Testosterone for Older Men

Peter ForsterPhysical Conditions and Health, Treatments of Depression

Does testosterone supplementation help older men with low testosterone improve their quality of life, mood and energy? Some of the “low T” advertisements on TV made it seem like the magic hormone that conquered aging. More recently the FDA has been expressing its concern about over-prescribing by, among other things, adding black box warnings on the labels of gel formulations of testosterone.

A just published article in the New England Journal of Medicine looked at 790 men 65 years and older with a serum testosterone concentration of less than 275 ng per deciliter and assigned them to either testosterone gel or placebo gel and followed them for one year. One year studies, while they don’t answer a lot of important long-term questions, are pretty much the gold standard for large clinical trials and so this study is unlikely to be replicated any time soon.

Each man participated in one or more of three trials—the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The Vitality Trial involved in assessments of fatigue, positive and negative mood symptoms (as measured by the Positive and Negative Affect Scale, or PANAS), and depression level (measured by Patient Health Questionnaire 9, or PHQ-9) after 3, 6, 9, and 12 months of treatment.

Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age during the treatment period. Among participants in the Vitality Trial, there were significant differences between the testosterone and placebo group in the PANAS positive affect score (mean difference, 0.47 points), the PANAS negative affect score (mean difference, −0.49 points), and the PHQ-9 depression score (mean difference, −0.72 points). The men who received testosterone were more likely than men who received placebo to report that their energy was better at the end of the trial.

The study also looked at effects on sexual function, and got a lot of press, most of which suggested that the effect was relatively trivial. However reviewing the data makes me wonder why this was the take-home lesson since the effect size in terms of enhancing sexual interest was really quite significant, larger than the effect size one sees with antidepressants used for people with depression. And whereas the effect on evidence was less significant, it was still at least as large as the effect size for antidepressants.

Effects on strength and endurance were less significant. Those could properly be considered marginal.

As the article and editorialists note, the question that remains unanswered is what the potential adverse effects are. We would need a much longer controlled trial like this one to properly assess those.


“Effects of Testosterone Treatment in Older Men” P.J. Snyder, S. Bhasin, G.R. Cunningham, A.M. Matsumoto, A.J. Stephens-Shields, J.A. Cauley, T.M. Gill, E. Barrett-Connor, R.S. Swerdloff, C. Wang, K.E. Ensrud, C.E. Lewis, J.T. Farrar, D. Cella, R.C. Rosen, M. Pahor, J.P. Crandall, M.E. Molitch, D. Cifelli, D. Dougar, L. Fluharty, S.M. Resnick, T.W. Storer, S. Anton, S. Basaria, S.J. Diem, X. Hou, E.R. Mohler III, J.K. Parsons, N.K. Wenger, B. Zeldow, J.R. Landis, and S.S. Ellenberg, for the Testosterone Trials Investigators* N Engl J Med 2016;374:611-24. DOI: 10.1056/NEJMoa1506119

For additional information

Mayo Clinic Article on Testosterone