Testosterone shows hurtful, helpful sides

A small but significant portion of men taking large doses of testosterone experience mania, although moderate doses of the male sex hormone show promise in boosting the mood and sex drive of HIV-infected men.

A pair of new studies offers a glimpse of the contrasting faces of the male sex hormone testosterone, at least from a psychiatric perspective. Testosterone has developed a negative image from reports of bodybuilders and athletes who become agitated and violent after injecting themselves with huge doses of the hormone or its synthetic relatives. The largest placebo-controlled study of testosterone use to date, published in the February Archives of General Psychiatry, confirms that a small but significant portion of men taking large doses of the hormone experiences symptoms of mania.

It remains unclear why these reactions plague some testosterone users but not others, asserts a research team headed by psychiatrist Harrison G. Pope Jr. of McLean Hospital in Belmont, Mass.

Testosterone’s sunnier countenance emerges in its ability, when given in moderate doses, to boost mood, energy, and sex drive in otherwise healthy men who produce unusually low levels of the hormone. Preliminary findings, also reported in the February Archives of General Psychiatry, suggest that testosterone use offers a comparable lift to men infected with the human immunodeficiency virus (HIV).

Pope’s group studied 56 healthy men, ages 20 to 50, who received six weekly testosterone injections in doses starting at 150 milligrams and rising to 600 mg. Participants also went through a separate trial of six weekly placebo injections. Neither volunteers nor experimenters knew when the sex hormone was being administered.

Of the total sample, 26 men reported at least 2 years of regular weight lifting. Half of the weight lifters acknowledged prior steroid use. During each trial and for 6 weeks after it ended, the researchers had a spouse or close friend of each participant maintain a diary of his behavior. The participants provided regular reports on their own mood, as well. In a further test of aggressive urges, the men periodically played a computer game that randomly deprived them of points and offered opportunities to take points away from an unseen opponent after these provocations.

Self-reported symptoms of mania, such as euphoria and an inability to sleep, rose moderately or sharply in 14 volunteers when they received the 600-milligram dose of testosterone. The rest cited minimal manic symptoms, even on the highest dose. However, the diaries and the computer game yielded no marked aggression differences between these two groups.

Other studies indicate that many users of testosterone or equivalent substances opt for 1,000 mg or more per week. Manic reactions to testosterone injections probably occur more often and with greater intensity in real-world situations, the researchers say.

The challenge remains to identify the mechanisms of testosterone’s action in the minority of individuals who respond to high doses with mood and aggression problems, remarks psychiatrist William R. Yates of the University of Oklahoma Sciences Center in Tulsa in a comment published with the new research.

In the other study, psychologist Judith G. Rabkin of Columbia University and her coworkers find that the injection of moderate testosterone doses enhances sex drive and energy, boosts mood, and increases muscle mass in men with symptoms of HIV infection.

The researchers randomly assigned 74 HIV-infected men to receive injections every other week of a placebo or 400 mg of testosterone. During the 6-week trial, symptoms abated dramatically in a large majority of the testosterone group but in only a minority of the placebo group. Beneficial effects of testosterone injections also appeared in a subsequent 12-week trial, in which participants were allowed to request testosterone treatments.