ORF02-04 - Metabolic Liver Disease in Reproductive-Age Women Referred for Polycystic Ovary Syndrome

BACKGROUND
Women with polycystic ovary syndrome (PCOS) face elevated risk for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the prevalence and optimal screening strategies in reproductive-age women remain unclear. This study evaluates the burden of MASLD and its metabolic and hormonal correlates, along with the performance of non-invasive measures of liver fibrosis in women referred for PCOS.

METHODS
We conducted a single-center study enrolling 93 women aged 18-44 referred to the Stanford Endocrinology Clinic for PCOS. Participants underwent clinical assessments, laboratory evaluations, and FibroScan to quantify steatosis (controlled attenuation parameter [CAP]) and fibrosis (liver stiffness measurement [LSM]). PCOS was diagnosed per Rotterdam criteria. Liver steatosis was defined as CAP >248 dB/m and fibrosis (≥F2) as LSM ≥8.2 kPa. Metabolic syndrome (MetS) score (0-5) was calculated based on BMI ≥ 25 kg/m2, prediabetes or diabetes, hypertension, triglyceride ≥ 150 mg/dL, and HDL-C < 50 mg/dL. Performance of FIB-4 (≥1.3) and SAFE (≥100) for detecting fibrosis was evaluated.

RESULTS
Majority (89%) met criteria for PCOS, while the remainder had other diagnoses associated with oligomenorrhea or idiopathic hyperandrogenism. Overall, 40.9% had liver steatosis and 94.7% of those with steatosis had MetS score ≥ 1, qualifying for MASLD. Prevalence of liver steatosis was similar in those with PCOS (42.2%) versus those without PCOS (30.0%, p=0.69). Liver fibrosis was detected in 6.5% of the cohort (4 with PCOS, 2 without PCOS) and in 13.2% of those with steatosis.
Women with steatosis were older (33.4 vs 29.8 years, p=0.01), heavier (BMI 33.0 vs 26.2 kg/m², p< 0.001), and had evidence of inflammation (WBC 8.6 vs 6.7×10³/μL, p< 0.001), hyperandrogenism (free testosterone 2.9 vs 1.7 pg/mL, p=0.04), and metabolic dysfunction (MetS score 2.3 vs 1.1, p< 0.001). Women with steatosis were also more likely to have infertility (29.7% vs 12.7%, p=0.04). Those with fibrosis had comparable metabolic dysfunction to those with steatosis. However, unlike the steatosis group, those with fibrosis did not exhibit elevated white blood cell or testosterone levels compared to those without fibrosis. Notably, PCOS status did not correlate with liver fibrosis prevalence.
Fibrosis scores showed poor sensitivity: FIB-4 (≥1.3) identified only 20% of fibrosis cases, while SAFE (≥100) detected 40%, despite high specificity (100% and 97.1%, respectively).

CONCLUSIONS
Young women referred for PCOS have high prevalence of liver steatosis and associated metabolic abnormalities. While 13.2% of those with steatosis had fibrosis, non-invasive fibrosis assessments missed 60-80% of cases, indicating a need for improved, age-appropriate screening strategies for all women with PCOS and with features of PCOS.