Raising testosterone in men ages 65 and older with low testosterone levels had a moderate benefit on sexual function and some benefit for mood and depressive symptoms, but no benefit on vitality or walking distance, a study found.
Researchers screened 51,085 men and enrolled 790 who met all the study criteria. Relatively few men had a sufficiently low testosterone level to qualify (a serum testosterone concentration <275 ng/dL). The enrollees had relatively high rates of coexisting conditions: 62.9% were obese, 71.6% had hypertension, and 14.7% had a history of myocardial infarction.
Each man in the Testosterone Trials participated in 1 or more of 3 trials, the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. Men received either testosterone gel (initial dose of 5 g daily, adjusted during the treatment) or placebo for 1 year. Results appeared Feb. 18 in the New England Journal of Medicine.
Sexual activity, as determined by the Psychosexual Daily Questionnaire score (PDQ-Q4; range, 0 to 12, with higher scores indicating a greater number of activities), increased more with testosterone treatment than with placebo. The treatment effect (the mean difference in the change in PDQ-Q4 score from baseline between participants assigned to testosterone and those assigned to placebo) was 0.58 (95% CI, 0.38 to 0.78; P<0.001) among Sexual Function Trial participants. Among all Testosterone Trials participants, the treatment effect was 0.62 (95% CI, 0.45 to 0.79; P<0.001). A greater increase in testosterone level during treatment was associated with a greater increase in the PDQ-Q4 score (P<0.001 by instrumental variable analysis).
Testosterone treatment was also associated with increased sexual desire according to scores on the sexual-desire domain of the Derogatis Interview for Sexual Functioning in Men–II (treatment effect, 2.93; 95% CI, 2.13 to 3.74; P<0.001) and increased erectile function according to the International Index of Erectile Function (treatment effect, 2.64; 95% CI, 1.68 to 3.61; P<0.001). Men in the testosterone group were more likely than those in the placebo group to report that their sexual desire had improved since the beginning of the trial (P<0.001).
Among men enrolled in the Physical Function Trial, there were no significant differences between the testosterone group and the placebo group in the primary outcome, which was the percentage of men whose 6-minute walking distance increased by at least 50 meters, the change from baseline in the 6-minute walking distance, or the percentage of men whose PF-10 score (the physical-function domain of the Medical Outcomes Study 36-Item Short-Form Health Survey) increased by at least 8 points. There was a significant between-group difference in the change from baseline in the PF-10 score (mean difference, 2.75 points; P=0.03).
Among all Testosterone Trials participants, there was a significant between-group difference in 4 measures: the percentage of men whose 6-minute walking distance increased by at least 50 meters (odds ratio, 1.76; P=0.003), the change from baseline in the 6-minute walking distance (mean difference, 6.69 meters; P=0.007), the percentage of men whose PF-10 score increased by at least 8 points (odds ratio, 1.50; P=0.02), and the change from baseline in the PF-10 score (mean difference, 3.06 points; P=0.002). Men who received testosterone were more likely than those who received placebo to perceive that their walking ability had improved since the beginning of the trial (P=0.002).
Among men enrolled in the Vitality Trial, testosterone treatment showed no significant benefit over placebo with respect to the primary outcome, an increase of at least 4 points in the Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue scale (odds ratio, 1.23; P=0.30). However, there appeared to be a small effect on the change from baseline in the FACIT–Fatigue score that did not reach significance (mean difference, 1.21 points; P=0.06).
The number of participants was too few to draw conclusions about the risks of testosterone treatment, the authors noted. The Testosterone Trials were partly funded by the National Institutes of Health. A pharmaceutical manufacturer also provided funding and donated the testosterone and placebo gels but did not participate in the design, conduct, or reporting of the trial.
“These results … should inform decisions about testosterone treatment for men 65 years of age or older whose levels are low for no apparent reason other than age,” they wrote. “Such decisions will also require knowing the risks of testosterone treatment, which will necessitate larger and longer trials.”
An editorial noted “the investigators have succeeded in conducting the kind of generally well-conceived studies that are sorely needed in the field.”
It continued, “The results show that testosterone therapy did yield certain benefits, but at this point their clinical importance is uncertain. Therapy was not a panacea, and the findings alone might be insufficient to support a decision to initiate testosterone therapy in symptomatic older men. The study confirmed that testosterone supplementation can yield improvements in sexual function, but the benefits were modest, tended to wane in the latter months of the treatment period, and, as the authors note, were not as robust as those of phosphodiesterase type 5 inhibitors.”