Effects of Supraphysiologic Doses of Testosterone on Mood and Aggression in Normal Men: A Randomized Controlled Trial
Abstract
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, > or =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.
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There is some limited direct evidence from well-designed, placebo-controlled trials that administration of testosterone or other androgens at supraphysiological doses directly affect mood and behavior, notably inducing hypomania.
“There is some limited direct evidence from well-designed, placebo-controlled trials that administration of testosterone or other androgens at supraphysiological doses directly affect mood and behavior, notably inducing hypomania (153).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [153]
Cites
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · see citing works
A Rating Scale for Mania: Reliability, Validity and Sensitivity
Young, R. C., Biggs, J. T., Ziegler, V. E., & Meyer, D. A. (1978) · British Journal of Psychiatry · doi:10.1192/bjp.133.5.429 · Cited by 8,744 · see citing works
Buss, A. H., & Perry, M. (1992) · Journal of Personality and Social Psychology · doi:10.1037/0022-3514.63.3.452 · Cited by 4,693 · see citing works
Generalized equations for predicting body density of men
Jackson, A. S., & Pollock, M. L. (1978) · British Journal Of Nutrition · doi:10.1079/bjn19780152 · Cited by 3,205 · see citing works
The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men
Bhasin, S., Storer, T. W., Berman, N., Callegari, C., Clevenger, B., Phillips, J., Bunnell, T. J., Tricker, R., Shirazi, A., & Casaburi, R. (1996) · New England Journal of Medicine · doi:10.1056/nejm199607043350101 · Cited by 1,659 · see citing works
Psychiatric and Medical Effects of Anabolic-Androgenic Steroid Use
Pope, H. G. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950050035004 · Cited by 606 · see citing works
Self-citationEstimated Prevalence of Anabolic Steroid Use Among Male High School Seniors
Buckley, W. E. (1988) · JAMA · doi:10.1001/jama.1988.03410230059028 · Cited by 530 · see citing works
Affective and psychotic symptoms associated with anabolic steroid use
Pope, H. G., & Katz, D. L. (1988) · American Journal of Psychiatry · doi:10.1176/ajp.145.4.487 · Cited by 492 · see citing works
Self-citationAndrogens, brain, and behavior
Rubinow, D. R., & Schmidt, P. J. (1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.8.974 · Cited by 417 · see citing works
Neuropsychiatric Effects of Anabolic Steroids in Male Normal Volunteers
Su, T. (1993) · JAMA · doi:10.1001/jama.1993.03500210060032 · Cited by 412 · see citing works
Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients.
Cohn, C. K., Shrivastava, R., Mendels, J., Cohn, J. B., Fabre, L. F., Claghorn, J. L., Dessain, E. C., Itil, T. M., & Lautin, A. (1990) · PubMed · Cited by 348 · see citing works
Skakkebæk, N. E., Bancroft, J., DAVIDSON, D. W., & Warner, P. (1981) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1981.tb00364.x · Cited by 335 · see citing works
Anabolic-Androgenic Steroid Use in the United States
Yesalis, C. E. (1993) · JAMA · doi:10.1001/jama.1993.03510100067034 · Cited by 317 · see citing works
Use of Multiple Drugs among Adolescents Who Use Anabolic Steroids
DuRant, R. H., Rickert, V. I., Ashworth, C. S., Newman, C. L., & Slavens, G. A. (1993) · New England Journal of Medicine · doi:10.1056/nejm199304013281304 · Cited by 280 · see citing works
The performance of the two‐stage analysis of two‐treatment, two‐period crossover trials
Freeman, P. R. (1989) · Statistics in Medicine · doi:10.1002/sim.4780081202 · Cited by 270 · see citing works
Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men
Bagatell, C. J., Heiman, J. R., Matsumoto, A. M., Rivier, J., & Bremner, W. J. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.2.8045977 · Cited by 244 · see citing works
The effects of exogenous testosterone on sexuality and mood of normal men.
