The Effects of Testosterone Replacement Therapy in Adult Men With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-analysis

INTRODUCTION:Sex steroids modulate metabolic dysfunction-associated steatotic liver disease (MASLD) pathobiology. We hypothesized that testosterone treatment (TT) modulates progression of MASLD and performed a systematic review to evaluate the efficacy of TT on liver steatosis and fibrosis.METHODS:We searched PubMed and Embase from inception until November 2023. We screened 1,489 studies and identified 9 eligible studies. We assessed risk of bias for randomized trials using RoB-2 "Cochrane risk of bias tool for randomized trials," nonrandomized studies using ROBINS-I tool "Risk of Bias In Nonrandomized Studies-of Interventions," and Murad's tool for single-arm studies. We pooled estimates using RevMan 5.RESULTS:Three randomized controlled trials|, 4 nonrandomized studies, and 2 single-arm studies were identified. The population of interest comprised men with MASLD. TT was administered at varying doses, routes, and frequencies, with follow-up ranging from 12 weeks to 8 years. Liver fibrosis and steatosis were assessed using liver biopsy in 3 studies, CT/MRI in 5, and serum scores in 2. All studies provided evidence of reduction in liver steatosis with TT compared with no TT. In addition, the LiFT (randomized controlled trials) trial demonstrated a resolution of MASLD/ metabolic dysfunction-associated steatohepatitis and a regression in liver fibrosis. TT led to decrease in liver enzymes. Studies were heterogenous in terms of population characteristics, treatment modalities, endpoints, and follow-up. Adverse events were comparable between the 2 groups.DISCUSSION:TT is a promising treatment option for men with MASLD and low testosterone. It may improve liver steatosis and reduce liver fibrosis. Large, double-blinded randomized placebo-controlled trials are needed.