Genetic Risk for PCOS/PMOS Is Associated with Hyperandrogenism but Not Irregular Menses in Adolescents and Young Adults

Abstract Context Diagnosing polycystic ovary syndrome, recently renamed polyendocrine metabolic ovarian syndrome (PMOS), during adolescence is challenging because menstrual irregularity and clinical signs suggesting hyperandrogenism are common. Recent international recommendations highlighted an “at risk for PMOS” category, defined by either menstrual regularity or hyperandrogenism, to guide surveillance; however, its prevalence and genetic correlates remain unknown. Objective To estimate the prevalence of PMOS and “at risk for PMOS” in adolescence and young adulthood and to assess associations with genetic risk for PMOS. Design/Setting/Participants Retrospective analysis of 1,533 participants from the ALSPAC study, a UK birth cohort, with sufficient data to classify menstrual regularity and hyperandrogenism, and a subset of 1,371 genotyped participants of European ancestry. Main Outcome Measures Prevalence of PMOS and “at risk for PMOS” and associations with a PMOS polygenic score (PGS). Results Among 1,533 participants, 49 (3%) met criteria for PMOS and 417 (27%) were “at risk for PMOS” (hyperandrogenism only, 276 [18%]; irregular menses only, 141 [9%]). A higher PMOS PGS was associated with hyperandrogenism only (OR per SD:1.22; 95% CI:1.07–1.39; P=4×10−3) but not with irregular menses only (OR:0.98; 95% CI:0.83–1.15; P=0.8). The association with PMOS was positive but not statistically significant (OR:1.28; 95% CI:0.88–1.87; P=0.2). Conclusions PMOS prevalence in adolescence and young adulthood was 3%, whereas over one-quarter met criteria for being “at risk for PMOS.” Genetic risk for PMOS was associated with hyperandrogenism but not isolated menstrual irregularity, suggesting androgen excess may represent a more specific early manifestation of inherited PMOS liability.