Efficacy of testosterone replacement therapy for treating metabolic disturbances in late-onset hypogonadism: a systematic review and meta-analysis

Purpose Late onset hypogonadism (LOH) is an age-dependent reduction of testosterone associated with alterations of metabolic profile, including glucose control, insulin sensitivity, and lipid profile. The purpose of this study was to investigate the efficacy of testosterone replacement therapy (TRT) for treating metabolic disturbances through a meta-analysis of randomized clinical trials (RCTs). Methods A systematic review of literature published from 1964 to November, 2019 was performed using the PubMed/Medline, Embase, and Cochrane databases. Among the 1562 articles screened, 17 articles were selected for qualitative analysis and 16 articles ( n = 1373) were included for data synthesis following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Criteria for final inclusion were RCTs. Results Sixteen studies were finally included (TRT group, n = 709; placebo group, n = 664). Among the metabolic markers, HbA1C [Mean difference (MD) = − 0.172, 95% CI − 0.329, − 0.015], HOMA IR (MD = − 0.514, 95% CI − 0.863, − 0.165), serum insulin (MD = − 12.622, 95% CI − 19.660, − 5.585), and leptin (MD = − 2.381, 95% CI − 2.952, − 1.810) showed significant improvement after TRT versus placebo. Among the lipid profiles, total cholesterol showed significant improvement (MD = − 0.433, 95% CI − 0.761, − 0.105) after TRT. However, HDL showed a decrease (MD = − 0.069, 95% CI − 0.121, − 0.018) after TRT. Among anthropometric markers, waist circumference showed significant improvement (MD = − 0.1640, 95% CI − 2.857, − 0.423). Conclusion This study demonstrated greater improvement in metabolic profiles for patients given TRT versus placebo. Further well-designed trials are needed to verify our findings and further elucidate effects of TRT on lipid profiles. This systematic review demonstrates that TRT can exert a net beneficial effect on metabolic profiles.