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

<b>Introduction</b>: 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. <b>Objective</b>: 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. <b>Patients and Methods</b>: 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. <b>Results</b>: 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 (<i>p</i> < 0.0001; gender × MASLD interaction <i>p</i> = 0.0462). Higher estradiol levels were associated with higher SHBG concentrations (<i>p</i> = 0.0009), although this association differed by sex (gender × log-estradiol interaction <i>p</i> = 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. <b>Conclusions</b>: 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.