The Role of Sex Hormone-Binding Globulin (SHBG) as a Marker of Metabolic Dysfunction-Associated Steatotic Liver Disease, with an Extended Analysis in Both Men and Women

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with insulin resistance and metabolic disturbances. Sex hormone-binding globulin (SHBG) is closely linked to metabolic regulation and has been shown to differ between individuals with and without MASLD. Objective: This study aimed to investigate the associations between SHBG and MASLD and their relationships with insulin resistance, body mass index (BMI), age, and sex in a combined male–female cohort. Patients and Methods: We studied 98 men and 54 women with MASLD and 74 men and 55 women without MASLD (aged 25–64 years). Participants underwent abdominal ultrasonography and fasting blood sampling, including measurements of glucose, liver enzymes, lipids, insulin, SHBG, estradiol, and testosterone. Results: SHBG levels were lower in individuals with MASLD than in controls, with a more pronounced reduction in women. MASLD status was associated with an approximately 10 nmol/L lower SHBG concentration (p < 0.0001; gender × MASLD interaction p = 0.0462). Higher estradiol levels were associated with higher SHBG concentrations (p = 0.0009), although this association differed by sex (gender × log-estradiol interaction p = 0.0147). Older age and higher total cholesterol levels were associated with higher SHBG levels, whereas higher triglyceride levels were associated with lower SHBG levels. Conclusions: SHBG showed significant associations with MASLD and with key metabolic and hormonal factors, including BMI, age, and sex. Inclusion of both men and women extends prior male-only research and provides a broader characterisation of sex-specific associations in MASLD.