deficiency, there are some suggestions that testosterone may have benefits for certain conditions in older men. In addition, the committee found no compelling evidence of major adverse side effects to testosterone therapy, but the evidence is far from adequate to document safety. Once more, the experience of the Women’s Health Initiative (WHI) and studies of hormone therapy in women provide stark evidence of the danger of prematurely asserting the safety of a drug, particularly when it is being prescribed to prevent illness that might never occur or to confer unproven protective effects, rather than treat clinically evident symptoms or disease.

In the case of postmenopausal hormone therapy, a substantial body of observational data existed on indicated potential benefits, such as reduced risk of cardiovascular outcomes, and there was a rapid rise in the use of hormone products from the 1970s through the 1990s (OTA, 1992). Only recently have the results from clinical trials (such as WHI) showed increased risk of cardiovascular outcomes among women taking the estrogen-progestin combination therapy, the opposite of expectations (Hulley et al., 1998; Rossouw et al., 2002; Rapp et al., 2003). Quality of life measures (in women who had no hot flashes) have not been found to differ between women assigned to estrogen-progestin therapy versus placebo (Hlatky et al., 2002).

Efficacy trials of testosterone therapy must be fielded to assess potential benefits, particularly in the older male population, which is more likely to exhibit low testosterone levels and experience symptoms that could benefit from treatment. These smaller more focused trials may additionally provide important information regarding dose regimen and delivery methods as well as inform decisions regarding study power for potential long-term studies. To collect reliable data on adverse events, monitoring must be conducted in a uniform and systematic manner.

Until the safety and efficacy of testosterone therapy in older men is established, the committee believes that its use is appropriate only for the indications approved by the FDA (the primary indication is the treatment of hypogonadism) and inappropriate for wide-scale use to prevent possible future disease or for enhancing strength or mood in otherwise healthy older males. Despite the increasing popularity of testosterone treatment, there is not a large body of data to suggest the efficacy of testosterone therapy in older men who do not meet the clinical definition of hypogonadism. Moreover, the effects of testosterone on the prostate, and its implications for cancer, warrant caution in extensive nontherapeutic use.

Establishing efficacy, with appropriate attention to safety, is the only way to justify widespread testosterone therapy. As outlined in Chapter 3, if smaller efficacy studies yield promising results, then it would be appropriate to field a larger study that could be statistically powered to assess



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