Mahmoud Maya, Kawtharany Hassan, Awali Mohamed, Mahmoud Nadine, Mohamed Islam, Syn Wing-Kin
Department of Internal Medicine, Saint Louis University, St Louis, Missouri, USA.
Evidence-Based Practice and Impact Center, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
Clin Transl Gastroenterol. 2025 Jan 1;16(1):e00787. doi: 10.14309/ctg.0000000000000787.
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.
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.
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.
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.
性类固醇调节代谢功能障碍相关脂肪性肝病（MASLD）的病理生物学。我们假设睾酮治疗（TT）可调节MASLD的进展，并进行了一项系统评价，以评估TT对肝脂肪变性和纤维化的疗效。
我们检索了从数据库建立至2023年11月的PubMed和Embase。我们筛选了1489项研究，确定了9项符合条件的研究。我们使用RoB-2“Cochrane随机试验偏倚风险工具”评估随机试验的偏倚风险，使用ROBINS-I工具“干预性非随机研究中的偏倚风险”评估非随机研究的偏倚风险，并使用穆拉德工具评估单臂研究的偏倚风险。我们使用RevMan 5汇总估计值。
确定了3项随机对照试验、4项非随机研究和2项单臂研究。感兴趣的人群包括患有MASLD的男性。TT以不同的剂量、途径和频率给药，随访时间从12周到8年不等。3项研究使用肝活检评估肝纤维化和脂肪变性，5项使用CT/MRI，2项使用血清评分。所有研究均提供证据表明，与未接受TT相比，接受TT可减轻肝脂肪变性。此外，LiFT（随机对照试验）试验证明MASLD/代谢功能障碍相关脂肪性肝炎得到缓解，肝纤维化有所消退。TT导致肝酶降低。研究在人群特征、治疗方式、终点和随访方面存在异质性。两组之间不良事件相当。
对于患有MASLD且睾酮水平低 的男性，TT是一种有前景的治疗选择。它可能改善肝脂肪变性并减少肝纤维化。需要进行大规模、双盲、随机、安慰剂对照试验。
