    <measurement group_id="O4" value="10.16" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="4"/>
                    <count group_id="O3" value="6"/>
                    <count group_id="O4" value="4"/>
                    <count group_id="O5" value="0"/>
                    <count group_id="O6" value="0"/>
                    <count group_id="O7" value="0"/>
                    <count group_id="O8" value="0"/>
                    <count group_id="O9" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.88" spread="0.17"/>
                    <measurement group_id="O2" value="9.97" spread="0.94"/>
                    <measurement group_id="O3" value="9.75" spread="0.27"/>
                    <measurement group_id="O4" value="10.48" spread="0.29"/>
                  </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>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A linear mixed-effects model was estimated for parieto-occipital peak alpha (Hz) as a function of time (0, 6, 12 month visits), group, and their interaction. Random intercepts were estimated for each participant. The OCP vs No OCP contrast was estimated here:</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.393</p_value>
            <p_value_desc>The a priori threshold for statistical significance was .05 and p-values were not adjusted for multiple comparisons given a priori orthogonal contrasts.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>.086</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.10</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Parameter reported indicates time x group interaction (OCP vs. No OCP). PBS participants are included in the OCP group.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A linear mixed-effects model was estimated for parieto-occipital peak alpha (Hz) as a function of time (0, 6, 12 month visits), group, and their interaction. Random intercepts were estimated for each participant. The cyclic vs. continuous microgestin contrast was run here</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.941</p_value>
            <p_value_desc>The a priori threshold for statistical significance was .05 and p-values were not adjusted for multiple comparisons given a priori orthogonal contrasts.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>.007</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.09</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Parameters reported indicates time x group (Continuous vs. Cyclic OCP) interaction. PBS participants are included in the continuous OCP group.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A linear mixed-effects model was estimated for parieto-occipital peak alpha (Hz) as a function of time (0, 6, 12 month visits), group, and their interaction. Random intercepts were estimated for each participant. The PBS-continuous microgestin vs. D+COS-continuous microgestin contrast was evaluated here</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.005</p_value>
            <p_value_desc>The a priori threshold for statistical significance was .05 and p-values were not adjusted for multiple comparisons given a priori orthogonal contrasts.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>.28</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>.10</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Parameter reported indicates time x group interaction (D+COS-continuous microgestin vs. PBS-continuous microgestin).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Surveys of adverse events were collected monthly over 1 Year</time_frame>
      <desc>We used a survey with prespecified questions. Please note, all-cause mortality or serious &amp; other AEs were not monitored in the &quot;no intervention arms&quot;. In the intervention arms, no formal query for mortality or serious AE was done, but we did monitor for them. For nonserious AEs, we report the frequency of ever reporting any queried event over the entire period. Participants varied in total AE form completion. Participants in the &quot;D+COS-no OC&quot; group did not receive AE questionnaires.</desc>
      <group_list>
        <group group_id="E1">
          <title>D+COS-no OC</title>
          <description>10 participants in the Dysmenorrhea + COS group will not receive an OC intervention. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.</description>
        </group>
        <group group_id="E2">
          <title>D+COS-cyclic Microgestin 1/20</title>
          <description>26 participants in the Dysmenorrhea + COS group will receive cyclic OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
cyclic microgestin 1/20: Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat</description>
        </group>
        <group group_id="E3">
          <title>D+COS-continuous Microgestin 1/20</title>
          <description>26 participants in the Dysmenorrhea + COS group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</description>
        </group>
        <group group_id="E4">
          <title>PBS-continuous Microgestin 1/20</title>
          <description>26 participants in the Painful Bladder Syndrome group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.&#xD;
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year</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="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Changes in vision</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Weight Gain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depressed, sad a lot</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Irritable</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Spotting (between periods)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Breast Tenderness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Decreased sex drive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Darkening of the skin or face</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
              </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>Small sample size due to higher than expected refusal of participants with DYSB to randomize to an OCP limits generalizability. As noted above, nonserious adverse events are reported as the frequency of ever reporting an event on a form, of any intensity.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Frank Tu</name_or_title>
      <organization>NorthShore University HealthSystem</organization>
      <phone>8475702520</phone>
      <email>ftu@northshore.org</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/NCT02214550
org study id: EH13-094
secondary id: 1R01DK100368-01
nct id: NCT02214550
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine if some women with dysmenorrhea (painful periods)
      are at higher future risk of developing chronic pelvic pain (CPP) and if oral contraceptives
      (OC) can be used to reverse this chronic pain risk.

      Investigators will examine whether dysmenorrhea produces CPP via repetitive cross organ
      sensitization (COS) episodes. The use of cyclical OCs to eliminate dysmenorrhea is expected
      to reduce COS and decrease the risk of developing CPP.
Endometrial shedding during the menstrual cycle elicits profound changes in neuronal activity
      and cytokine concentrations producing moderate to severe pelvic pain in more than 20% of
      reproductive-age women. One out of every five of those women in turn will develop chronic
      pelvic pain (CPP), yet women without dysmenorrhea rarely report CPP. CPP disorders such as
      irritable bowel syndrome (IBS) and painful bladder syndrome (PBS) can cause severe,
      unrelenting pain due to a lack of effective treatments.

      This study consists of 2 aims.

      Aim #1: To determine if dysmenorrhea with concomitant bladder pain sensitivity exhibits
      neurophysiological features consistent with established CPP. Women with chronic pain or
      dysmenorrhea without COS will be used as controls. Quantitative sensory testing (QST) and a
      noninvasive bladder pain test that investigators validated previously be used to determine
      whether impairments in descending inhibition and pelvic sensitivity are responsible for
      vulnerability to COS in women with dysmenorrhea. EEG will be recorded to look for differences
      in brain activity in response to sensory stimulation between participants cohorts.

      Aim #2: To differentiate the individual contributions of circulating sex hormones and
      repeated sensitizing events (painful menses) on descending and peripheral mechanisms of
      bladder pain. The same QST/bladder pain measures studied in Aim #1 will be retested within
      the dysmenorrhea+COS group following a one-year randomized trial of cyclical OCs vs.
      continuous OCs vs. no treatment. An observational arm of PBS participants will receive
      continuous OCs and serve as controls.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Change in Participant Bladder Pain Sensitivity From Baseline.
time frame: 0 (baseline), 6 month, and 12 month visits
description: Score on a scale. Specifically, we used a Visual Analog Scale- 0 through 100 scale with 0 being no pain and 100 worst pain imaginable. Results from the visual analog scale (VAS) of the bladder filling test at the initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in pain. Bladder pain ratings at first urge will be used at the outcome measure.
measure: Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline
time frame: 0 (baseline), 6 months and 12 months
description: Results from the QST testing performed at initial, 6 month and 12 month visits will be compared to determine if participants in each of the treatment groups had a reduction in sensitivity from baseline. Specifically, measure reported is the pressure pain threshold in newtons observed at the transition from pressure to pain transvaginally at the 12 o'clock position (anteriorly against the bladder). Lower values (pressure) indicate greater sensitivity.
measure: Differences in EEG Recorded Cortical Activity Among Participants
time frame: Baseline, 6 months and 12 months
description: We obtained the peak alpha frequency at the right and left parietal occipital electrodes and averages of the two sides were assessed at Baseline, 6 month, and 12 Month to determine whether differences in resting state brain activity at parieto-occipital electrode sites are affected by oral contraceptives
arm group label: D+COS-no OC
arm group type: No Intervention
description: Ten participants in the Dysmenorrhea + COS group will not receive an OC intervention. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.
arm group label: D+COS-cyclic microgestin 1/20
arm group type: Active Comparator
description: 26 participants in the Dysmenorrhea + COS group will receive cyclic OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.
arm group label: D+COS-continuous microgestin 1/20
arm group type: Active Comparator
description: 26 participants in the Dysmenorrhea + COS group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.
arm group label: PBS-continuous microgestin 1/20
arm group type: Active Comparator
description: 26 participants in the Painful Bladder Syndrome group will receive continuous OC. Monthly questionnaires will be completed for 1 yr. QST will be repeated at 6 months and 12 months. A yearly follow-up questionnaire will be completed for 5 years.
