Dysmenorrhea is often linked to uterine inflammation, but the additional factors and pathways that contribute to its pathophysiology remain poorly understood. Given growing evidence linking endoplasmic reticulum (ER) stress to inflammation and pain sensitization, we examined circulating ER stress-associated heat shock proteins (HSPs) GRP78 and gp96 in individuals with dysmenorrhea (n = 82), a dysmenorrhea subtype with bladder pain sensitivity (DYSB, n = 26) previously shown to increase risk for chronic pain, and controls (n = 19). After correcting for Menstrual phase, naproxen exposure, and oral contraceptive use, GRP78 was higher in DYSB than in DYS (ratio 1.33; p = .028), while gp96 was lower in both DYS (ratio 0.62; p = .019) and DYSB (ratio 0.59; p = .031) compared to controls. gp96 was also lower during the menstrual phase with naproxen compared to the non-menstrual phase (ratio 0.73; p = .014), whereas GRP78 was not significantly affected by menstrual phase, naproxen, or oral contraceptive use, and neither protein was associated with anxiety, depression, or sleep disturbance scores. These cross-sectional findings suggest that dysmenorrhea, particularly the bladder-sensitive subtype (DYSB), is associated with divergent circulating levels of two ER stress-related proteins. The inverse pattern of higher GRP78 and lower gp96 levels points to selective, rather than global, ER chaperone dysregulation as a candidate mechanism. However, future mechanistic and longitudinal investigations will be required to establish whether GRP78 and gp96 carry predictive or pathophysiological relevance.

Somatic symptoms are common in adolescence and can predict later emotional distress, academic challenges, and chronic health problems. Their developmental origins, particularly before menarche, remain poorly understood. This cross-sectional study examined associations between psychological distress, parental modeling of pain behavior, pain sensitivity, and somatic symptom burden in premenarchal adolescents. A community sample of 228 adolescents (Age M = 11.3, SD = 0.9) completed standardized measures of anxiety, depression, stress, somatic symptoms, and parent-reported pain modeling. Participants also underwent laboratory-based bladder and pressure pain threshold testing. In multivariable regression, Tanner stage ( β = .11), anxiety (.31), depression (.23), parental pain modeling (.15), and visceral pain sensitivity (.13) were independently associated with greater somatic symptoms. Results highlight a constellation of psychological, familial, and physiological factors related to somatic symptoms in early adolescence, suggesting that early identification of these risks could inform prevention strategies before puberty, when more persistent symptom patterns may emerge.

Dysmenorrhea is highly prevalent and undertreated, substantially impairing quality of life in reproductive-age individuals. Excessive uterine contractility is widely considered a key mechanistic contributor to menstrual pain. We conducted a systematic search of PubMed and Embase from inception to 24 July 2024 using MeSH and Emtree terms related to dysmenorrhea, uterine contractions and pharmacologic therapy. We included English-language human clinical trials in non-pregnant, reproductive-age participants with primary dysmenorrhea evaluating drugs intended to reduce uterine contractions and menstrual pain, compared with placebo or pre-treatment baseline. Two reviewers independently extracted data using a piloted Cochrane-based form; risk of bias was assessed using RoB 2 and ROBINS-I with disagreements resolved by consensus. Across 25 eligible trials (447 participants), nonsteroidal anti-inflammatory drugs (NSAIDs) most consistently reduced both menstrual pain and uterine contractions. Smaller trials suggested potential benefits for additional pharmacologic classes, including prostaglandin synthesis inhibitors, vasopressin antagonists, beta-adrenergic agonists, combined oral contraceptives, calcium channel blockers, and selective estrogen receptor modulators, whereas oxytocin antagonists showed mixed results. Risk of bias was low in nine studies, moderate in 12, and high in four. These findings support that established therapies for dysmenorrhea (NSAIDs and hormonal contraception) reduce pain and uterine activity, and suggest that other contractility-targeting agents warrant further rigorous evaluation, particularly given meaningful non-response to NSAIDs. PROSPERO registration: CRD42023442828 (registered 24 July 2023).

