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

All 9 eligible studies provided evidence of reduction in liver steatosis with testosterone treatment compared with no testosterone treatment.

• 1,489 studies were screened and 9 eligible studies were identified
• Studies included 3 randomized controlled trials, 4 nonrandomized studies, and 2 single-arm studies
• The population of interest comprised men with MASLD
• Liver steatosis was assessed using liver biopsy in 3 studies, CT/MRI in 5 studies, and serum scores in 2 studies

The LiFT randomized controlled trial demonstrated resolution of MASLD/metabolic dysfunction-associated steatohepatitis and regression in liver fibrosis with testosterone treatment.

• This was the only RCT specifically noted to show regression in liver fibrosis
• The LiFT trial also demonstrated resolution of MASLD/metabolic dysfunction-associated steatohepatitis
• Liver fibrosis assessment was performed via liver biopsy in 3 of the 9 studies

Testosterone treatment led to a decrease in liver enzymes across studies.

• Pooled estimates were calculated using RevMan 5
• This finding was reported across the heterogeneous study pool
• Studies varied in population characteristics, treatment modalities, endpoints, and follow-up duration

Testosterone treatment was administered at varying doses, routes, and frequencies with follow-up ranging from 12 weeks to 8 years.

• Follow-up duration ranged from 12 weeks to 8 years across the 9 studies
• Studies were heterogeneous in terms of population characteristics, treatment modalities, endpoints, and follow-up
• Risk of bias for randomized trials was assessed using RoB-2, nonrandomized studies using ROBINS-I tool, and single-arm studies using Murad's tool

Adverse events were comparable between the testosterone treatment and no testosterone treatment groups.

• Adverse event profiles were assessed across the 9 eligible studies
• No significant difference in adverse events was reported between the two groups
• Studies were identified from PubMed and Embase searches from inception until November 2023

Large, double-blinded randomized placebo-controlled trials are needed to further evaluate testosterone treatment for MASLD.

• Current evidence is limited by heterogeneity in population characteristics, treatment modalities, endpoints, and follow-up
• Only 3 of the 9 included studies were randomized controlled trials
• The existing evidence base comprised only 9 studies identified from a screen of 1,489 studies