Background: Metabolic-associated fatty liver disease (MAFLD) is a spectrum of liver diseases linked to insulin resistance (IR), type 2 diabetes, and metabolic disorders. IR accelerates fat accumulation in the liver, worsening MAFLD. Regular physical activity and weight loss can improve liver function, reduce fat, and lower cardiovascular risk. This study examines the role of sex hormone-binding globulin (SHBG) in MAFLD, focusing on its potential as a biomarker and its relationship with insulin resistance. Methods: The study included 98 male patients (ages 30–55) with MAFLD, identified through systematic examinations, and 74 healthy male controls. All participants underwent abdominal ultrasound and blood tests after fasting, assessing markers such as glucose, liver enzymes (AST, ALT, γGT), lipids (cholesterol, triglycerides), insulin, SHBG, estradiol, and testosterone. SHBG levels were analyzed in relation to body mass index (BMI) and age. Results: A significant association was found between low SHBG levels and the presence of fatty liver. Individuals with MAFLD had lower SHBG levels compared to controls. BMI and age were key factors influencing SHBG, with higher BMI linked to lower SHBG in younger men, while SHBG remained stable in older individuals regardless of BMI. Conclusion: SHBG may serve as a valuable biomarker for early detection and risk assessment of MAFLD. The complex relationship between SHBG, BMI, and age highlights the importance of considering both hormonal and metabolic factors when assessing fatty liver risk. Our findings support the need for comprehensive metabolic evaluations in clinical practice.

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.