Chronic Pain Risk Associated With Menstrual Period Pain

Phase 4

Completed

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

Interventions: Drug: cyclic microgestin 1/20
Drug: continuous microgestin 1/20

Registration Number: NCT02214550

Lead Sponsor: NorthShore University HealthSystem

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 353

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
D+COS-cyclic microgestin 1/20	cyclic microgestin 1/20	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.
PBS-continuous microgestin 1/20	continuous microgestin 1/20	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.
D+COS-continuous microgestin 1/20	continuous microgestin 1/20	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.

Primary Outcome Measures

Name	Time	Method
Change in Participant Bladder Pain Sensitivity From Baseline.	0 (baseline), 6 month, and 12 month visits	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.

Secondary Outcome Measures

Name	Time	Method
Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline	0 (baseline), 6 months and 12 months	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.
Differences in EEG Recorded Cortical Activity Among Participants	Baseline, 6 months and 12 months	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