Introduction: Up to 40% of men with type 2 diabetes (T2DM) and metabolic syndrome (MetS) have hypogonadotrophic hypogonadism (HH). Men with HH are at increased risk of cardiovascular (CV) and all-cause mortality, as well as of the development of incident T2DM.

Aim: To review the current literature on the metabolic effects of testosterone therapy (TTh) in men with T2DM and MetS.

Methods: We searched MEDLINE, Embase, and Cochrane Reviews for articles on T2DM, HH, testosterone deficiency, and CV and all-cause mortality published between May 2005 and July 2018, yielding 1817 articles, including 54 clinical trials and 32 randomized controlled trials (RCTs).

Main outcome measures: The main outcomes were glycemic control, insulin resistance, lipid profile, and metabolic markers associated with increased CV risk.

Results: RCTs of TTh suggest significant benefits for sexual function, quality of life, glycemic control, insulin sensitivity, anemia, bone density, and fat and lean muscle mass that might be expected to translate into reduced long-term morbidity and mortality. Several longitudinal and observational studies suggest long-term sustained improvements in metabolic parameters and a trend toward reduced CV and all-cause mortality, especially in men at increased CV risk, such as those with T2DM and MetS. The greatest benefit is seen in those men treated with TTh to target levels and for longer durations.

Conclusion: Meta-analyses of RCTs, rather than providing clarification, may have further confused the issue by including underpowered studies of inadequate duration, multiple therapy regimens, some obsolete or withdrawn, and built-in bias in terms of studies included or excluded from analysis. Hackett G. Metabolic Effects of Testosterone Therapy in Men with Type 2 Diabetes and Metabolic Syndrome. Sex Med Rev 2019;7:476-490.