OBJECTIVE:To examine how eicosanoid levels in menstrual effluent of adolescents within 3 years of menarche relate to the severity of menstrual pain. DESIGN:Prospective cohort study. SETTING:Community teaching hospital. POPULATION OR SAMPLE:Adolescents within 3 years after menarche. METHODS:Participants provided a menstrual effluent sample between 4 and 30 months after menarche. Eicosanoid and oxylipin concentrations were measured in the menstrual effluent. We compared effluent concentrations of participants with menstrual pain (n = 33) to age-matched pain-free controls (n = 18). MAIN OUTCOME MEASURES:Eicosanoid and oxylipin concentrations in menstrual effluent. RESULTS:Participants with dysmenorrhea had higher PGF2α (4.5 [1.6, 8.9] ng/mL, p = 0.014) than controls (1.1 [0.07, 4.4] ng/mL). However, differences in PGE2 (7.1 [2.6, 10.1] vs. 3.5 [1.0, 5.1], p = 0.053) and 12-HETE (36.3 [23.7, 60.7] vs. 29.6 [13.4, 51.5], p = 0.305) were not significant. The correlations between PGF2α (r = 0.37, p = 0.004) or PGE2 concentration (r = 0.28, p = 0.046) and menstrual pain intensity were moderate to small. Overall, there were positive correlations between menstrual volume and eicosanoid concentrations (r's > 0.4, p's < 0.001). Participants with dysmenorrhea taking analgesics had more PGF2α (66.2 [43.0, 164.7]) than controls (19.1 [6.0, 47.5], p = 0.04). LC-MS/MS revealed higher concentrations of 12-HETE, 14,15-EET, 15-HETE, 18cdLTB4, LTB4 and PGF2α-and lower 6-kPGF1α-in the effluent of participants with dysmenorrhea compared to controls. CONCLUSIONS:Elevated PGF2α in adolescents with dysmenorrhea, modest correlations between prostaglandin concentrations and menstrual pain, and the identification of additional oxylipins suggest that inflammatory processes beyond the prostaglandin pathway contribute to dysmenorrhea.

