MON-221 Differences in the Bile Acid Pool in Post-Menarcheal Adolescents on a Trajectory Towards Polycystic Ovary Syndrome

Abstract Disclosure: H. Lamar: None. H. Vanden Brink: None. Introduction: PCOS is a common endocrine disorder that emerges in the years after menarche. However, the pathogenesis of PCOS as symptoms manifest is poorly understood, impairing early detection and optimal preventative or management strategies. We recently reported shifts in bile acid (BA) isoforms as a potential modulator of pubertal timing in rodent models and observed similar differences in pre- versus post-menarcheal females. Whether a divergence in BA isoforms also occurs in the post-menarcheal years as adolescents undergo reproductive axis maturation is unclear. Objective: To determine whether differences in the BA pool emerge among post-menarcheal adolescents on a trajectory towards PCOS versus No PCOS and the individual diagnostic features of PCOS. Methods: We conducted an ancillary study from a prospective cohort of 28 post-menarcheal adolescent females. Assessment of clinical symptoms of PCOS, fasting venipuncture, and anthropometry were serially obtained at the following timepoints: 6-10, ∼12, ∼18, and ∼24 months post-menarche. BAs were measured from stored plasma (Columbia Metabolomic Core). Participants were phenotyped at their final study visit using the 2023 International Guidelines for PCOS (No PCOS (32%), PCOS Risk (43%), and PCOS (25%)) and by diagnostic features (Irregular (57%) vs Regular (43%) menstrual cycles; biochemically hyperandrogenic [Free Androgen Index or Total Testosterone; 21%, HA] vs normoandrogenic [79%, NA]). Differences in BA outcomes over time and by final phenotype were conducted using mixed models. Percentages are expressed as % of total BA pool. Models were adjusted for body fat % measured via bioimpedance. Results: The proportion of total secondary BAs was higher during the first two post-menarcheal years in adolescents who ultimately met criteria for PCOS vs PCOS Risk and No PCOS (57 ± 13.3% vs 42 ± 18.3 vs 37 ± 16.9%; p = 0.0499). Similarly, adolescents who developed irregular menstrual cycles had a greater proportion of secondary BAs versus regular menstrual cycles (51 ± 16.1% vs 35 ± 16.7%, p = 0.035). Both total secondary BAs and specifically deoxycholic acid (DCA) were elevated during study participation in the adolescents who would meet criteria for HA versus NA (total secondary: 55 ± 15.7% vs 41 ± 17.6%; p = 0.005; DCA: 33 ± 10.3% vs 19 ± 12.6% p = 0.002). Similarly, conjugated primary BAs were lower among those who met criteria for HA vs NA (33 ± 9.3 vs 48 ± 15.4%; p = 0.023). No differences in other BA outcomes were detected, nor did the trajectory of BAs diverge (phenotype-by-time interaction; p>0.05). Conclusion: Bile acid isoforms differ in post-menarcheal adolescents on a trajectory towards PCOS. A higher proportion of secondary BAs and lower proportion of primary conjugated BAs was associated with the emergence of HA. Whether differences in the bile acid pool are correlative or contributes to the pathogenesis of PCOS is an area of future research. Presentation: Monday, July 14, 2025