Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy (TRT) on hypogonadal men with type 2 diabetes mellitus (T2DM). A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials (RCTs) were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaborations Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5-months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels (mean difference (MD): 1.10; 95% confidence interval (CI) (1.88, 0.31)), fasting serum insulin levels (MD: 2.73; 95% CI (3.62, 1.84)), HbA1c % (MD: 0.87; 95% CI (1.32, 0.42)) and triglyceride levels (MD: 0.35; 95% CI (0.62, 0.07)). The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM.