The Bidirectional Association Between MASLD and Male Hypogonadism: An Updated Meta-Analysis

Metabolic dysfunction-associated steatotic liver disease (MASLD) and male hypogonadism are increasingly prevalent, metabolically interrelated conditions. Testosterone (T) deficiency has been implicated in hepatic lipid dysregulation, insulin resistance, and visceral adiposity, whereas MASLD may impair the hypothalamic-pituitary-gonadal axis. We conducted a systematic review and meta-analysis to evaluate the bidirectional association between circulating T levels and MASLD in adult men.

Following PRISMA guidelines, a literature search was performed from inception to July 31, 2025. Twenty-eight studies met the inclusion criteria (9 comparing hypogonadal vs. eugonadal men; 19 comparing MASLD vs. non-MASLD men). Random-effects models were used to pool effect sizes for dichotomous and continuous outcomes. Meta-regression analyses assessed the influence of age, anthropometric features, glycemic markers, liver enzymes, and hormonal parameters.

Hypogonadal men showed a significantly higher prevalence of MASLD than eugonadal men (p = 0.001) and exhibited higher fatty liver index scores (p < 0.001). Total T concentrations were significantly lower in men with MASLD than in controls (p = 0.014). Meta-regression analyses did not identify significant effects of study-level differences in age, body mass index, or biochemical variables on the observed associations. Sex hormone-binding globulin levels were also significantly reduced in MASLD (p < 0.001), with age emerging as the only significant modifier. No significant differences were observed for luteinizing hormone, estradiol, or fibrosis-4 index. Across studies evaluating MASLD severity, moderate-to-severe disease was associated with lower T levels, particularly in analyses based on imaging.

This meta-analysis supports a clinically relevant association between testosterone deficiency and MASLD, although evidence for the bidirectional nature of this relationship remains asymmetric but supports a clinically relevant endocrine-hepatic axis. T deficiency appears independently linked to MASLD onset and severity beyond the effects of age and adiposity. These findings underscore the need for reciprocal screening of liver health and gonadal status in at-risk men and highlight the importance of prospective studies and randomized trials to determine whether correcting T deficiency may modify MASLD progression.