Anderson, R. A., Bancroft, J., & Wu, F. C. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.75.6.1464655 · Cited by 238 · see citing works
Symptoms and correlates of anabolic‐androgenic steroid dependence
Brower, K. J., Blow, F. C., YOUNG, J. P., & Hill, E. (1991) · British Journal of Addiction · doi:10.1111/j.1360-0443.1991.tb03101.x · Cited by 206 · see citing works
Kouri, E. M., Lukas, S. E., Pope, H. G., & Oliva, P. S. (1995) · Drug and Alcohol Dependence · doi:10.1016/0376-8716(95)01192-7 · Cited by 196 · see citing works
Self-citationHooked on hormones? An anabolic steroid addiction hypothesis
Kashkin, K. B. (1989) · JAMA · doi:10.1001/jama.262.22.3166 · Cited by 193 · see citing works
Testosterone Therapy for Low Sexual Interest and Erectile Dysfunction in Men: a Controlled Study
O'Carroll, R., & Bancroft, J. (1984) · British Journal of Psychiatry · doi:10.1192/bjp.145.2.146 · Cited by 188 · see citing works
Fat-Free Mass Index in Users and Nonusers of Anabolic-Androgenic Steroids
Kouri, E. M., Pope, H. G., Katz, D. L., & Oliva, P. S. (1995) · Clinical Journal of Sport Medicine · doi:10.1097/00042752-199510000-00003 · Cited by 170 · see citing works
Self-citationTricker, R., Casaburi, R. H., Storer, T. W., Clevenger, B., Berman, N., Shirazi, A., & Bhasin, S. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.10.8855834 · Cited by 164 · see citing works
Aguilera, R., Becchi, M., Casabianca, H., et al. (1996) · Journal of Mass Spectrometry · doi:10.1002/(sici)1096-9888(199602)31:2 · Cited by 157 · see citing works
Violence Toward Women and Illicit Androgenic-Anabolic Steroid Use
Choi, P. Y. L., & Pope, H. G. (1994) · Annals of Clinical Psychiatry · doi:10.3109/10401239409148835 · Cited by 153 · see citing works
Self-citationPsychosexual effects of three doses of testosterone cycling in normal men
Yates, W. R., Perry, P. J., MacIndoe, J., Holman, T., & Ellingrod, V. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00028-6 · Cited by 133 · see citing works
Psychiatric Effects and Psychoactive Substance Use in Anabolic-Androgenic Steroid Users
Malone, D. A., Dimeff, R. J., Lombardo, J. A., et al. (1995) · Clinical Journal of Sport Medicine · doi:10.1097/00042752-199501000-00005 · Cited by 129 · see citing works
Forbes, G. B. (1992) · JAMA · doi:10.1001/jama.1992.03480030075040 · Cited by 126 · see citing works
High‐dose anabolic steroids in strength athletes: Effects upon hostility and aggression
Choi, P. Y. L., Parrott, A. C., & Cowan, D. (1990) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.470050407 · Cited by 116 · see citing works
Analytical chemistry at the Games of the XXIIIrd Olympiad in Los Angeles, 1984.
Catlin, D. H., Kammerer, R. C., Hatton, C. K., et al. (1987) · Clinical Chemistry · doi:10.1093/clinchem/33.2.319 · Cited by 113 · see citing works
Violent crime possibly associated with anabolic steroid use
Conacher, G. N., & Workman, D. G. (1989) · American Journal of Psychiatry · doi:10.1176/ajp.146.5.679b · Cited by 112 · see citing works
Randomized controlled trial of testosterone in myotonic dystrophy
Griggs, R. C., Pandya, S., Florence, J. M., Brooke, M. H., Kingston, W. J., Miller, J. P. V., Chutkow, J. G., Herr, B. E., & Moxley, R. T. (1989) · Neurology · doi:10.1212/wnl.39.2.219 · Cited by 111 · see citing works
Bahrke, M. S., Wright, J. E., Strauss, R. H., & Catlin, D. H. (1992) · The American Journal of Sports Medicine · doi:10.1177/036354659202000613 · Cited by 100 · see citing works
Schulte-Beerbühl, M., & Nieschlag, E. (1980) · Fertility and Sterility · doi:10.1016/s0015-0282(16)44543-7 · Cited by 96 · see citing works
Psychiatric Symptoms Associated with Anabolic Steroids: A Controlled, Retrospective Study
Perry, P. J., Yates, W. R., & Andersen, K. (1990) · Annals of Clinical Psychiatry · doi:10.3109/10401239009150000 · Cited by 88 · see citing works
Anabolic-androgenic steroid use among 133 prisoners
Pope, H. G., Kouri, E. M., Powell, K. F., Campbell, C., & Katz, D. L. (1996) · Comprehensive Psychiatry · doi:10.1016/s0010-440x(96)90013-9 · Cited by 73 · see citing works
Self-citationPsychological and serum homovanillic acid changes in men administered androgenic steroids
Hannan, C. J., Friedl, K. E., ZOLD, A., Kettler, T., & Plymate, S. R. (1991) · Psychoneuroendocrinology · doi:10.1016/0306-4530(91)90019-p · Cited by 73 · see citing works
Anabolic steroid use by amateur athletes: effects upon psychological mood states.
Parrott, A. C., Choi, P. Y. L., & Davies, M. (1994) · PubMed · Cited by 65 · see citing works
The AB/BA crossover: past, present and future?