Background: Dysmenorrhea (menstrual pain) negatively impacts the quality of life for many individuals and is often refractory to treatment. Although the mechanisms responsible for pain are not fully understood, it is widely hypothesized that menstrual pain is caused by uterine contractions. However, prior research involved either invasive methods, which could provoke contractions, or small sample sizes. To address this knowledge gap, the present study used a novel magnetic resonance imaging (MRI)-based strategy that allows for noninvasive measurement of uterine contractions. Using cine (continuous)-T2 weighted sequences, which capture one frame every 2 seconds over a 10 minute window, it is possible to visualize uterine contractions. Because our strategy was noninvasive and well tolerated, it was feasible to accommodate a larger sample size. Methods: The study objective was to evaluate whether participants with menstrual pain were more likely to have differences in uterine contractile occurrence, frequency, or duration. Reproductive-age menstruating women were enrolled, and the presence of conditions associated with secondary dysmenorrhea, including fibroids and endometriosis, was also assessed. In order to study the role of myometrial contractions in menstrual pain, we performed continuous MRI sequences and evaluated myometrial activity including frequency and duration of uterine contractions. Ninety-eight participants with primary dysmenorrhea, 28 pain-free controls, 17 with endometriosis, and 8 with fibroids had menstrual pain during imaging and sufficient image quality for uterine evaluation with MRI. Participants underwent MRI during the first 48 hours of menstrual bleeding onset and were asked to avoid taking analgesic medications prior. MRI data was acquired on a 3.0T whole-body scanner (Siemens Skyra) using a high performance body coil. Continuous MRI was acquired using half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence. Associated participant pain ratings were obtained using the numerical rating scale from 0 (no pain at all) to 10 (worst pain imaginable). Eligible dysmenorrhea participants were required to have reported menstrual pain greater than 5 without pain relievers. Five reviewers naive to participant diagnoses viewed digitally archived cineMRI clips and double-scored the frequency and duration of uterine contractions. Uterine contractions (>=10 seconds) were differentiated from peristalsis (<10 seconds) by duration of myometrial activity. All reviewers underwent extensive training in uterine event coding, but none had formal professional training in radiological assessment. To assess uterine activity, a region of interest was drawn over the uterine corpus perpendicular to the axis of the cervix. Myometrial event frequency was identified by counting the episodes of changed myometrial signal intensity over time. Kappa statistics were calculated for interrater reliability. A Pearson Chi square test was used to evaluate the proportion of subjects with or without contractions and among different races. Mann Whitney U tests and Kruskal-Wallis tests were used to compare pain-free controls to dysmenorrhea and secondary dysmenorrhea groups respectively Results: Inter-reviewer reliability to identify uterine contraction frequency and duration was analyzed, yielding a high agreement between reviewers to identify myometrial events (Kappa agreement = 97%, p<0.001). Participants with primary dysmenorrhea were more likely to have uterine contractions (90%) compared to pain-free controls (61%, p=0.001). Additionally, participants with primary dysmenorrhea had a higher frequency of uterine contractions (3.38 contractions/10 min) in comparison to pain-free controls (1.88 contractions/10 min, p=0.003). In analyses including participants with endometriosis and fibroids, those with a secondary dysmenorrhea diagnosis experienced more uterine contractions (p=0.004) and higher contraction frequency (p=0.028) compared to pain-free controls. Specifically, 76% of participants with endometriosis and 75% of participants with fibroids experienced uterine contractions. The duration of uterine contractions was no different between participants with dysmenorrhea [median (IQR):47 (32,67) seconds] and pain-free controls [median (IQR):47 (26,140) seconds], (p=0.83). Additionally, no significant differences were observed between participants with secondary dysmenorrhea due to endometriosis [median (IQR):46 (34,81)] or fibroids [median (IQR):53 (31,61)] and pain-free controls [median (IQR:47 (26,140). (p=1.0). Discussion: Overall, cineMRI uterine contraction measurements were highly consistent across reviewers, suggesting that uterine contractility can be reliably measured. For the first time using a noninvasive method and a moderate-sized cohort, it is demonstrated that uterine contractions occur in the vast majority of participants with either primary or secondary dysmenorrhea. However, uterine contractions were also observed in more than half of pain-free controls. Given that uterine contractions can occur even in the absence of menstrual pain, there are likely additional underlying mechanisms responsible for uterine pain. As our prior work has found evidence of pelvic visceral hypersensitivity to bladder distension among many dysmenorrhea sufferers, we hypothesize that a similar visceral hypersensitivity to uterine contractions may be necessary for the perception of menstrual pain.

OBJECTIVES:This study aimed to identify menstrual pain trajectories over 2 years in young women with moderate-to-severe intensity, and determine baseline factors, including modifiable variables, that differentiate these trajectories. METHODS:This secondary analysis of a prospective cohort study included 157 women aged 18-45 years, enriched for moderate-to-severe menstrual pain. Pain during periods (without/before analgesic use) was reported at 3 visits: baseline, Year 1 and Year 2. Baseline measures included non-menstrual pelvic pain (NMPP), anxiety, depression, pain catastrophizing, somatic sensitivity, and sleep disturbance. Hormonal contraceptive use, pregnancies, and menstrual suppression were tracked annually. We performed growth mixture modelling to identify pain trajectories. RESULTS:Four trajectories emerged: high-stable pain (63%), low-stable pain (15%), improving pain (11%), and worsening pain (11%). High-stable pain was characterized by higher baseline NMPP, somatic sensitivity, and sleep disturbance compared with low-stable pain. The improving group had greater hormonal contraceptive use at follow-up (primarily combined oral contraceptives; regimen patterns inconsistently reported) compared with the high-stable group. No predictors of the worsening trajectory group were identified. Very few pregnancies occurred over the follow-up period. CONCLUSIONS:Most menstrual pain trajectories remained stable over 2 years. Because women in the high-stable group demonstrated a broader burden of symptoms-NMPP, somatic sensitivity, and sleep disturbance-future studies should focus on multidisciplinary approaches, such as sleep optimization, complementing traditional use of non-steroidal anti-inflammatories. Future work is also needed to understand how pregnancy and tolerance of hormonal therapy may influence adverse symptom trajectories.

