Menstrual Disorder Frequency Across Ibuprofen and Oral Contraceptive Treatment Modalities in Reproductive-Age Women: A Population-Based Analysis Using the NIH All of Us Research Program.

Abstract

Introduction: Despite the widespread use of nonsteroidal anti-inflammatory drugs and oral contraceptives (OC), population-level analyses on how menstrual disorder diagnoses vary across ibuprofen and OC use remain limited. Prior studies emphasize treatment efficacy for individual conditions rather than cross-sectional diagnosis co-occurrence across these treatment categories. The NIH All of Us Research Program enables age-stratified analyses of menstrual disorder diagnoses across ibuprofen and OC use.

Methods: We conducted a retrospective cross-sectional analysis of female participants 18-35 years old using All of Us data from electronic health records, survey responses, and physical measurements. Participants were stratified into ages 18-24 and 25-35 years and grouped by recorded ibuprofen only, OC only, or ibuprofen + OC exposure. Standardized Observational Medical Outcomes Partnership concept sets identified dysmenorrhea, irregular menstruation, excessive/heavy bleeding, and amenorrhea. Pairwise chi-square tests compared diagnosis presence across treatment groups. The Holm-Bonferroni (HB) adjustment was applied. Treatment duration, dose, adherence, and temporal sequencing relative to diagnosis could not be established.

Results: In women aged 18-24 years, no significant differences in diagnosis prevalence were observed between treatment groups (ibuprofen: n = 2832; OC: n = 4256; and combination: n = 2315). Between-group prevalence differences were modest (0.9 to 2.1 percentage points) and did not remain significant after HB correction (all HB adjusted p > 0.05). Women aged 25-35 years (ibuprofen: n = 9533; OC: n = 9517; and combination: n = 9617) had OC use associated with lower dysmenorrhea prevalence versus combination use (prevalence difference: 1.4%; HB-adjusted p < 0.05). Irregular menstruation was more frequent in the OC group than in the ibuprofen group (2.1%; HB-adjusted p < 0.05). Excessive/heavy bleeding was more prevalent with ibuprofen use than with OC use and combination therapy (2.2% and 1.6%, respectively; HB-adjusted p < 0.05). Amenorrhea prevalence did not differ significantly (≤0.9%; HB-adjusted p > 0.05).

Conclusions: Menstrual disorder diagnosis frequencies differed across ibuprofen and OC exposure groups, primarily among women 25-35 years old. Longitudinal studies with untreated comparators and better characterizations of treatment timing, dose, and duration are needed.