The studies by Pope et al,1 Rabkin et al,2 and Tuiten et al,3 and the commentary by Yates4 on the risks and benefits of the use of testosterone in psychiatry, emphasize the relevance of androgens in the regulation of mood and behavior in humans. We wish to add a caveat to the interpretation of the Rabkin article, though. Although Rabkin et al reported the efficacy of testosterone (T) in treating depressed mood, there were no significant effects of T observed on the affective symptoms subscale of the Hamilton Rating Scale scores. Significance was identified, however, by the Somatic Symptoms Subscale in both the total group of men and the subgroup of men meeting criteria for depression. Rabkin's study, then, like that of Grinspoon et al,5 suggests that the ostensible effects of T on mood are secondary to its remediation of somatic symptoms such as fatigue, which is probably mediated by increased body weight.5 We therefore cannot presume that T has direct psychoactive effects on mood. We also wanted to point out that androgens affect a wide array of tissues in addition to the brain, including tissues (like the prostate) that may undergo androgen-stimulated malignant transformation. To gain a full understanding of the the potential adverse effects of T on other tissues, follow-up studies would have to be conducted. For these reasons, we do not recommend the generalized prescription of these compounds for the routine treatment of depression. With the development of selective androgen receptor modulators, a more tissue-specific effect of androgens on the central nervous system might be possible, permitting more precise determination of the psychotropic effects of androgens.
Daly RC, Schmidt PJ, Roca CA, Rubinow DR. Testosterone's Effects Not Limited to Mood. Arch Gen Psychiatry. 2001;58(4):403–404. doi: