Chronic Pain, Cystitis, Interstitial, Dysmenorrhea, Endometriosis, Migraine Disorders, Pelvic Pain, Visceral Pain
Conditions
Keywords
Cystitis, Interstitial, Dysmenorrhea, Migraine Disorders, Cross Organ Sensitization, Pelvic Pain, Endometriosis, Contraceptives, Oral, Birth Control Pills, Painful Bladder Syndrome, Visceral Pain, Chronic Pain
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.
Interventions
DRUGcyclic 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
DRUGcontinuous microgestin 1/20
Continuous OC use - Pills containing hormones will be taken every day for 1 year
Sponsors
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Endeavor Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
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 no intervention' arms.
Participants by arm
| Arm | Count |
|---|---|
| D+COS-no OC 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. | 6 |
| D+COS-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.
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 | 4 |
| D+COS-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.
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year | 8 |
| PBS-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.
continuous microgestin 1/20: Continuous OC use - Pills containing hormones will be taken every day for 1 year | 15 |
| No Intervention: Healthy Controls Healthy control cases will have average pain ≤ 3/10 with menses or with withdrawal uterine bleeding from cyclical OCs and b) \< 2 migraines per year will be recruited preferentially. | 37 |
| No Intervention Chronic Pain (Positive Controls) 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). | 31 |
| No Intervention: Dysmenorrhea (D) 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 \<16 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1. | 102 |
| No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS) will meet criteria for Dysmenorrhea cases, with \>15 bladder pain on a 0-100 visual analogue scale (VAS) during either first sensation or first urge at assessment visit #1. | 34 |
| No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC) Diagnosis of PBS participants will be confirmed by medical records indicating chronic (\>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. | 10 |
| Total | 247 |
Baseline characteristics
| Characteristic | D+COS-no OC | D+COS-cyclic Microgestin 1/20 | D+COS-continuous Microgestin 1/20 | PBS-continuous Microgestin 1/20 | No Intervention: Healthy Controls | No Intervention Chronic Pain (Positive Controls) | No Intervention: Dysmenorrhea (D) | No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS) | No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 24.7 years STANDARD_DEVIATION 5.5 | 20.00 years STANDARD_DEVIATION 1.41 | 22.2 years STANDARD_DEVIATION 4.06 | 30.4 years STANDARD_DEVIATION 5.93 | 23.9 years STANDARD_DEVIATION 7.1 | 27.5 years STANDARD_DEVIATION 6.2 | 24.1 years STANDARD_DEVIATION 6.7 | 24.7 years STANDARD_DEVIATION 6.5 | 26.8 years STANDARD_DEVIATION 5.5 | 26.1 years STANDARD_DEVIATION 6.43 |
| Bladder Pain Sensitivity | 38.2 Visual Analog Scale STANDARD_DEVIATION 13.5 | 37.0 Visual Analog Scale STANDARD_DEVIATION 10.7 | 41.2 Visual Analog Scale STANDARD_DEVIATION 16.9 | 47.9 Visual Analog Scale STANDARD_DEVIATION 12.9 | 2.2 Visual Analog Scale STANDARD_DEVIATION 2.8 | 17.3 Visual Analog Scale STANDARD_DEVIATION 17.3 | 4.1 Visual Analog Scale STANDARD_DEVIATION 4.2 | 33 Visual Analog Scale STANDARD_DEVIATION 13.9 | 49.0 Visual Analog Scale STANDARD_DEVIATION 26.4 | 43.0 Visual Analog Scale STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 29 Participants | 15 Participants | 7 Participants | 0 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 8 Participants | 15 Participants | 34 Participants | 2 Participants | 87 Participants | 27 Participants | 10 Participants | 192 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Quantitative Sensory Testing (QST) parameters regarding pelvic hyperalgesia | 5.95 Newtons STANDARD_DEVIATION 3.96 | 9.38 Newtons STANDARD_DEVIATION 6.56 | 13.8 Newtons STANDARD_DEVIATION 11.9 | 8.21 Newtons STANDARD_DEVIATION 6.04 | 11.6 Newtons STANDARD_DEVIATION 6.4 | 6.9 Newtons STANDARD_DEVIATION 4.5 | 8.9 Newtons STANDARD_DEVIATION 5.6 | 7.2 Newtons STANDARD_DEVIATION 5.2 | 6.9 Newtons STANDARD_DEVIATION 3.2 | 9.43 Newtons STANDARD_DEVIATION 7.92 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 9 Participants | 0 Participants | 15 Participants | 7 Participants | 0 Participants | 36 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 21 Participants | 6 Participants | 0 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 13 Participants | 1 Participants | 2 Participants | 20 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 3 Participants | 12 Participants | 21 Participants | 28 Participants | 53 Participants | 20 Participants | 8 Participants | 151 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 8 Participants | 15 Participants | 37 Participants | 31 Participants | 102 Participants | 34 Participants | 10 Participants | 247 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 | 0 / 8 | 0 / 6 |
| other Total, other adverse events | 0 / 0 | 4 / 4 | 8 / 8 | 6 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 | 0 / 8 | 0 / 6 |
Outcome results
Primary
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.
