Authors Basaria S, Coviello AD, Travison TG, et al
Review Date Aug 2010
Citation N Engl J Med 2010;363:109-122
Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. However, the safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied.
To report adverse events associated with testosterone treatment in a trial of older men with limited mobility.
Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng/dl (3.5 to 12.1 nmol/L) or a free serum testosterone level of less than 50 pg/ml (173 pmol/L) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group.
A total of 209 men (mean age=74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidaemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events; 7 men in the testosterone group and 1 in the placebo group had atherosclerosis-related events.
The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press (trial primary outcome measure) and chest-press strength and in stair climbing while carrying a load.
In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy.
Points to Note
- The finding of a higher prevalence of adverse cardiovascular events in the testosterone group found in this study of older men with limited mobility is not supported or refuted by other studies. However, it was considered of sufficient concern to terminate the trial earlier than planned.
- Findings should be treated with caution because a) cardiovascular events were not a planned primary or secondary outcome in the trial b) the number of events was small c) the trial was stopped early.
- The CV events recorded in the trial were quite diverse making a common etiologic mechanism related to testosterone treatment more difficult to argue.
- Further studies are needed to confirm these findings and to look at other population groups of men.