Chronic Pain Risk Associated With Menstrual Period Pain

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Deciphering the Hormonal and Nociceptive Mechanisms Underlying Bladder Pain

Conditions
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Pelvic Pain, Cystitis, Interstitial, Dysmenorrhea, Migraine Disorders, Endometriosis, Visceral Pain, Chronic Pain

Intervention / Treatment
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* Drug: cyclic microgestin 1/20
* Drug: continuous microgestin 1/20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All Reproductive age women (18-45) For dysmenorrhea and D+COS group only: Participants must have had regular (22-45 day) menstrual cycles over at least a two month period preceding testing Exclusion Criteria: All presence of active pelvic or abdominal malignancies (primary or metastatic) active genitourinary infection in the last four weeks unable to read or comprehend the informed consent in English unwilling to undergo pelvic examination/testing presence of hypertension or risk for developing hypertension, and For dysmenorrhea and D+COS group only: absence of regular menses (including current pregnancy, recent pregnancy, or active breast feeding) unwilling to take either cyclic or combined OCs unwilling to withdraw from OCs for two months prior to the sensory testing study visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: D+COS-no OC<br>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. | |
| Active Comparator: D+COS-cyclic microgestin 1/20<br>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. | Drug: cyclic microgestin 1/20<br>* 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<br>* Other names: loestrin 1/20;|
| Active Comparator: D+COS-continuous microgestin 1/20<br>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. | Drug: continuous microgestin 1/20<br>* Continuous OC use - Pills containing hormones will be taken every day for 1 year<br>* Other names: loestrin 1/20;|
| Active Comparator: PBS-continuous microgestin 1/20<br>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. | Drug: continuous microgestin 1/20<br>* Continuous OC use - Pills containing hormones will be taken every day for 1 year<br>* Other names: loestrin 1/20;|
| No Intervention: No Intervention: Pain Discovery Aim<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Participant Bladder Pain Sensitivity From Baseline. | 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. | 0 (baseline), 6 month, and 12 month visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | 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. | 0 (baseline), 6 months and 12 months | 
| Differences in EEG Recorded Cortical Activity Among Participants | 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 | Baseline, 6 months and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystitis, Interstitial, Dysmenorrhea, Migraine Disorders, Cross Organ Sensitization, Pelvic Pain, Endometriosis, Contraceptives, Oral, Birth Control Pills, Painful Bladder Syndrome, Visceral Pain, Chronic Pain