EP1363 - ECE_3272 - Central adiposity drives persistent MASLD risk in postmenopausal women with a phenotype of Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) is increasingly recognised as a lifelong endocrine–metabolic condition, yet its contribution to metabolic dysfunction–associated steatotic liver disease (MASLD) beyond the reproductive years remains uncertain. Menopause is accompanied by adverse changes in fat distribution and metabolic risk, raising the question of whether PCOS-related susceptibility to MASLD persists after menopause and whether this risk is driven by overall obesity or by central adiposity. Addressing this gap has direct implications for long-term endocrine follow-up and prevention strategies in women with a history of PCOS. We performed a cross-sectional analysis of 776 postmenopausal women (mean age 63.4 ± 7.0 years; mean menopausal duration 11.2 ± 8.3 years), including 101 (17.2%) with a PCOS phenotype defined by a documented history of oligo-/amenorrhoea and/or clinical hyperandrogenism. MASLD was defined using hepatic steatosis index (HSI≥36) in combination with metabolic dysfunction, defined as the presence of at least one cardiometabolic abnormality, including overweight or obesity, impaired glucose metabolism or type 2 diabetes, hypertension, dyslipidaemia, or insulin resistance. Multivariable logistic regression models examined associations between PCOS and MASLD, adjusting for smoking and menopausal duration. To dissect the role of adiposity, separate models incorporated body mass index (BMI), waist circumference, mid-upper arm circumference, and triceps skinfold thickness. Effect-modification analyses tested interactions between PCOS and adiposity measures, with robustness assessed using bootstrap resampling (1000 iterations). Model performance was evaluated using Nagelkerke R2. MASLD prevalence was significantly higher in women with PCOS than in those without PCOS (59.3% vs 45.3%, P = .048). PCOS remained independently associated with MASLD after adjustment (adjusted OR = 1.82, 95%CI 1.02-3.24). While all adiposity measures were strong predictors of MASLD, only central adiposity demonstrated robust effect modification. A significant PCOS × waist circumference interaction persisted after bootstrap validation (bootstrap P = .028), whereas interactions with BMI and peripheral adiposity measures were not robust. Although BMI-based models showed higher overall explanatory power (Nagelkerke R2 0.592), only waist-based models identified a stable interaction with PCOS (Nagelkerke R2 0.392). PCOS confers persistent susceptibility to MASLD well beyond menopause, with risk preferentially mediated through central fat accumulation rather than overall obesity. These findings identify central adiposity as a key mechanistic link between PCOS and MASLD and support prioritising waist circumference over BMI for long-term hepatic and metabolic risk stratification in postmenopausal women with a history of PCOS.