Time frame: 0 (baseline), 6 month, and 12 month visits
Population: Some participant data were missing due to task error or attrition.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D+COS-no OC | Change in Participant Bladder Pain Sensitivity From Baseline. | Month 6 | 44.5 score on a scale | Standard Deviation 18.5 |
| D+COS-no OC | Change in Participant Bladder Pain Sensitivity From Baseline. | Baseline | 38.2 score on a scale | Standard Deviation 13.5 |
| D+COS-no OC | Change in Participant Bladder Pain Sensitivity From Baseline. | Month 12 | 47.0 score on a scale | Standard Deviation 17.3 |
| D+COS-cyclic Microgestin 1/20 | Change in Participant Bladder Pain Sensitivity From Baseline. | Baseline | 37.0 score on a scale | Standard Deviation 10.7 |
| D+COS-cyclic Microgestin 1/20 | Change in Participant Bladder Pain Sensitivity From Baseline. | Month 12 | 34.0 score on a scale | Standard Deviation 23.5 |
| D+COS-cyclic Microgestin 1/20 | Change in Participant Bladder Pain Sensitivity From Baseline. | Month 6 | 32.0 score on a scale | Standard Deviation 21.2 |
| D+COS-continuous Microgestin 1/20 | Change in Participant Bladder Pain Sensitivity From Baseline. | Month 6 | 18.6 score on a scale | Standard Deviation 14.7 |
| D+COS-continuous Microgestin 1/20 | Change in Participant Bladder Pain Sensitivity From Baseline. | Month 12 | 8.6 score on a scale | Standard Deviation 10 |
| D+COS-continuous Microgestin 1/20 | Change in Participant Bladder Pain Sensitivity From Baseline. | Baseline | 41.2 score on a scale | Standard Deviation 16.9 |
| PBS-continuous Microgestin 1/20 | Change in Participant Bladder Pain Sensitivity From Baseline. | Month 12 | 38.8 score on a scale | Standard Deviation 21.1 |
| PBS-continuous Microgestin 1/20 | Change in Participant Bladder Pain Sensitivity From Baseline. | Baseline | 47.9 score on a scale | Standard Deviation 12.9 |
| PBS-continuous Microgestin 1/20 | Change in Participant Bladder Pain Sensitivity From Baseline. | Month 6 | 41.4 score on a scale | Standard Deviation 21.6 |
| No Intervention: Healthy Controls | Change in Participant Bladder Pain Sensitivity From Baseline. | Baseline | 2.2 score on a scale | Standard Deviation 2.8 |
| No Intervention Chronic Pain (Positive Controls) | Change in Participant Bladder Pain Sensitivity From Baseline. | Baseline | 17.3 score on a scale | Standard Deviation 17.3 |
| No Intervention: Dysmenorrhea (D) | Change in Participant Bladder Pain Sensitivity From Baseline. | Baseline | 4.1 score on a scale | Standard Deviation 4.2 |
| No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS) | Change in Participant Bladder Pain Sensitivity From Baseline. | Baseline | 33 score on a scale | Standard Deviation 13.9 |
| No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC) | Change in Participant Bladder Pain Sensitivity From Baseline. | Baseline | 49.0 score on a scale | Standard Deviation 26.4 |
Comparison: 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.p-value: 0.02Mixed Models Analysis
Comparison: 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.p-value: 0.08Mixed Models Analysis
Comparison: 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.p-value: 0.023Mixed Models Analysis
Secondary
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.
