Association Between Polycystic Ovary Syndrome and Metabolic Dysfunction-Associated Steatotic Liver Disease Fibrosis Severity

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). However, there is limited data comparing female patients with both PCOS and MASLD to those with MASLD alone. This study aims to evaluate differences in metabolic profiles and liver disease severity between these cohorts. METHODS: In this single-center retrospective study, adult patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD) were stratified into 3 cohorts: (1) females with both polycystic ovary syndrome (PCOS) and MASLD, (2) females with MASLD without PCOS, and (3) males with MASLD. The primary outcome was the stage of liver fibrosis at the time of MASLD diagnosis, evaluated using noninvasive fibrosis assessment tools including the NAFLD Fibrosis Score, FIB-4 Index, transient elastography, magnetic resonance elastography, and, when available, liver biopsy histology. Statistical analyses included analysis of variance (ANOVA), Pearson χ 2 test, Kruskal-Wallis test, multivariable logistic regression, and propensity score matching, followed by Wilcoxon rank-sum testing for group comparisons. RESULTS: A total of 885 patients were included in the analysis: 286 females with both PCOS and MASLD, 521 females with MASLD alone, and 78 age-matched males with MASLD. Females with PCOS were diagnosed with MASLD at a significantly younger age (median 32.5 y) compared with females without PCOS (median 54.0 y) and males (median 36.0 y; P <0.001). They also had a higher median BMI (37.3 kg/m²). In multivariable analysis adjusted for age and BMI, PCOS was not independently associated with more advanced liver fibrosis. Metformin use was associated with significantly lower odds of advanced fibrosis (OR: 0.59, 95% CI: 0.36-0.98; P =0.039), whereas diabetes was associated with increased odds (OR: 2.34, 95% CI: 1.23-4.46; P =0.010). In a propensity score-matched analysis controlling for age and diabetes, females with PCOS were diagnosed at a significantly lower fibrosis stage compared with females with MASLD alone (Wilcoxon statistic W = 22,160; P =4.35 × 10⁻¹⁶). DISCUSSION: Females with PCOS were diagnosed with MASLD at a significantly younger age and had a higher BMI compared with non-PCOS controls, yet exhibited a more favorable fibrosis profile than both females and males with MASLD alone. After adjusting for age, diabetes, and metformin use, PCOS was not independently associated with greater fibrosis severity. Notably, metformin-a first-line therapy for PCOS and diabetes-was associated with a potential protective effect against advanced fibrosis. These findings suggest that early screening for MASLD in individuals with PCOS may facilitate diagnosis at a more reversible stage of liver disease, underscoring the importance of proactive monitoring and management in this high-risk population.