madman
Super Moderator
Table 1. Testosterone treatment vs no testosterone in adult men with MASH/MASLD
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.
This systematic review has several strengths. It stands as the first comprehensive systematic review to compile and assess all clinical studies concerning the effects of testosterone treatment inpatients with MASLD/MASH. Our findings highlight the potential benefits of testosterone for patients with MASLD, including improvement in liver steatosis, fibrosis, resolution of MASLD/MASH, and reduction in liver enzymes. There are some limitations to consider in this systematic review mainly related to the significant heterogeneity across study designs, interventions (testosterone, Reandron, LPCN 1144, and AndroGel), intervention routes (oral, topical, and parenteral), doses and durations, and outcome assessments. These factors limit the comparability of published studies. An additional limitation is the small number of patients in both arms leading to imprecision.
In conclusion, testosterone treatment shows potential as an effective intervention for enhancing liver parameters and histopathologic endpoints in patients with MASLD/MASH. Nonetheless, recommending testosterone for patients with MASLD/MASH at this stage would be premature because of existing limitations in evidence. Therefore, further high-quality trials are essential to expand our understanding of TT benefits in this context. Anticipated results from ongoing clinical trials are expected to provide additional insights into the efficacy of testosterone in managing MASLD/MASH.
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.
This systematic review has several strengths. It stands as the first comprehensive systematic review to compile and assess all clinical studies concerning the effects of testosterone treatment inpatients with MASLD/MASH. Our findings highlight the potential benefits of testosterone for patients with MASLD, including improvement in liver steatosis, fibrosis, resolution of MASLD/MASH, and reduction in liver enzymes. There are some limitations to consider in this systematic review mainly related to the significant heterogeneity across study designs, interventions (testosterone, Reandron, LPCN 1144, and AndroGel), intervention routes (oral, topical, and parenteral), doses and durations, and outcome assessments. These factors limit the comparability of published studies. An additional limitation is the small number of patients in both arms leading to imprecision.
In conclusion, testosterone treatment shows potential as an effective intervention for enhancing liver parameters and histopathologic endpoints in patients with MASLD/MASH. Nonetheless, recommending testosterone for patients with MASLD/MASH at this stage would be premature because of existing limitations in evidence. Therefore, further high-quality trials are essential to expand our understanding of TT benefits in this context. Anticipated results from ongoing clinical trials are expected to provide additional insights into the efficacy of testosterone in managing MASLD/MASH.
