Prediagnostic Evolution of Polyendocrine Metabolic Ovarian Syndrome (PMOS): Pediatric Obesity, 10–15 Years of Elevated Weight, and Adiposity Rewiring

Polyendocrine metabolic ovarian syndrome (PMOS), previously referred to as polycystic ovary syndrome, is conventionally diagnosed through reproductive manifestations, although its metabolic evolution before diagnosis remains poorly defined. Here we conducted an observational study of de-identified electronic health records from a large federated US network to characterize the prediagnostic evolution of PMOS through four complementary analyses. First, across a reference landscape of 1,929 clinical conditions spanning 15,087,821 people, PMOS combined high body weight at diagnosis of 94.3 kg with marked five-year prediagnostic weight gain of 10.0 kg, corresponding to 15.6%, positioning it alongside insulin resistance, metabolic syndrome and obesity rather than reproductive disorders. This condition-wide pattern placed PMOS within the metabolic disease landscape and raised the question of when the anthropometric divergence begins. Second, among 104,003 women receiving their first recorded PMOS diagnosis at a mean age of 30.9 years (s.d. 9.5) and matched controls, BMI was already higher at the earliest 15-year lookback during adolescence, averaging 23 kg m⁻² versus 20 kg m⁻², respectively (P < 0.001). During the final five years before diagnosis, mean weight increased from 85.9 kg to 94.0 kg, an 8.1 kg gain corresponding to 9.4%, and was 17.9 kg higher than in matched controls at diagnosis (94.0 kg vs 76.1 kg, P < 0.001). This established that the PMOS-associated weight gap was present during adolescence rather than emerging only near reproductive-age diagnosis. Third, among 809,719 women with BMI recorded between 5 and 20 years of age, 19,681 subsequently received a PMOS diagnosis. Ten-year cumulative PMOS incidence increased progressively from 3.3% with healthy BMI to 17.9% with obesity class III, corresponding to an RR of 5.4 (P < 0.001). Black women constituted 11.1% of the healthy-BMI group and 26.5% of the obesity class III group, a 2.4-fold difference across increasing adiposity bands (each band versus healthy BMI, P < 0.001). Thus, early-life adiposity not only preceded PMOS diagnosis but stratified subsequent incidence across a pronounced dose gradient. Fourth, among 1,416 matched case–control pairs with AI-extracted serial body-composition measurements, women with PMOS had 9.8 kg greater fat mass at diagnosis than controls (55.4 kg vs 45.6 kg, P < 0.001). Despite greater absolute lean mass, their lean-mass proportion was 3.8 percentage points lower (52.0% vs 55.8%, P < 0.001). Approximately 72% of the 14.1 kg excess total weight near diagnosis was non-lean mass, revealing that the prediagnostic weight excess was predominantly adipose. Together, these analyses trace an adiposity-linked prediagnostic continuum that begins during pediatric and adolescent years, stratifies more than fivefold variation in subsequent PMOS incidence and culminates in predominantly adipose weight excess before reproductive-age diagnosis.