S2688 Association of Sex Hormone Binding Globulin and Sex Hormones With Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis

Introduction: Metabolic dysfunction-associated liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are among the leading causes of chronic liver disease worldwide. Sex hormone-binding globulin (SHBG) and endogenous sex hormones have been shown to play an important role in hepatic steatosis. We conducted a systematic review and meta-analysis to evaluate the association between these sex hormones, MASLD, and MASH. Methods: A comprehensive systematic literature search was conducted on PubMed, Cochrane CENTRAL, Embase, and Scopus from inception through March 2025. Studies showing an association between SHBG or endogenous sex hormones with either MASLD or MASH were included. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a generalized linear model (GLM) on Rstudio (v4.1.1). Statistical significance was defined as P-value < 0.05. Results: A total of 27 observational studies comprising 582,698 patients (419,196 in the MASLD/MASH group and 163,502 in the control group) were included in this meta-analysis. SHBG was significantly associated with reduced odds of MASLD/MASH (OR: 0.53; 95% CI: 0.36-0.79; P = 0.0016). Among sex hormones, estrogen demonstrated a modest but significant protective association (OR: 0.96; 95% CI: 0.93-1.00; P = 0.0252). No significant associations were observed with testosterone (OR: 1.18; 95% CI: 0.85-1.62; P = 0.3183), luteinizing hormone (OR: 1.09; 95% CI: 0.83-1.45; P = 0.5351), or follicle stimulating hormone (OR: 0.79; 95% CI: 0.46-1,38; P = 0.4131). Conclusion: Our study suggests that SHBG and estrogen are significantly associated with lower odds of MASLD/MASH, suggesting a potential protective endocrine mechanism. Testosterone, follicle-stimulating hormone, and luteinizing hormone, however, were not found to be associated with disease risk. Further prospective studies and trials are required to elucidate causal pathways, clinical utility in risk stratification, and to generate more robust evidence of the outcomes among patients with either MASLD or MASH.