Testosterone replacement therapy: association with mortality in high‐risk patient subgroups

Abstract

AbstractObjectivesWe describe studies determining the association between testosterone therapy (TTh) and mortality.Materials & methodsWe used a registry database of 737 men with adult‐onset testosterone deficiency defined as presenting with low serum total testosterone (TT) levels ≤12.1 nmol/L and associated symptoms over a near 10‐year follow‐up. We compared associations between testosterone undecanoate (TU), cardio‐metabolic risk factors and mortality using non‐parametric statistics followed by separate Cox regression models to determine if any association between TU and morality was independent of age and cardio‐metabolic risk factors. Finally, the association between TU and mortality was studied in men stratified by cardio‐metabolic risk.ResultsDuring a median follow‐up interquartile range (IQR) of 114 (84–132) months, 94 of the 737 men died. TU (ref: non‐treatment) was associated with mortality; hazard ratio = 0.23, 95% confidence intervals = 0.14–0.40. Cox's regression models showed the above association to be independent of baseline age, waist circumference, hemoglobin A1c, lipids, blood pressure, smoking, and type 2 diabetes. These variables remained associated with mortality. We finally stratified the men by the high‐risk baseline variables and established that the association between mortality and TU was only evident in men at higher risk. A possible explanation could lie with the “law of initial value,” where greater improvements are evident following treatment in patients with worse baseline values.ConclusionsThis study with long follow‐up confirms that TTh is associated with lower mortality in men with adult‐onset TD. This association was evident only in men with greater cardio‐metabolic risk factors who demonstrated greater benefit.