Menstrual symptoms and infertility odds among individuals with co-occurring endometriosis and polyendocrine metabolic ovarian syndrome

Objective: To study the prevalence of co-occurring endometriosis and polyendocrine metabolic ovarian syndrome (PMOS), estimate infertility odds, and characterize menstrual symptom profiles associated with this combined phenotype in a population cohort. Design: Prospective digital cohort in the United States (US). Subjects: 90,714 consented participants enrolled between November 2019 and June 2025 who completed relevant surveys; a subset of 25,152 participants with menstrual cycle logs linked to monthly surveys contributed to symptom analyses. Exposure: Participants were classified by self-reported physician diagnosis into four groups: endometriosis alone, PMOS alone, co-occurring endometriosis and PMOS (endometriosis+PMOS), or neither condition (reference group). Main Outcome Measures: (1) Odds of self-reported physician-diagnosed infertility (ever/never, cross-sectional), estimated using multivariable logistic regression adjusted for age, race/ethnicity, and subjective socioeconomic status; (2) number of adverse menstrual symptoms logged per cycle, assessed using negative binomial mixed-effects models adjusted for age, race/ethnicity, and hormonal contraceptive use. Results: Among 90,714 participants, the mean age was 35.1 years (standard deviation: 11.6) and the majority identified as non-Hispanic White (72%). Prevalence estimates were 11% for PMOS alone, 6% for endometriosis alone, and 2% for endometriosis+PMOS. Individuals with endometriosis+PMOS more frequently reported unemployment, low socioeconomic status, active smoking, poorer subjective health, early menarche, current irregular cycles, and a broad range of comorbidities. Infertility odds were highest for endometriosis+PMOS (odds ratio: 12.49 [95% confidence interval: 11.13-13.99]), followed by PMOS alone (6.12 [5.69-6.59]) and endometriosis alone (4.31 [3.93-4.72]), with the combined effect exceeding additive expectations (relative excess risk due to interaction: 3.05 [1.65-4.46]). Individuals with endometriosis+PMOS logged 11% more symptoms per cycle than those with neither condition (incidence rate ratio: 1.11 [1.04-1.19]) and had the highest odds of logging pelvic pain, fatigue, and sleep changes, among other symptoms. Conclusion: In this large US digital cohort, co-occurring endometriosis and PMOS affected 1 in 50 participants and was associated with markedly elevated infertility odds exceeding additive expectations, and a heightened menstrual symptom burden. Several risk factors and health impacts characteristic of each condition appeared amplified in individuals with both conditions, suggesting a subgroup with compounded clinical complexity and greater care needs.