Large Trial Suggests Testosterone Offers Moderate Benefits

As men get older, their testosterone levels commonly drop, and as these changes take place, some men experience decreased energy, sexual function, and mood. While previous trials of testosterone treatment in men aged 65 and older have consistently found testosterone increased muscle mass and decreased fat mass, the data on its effects on physical performance, sexual function, and more have been inconsistent.

“In extreme cases of hypogonadism due to testicular disease, absolutely [testosterone treatment] is an important therapy,” said Harrison Pope Jr., M.D., a professor of psychiatry at Harvard Medical School and director of the Biological Psychiatry Laboratory at Boston’s McLean Hospital. “But when you’re in the gray zone and seeing a patient with mild depression and a lower sex drive than normal for his age, we just don’t know where testosterone therapy stands.”

Pope told Psychiatric News that the insufficient evidence to support testosterone for improving the physical and mental health of older men has led to a differing of opinions about whether or not it’s a viable option for patients: “You see viewpoints ranging from these anti-aging clinics that swear by the power of testosterone to more conservative clinicians who don’t think it should be used at all.”

In 2003, Pope and colleagues published a pilot study of 22 men with depression (including younger men) that found treatment with testosterone gel reduced symptoms of depression (Psychiatric News, February 7, 2003); a larger follow-up of about 100 patients several years later, though, failed to replicate this effect.

In the February 23 issue of the New England Journal of Medicine, a team of researchers reported on the effects of one year of testosterone gel treatment on the physical activity, sexual function, and vitality and mood of 800 men 65 years and older with low testosterone levels. The results are part of Testosterone Trials—a coordinated set of seven double-blind, placebo-controlled trials that are also examining the effects of testosterone gel on cognitive function, cardiovascular risk, anemia, and bone density.

In the NEJM paper, the authors described how testosterone therapy produced a clear and robust improvement in both sexual desire and erectile function when compared with a placebo gel, but there were no significant changes in physical function (measured by walking distance over time) or fatigue.

Men who took testosterone gel for 12 months reported improvements in positive and negative mood symptoms (as measured by the Positive and Negative Affect Scale) and depression levels (as measured by the Patient Health Questionnaire).

Pope, who was not involved in this study but has collaborated with some of the investigators, was cautious about what the results of the trial say about the effects of testosterone on the mood of men with low testosterone levels.

“By enrolling a large number of participants, the investigators could identify statistically meaningful changes in depression, but were they clinically meaningful changes?” he asked.

Pope noted that testosterone therapy is not a quick solution, and questions about long-term safety, especially cardiovascular problems associated with the treatment, linger.

“Suppose you are convinced that testosterone offers a genuine effect, you face a difficult quandary. You can commit that patient to testosterone for several years or more, without a clear knowledge of the risk-benefit ratio,” he said.

“But, this therapy does suppress natural testosterone production, so if you decide to take the patient off testosterone after a year or so, it may take weeks or even months for the factory to come back online,” he continued.

The results of the other components of the Testosterone Trials will be forthcoming, including the important issue of cardiovascular safety and effects of testosterone therapy on cognition.

“I do believe in my heart that testosterone therapy does offer some antidepressant properties in men with low testosterone,” Pope said. “But it’s not a consistent effect, and that is important. A physician should exercise sound clinical judgment that considers all of a patient’s physical and emotional condition.” ■