Circulating sex steroids and bladder pain sensitivity in dysmenorrhea.

Although elevated estradiol levels facilitate chronic pelvic pain in animal models, it remains to be determined whether sex steroid levels are altered in a cross-section of women with chronic pelvic pain (CPP) and those at-risk for developing CPP. We sought to determine if sex steroid levels are increased in women with menstrual pain and whether those changes were more extreme in two groups of women with worsened pelvic pain profiles: a) dysmenorrhea plus evidence of bladder pain sensitivity and b) bladder pain syndrome. Serum samples were collected during the mid-luteal phase to measure estradiol, progesterone, testosterone, and sex hormone-binding globulin. We also compared quantitative sensory testing profiles to evaluate how sex steroid differences influence proposed pain sensitivity mechanisms. Women with combined dysmenorrhea and bladder sensitivity had higher estradiol concentrations than controls (487 [IQR 390 - 641] vs 404 [336 - 467] pmol/L, p = 0.042). Bladder pain syndrome participants had greater sex hormone-binding globulin than controls (83 [71 - 108] vs 55 [42 - 76 nmol/L; p = 0.027). Levels of pain sensitivity and mood were different across the groups, but the only significant relationship to sex steroids was that sex hormone-binding globulin was correlated to somatic symptoms (r = 0.26, p = 0.03). These findings show women potentially at-risk for CPP and women with diagnosed CPP exhibit altered circulating levels of sex steroids. Because these hormonal differences appear to be independent of mood or pain sensitivity, the role of sex steroids in the emergence of CPP may be via sensitization of visceral afferents.

Dysmenorrhea subtypes exhibit differential quantitative sensory assessment profiles.

Women who develop bladder pain syndrome (BPS), irritable bowel syndrome, or dyspareunia frequently have an antecedent history of dysmenorrhea. Despite the high prevalence of menstrual pain, its role in chronic pelvic pain emergence remains understudied. We systematically characterized bladder, body, and vaginal mechanical sensitivity with quantitative sensory testing in women with dysmenorrhea (DYS, n = 147), healthy controls (HCs) (n = 37), and women with BPS (n = 25). Previously, we have shown that a noninvasive, bladder-filling task identified a subset of women with both dysmenorrhea and silent bladder pain hypersensitivity, and we repeated this to subtype dysmenorrhea sufferers in this study (DYSB; n = 49). DYS, DYSB, and BPS participants had lower vaginal mechanical thresholds and reported more pain to a cold stimulus during a conditioned pain modulation task and greater pelvic examination after-pain than HCs (P's < 0.05). DYSB participants also had reduced body mechanical thresholds and less conditioned pain modulation compared to HCs and DYS participants (P's < 0.05). Comparing quantitative sensory testing results among the DYS and HC groups only, provoked bladder pain was the only significant predictor of self-reported menstrual pain (r = 0.26), bladder pain (r = 0.57), dyspareunia (r = 0.39), and bowel pain (r = 0.45). Our findings of widespread sensory sensitivity in women with dysmenorrhea and provoked bladder pain, much like that observed in chronic pain, suggest a need to study the trajectory of altered mechanisms of pain processing in preclinical silent visceral pain phenotypes to understand which features convey inexorable vs modifiable risk.

Clinical profile of comorbid dysmenorrhea and bladder sensitivity: a cross-sectional analysis.

BACKGROUND: Antecedents of chronic pelvic pain are not well characterized, but pelvic organ visceral sensitivity is a hallmark of these disorders. Recent studies have identified that some dysmenorrhea sufferers are much more likely to exhibit comorbid bladder hypersensitivity. Presumably, these otherwise healthy women may be at higher risk of developing full-blown chronic bladder pain later in life. To encourage early identification of patients harboring potential future risk of chronic pain, we describe the clinical profile of women matching this putative pain-risk phenotype. OBJECTIVE(S): The objectives of the study were to characterize demographic, menstrual, pelvic examination, and psychosocial profiles of young women with comorbid dysmenorrhea and bladder hypersensitivity, defined using a standardized experimental visceral provocation test, contrasted with healthy controls, pure dysmenorrhea sufferers, and women with existing bladder pain syndrome. STUDY DESIGN: This prospective cohort study acquired data on participants with moderate to severe dysmenorrhea (n = 212), healthy controls (n = 44), and bladder pain syndrome (n = 27). A subgroup of dysmenorrhea patients was found on screening with noninvasive oral water challenge to report significantly higher bladder pain during experimentally monitored spontaneous bladder filling (>15 out of 100 on visual analogue scale, based on prior validation studies) and separately defined as a group with dysmenorrhea plus bladder pain. Medical/menstrual history and pain history were evaluated with questionnaires. Psychosocial profile and impact were measured with validated self-reported health status Patient Reported Outcomes Measurement Information System short forms and a Brief Symptom Inventory for somatic sensitivity. Pelvic anatomy and sensory sensitivity were examined via a standardized physical examination and a tampon provocation test. RESULTS: In our largely young, single, nulliparous cohort (24 ± 1 years old), approximately a quarter (46 out of 212) of dysmenorrhea sufferers tested positive for the dysmenorrhea plus bladder pain phenotype. Dysmenorrhea-only sufferers were more likely to be African American (24%) than healthy controls (5%, post hoc χ2, P = .007). Pelvic examination findings did not differ in the nonchronic pain groups, except for tampon test sensitivity, which was worse in dysmenorrhea plus bladder pain and dysmenorrhea sufferers vs healthy controls (2.6 ± 0.3 and 1.7 ± 0.2 vs 0.7 ± 0.2, P < .05). Consistent with heightened pelvic sensitivity, participants with dysmenorrhea plus bladder pain also had more nonmenstrual pain, dysuria, dyschezia, and dyspareunia (P's < .05). Participants with dysmenorrhea plus bladder pain had Patient Reported Outcomes Measurement Information System Global Physical T-scores of 47.7 ± 0.9, lower than in women with dysmenorrhea only (52.3 ± 0.5), and healthy controls 56.1 ± 0.7 (P < .001). Similarly, they had lower Patient Reported Outcomes Measurement Information System Global Mental T-score than healthy controls (47.8 ± 1.1 vs 52.8 ± 1.2, P = .017). Similar specific impairments were observed on Patient Reported Outcomes Measurement Information System scales for anxiety, depression, and sleep in participants with dysmenorrhea plus bladder pain vs healthy controls. CONCLUSION: Women with dysmenorrhea who are unaware they also have bladder sensitivity exhibit broad somatic sensitivity and elevated psychological distress, suggesting combined preclinical visceral sensitivity may be a precursor to chronic pelvic pain. Defining such precursor states is essential to conceptualize and test preventative interventions for chronic pelvic pain emergence. Dysmenorrhea plus bladder pain is also associated with higher self-reported pelvic pain unrelated to menses, suggesting central nervous system changes are present in this potential precursor state.