Dysmenorrhea (period pain) affects over 40% of women and is a leading cause of missed school and workdays. However, the molecular mechanisms underlying this pain are not fully understood. We conducted a systematic review (Prospero registration: CRD42024535081) to identify and evaluate the biomolecules in menstrual effluent that may contribute to dysmenorrhea and assess how non-hormonal medications (e.g. NSAIDs) impact these biomarkers. Fifteen studies involving two hundred twenty-three participants met the inclusion criteria. We used the Newcastle-Ottawa Scale (for observational studies) and the Cochrane RoB2 tool (for randomized controlled trials) to evaluate the risk of bias and the quality of studies. Eight studies consistently reported elevated prostaglandin levels in the menstrual effluent of women with dysmenorrhea, though sample sizes were generally small, and methodological issues were noted. Seven studies demonstrated that NSAIDs reduce prostaglandin concentrations; however, these trials utilized multiple-day dosing protocols instead of single-dose regimens, leaving questions about acute treatment effects. Two studies highlighted alternative molecular targets, such as 12-HETE and platelet-activating factor (PAF), that may also play key roles in menstrual pain. Overall, elevated prostaglandins are a recurring finding, but the limited scope and design of existing studies indicate a need for larger, methodologically rigorous investigations. Nevertheless, the few studies that identified molecules other than prostaglandins suggest there are viable druggable targets for clinical trials to reduce menstrual pain.

Widespread pain in adolescence is linked with poor mental health, pain, and somatic symptoms in childhood. This prospective study in 207 premenarchal adolescents used quantitative sensory testing (QST) and multimodal hypersensitivity (MMH) measures to assess somatosensory system function and identify predictors for widespread pain (≥3/7 sites). We hypothesized that premenarchal pain, somatic symptoms, psychological factors, and somatosensory system function would predict postmenarchal widespread pain, which would be associated with greater menstrual pain intensity. At premenarchal and postmenarchal study visits, participants completed measures of somatic symptoms, a pain body map, psychosocial questionnaires, QST, and experimental MMH measures including auditory, visual, and visceral stimulation. Electroencephalography (EEG) was collected during auditory and visual tasks to identify neural correlates of MMH. Premenarchal widespread pain was reported by 25% of participants, whereas 29% developed new incident widespread pain postmenarche. Adolescents with postmenarchal widespread pain reported greater menstrual pain intensity (median [interquartile range] 47 [28-61]; 0-100 visual analog scale) than those without (24 [8-50], P = 0.001). Elevated somatic symptoms ( P = 0.012), stress ( P = 0.015), and sensitivity to visceral (bladder filling) ( P = 0.046) and unpleasant visual stimuli ( P = 0.043) were significant predictors of postmenarche widespread pain. A multivariable regression model found premenarchal body map score (OR = 1.75, 95% CI [1.20, 2.55]), somatic symptoms (OR = 1.47, 95% CI [1.03, 2.11]), and visual hypersensitivity (OR = 1.62, 95% CI [1.12, 2.33]) predicted postmenarchal widespread pain. No EEG differences in early cortical sensory processing were found. Our results suggest that increased sensitivity to multimodal unpleasant and painful stimuli represents a novel risk factor for postmenarche widespread pain.

