Testosterone Replacement Therapy: New Data on Efficacy and Cardiovascular Safety.

Abstract

numerous studies on this subject. This literature presents some of the most controversial group of papers that I have reviewed, with some studies suggesting that testosterone use is associated with an increase in adverse cardiac events including major adverse cardiac events (cardiovascular death, myocardial infarction, stroke), whereas others suggest just the opposite. The problem is that many of these studies are observational, the testosterone preparations vary, not all studies have followed up the testosterone levels once therapy is started, some studies included soft end points to describe the adverse cardiac events, the cardiac events were not prespecified as the primary outcome, the duration of follow-up was short, the baseline characteristics of the patients were very heterogeneous with varying degrees of underlying risk factors, and other issues that we have described. The only way this issue will ever truly be resolved is for a large prospective, randomized, blinded, long-term study to be carried out with major adverse cardiac events as the primary end point. It is my understanding that an industry consortium is developing such a protocol. However, it will be many years before data are available. In the meantime, the Food and Drug Administration has released new restrictions on the labeling for testosterone replacement therapy, as recently described. 3 Although testosterone is known to be effective in patients with primary hypogonadism, the significance of the low testosterone associated with aging has been debated. There are mixed data suggesting that in these types of patients, testosterone replacement may improve sexual functioning (improved libido and erectile function), improve muscle mass, decrease fat mass, improve muscle strength, and perhaps improve mood and energy level. The Testosterone Trials, sponsored by the National Institutes of Health, were conducted to help clarify the confusing literature on testosterone replacement therapy, and the data from these clinical trials are now emerging. 5 These studies may answer some of the unresolved issues surrounding testosterone replacement therapy. They consist of 7 double-blinded, Placebo-controlled, interlinked multicenter studies in which men who were 65 years and older with serum testosterone levels that averaged <275 ng/dL were randomized to testosterone gel versus placebo gel for 1 year, with efficacy assessment at baseline and then every 3 months for 1 year. Results from 3 of these trials were recently reported. To be eligible for the Sexual Function Trial, men had to report decreased libido on questionnaires; to be eligible for the Physical Function Trial, men had to report difficulties walking or climbing stairs; and to be eligible