The Effect of Testosterone Replacement Therapy on Nonalcoholic Fatty Liver Disease in Older Hypogonadal Men

Abstract

Context: Male hypogonadism is associated with visceral obesity and the metabolic syndrome: factors important for the development of nonalcoholic fatty liver disease (NAFLD). The Testosterone Trials (The T Trials) showed testosterone (T) treatment compared with placebo in older hypogonadal men was associated with decreases in cholesterol and insulin levels suggesting that T treatment may improve NAFLD. Objective: Compare effects of T vs placebo treatment on NAFLD scores and liver scans in elderly hypogonadal men. Methods: Secondary data analyses from 479 older hypogonadal men with total T < 275 ng/dL from The T Trials were performed. Three clinical liver fat scores - lipid accumulation product index, hepatic steatosis index, nonalcoholic fatty liver disease-metabolic syndrome score - and liver computed tomography (CT) Hounsfield units and liver to spleen ratio were evaluated at baseline and 12 months after treatment. Results: There were no statistically significant differences of change in lipid accumulation product index (P =. 98), hepatic steatosis index (P =. 67), and nonalcoholic fatty liver disease-metabolic syndrome (P =. 52) in 246 men treated with T compared with 233 treated with placebo for 12 months. Liver CT showed no statistically significant difference of change in Hounsfield units (P =. 24; n = 71 for T, n = 69 for placebo) and liver to spleen ratio (P =. 74; n = 55 for T, n = 62 for placebo) between the 2 groups. Conclusions: Our study did not show improvement of NAFLD in older hypogonadal men after 12 months of T vs placebo treatment, as assessed by 3 clinical scores and liver CT for hepatic steatosis. Future studies with longer treatment duration and additional NAFLD diagnostic modalities as primary outcome are warranted.