BACKGROUND: The mechanisms responsible for menstrual pain are poorly understood. However, dynamic, noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and testing novel treatments. OBJECTIVE: To study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional magnetic resonance imaging parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions. STUDY DESIGN: We performed functional magnetic resonance imaging on participants with and those without dysmenorrhea during menses and outside menses. To clarify whether regional changes in oxygen availability and perfusion occur, functional magnetic resonance imaging R2* measurements of the endometrium and myometrium were obtained. R2* measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify if changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment. RESULTS: During menstruation, a notable increase in R2* values, indicative of tissue ischemia, was observed in both the myometrium (beta +/- standard error of the mean, 15.74 +/- 2.29 s(-1); P=.001; q=.002) and the endometrium (26.37 +/- 9.33 s(-1); P=.005; q=.008) of participants who experienced dysmenorrhea. A similar increase was noted in the myometrium (28.89 +/- 2.85 s(-1); P=.001; q=.002) and endometrium (75.50 +/- 2.57 s(-1); P=.001; q=.003) of pain-free controls. Post hoc analyses revealed that the R2* values during menstruation were significantly higher among the pain-free controls (myometrium, P=.008; endometrium, P=.043). Although naproxen sodium increased the endometrial R2* values among participants with dysmenorrhea (48.29 +/- 15.78 s(-1); P=.005; q=.008), it decreased myometrial R2* values among pain-free controls. The Doppler findings were consistent with the functional magnetic resonance imaging (-8.62 +/- 3.25 s(-1); P=.008; q=.011). The pulsatility index (-0.42 +/- 0.14; P=.004; q=.004) and resistance index (-0.042 +/- 0.012; P=.001; q=.001) decreased during menses when compared with the measurements outside of menses, and the effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping. CONCLUSION: Functional magnetic resonance imaging and Doppler metrics suggest that participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacologic effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects in participants with dysmenorrhea.

Abstract Introduction Puberty encompasses a multitude of physical, hormonal, and psychological changes. Additionally, adolescents also experience a delay in circadian rhythm, increasing their vulnerability to insufficient sleep. Even though puberty and sleep share a strong association, few studies have explored the shift in sleep after the onset of menstruation (i.e., menarche). This longitudinal, multimethod study examines sleep health parameters before and after menarche among a community sample of females. Methods Biological females (n = 47; 74% white) from a Midwestern metropolitan area were recruited as part of a larger study on menarche. Participants completed two lab visits: Time 1 (T1: prior to menarche; Mage = 11.3, SDage = 1.0) and Time 2 (T2: 3-9 months post-menarche; Mage = 12.6, SDage = 1.0). An actigraph wristwatch was worn for 7 days following each lab visit to measure dimensions of sleep health including bedtime, wake time, time in bed, and total sleep time. Phillips Actiware Software was used to score actigraphy data; SPSS 27 was used to perform paired sample t-tests to explore changes over time. Results Following menarche, there were significant differences in several parameters of sleep health including: 1) a 1.7-hour delay in bedtime (T1M = 21:45, T1SD = 1:02; T2M = 23:29, T2SD = 3:07, t(46) = (3.37), p = (.002), 2) less time in bed (T1M = 542, T1SD = :48; T2M = 518, T2SD = :58), t(46) = (2.67), p (.01), and 3) a 27-minute decrease in total sleep time (T1M = 482, T1SD = :40; T2M = 455, T2SD = :51), t(46) = (3.32), p = (.002). Overall, these results indicate participants are sleeping significantly less in the months following menarche. Conclusion Findings confirm that biological females experience changes in sleep behaviors within 9 months of menarche. Chronic sleep loss and daytime sleepiness worsens throughout adolescence, furthering the risk for cognitive and behavioral issues. Data collection is ongoing and future analyses will examine sleep variability across this transitional point in development. This is one of the first studies to examine the sleep-wake experience of females across menarche. Support (if any)

