EP575 - ECE_1616 - Metabolic dysfunction–associated steatotic liver disease and testosterone serum levels: converging evidence from real-world observational data and meta-analysis

Abstract

Low testosterone has been increasingly associated with metabolic dysfunction–associated steatotic liver disease (MASLD), yet the strength, direction, and clinical relevance of this relationship remain incompletely defined, particularly with respect to liver fibrosis. To investigate the association between male hypogonadism and MASLD through a dual approach, combining a real-world observational study with a systematic meta-analysis of the available literature, and to explore the potential impact of testosterone replacement therapy (TRT). A prospective, cross-sectional, case–control observational study was carried out, including 75 men referred for sexual dysfunction or infertility, stratified into hypogonadal (n = 59) and eugonadal (n = 16) groups according to baseline testosterone serum levels. MASLD was assessed using indirect indices (Hepatic Steatosis Index, Fatty Liver Index), qualitative ultrasound, and controlled attenuation parameter (CAP), while liver fibrosis was evaluated by transient elastography and 2D shear-wave elastography. Hypogonadal men were further classified according to TRT status. The testosterone/MASLD relationship was subsequently assessed in a meta-analysis of 28 cross-sectional and longitudinal studies available in the literature. MASLD prevalence was significantly higher in hypogonadal men than in controls when combining ultrasound and biochemical criteria (85.5% vs 50.0%, P = .023). Liver fibrosis, assessed by imaging techniques, was detected exclusively in hypogonadal patients (18.6% vs 0%, P = .057). Body mass index (BMI) emerged as the strongest predictor of both MASLD and fibrosis (P < .001 and P = .011), particularly in testosterone-naïve men (P < .001 and P = .033), whereas this association was attenuated in patients receiving TRT (P = .166 and P = .130). The meta-analysis (1636 hypogonadal vs 4587 eugonadal men) confirmed a significantly higher prevalence of MASLD among hypogonadal men compared with eugonadal controls (P = .001), independent of age (P = .274) and BMI (P = .219). This dual-approach study confirms a bidirectional association between male hypogonadism and MASLD. Real-world data support meta-analytic evidence and suggest that testosterone deficiency contributes to hepatic steatosis and fibrosis mainly through increased adiposity, while TRT may mitigate liver risk by modulating body composition and metabolic dysfunction.