Cardiovascular benefits and risks of testosterone replacement therapy in hypogonadal men with type 2 diabetes mellitus and/or the metabolic syndrome: a systematic review

Background: Because of the paucity of large randomised controlled trials (RCTs) in men with type 2 diabetes mellitus (T2DM) and/or the metabolic syndrome (MS), the majority of evidence for use of testosterone replacement therapy (TRT) on the cardiovascular (CV) system in such men is derived from observational studies and systematic reviews.Methods: We carried out an extensive retrospective review of the literature, comparing the major comparative trials that involved TRT in hypogonadal men with T2DM and/or MS and focused on CV outcomes.Results: Of 311 studies initially identified, 25 studies (12 RCTs and 13 non-RCTs) with a total number of 729,927 participants were deemed eligible for further review. Three RCTs and one non-RCT were excluded as these had not measured all-cause mortality and CV events as primary outcomes. Benefits of TRT on myocardial infarction were observed in two RCTs which were reviewed, while the rest demonstrated a neutral effect on CV events. In the non-RCTs, seven studies observed reduced all-cause mortality and/or major adverse CV events in the TRT group compared with the placebo group.Conclusions: This retrospective and systematic review of the literature suggests protective effects of TRT against all-cause mortality and major adverse cardiac events in hypogonadal men with T2DM and/or MS, although these results need to be interpreted cautiously.