Testosterone-Induced Alterations in Mood and Aggression
ABSTRACT & COMMENTARY
Source: Pope HG Jr, et al. Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: A randomized controlled trial. Arch Gen Psychiatry 2000;57: 133-140.
Despite the fact that exogenously administered testosterone is thought to be associated with mood disturbances and aggression, there exists little prospective evidence of this phenomenon. The current study assesses the behavioral and mood effects of sustained supraphysiologic doses of testosterone cypionate in a randomized, placebo-controlled, crossover design. Subjects (56 males, 20-50 years of age) received testosterone cypionate for six weeks in doses rising to 600 mg/wk, and placebo for six weeks, separated by a six-week washout period. 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 spouse, girlfriend, or other close acquaintance. Subjects with past or current mental illnesses were excluded, as well as those who were receiving psychotropic medications, those who used anabolic steroids in the previous 90 days, and those who had clinically significant medical illnesses.
The results showed testosterone treatment significantly increased manic scores on the YMRS (P = 0.002), manic scores on daily diaries (P = 0.003), and aggressive responses on the Point Subtraction Aggression Paradigm (P = 0.03). Self-rated measures revealed increases in verbal hostility and phobic anxiety. Diaries from significant others failed to show a significant effect, although manic scores on participants’ and significant others’ diaries correlated highly at the end of the testosterone treatment period (Spearman Y = 0.59; P < 0.001). Physiologic measures (weight, lean body mass, liver enzymes, etc.) showed the expected effects of testosterone treatment.
COMMENT BY MICHAEL F. BARBER, PharmD
Although the observed effects on manic ratings were significantly higher at the end of the testosterone treatment phase (mean testosterone effect on YMRS was an increase of 2.6), there were only eight subjects with marked changes (6 became mildly hypomanic, 2 became markedly hypomanic), while the other 42 subjects showed very little change (perhaps median values would have been less impressive than mean values). While this disparity could be a result of failure to control some key study variables, it is quite possible that the results illustrate that only a subset of males will have significant increases in psychopathology due to supraphysiologic doses of testosterone. Perhaps a genetic vulnerability to the drug effect may account for the differences in response. It would be interesting to have follow-up information on the eight responders over several years to determine if they ever become manic or hypomanic during times when they are not using testosterone. Regardless, given the potentially dangerous sequelae of increases in manic and aggressive symptoms, the use of supraphysiologic doses of testosterone should be viewed as an important risk factor for violence. Health care professionals who suspect that their patients are using anabolic steroids should consider informing the patients and their families of such potential risks. While many clinicians probably already discuss some risks, they can cite this trial as further evidence of both behavioral and health risks.
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