Effects of supraphysiologic doses of testosterone on mood and aggression in normal men - A randomized controlled trial

Background: Field studies of illicit anabolic-androgenic steroid users sugg est that some develop manic or aggressive reactions to these drugs-a potent ial public health problem. However, controlled laboratory evaluations of th ese effects remain limited. Methods: In a randomized, placebo-controlled, crossover trial, we administe red testosterone cypionate for 6 weeks in doses rising to 600 mg/wk and pla cebo for 6 weeks, separated by 6 weeks of no treatment, to 56 men aged 20 t o 50 years. Psychiatric outcome measures included the Young Mania Rating Sc ale (YMRS), the Point Subtraction Aggression Paradigm (a computerized provo cation 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 th e participant well. Results: Testosterone treatment significantly increased manic scores on the YMRS (P =.002), manic scores on daily diaries (P=.003), visual analog rati ngs of liking the drug effect (P =.008), and aggressive responses on the Po int Subtraction Aggression Paradigm (P =.03). Drug response was highly vari able: 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 marke dly hypomanic (YMRS score, greater than or equal to 20). The 8 "responders" and 42 "non-responders" did not differ significantly on baseline demograph ic, psychological, laboratory, or physiological measures. Conclusions: Testosterone administration, 600 mg/wk increased ratings of ma nic symptoms in normal men. This effect, however, was not uniform across in dividuals; most showed little psychological change, whereas a few developed prominent effects. The mechanism of these variable reactions remains uncle ar.