Exogenous testosterone, cardiovascular events, and cardiovascular risk factors in elderly men: a review of trial data.

INTRODUCTION Increasing interest in the use of supplemental testosterone has led to a heightened focus on the safety of testosterone in elderly males, with a particular emphasis on cardiovascular risk. AIMS To evaluate, based on available clinical trial data, whether exogenous testosterone administration in middle-aged to elderly men increases cardiovascular risk, and to assess whether these effects differ in hypogonadal vs. eugonadal subjects. METHODS MEDLINE search from 2004 to present of all meta-analyses and randomized, controlled clinical trials of testosterone administration in male subjects ≥ 45 years old that included measurements of cardiovascular outcomes or known cardiovascular risk factors before and after treatment with testosterone. MAIN OUTCOME MEASURES The effects of testosterone treatment on cardiovascular events and cardiovascular risk factors were assessed. RESULTS In clinical trials where testosterone has been used in patients with preexisting cardiovascular conditions, the effect on disease symptoms has typically been either neutral or beneficial. Based on clinical trial data, testosterone treatment has minimal effect on cardiovascular risk factors with the exception of an increase in hematocrit, which is consistently seen with testosterone treatment, and a decrease in high-density lipoprotein cholesterol, which is an inconsistent response. Responses of hypogonadal and eugonadal men to testosterone treatment in terms of cardiovascular risk are generally similar. Testosterone treatment has not been reported to increase the incidence of cardiovascular events with the possible exception of one trial in frail elderly men. CONCLUSIONS Available clinical trial data indicate that the use of testosterone in middle-aged to elderly men does not increase cardiovascular risk nor does it unfavorably modify cardiovascular risk profile. Prospective data from large, well-designed, long-term trials of testosterone treatment are lacking and will be required to verify the cardiovascular efficacy/safety of chronic treatment.