Background:Uterine fibroid (UF) growth rate and future morbidity cannot be predicted. This can lead to sub-optimal clinical management, with women being lost to follow-up and later presenting with severe disease that may require hospitalization, transfusions, and urgent surgical interventions. Multi-parametric quantitative magnetic resonance imaging (MRI) could provide a biomarker to predict growth rate facilitating better-informed disease management and better clinical outcomes. We assessed the ability of putative quantitative and qualitative MRI predictive factors to predict UF growth rate. Methods:Twenty women with UFs were recruited and completed baseline and follow-up MRI exams, 1-2.5 years apart. The subjects filled out symptom severity and health-related quality of life questionnaires at each visit. A standard clinical pelvic MRI non-contrast exam was performed at each visit, followed by a contrast-enhanced multi-parametric quantitative MRI (mp-qMRI) exam with T2, T2*, and apparent diffusion coefficient (ADC) mapping and dynamic contrast-enhanced MRI. Up to 3 largest fibroids were identified and outlined on the T2-weighted sequence. Fibroid morphology and enhancement patterns were qualitatively assessed on dynamic contrast-enhanced MRI. The UFs' volumes and average T2, T2*, and ADC values were calculated. Pearson correlation coefficients were calculated between UF growth rate and T2, T2*, ADC, and baseline volume. Multiple logistic regression and receiver operating characteristic (ROC) analysis were performed to predict fast-growing UFs using combinations of up to 2 significant predictors. A significance level of alpha =0.05 was used. Results:Forty-four fibroids in 20 women had growth rate measurement available, and 36 fibroids in 16 women had follow-up quantitative MRI available. The distribution of fibroid growth rate was skewed, with approximately 20% of the fibroids exhibiting fast growth (>10 cc/year). However, there were no significant changes in median baseline and follow-up values of symptom severity and health-related quality of life scores. There was no change in average T2, T2*, and ADC at follow-up exams and there was a moderate to strong correlation to the fibroid growth rate in baseline volume and average T2 and ADC in slow-growing fibroids (<10 cc/year). A multiple logistic regression to identify fast growing UFs (>10 cc/year) achieved an area under the curve (AUC) of 0.80 with specificity of 69% at 100% sensitivity. Conclusions:The mp-qMRI parameters T2, ADC, and UF volume obtained at the time of initial fibroid diagnosis may be able to predict UF growth rate. Mp-qMRI could be integrated into the management of UFs, for individualized care and improved clinical outcomes.

Widespread body pain can emerge in adolescence and is a risk factor for chronic widespread pain conditions in adulthood, such as fibromyalgia, that negatively impact quality of life. In this longitudinal study we identified predictors for developing widespread body pain (pain in at least 3/7 sites) across menarche in adolescents. Over pre- and post- menarchal study visits spanning an average of 2.6 years, 178 participants completed a bodymap questionnaire as well as psychosocial questionnaires, quantitative sensory testing (including unpleasant visual and auditory stimuli), and a provoked visceral pain task that measures bladder sensitivity. Bodymap analysis revealed that one quarter (n=44) of participants had widespread pain at the baseline pre-menarche visit. Another quarter of participants (n=45) would develop widespread pain by post-menarche follow-up visit, while the other half (n=89) did not develop widespread pain at any time point. Neither baseline pressure pain thresholds, cold pain ratings, nor conditioned pain modulation predicted the development of widespread pain. Menstrual pain was not associated with widespread pain at post-menarche follow up visits. However, greater sensitivity to visceral (bladder) provocation (p<0.001) as well as unpleasant auditory (p<0.01) and visual stimuli (p<0.01) at baseline did predict widespread pain development. Other baseline predictors of widespread pain included higher anxiety, depression, somatization and stress and lower positive affect. These results suggest that - in addition to psychosocial factors - increased sensitivity to unpleasant and painful stimuli across multiple modalities is a risk factor for pain spread in adolescents. Funding: R01HD096332.

