Sexual health, even into older age, is important to many people. A new paper reports that older men with hypogonadism who take testosterone experience significant improvements in sexual activity, erectile function and libido. Testosterone therapy has long been a matter of interest (and controversy) for physicians, and this study is a landmark one that is worthy of further discussion.
Refers to Snyder. P. J. et al. Effects of testosterone treatment in older men. N. Engl. J. Med. 347, 611–624 (2016)
Sexual health is an important component of overall health. According to the World Health Organization, “Health programme managers, policy-makers and care providers need to understand and promote the potentially positive role sexuality can play in people's lives and to build health services that can promote sexually healthy societies” (Ref. 1). Recently, Snyder and colleagues2 reported on the effects of testosterone treatment in older men in the New England Journal of Medicine. They found that men with hypogonadism who used testosterone gel reported greater improvements in sexual activity, sexual desire and erectile function than did men who used placebo gel.
In their research, Snyder et al.2 randomly assigned 790 men aged ≥65 years with symptomatic low serum testosterone (<9.5 nmol/l (<275 ng/dl)) to receive 1% testosterone gel or placebo. Men were recruited to participate in one of three separate studies (investigating sexual function, physical function or vitality). All men in the sexual function study had low libido at entry. The three studies used common methodologies so that comparisons could be made between groups, and outcomes were evaluated for men using testosterone and placebo gels. The studies were not designed to evaluate the safety of testosterone, but the authors did report on adverse events.
Following 1 year of therapy, the authors found that for the 230 men in the sexual function study, use of testosterone gel was associated with significant increases in sexual activity, sexual desire and erectile function compared with use of placebo gel. Additionally, when data from the three studies were combined, men using testosterone gel reported increases in sexual activity and were able to walk longer distances in 6 minutes than those using placebo gel. Adverse events were similar in the treatment and control groups.
Over the past decade, considerable academic attention has been given to the appropriateness, effectiveness and safety of testosterone prescriptions. As with many controversial areas, research into testosterone therapy started with smaller case reports and progressed to larger, retrospective cohort and case–control studies. Many of these manuscripts closed with paragraphs calling for prospective, randomized, placebo-controlled evaluations of the efficacy of testosterone therapy, especially in older men. The study by Snyder et al.2 is the first of several planned reports designed to provide level one evidence on this topic.
In clinical practice, we often care for older men who have hypogonadism and are concerned about decreased sexual function and erectile quality. Explaining the aetiology of the decline in sexual health is sometimes challenging, and providers are left wondering whether treating the hypogonadism would be a reasonable intervention. The results of the study by Snyder et al.2 provide strong evidence to support using testosterone to treat older hypogonadal men who complain of substantial decreases in sexual function, erectile function and sexual desire. Clinicians could use these data when counselling men with hypogonadism about the potential benefits of testosterone therapy and balancing those benefits against the potential risks of the medication.
Results from the study by Snyder et al.2 align with findings from multiple previous studies that suggested that testosterone therapy resulted in improvements in libido3, erectile function4 and physical functioning5 in symptomatic, hypogonadal men. Comparing the results from Snyder et al.2 to the results from the Testosterone in Older Men with Mobility Limitations (TOM) trial is very interesting6. The TOM trial was another placebo-controlled, blinded, prospective study designed to evaluate the effects of testosterone therapy on physical functioning and vitality in men with hypogonadism aged ≥65 years. Adverse cardiovascular events were not primary outcomes of the TOM trial, but its data and safety monitoring board terminated the trial early because of an increased incidence of cardiovascular events in the testosterone arm. At the time that the analysis of adverse events was performed, the TOM trial had enrolled 209 patients.
Snyder et al.2 enrolled 790 patients in their study, and 705 men completed 12 months of treatment. Although adverse events were not primary outcomes of the study, of note is that rates of cardiovascular adverse events were similar in the treatment and control groups. Seven men in each group had myocardial infarction, stroke or death from cardiovascular causes. Increases in serum prostate-specific antigen of >0.035 nmol/l (>1.0 ng/ml) were more frequent in the treatment group, but only one diagnosis of prostate cancer was made in this group. Unlike the TOM trial, the study by Snyder et al.2 was not terminated by its data and safety monitoring board.
Like all medications, testosterone has adverse effects. The adverse effects and potential risks associated with testosterone have received significant attention over the past several years, and the Food and Drug Administration (FDA) in the USA mandated in 2014 that testosterone labels mention that testosterone therapy might be associated with an increased risk of cardiovascular events7.
One of the major limitations of the study by Snyder et al.2 is that testosterone safety was not a primary outcome. From the perspective of some patients and providers, concerns about the safety of testosterone therapy remain a major barrier to its use. Future studies must be designed to definitively address concerns about testosterone safety. Such studies should also examine which set of patients obtain the most reliable benefits from testosterone, and what combinations of medications (such as testosterone and phosphodiesterase type 5 inhibitors) can be most effective in assisting patients with hypogonadism who experience declines in sexual health.
The importance of sexual health is often de-emphasized8, but it is an integral part of overall well-being. Sexual function, even into older age, is important to many people, and loss of sexual function can be treated if a patient desires. The study by Snyder et al.2 offers important information for patient counselling, and supports the concept that treating low serum testosterone levels can increase libido, erectile function and sexual activity in some older, hypogonadal men.
World Health Organization. Department of Reproductive Health and Research. Defining sexual health: Report of a technical consultation on sexual health, 28–31 January 2002, Geneva. [online], (2006).
Synder, P. J. et al. Effects of testosterone treatment in older men. N. Engl. J. Med. 347, 611–624 (2016).
Steidle, C. et al. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J. Clin. Endocrinol. Metab. 88, 2673–2681 (2003).
Jain, P., Rademaker, A. W. & McVary, K. T. Testosterone supplementation for erectile dysfunction: results of a metaanalysis. J. Urol. 164, 371–375 (2000).
Page, S. T. et al. Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum. J. Clin. Endocrinol. Metab. 90, 1502–1510 (2005).
Basaria, S. et al. Adverse events associated with testosterone administration. N. Engl. J. Med. 363, 109–122 (2010).
US Food & Drug Administration. FDA drug safety communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. [online], (2014).
Kolata, G. Testosterone gel has modest benefits for men, study says. The New York Times [online], (2016).
James Dupree declares contract grant support from Blue Cross Blue Shield of Michigan for his roles with the Michigan Value Collaborative and the Michigan Urologic Surgery Improvement Collaborative.
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Dupree, J. Testosterone therapy and sexual health in hypogonadal men. Nat Rev Urol 13, 244–245 (2016). https://doi.org/10.1038/nrurol.2016.66