Testosterone Therapy: Randomized Trials Suggest Modest Benefits in Some Patients

By Allan S. Brett, MD

Dr. Brett is editor-in-chief of NEJM Journal Watch General Medicine, from which this story was adapted. Full coverage is available to subscribers at the link below.

Testosterone therapy improved sexual and physical function modestly in symptomatic older men with low testosterone levels — but the proportion of men who benefited was low — in the NIH-supported "Testosterone Trials" (TT) published in the New England Journal of Medicine.

Some 790 symptomatic older men with serum testosterone levels averaging <275 ng/dL were randomized to receive testosterone gel or placebo for 1 year. Qualifying symptoms were decreased libido (for the Sexual Function Trial), difficulty walking or climbing stairs (Physical Function Trial), or fatigue (Vitality Trial).

For primary endpoints, results with active treatment versus placebo were as follows:

• Sexual function scores improved significantly both in the Sexual Function Trial and among all TT participants, but improvement was only about 0.6 points on a 12-point scale.

• A small increase in the proportion of men whose 6-minute walk distance improved by ≥50 meters was not significant in the Physical Function Trial but was significant among all TT participants.

• The proportion of men who improved by ≥4 points on a 52-point fatigue scale did not increase significantly either in the Vitality Trial or among all TT participants.

Frequencies of adverse events with testosterone and placebo were generally similar, but testosterone recipients were more likely to develop polycythemia and increased prostate-specific antigen levels.

Comment: Although the results could justify testosterone treatment in men who meet the study's fairly restrictive enrollment criteria, patients should understand that benefits were rather limited and long-term safety remains unclear.