Hard-to-Treat Men May Have Low Levels of the Male Hormone

Testosterone replacement therapy was commonly prescribed 50 years ago for depression in men, but the treatment was all but abandoned with the introduction of antidepressant drugs. Now new research suggests the male hormone may have been rejected too quickly.

A small study from Harvard Medical School's McLean Hospital showed that nearly half of the men who had not responded to conventional depression treatment had low or low-to-normal testosterone levels. And several showed dramatic improvement when the male hormone was given along with antidepressants.

Although the findings are preliminary, they suggest that lower-than-normal testosterone levels may be common in depressed men who fail to get better when taking antidepressants, says lead researcher Harrison G. Pope, Jr., MD.

"We were astonished to find that nearly half of the men in our study had low or borderline testosterone levels," he tells WebMD. "It may turn out that there is a weak relationship between testosterone and depression in general, but a much stronger relationship between testosterone and depression that does not respond to treatment."

Until a decade ago, testosterone had to be given by injection. But its use widened with the introduction of testosterone patches, and, more recently, a gel that allows testosterone to be absorbed through the skin.

The study, reported this month in the American Journal of Psychiatry, included 22 depressed men with low to low-to-normal testosterone levels who did not respond to antidepressants. Half of the men received the testosterone gel for eight weeks, the other half received a placebo gel, and all continued taking antidepressant medications.

Pope tells WebMD that about a third of the men who received the testosterone treatment showed dramatic improvement in mood, anxiety, and other measures of depression. The remaining men showed either some improvement or none.

"The $64,000 question is why some of these men responded so dramatically and others did not respond at all," Pope says. "I have also seen this in my research on anabolic steroid abuse. Most steroid users -- even those who take extremely high doses -- do not exhibit striking mood changes, but others do."

While the findings need to be confirmed in larger studies, Pope says depressed men who are not responding to treatment may want to have their testosterone level checked. Testosterone replacement might be considered for those with low levels of the male hormone, but the researcher cautions that the health risks of long-term supplementation -- which include prostate cancer -- are not well understood.

He speculates that much lower dosages of testosterone than those given to men may also prove beneficial in certain groups of depressed women.

Depression expert Douglas G. Jacobs, MD, tells WebMD that the new findings may have important implications for treating patients who do not respond to conventional therapies.

"Our understanding of depression is certainly greater than it was 30 years ago, but the biology of depression is extremely complex," says Jacobs, founder and executive director of National Depression Screening Day. "Certainly the relationship between hormone and mood has a long history in psychiatry and anything that further contributes to our understanding of this relationship is positive."