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.