ORIGINAL ARTICLES Psychosexual Effects of Three Doses of Testosterone Cycling in Normal Men William R. Yates, Paul J. Perry, John MacIndoe, Tim Holman, and Vicki Ellingrod Background: Testosterone is receiving increased atten- tion for contraceptive and therapeutic indications. The potential psychosexual side effects of testosterone therapy and withdrawal are unclear. Methods: Healthy men between the ages of 21 and 40 years were recruited via advertisement for a randomized, controlled, double-blind study of acute and withdrawal effects of three doses of testosterone. Two weeks of placebo injections were followed by one of three random- ized weekly doses of testosterone cypionate (100 mg, 250 mg, or 500 mg) for the next 14 weeks. Twelve weeks of placebo injections followed during the withdrawal phase of the study. Psychosexual effects were monitored throughout the study. Results: All doses of testosterone demonstrated only minimal effects on measures of mood and behavior during acute and withdrawal phases for all study completers. There were no effects on psychosexual function. There was no evidence of a dose-dependent effect on any measure. One noncompleter on 500 mg of testosterone developed a brief syndrome with symptoms similar to an agitated and irritable mania. Conclusions: Doses of testosterone up to five times physiologic replacement dose appear to have minimal risk of adverse psychosexual effects in the majority of normal men; however, beginning at around 500 mg per week of testosterone cypionate, a minority of normal men may experience significant adverse psychological effects. Be- cause illicit anabolic steroid users may use larger doses of multiple drugs under less restrictive conditions, our study may significantly underestimate the psychological effect of steroid use in the community. Biol Psychiatry 1999;45: 254 –260 © 1999 Society of Biological Psychiatry Key Words: Testosterone, anabolic steroids, aggression, sexual behavior Introduction T estosterone therapy is receiving increased attention as a potential contraceptive agent (World Health Orga- nization Task Force on Methods for the Regulation of Male Fertility 1990), for the treatment of the psychological and physiological effects of aging in men (Tenover 1994), and for the treatment of wasting and debilitating illnesses like AIDS (Rabkin et al 1995). Important questions about the potential psychological and sexual effects of testoster- one treatment remain unanswered. Some safety concerns stem from adverse effects of anabolic–androgenic steroid compounds reported in illicit users. Estimates from the U.S. National Household Survey on Drug Abuse put the number of current or former illicit users of anabolic–androgenic steroid (AAS) compounds at more than one million (Yesalis et al 1993; Yesalis and Bahrke 1995). The Interagency Task Force on Anabolic Steroids Report from the U.S. Department of Health and Human Services recently recommended research is needed to “untangle the neuropsychiatric effects of specific ana- bolic steroids used alone and in combination given that the population at risk takes these substances in variable doses and types and alters the cycle length over time” (U.S. Department of Health and Human Services 1990). The potential psychiatric effects of AAS compounds cross several psychological domains. AAS compounds in male users may increase irritability and aggressive behav- ior (Yates et al 1992; Perry et al 1992; Choi and Pope 1994; Pope and Katz 1994). These potential effects of AAS compounds may result in harm to others through assault, domestic violence, and potentially through homi- cide. AAS may also have significant effects on the regulation of mood (Pope and Katz 1988). Case reports have linked AAS to mania as well as depression and suicide (Perry et al 1992; Elofson and Elofson 1990). Psychotic symptoms have also been noted in conjunction with AAS as well as disorders of body image (Pope et al 1993). Fewer studies have examined the potential sexual ef- fects of AAS in male and female users. Supraphysiologic doses of testosterone and other AAS compounds may result in disturbed sexual behavior and impotence (Moss et al 1993). Some of the psychosexual effects of AAS compound use may be due to withdrawal effects (Brower 1994; Feinberg et al 1997). From the Department of Psychiatry and Department of Family Practice, University of Oklahoma College of Medicine, Tulsa, Oklahoma (WRY); Department of Pharmacy (PJP, TH, VE), Department of Psychiatry (PJP), and Department of Internal Medicine (JM), University of Iowa College of Medicine, Iowa City, Iowa. Address reprint requests to Dr. W.R. Yates, Department of Psychiatry, University of Oklahoma, 2808 South Sheridan Road, Tulsa, OK 74129-1077. Received September 2, 1997; revised January 5, 1998; accepted January 9, 1998. © 1999 Society of Biological Psychiatry 0006-3223/99/$19.00 PII S0006-3223(98)00028-6