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Effects of Supraphysiologic Doses of Testosterone on Mood and Aggression in Normal Men
A Randomized Controlled Trial
Harrison G. Pope, Jr, MD, MPH;
Elena M. Kouri, PhD;
James I. Hudson, MD, SM
Arch Gen Psychiatry. 2000;57:133-140.
Background Field studies of illicit anabolic-androgenic steroid users suggest that some develop manic or aggressive reactions to these drugs—a potential public health problem. However, controlled laboratory evaluations of these effects remain limited.
Methods In a randomized, placebo-controlled, crossover trial, we administered testosterone cypionate for 6 weeks in doses rising to 600 mg/wk and placebo for 6 weeks, separated by 6 weeks of no treatment, to 56 men aged 20 to 50 years. Psychiatric outcome measures included the Young Mania Rating Scale (YMRS), the Point Subtraction Aggression Paradigm (a computerized provocation test of aggression), the Aggression Questionnaire of Buss and Perry, the Symptom Checklist-90-R, daily diaries of manic and depressive symptoms, and similar weekly diaries completed by a "significant other" who knew the participant well.
Results Testosterone treatment significantly increased manic scores on the YMRS (P=.002), manic scores on daily diaries (P=.003), visual analog ratings of liking the drug effect (P=.008), and aggressive responses on the Point Subtraction Aggression Paradigm (P=.03). Drug response was highly variable: of 50 participants who received 600 mg/wk of testosterone cypionate, 42 (84%) exhibited minimal psychiatric effects (maximum YMRS score, <10), 6 (12%) became mildly hypomanic (YMRS score, 10-19), and 2 (4%) became markedly hypomanic (YMRS score,  20). The 8 "responders" and 42 "nonresponders" did not differ significantly on baseline demographic, psychological, laboratory, or physiological measures.
Conclusions Testosterone administration, 600 mg/wk increased ratings of manic symptoms in normal men. This effect, however, was not uniform across individuals; most showed little psychological change, whereas a few developed prominent effects. The mechanism of these variable reactions remains unclear.
From the Biological Psychiatry Laboratory, McLean Hospital, Belmont; and Department of Psychiatry, Harvard Medical School (Drs Pope, Kouri, and Hudson), and Department of Biostatistics, Harvard School of Public Health (Dr Hudson), Boston, Mass.
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