Testosterone treatment in older men: clinical implications and unresolved questions from the Testosterone Trials.

Abstract

A decrease in the concentration of circulating testosterone in many older men is a biomarker and possibly a rectifiable contributing factor to ill health. Low circulating testosterone concentration has been associated with cardiovascular disease, reduced cognition, fracture risk, and anaemia. However, randomised placebo-controlled trials are essential to clarify the benefits and possible risks of testosterone treatment in men without hypothalamic, pituitary, or testicular disease. The Testosterone Trials (T-Trials) were a coordinated set of trials that, following a screening-to-enrolment ratio of 65:1, randomly assigned 790 men aged 65 years or older who had a baseline testosterone concentration of less than 9·54 nmol/L and symptoms consistent with hypogonadism, but no recognisable hypothalamic-pituitary-testicular axis pathology, to daily transdermal testosterone or placebo for 12 months. In the main trial, testosterone treatment resulted in a modest benefit for sexual function, whereas the other primary outcomes of vitality and physical function were not met. Data from concomitant substudies raised a possible concern over changes in coronary plaque volume, showed a neutral effect on memory and other cognitive functions, and revealed improvements in volumetric bone mineral density and anaemia. Although insufficient to alter the existing clinical equipoise, the T-Trials provided substantial new data on organ-specific outcomes for testosterone treatment in older men. Further clinical trials are necessary to determine whether testosterone treatment will translate into patient-valued health outcomes and to clarify effects on the cardiovascular system.