Testosterone therapy provides minor benefits in older men with low testosterone

A multi-center study has shown for the first time that testosterone treatment in older men moderately improved sexual function, modestly raised mood and increased walking distance, and slightly reduced depressive symptoms, according to results published February 18, 2016 in The New England Journal of Medicine. However, the treatment didn’t increase vitality.

This study reported on the first findings from the Testosterone Trials (TTrials), the largest trials to examine the efficacy of testosterone treatment in 790 men age 65 and older (average age 72) whose serum testosterone levels are low (less than 275 ng/dl) due to age-related symptoms only. The current study involved the first three trials—Sexual Function, Physical Function, and Vitality—of a total of seven trials.

“The results of the TTrials show for the first time that testosterone treatment of older men who have unequivocally low testosterone levels does have some benefit,” said principal investigator Peter J. Snyder, MD, Professor in the Division of Endocrinology, Diabetes and Metabolism at the Perelman School of Medicine at the University of Pennsylvania, in Philadelphia, PA.

“However, decisions about testosterone treatment for these men will also depend on the results of the other four trials—Cognitive Function, Bone, Cardiovascular, and Anemia—and the risks of testosterone treatment,” Dr. Snyder added.

A 2003 report from the Institute of Medicine concluded that not enough evidence existed that testosterone treatment in older men offered any beneficial effects, and called for clinical trials to further investigate these questions. The Testosterone Trials were designed to provide the answers.

The TTrials were conducted at 12 medical centers across the US. Participants were randomized into two groups for one year. Subjects in the first group took a daily 1% testosterone gel (5g) and those in the control group took a daily placebo gel. Each man participated in one or more of three trials. The investigators evaluated efficacy at 3, 6, 9, and 12 months, and analyzed the results from the three trials:

• Sexual Function: In men with low sexual function, testosterone treatment increased sexual activity, sexual desire, and erectile function more than placebo treatment. Change was measured by differences in scores on three standard sexual function questionnaires.
• Physical Function: In men with difficulty walking, testosterone treatment did not significantly affect walking ability (as measured by the distance they could walk in 6 minutes) among those enrolled specifically in the Physical Function Trial. However, when men in all 3 trials were included, walking speed and distance did improve among those who received testosterone compared with those who received placebo.
• Vitality: In men with symptoms of low vitality and fatigue, testosterone treatment did not significantly affect fatigue symptoms, but had modest favorable effects on mood. Despite a minimal reported difference between those treated and those on placebo, men in the testosterone-treated group were more likely to report that their energy was better at the end of the trial than men in the placebo group.

Across the three trials, adverse events—including heart attack, stroke, other cardiovascular events, and prostate conditions—were comparable for men who received testosterone and those who received placebo. However, the number of men in the TTrials was too small to draw conclusions about the risk of testosterone treatment, the researchers noted.

“There is considerable controversy about possible adverse effects of testosterone therapy in older men, and these studies do not resolve this controversy,” wrote Eric S. Orwoll, MD, of the Division of Endocrinology, Diabetes, and Clinical Nutrition at Oregon Health and Science University, Portland, OR, in a related commentary in The New England Journal of Medicine.

“A larger and longer-term trial will be needed to have more definitive results regarding safety,” said co-author Marco Pahor, MD, Director of the University of Florida Institute on Aging, in Gainesville, FL. “However, this trial did not confirm earlier, smaller trials that raised serious concerns regarding cardiovascular safety.”

The TTrials were supported by a grant from the National Institute on Aging/National Institutes of Health, and received funding from AbbVie, which manufactures and donated the testosterone gel.