Circulating Estradiol as an Independent Risk Factor for Metabolic Dysfunction–Associated Steatotic Liver Disease and Fibrosis Risk in Women: Evidence From a Multicenter Health-Checkup Cohort

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) shows marked sexual dimorphism, with estrogen believed to be liver-protective.This study investigated the independent association between circulating estradiol levels, MASLD, and advanced fibrosis (defined by fibrosis index-4 [FIB-4] ≥ 1.3) in Korean women, utilizing stratified analyses by age and body mass index (BMI) to identify context-dependent effects.Methods: We analyzed cross-sectional data from the Korean Health Screening-Based Metabolic Dysfunction-Associated Steatotic Liver Disease Registry, including 995 women (352 with MASLD).Multivariable logistic regression was used to evaluate the association of log2-transformed estradiol with MASLD and high-risk fibrosis, stratified by age (proxy for menopausal status, ≥ 50 vs.< 50 years) and BMI (≥ 25 vs. < 25 kg/m 2 ).Results: In multivariable analysis of the entire cohort, lower estradiol levels were independently associated with MASLD (adjusted odds ratio [aOR], 0.88; 95% confidence interval [CI], 0.79-0.98;P = 0.025).This association was particularly evident in women with lower BMI (aOR, 0.84; 95% CI, 0.71-0.98),but not in high BMI women, suggesting attenuation of estrogen's metabolic protection in the presence of obesity.Estradiol demonstrated a strong and consistent inverse association with FIB-4 ≥ 1.3 (aOR, 0.65; 95% CI, 0.56-0.75;P < 0.001).This protective antifibrotic effect remained robust across