Abstract Introduction Adolescence is marked by shifts in sleep, both in terms of timing and quality. Little is known about how these disruptions in sleep relate to pain and executive functioning (EF) following the onset of menstruation (e.g., menarche) in females. This study examines the relations between 1) sleep disturbances and pain, 2) sleep disturbances and EF, and 3) pain and EF in a sample of adolescents who experienced menarche in the past year. Methods A community sample of biological females (n = 159; M age = 12.8; SD age = 1.1; 74% white) and their caregivers were recruited from a Midwestern metropolitan area. Caregivers reported on demographics, sleep disturbance (PROMIS Sleep Disturbance Short Form), and EF problems (BRIEF scales: Inhibitory Control (IC), Emotion Control (EC), Shift (S), Working Memory (WM), and Task Switching (TS) subscales). Adolescents reported on somatic symptoms (Children’s Somatic Symptom Inventory: CSSI) and period pain (“Over the last three months, what was the average cramping pain you experienced with your period?”; rating scale 0 [no pain] to 10 [worst pain imaginable]). Results A series of linear regressions investigated the relation between sleep, pain, and EF. Participants with higher somatic symptoms, but not greater period pain, experienced more sleep disturbance (β =.098, p=.032). More sleep disturbance was associated with more EF problems including EC (β = .016, p<.001), S (β =.169, p<.001), WM (β = .136, p=.01), and TS (β = .169, p<.001). There were no significant associations between either somatic symptoms or period pain and EF problems. Thus, adolescents who experienced more sleep disturbance exhibited higher levels of somatic symptoms and more difficulty with emotional regulation, cognitive flexibility, and memory. Conclusion Preliminary results indicate that sleep disturbance in the year following menarche is related to more somatic symptoms, but not more period pain. Further, sleep disturbance appears to be closely linked to EF problems. Data collection is ongoing, and actigraphy data on sleep (duration, quality) will be used to further investigate how sleep relates to pain and EF during this important developmental transition. Support (if any)

Background: Dyspareunia, defined as pain before, during or after intercourse, is a subset of female sexual dysfunction with overlapping gynecologic, urologic and psychosocial etiologies. Aim: This study aimed to evaluate the impact of menstrual pain and visceral hypersensitivity on sexual function and to identify risk factors for sexual pain in healthy reproductive-age females. Methods: In this prospective cohort study, we evaluated gynecologic and psychologic self-reported histories, validated sexual function questionnaires, and conducted a standardized gynecologic examination enhanced by quantitative sensory testing in reproductive-aged females with menstrual pain versus pain-free controls. Correlation analysis was conducted between the Female Sexual Function Index (FSFI) pain subdomain score and a priori hypothesized risk factors for dyspareunia: menstrual pain severity, experimentally provoked bladder sensitivity, anxiety, depression, pain catastrophizing, and vaginal pressure-pain sensitivity. Outcomes: The primary outcome was severity of sexual pain as measured by the FSFI, comparing participants with moderate-to-severe dysmenorrhea (n = 99), dysmenorrhea with bladder hypersensitivity (n = 49) identified on non-invasive oral water challenge, and pain-free controls (n = 37). Results: In our young (median age 22 [IQR 19, 29]), nulliparous, predominantly heterosexual cohort (78.3%, 144/185), 64.3% (119/185) engaged in sexual intercourse within the four-week recall period. The median total FSFI score was 27.2 (22.0, 30.2). Across groups, only the dysmenorrhea with bladder hypersensitivity phenotype met the threshold for sexual dysfunction as measured by total FSFI score (24.6 [20.0, 28.1], p = 0.008). Dysfunction was driven by difficulties with lubrication and higher pain levels during and after intercourse. On physical examination, those with and without dyspareunia were largely indistinguishable, with little to no tenderness of the pelvic floor, bladder, uterus and uterosacral ligaments. Amongst the six hypothesized risk factors for sexual pain, only experimentally provoked bladder pain was significantly associated with the severity of dyspareunia (r = 0.41, corrected p < 0.001). Clinical implications: Young, otherwise healthy individuals with dysmenorrhea and occult visceral hypersensitivity exhibit signs of sexual dysfunction and significantly higher rates of dyspareunia in the absence of reliable clinical examination findings. Strengths and limitations: Strengths include the use of a nonclinical sample of almost exclusively nulliparous females with no co-morbid pelvic pain diagnoses and prospective diary confirmation of dysmenorrhea severity. The study is limited by the narrow heteronormative, cisnormative sexual experience of penile-vaginal intercourse captured by the FSFI. Conclusion: Sexual pain is more prevalent in those with dysmenorrhea with bladder hypersensitivity than isolated dysmenorrhea, suggesting visceral hypersensitivity may be a non-structural mechanistic driver for dyspareunia.