Testosterone therapy provides small to moderate benefits in sexual function and mood, but none in walking distance or vitality among symptomatic older men with low serum levels of the hormone, according to a report published online February 18 in the New England Journal of Medicine.

These are among the long-awaited findings of the first three of the seven testosterone trials, which all are parallel randomized double-blind placebo-controlled studies involving 790 men at 12 sites and which were called for by the Institute of Medicine because existing evidence supporting the use of testosterone treatment was inadequate and equivocal. All seven studies have been completed, but only the results of the sexual function trial, the physical function trial, and the vitality trial are reported here.

The findings apply only to men similar to the study participants: those aged 65 years or older who have average serum testosterone levels of less than 275 ng/dL and report corresponding sexual, physical, or mood symptoms. The testosterone trials were funded chiefly by the National Institutes of Health; AbbVie also provided financial support and donated the testosterone and placebo gels used in the studies, but did not participate in the design or conduct of the trials or in the collection, analysis, or reporting of the data, said Dr. Peter J. Snyder of the division of endocrinology, diabetes, and metabolism at the University of Pennsylvania, Philadelphia, and his associates.

The investigators noted that relatively few (14.7%) of the more than 51,000 men who were screened to participate in the testosterone trials had sufficiently low testosterone to qualify, and only 790 men (1.5%) ultimately enrolled. The average age was 72 years, and approximately 90% of the participants were white. Coexisting conditions were common, including obesity (63%), hypertension (72%), a history of MI (15%), diabetes (33%), and sleep apnea (20%).

Compared with placebo, 1 year of testosterone treatment raised serum levels to the mid-normal range for younger men (those aged 19-40 years).

The primary outcome of the sexual function trial – change from baseline in the score for sexual activity on the psychosexual daily questionnaire – increased more in men who received active treatment than in those who received placebo. Secondary outcomes of increased sexual desire and increased erectile function also favored the testosterone group, and participants in that group were more likely to report that their sexual desire had improved with treatment. The findings were similar across participants in all three of the testosterone trials, the investigators said (New Engl J Med. 2016 Feb 18 doi: 10.1056/NEJMoa1506119). The primary outcome of the physical function trial, the percentage of men who increased their distance on the 6-minute walk test by at least 50 meters, was not significantly different between the testosterone (20.3%) and placebo (12.1%) groups, nor was the change from baseline in 6-minute walk distance or the percentage of men whose score on the physical-function domain of the short-form health survey increased by 8 points or more. However, when participants in all three testosterone trials were considered as a whole, the active-treatment group showed significantly greater improvement in all these domains. And men in the testosterone group were more likely to report that their walking ability had improved with treatment.

The primary outcome of the vitality trial, an increase of at least 4 points in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, also did not differ between the men who received testosterone and those who received placebo. But again, when participants in all three testosterone trials were considered as a whole, men in the testosterone group showed a greater improvement since baseline in SF-36 vitality scores, as well as greater increases in Positive and Negative Affect Schedule (PANAS) positive-affect scores and greater declines in PANAS negative-affect scores. The men given testosterone also were more likely to report that their energy was better after treatment.

These findings suggest that even though testosterone therapy had only small to moderate effects on sexual function and on some measures of physical function and mood, those effects might be clinically relevant, Dr. Snyder and his associates said.

Regarding adverse effects, 3 cases of prostate cancer developed in the active-treatment group and 1 in the placebo group, and there was no difference between the two groups in urinary symptoms. However, the sample size was too small to reliably assess the treatment’s effect on risk of these conditions. Similarly, no pattern of increased cardiovascular risk was identified, but the sample size was too small to detect anything but a large increase in this risk, they added.

This study was supported by the National Institute on Aging, the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, AbbVie, and several other groups. Dr. Snyder reported receiving consulting fees from Watson Laboratories; his associates reported ties to numerous industry sources.

Testosterone: Moderate sexual, mood benefits; no vitality benefit