arm group label: No Intervention: Pain Discovery Aim
arm group type: No Intervention
description: 255 Reproductive-age women (18-45) will be identified and divided into 5 groups
Healthy Controls Chronic Pain (Positive Controls) Dysmenorrhea (D) Dysmenorrhea with Cross Organ Sensitization (D+COS) Painful bladder syndrome (PBS)/interstitial cystitis (IC) After a screening, dysmenorrhea with COS and PBS participants will be compared with controls. Daily Diaries will be completed for 1-3 months. During the luteal phase of the participants' menstrual cycle or a predetermined time, participants will complete aim #1 testing consisting of a battery of questionnaires, bladder sensitivity testing, quantitative sensory testing (QST), a blood draw and EEG testing. All participants will also complete a yearly follow-up questionnaire for 5 years.
intervention type: Drug
intervention name: cyclic microgestin 1/20
description: Cyclic OC Use - Participants will ingest pills containing active hormones for 21 days followed by 7 days of no pills, and then the cycle will repeat
arm group label: D+COS-cyclic microgestin 1/20
other name: loestrin 1/20
intervention type: Drug
intervention name: continuous microgestin 1/20
description: Continuous OC use - Pills containing hormones will be taken every day for 1 year
arm group label: D+COS-continuous microgestin 1/20
arm group label: PBS-continuous microgestin 1/20
other name: loestrin 1/20
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Frank Tu, MD, MPH
role: Principal Investigator
affiliation: NorthShore University HealthSystem
facility: 
country: United States
url: http://bit.ly/WeJRsW
description: Click here for more information about this study: CRAMPP
citation: Tu FF, Epstein AE, Pozolo KE, Sexton DL, Melnyk AI, Hellman KM. A noninvasive bladder sensory test supports a role for dysmenorrhea increasing bladder noxious mechanosensitivity. Clin J Pain. 2013 Oct;29(10):883-90. doi: 10.1097/AJP.0b013e31827a71a3.
PMID: 23370073
citation: Tu FF, Fitzgerald CM, Kuiken T, Farrell T, Norman Harden R. Vaginal pressure-pain thresholds: initial validation and reliability assessment in healthy women. Clin J Pain. 2008 Jan;24(1):45-50. doi: 10.1097/AJP.0b013e318156db13.
PMID: 18180636
citation: Zondervan KT, Yudkin PL, Vessey MP, Jenkinson CP, Dawes MG, Barlow DH, Kennedy SH. Chronic pelvic pain in the community--symptoms, investigations, and diagnoses. Am J Obstet Gynecol. 2001 May;184(6):1149-55. doi: 10.1067/mob.2001.112904.
PMID: 11349181
citation: Westling AM, Tu FF, Griffith JW, Hellman KM. The association of dysmenorrhea with noncyclic pelvic pain accounting for psychological factors. Am J Obstet Gynecol. 2013 Nov;209(5):422.e1-422.e10. doi: 10.1016/j.ajog.2013.08.020. Epub 2013 Aug 22.
PMID: 23973396
citation: Brotzner CP, Klimesch W, Doppelmayr M, Zauner A, Kerschbaum HH. Resting state alpha frequency is associated with menstrual cycle phase, estradiol and use of oral contraceptives. Brain Res. 2014 Aug 19;1577(100):36-44. doi: 10.1016/j.brainres.2014.06.034. Epub 2014 Jul 7.
PMID: 25010817
responsible party type: Principal Investigator
investigator affiliation: NorthShore University HealthSystem
investigator full name: Frank Tu
investigator title: Division Director, Gynecological Pain and Minimally Invasive Surgery, Department of Obstetrics and Gynecology
mesh term: Migraine Disorders
mesh term: Endometriosis
mesh term: Cystitis
mesh term: Cystitis, Interstitial
mesh term: Chronic Pain
mesh term: Pelvic Pain
mesh term: Dysmenorrhea
mesh term: Visceral Pain
mesh term: Norethindrone acetate, ethinyl estradiol, ferrous fumarate drug combination
mesh term: Norinyl
mesh term: Mestranol
mesh term: Norethindrone
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Small sample size due to higher than expected refusal of participants with DYSB to randomize to an OCP limits generalizability. As noted above, nonserious adverse events are reported as the frequency of ever reporting an event on a form, of any intensity.
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