Since articles were published in 2014 suggesting potential cardiovascular risks associated with testosterone replacement therapy, substantial concern has been expressed regarding the use of testosterone in men with aging-associated hypogonadism, also referred to as partial androgen deficiency of the aging male (or andropause). Although small, well-designed studies have suggested symptomatic benefit for men with low T and associated symptoms, my choice for this year’s top story, “Effects of testosterone treatment in older men,” written by Snyder et al and published in The New England Journal of Medicine, is the first large-scale publication to document benefit of androgen replacement therapy.1 For symptomatic men who were 65 years of age or older, raising total serum testosterone concentrations from low (<275 ng/dL) to the mid–normal range was associated with a moderate benefit in sexual function and some benefit in mood/depressive symptoms. Men with low T and impaired physical function did not appear to benefit from treatment in this placebo-controlled, randomized trial.
This larger study, supported by the NIH, documents the benefit of treatment for symptomatic men with low T when symptoms are related to sexual function or mood. Safety issues need more information—that is, demonstration that men with low T who receive replacement do not have risks of cardiovascular disease related to therapy. Since the FDA limited the indications for testosterone therapy to exclude aging-associated low levels, the majority of men with low T receiving testosterone treatment have been treated “off-label.” With continued documentation of the long-term safety of testosterone treatment from a cardiovascular standpoint and in terms of thromboembolic events, clinicians can be reassured that there is support for the continued off-label treatment of men with aging-associated symptomatic low T.2,3 Definitive evidence of safety and efficacy for testosterone treatment of men with low T will require additional studies. However, the concerns raised by Vigen et al and Finkle et al in observational studies appear to be mitigated by these new data.4,5
Personally, I still treat aging men with symptomatic low T, despite this being an off-label indication.
Disclosure: The commentator does not receive funding from any pharmaceutical company that produces a testosterone product.