Long-term testosterone therapy in type 2 diabetes is associated with reduced mortality without improvement in...

To further characterize the beneficial impact of testosterone replacement therapy (TRT) on the association between mortality and hypogonadism (HG) in men with type 2 diabetes (T2DM), by determining, firstly, if changes in cardiovascular disease (CVD) risk factors after TRT play a role, secondly, whether the reduction in mortality is lost when TRT is discontinued and, finally, the presence of subgroups where benefit may be greater.

We studied 857 men with T2DM, screened for the BLAST randomized controlled trial, over 3.8 years of follow-up. The men were stratified first by testosterone levels: group 1: total testosterone (TT) >12 nmol/L and free testosterone (FT) >0.25 nmol/L; Group 2: TT ≤12 nmol/L or FT ≤0.25 nmol/L. Group 2 was further stratified into those not on TRT (Group 2a) and those on TRT (Group 2b). Group 2b was further stratified by whether TRT was discontinued (Group 2b1) or not (Group 2b2). The principal outcome, mortality, was studied using Cox regression.

We found that TRT was not associated with improvements in CVD risk factors. CVD risk factors (baseline and changes during follow-up) were not associated with mortality. Men in Group 1 and Group 2b were found to have lower mortality (reference: Group 2a), even with CVD risk factors included in the regression models. Mortality was lower in men in Group 2b1 (6.2%) and Group 2b2 (0%) compared with those in Group 2a (16.9%). The lower mortality associated with Group 1 and Group 2b was observed primarily in older (>64.6 years) and less overweight (≤93.8 kg) men.

The benefits associated with normal testosterone levels and TRT (even after discontinuation) do not appear to be related to improvements in the CVD risk factors studied. In view of TRT having greater impact in men of lower weight, better outcomes may be achieved with concurrent TRT and weight reduction programmes.