Time frame: 0 (baseline), 6 months and 12 months
Population: Some participants have missing data due to equipment malfunction or reported pain testing as too painful.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D+COS-no OC | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Month 6 | 5.40 Newtons | Standard Deviation 5.71 |
| D+COS-no OC | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Baseline | 5.95 Newtons | Standard Deviation 3.96 |
| D+COS-no OC | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Month 12 | 7.36 Newtons | Standard Deviation 8.67 |
| D+COS-cyclic Microgestin 1/20 | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Baseline | 9.38 Newtons | Standard Deviation 6.56 |
| D+COS-cyclic Microgestin 1/20 | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Month 12 | 7.74 Newtons | Standard Deviation 6.13 |
| D+COS-cyclic Microgestin 1/20 | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Month 6 | 13.9 Newtons | Standard Deviation 12.9 |
| D+COS-continuous Microgestin 1/20 | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Month 6 | 12.3 Newtons | Standard Deviation 10.1 |
| D+COS-continuous Microgestin 1/20 | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Month 12 | 9.94 Newtons | Standard Deviation 6.8 |
| D+COS-continuous Microgestin 1/20 | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Baseline | 13.8 Newtons | Standard Deviation 11.9 |
| PBS-continuous Microgestin 1/20 | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Month 12 | 5.59 Newtons | Standard Deviation 1.85 |
| PBS-continuous Microgestin 1/20 | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Baseline | 8.21 Newtons | Standard Deviation 6.04 |
| PBS-continuous Microgestin 1/20 | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Month 6 | 3.39 Newtons | Standard Deviation 1.93 |
| No Intervention: Healthy Controls | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Baseline | 11.6 Newtons | Standard Deviation 6.4 |
| No Intervention Chronic Pain (Positive Controls) | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Baseline | 6.9 Newtons | Standard Deviation 4.5 |
| No Intervention: Dysmenorrhea (D) | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Baseline | 8.9 Newtons | Standard Deviation 5.6 |
| No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS) | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Baseline | 7.2 Newtons | Standard Deviation 5.2 |
| No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC) | Change in Quantitative Sensory Testing (QST) Parameters Regarding Pelvic Hyperalgesia From Baseline | Baseline | 6.9 Newtons | Standard Deviation 3.2 |
Comparison: 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.p-value: 0.2315Mixed Models Analysis
Comparison: 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.p-value: 0.4097Mixed Models Analysis
Comparison: 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.p-value: 0.6341Mixed Models Analysis
Secondary
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
Time frame: Baseline, 6 months and 12 months
Population: Some participant data were missing due to attrition, or lack of available equipment on day of study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D+COS-no OC | Differences in EEG Recorded Cortical Activity Among Participants | Baseline | 10.03 Hertz | Standard Error 0.26 |
| D+COS-no OC | Differences in EEG Recorded Cortical Activity Among Participants | Month 12 | 9.88 Hertz | Standard Error 0.17 |
| D+COS-no OC | Differences in EEG Recorded Cortical Activity Among Participants | Month 6 | 10.10 Hertz | Standard Error 0.24 |
| D+COS-cyclic Microgestin 1/20 | Differences in EEG Recorded Cortical Activity Among Participants | Month 12 | 9.97 Hertz | Standard Error 0.94 |
| D+COS-cyclic Microgestin 1/20 | Differences in EEG Recorded Cortical Activity Among Participants | Baseline | 10.0 Hertz | Standard Error 0.59 |
| D+COS-cyclic Microgestin 1/20 | Differences in EEG Recorded Cortical Activity Among Participants | Month 6 | 10.01 Hertz | Standard Error 0.1 |
| D+COS-continuous Microgestin 1/20 | Differences in EEG Recorded Cortical Activity Among Participants | Month 6 | 10.19 Hertz | Standard Error 0.26 |
| D+COS-continuous Microgestin 1/20 | Differences in EEG Recorded Cortical Activity Among Participants | Month 12 | 9.75 Hertz | Standard Error 0.27 |
| D+COS-continuous Microgestin 1/20 | Differences in EEG Recorded Cortical Activity Among Participants | Baseline | 10.05 Hertz | Standard Error 0.07 |
| PBS-continuous Microgestin 1/20 | Differences in EEG Recorded Cortical Activity Among Participants | Month 12 | 10.48 Hertz | Standard Error 0.29 |
| PBS-continuous Microgestin 1/20 | Differences in EEG Recorded Cortical Activity Among Participants | Baseline | 10.13 Hertz | Standard Error 0.08 |
| PBS-continuous Microgestin 1/20 | Differences in EEG Recorded Cortical Activity Among Participants | Month 6 | 10.16 Hertz | Standard Error 0.18 |
| No Intervention: Healthy Controls | Differences in EEG Recorded Cortical Activity Among Participants | Baseline | 10.03 Hertz | Standard Error 0.06 |
| No Intervention Chronic Pain (Positive Controls) | Differences in EEG Recorded Cortical Activity Among Participants | Baseline | 10.15 Hertz | Standard Error 0.07 |
| No Intervention: Dysmenorrhea (D) | Differences in EEG Recorded Cortical Activity Among Participants | Baseline | 10.12 Hertz | Standard Error 0.04 |
| No Intervention: Dysmenorrhea With Cross Organ Sensitization (D+COS) | Differences in EEG Recorded Cortical Activity Among Participants | Baseline | 9.96 Hertz | Standard Error 0.06 |
| No Intervention: Painful Bladder Syndrome (PBS)/Interstitial Cystitis (IC) | Differences in EEG Recorded Cortical Activity Among Participants | Baseline | 10.0 Hertz | Standard Error 0.07 |
Comparison: 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:p-value: 0.393Mixed Models Analysis
Comparison: 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 herep-value: 0.941Mixed Models Analysis
Comparison: 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 herep-value: 0.005Mixed Models Analysis