High Prevalence of Adolescents At Risk for PCOS and Links to Genetic Susceptibility to PCOS

ImportanceDiagnosis of polycystic ovary syndrome (PCOS) in adolescence is challenging because menstrual irregularity and hyperandrogenism are common in adolescents. Recent international guidelines highlighted an at risk for PCOS category based on either menstrual regularity or hyperandrogenism; however, its population prevalence and genetic correlates remain unknown. ObjectiveTo estimate the prevalence of PCOS and at risk for PCOS in adolescence and evaluate associations with genetic risk for PCOS. Design, Settings, and ParticipantsPopulation-based analysis of 1,533 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) with sufficient reproductive data. ExposurePolygenic score (PGS) for PCOS derived from the largest genome-wide association study in European women. Main Outcomes and MeasuresGuideline-defined PCOS (presence of both irregular menses and hyperandrogenism) and at risk for PCOS (presence of one feature). ResultsPCOS prevalence was 3.2%, while 27.2% met criteria for being at risk for PCOS. A higher PCOS PGS was associated with hyperandrogenism (OR per SD increase in PGS: 1.22; 95% CI, 1.07-1.39; P=4x10-3) but not irregular menses. Conclusions and RelevanceOver one-fourth of adolescents met criteria for being at risk for PCOS. Genetic risk for PCOS was associated with hyperandrogenism but not isolated menstrual irregularity, suggesting that androgen excess is a more specific early manifestation of inherited PCOS liability.