Testosterone therapy of men with type 2 diabetes mellitus - a randomized, double-blinded, placebo-controlled study

The prevalence of chronic diseases including obesity and type 2 diabetes mellitus (T2D) are increasing. The usage of testosterone replacement therapy (TRT) has escalated in the Western countries during the past decades especially in aging men without clear organic indication for TRT although the safety of long-term TRT has not been clarified regarding the risk of cardiovascular disease (CVD). Aging men with T2D have an increased risk of CVD and these patients are often characterized by lowered T-levels, ectopic fat depots, a deranged adipokine profile with e.g. low adiponectin levels and hyperleptinaemia. However, the causal relations are unclear, and lowered T-levels could simply be a marker of illness, i.e. T2D and obesity. The aim of this randomized, double-blind, placebo-controlled study was to contribute to the clarification of the beneficial and potential harmful effects of testosterone therapy in aging men with T2D. Our results did not support evidence to beneficial effects of testosterone therapy on insulin resistance, glycemic control, or on substrate-oxidation in aging men with T2D and we cannot recommend TRT as a novel treatment for T2D. Regarding risk of CVD, the substantially reduction in subcutaneous fat (thigh and abdomen) and HDL-cholesterol levels along with unchanged ectopic fat (visceral and hepatic) during TRT might suggest an increased CVD risk. However, TRT has an ambiguous impact on the adipokine profile with a potential harmful decrease in levels of adiponectin, whereas the decrease in leptin levels and leptin: adiponectin ratio could reflect an amelioration of the CVD risk linked to hyperleptinaemia in aging men with T2D. We found that TRT for 24 weeks in aging men with T2D and lowered bio-available T-levels improved body composition with an increase in LBM and a reduction in regional and TFM. In addition to increased lean leg mass, TRT preserved knee-extensor muscle mechanical function. Although physical function was unchanged, TRT may potentially diminish the risk of developing sarcopenia resulting in a longer independent life and shorten the length of rehabilitation periods. It is still unclear whether the positive effects of TRT on muscle mass and muscle mechanical function outweigh potential negative effects especially regarding the risk for CVD. In conclusion, testosterone replacement therapy is indicated in men with clinically symptomatic hypogonadism regardless of status for T2D.