Senn, S. J. (1994) · Statistical Methods in Medical Research · doi:10.1177/096228029400300402 · Cited by 63 · see citing works
Psychological characteristics of adolescent steroid users.
Burnett, K. F., & Kleiman, M. E. (1994) · PubMed · Cited by 57 · see citing works
Hormone kinetics after intramuscular testosterone cypionate
Nankin, H. R. (1987) · Fertility and Sterility · doi:10.1016/s0015-0282(16)59237-1 · Cited by 54 · see citing works
Brief anabolic steroid use and sustained behavioral reaction
OH, J. J., Rummans, T. A., O'Connor, M. K., et al. (1992) · American Journal of Psychiatry · doi:10.1176/ajp.149.2.271b · Cited by 53 · see citing works
Conspecific aggression influences food carrying: Studies on a wild population of Rattus norvegicus
Whishaw, I. Q., & Whishaw, G. E. (1996) · Aggressive Behavior · doi:10.1002/(sici)1098-2337(1996)22:1 · Cited by 45 · see citing works
Testosterone intake and aggressiveness: Real effect or anticipation?
Björkqvist, K., Nygren, T., Björklund, A.-C., & Björkqvist, S.-E. (1994) · Aggressive Behavior · doi:10.1002/1098-2337(1994)20:1 · Cited by 44 · see citing works
Bahrke, M. S., & Yesalis, C. E. (1994) · Sports Medicine · doi:10.2165/00007256-199418050-00003 · Cited by 40 · see citing works
Personality, Mood, and Psychiatric Symptoms Among Anabolic Steroid Users
Moss, H. B., Panzak, G. L., & Tarter, R. E. (1992) · American Journal on Addictions · doi:10.1111/j.1521-0391.1992.tb00357.x · Cited by 37 · see citing works
A Study of Male and Female Aggressive Responding Under Conditions Providing an Escape Response
Allen, T. J., Dougherty, D. M., Rhoades, H. M., & Cherek, D. R. (1996) · The Psychological Record · doi:10.1007/bf03395190 · Cited by 29 · see citing works
Stanley, A. K., & Ward, M. (1994) · Medicine Science and the Law · doi:10.1177/002580249403400115 · Cited by 22 · see citing works
Riem, K. E., & Hursey, K. G. (1995) · Clinical Psychology Review · doi:10.1016/0272-7358(95)00013-f · Cited by 16 · see citing works
Bidwill, M. J., & Katz, D. L. (1989) · University of Miami School of Law Institutional Repository (University of Miami) · Cited by 2 · see citing works
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Reardon, C. L., Hainline, B., Aron, C. M., Baron, D., Baum, A. L., Bindra, A., Budgett, R., Campriani, N., Castaldelli-Maia, J. M., Currie, A., et al. (2019) · British Journal of Sports Medicine · doi:10.1136/bjsports-2019-100715 · Cited by 1,277 · see citing works
Russo, S. J., Murrough, J. W., Han, M.-H., Charney, D. S., & Nestler, E. J. (2012) · Nature Neuroscience · doi:10.1038/nn.3234 · Cited by 1,206 · see citing works
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Olivardia, R., Pope, H. G., Borowiecki, J. J., & Cohane, G. H. (2004) · Psychology of Men & Masculinity · doi:10.1037/1524-9220.5.2.112 · Cited by 614 · see citing works
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Cafri, G., Thompson, J. K., Ricciardelli, L., McCabe, M., Smolak, L., & Yesalis, C. (2005) · Clinical Psychology Review · doi:10.1016/j.cpr.2004.09.003 · Cited by 504 · see citing works
Popma, A., Vermeiren, R., Geluk, C. A. M. L., Rinne, T., van den Brink, W., Knol, D. L., Jansen, L. M. C., van Engeland, H., & Doreleijers, T. A. H. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.006 · Cited by 290 · see citing works
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- Authors
- Pope, H. G., Kouri, E. M., & Hudson, J. I.
- Affiliations
- Harvard University (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2000-02-01
- Volume
- 57
- Issue
- 2
- Pages
- 133
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2003550381
- Cited by
- 556
- References
- 50
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 8 · 2023: 8 · 2022: 17 · 2021: 21 · 2020: 23 · 2019: 19 · 2018: 18 · 2017: 17 · 2016: 25 · 2015: 31 · 2014: 20 · 2013: 25 · 2012: 29
- FWCI
- 14.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01da006543-07)
- National Institute on Drug Abuse (R01 DA-06543)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- testosterone cypionate, anabolic steroids, mania, hypomania, aggression, mood, placebo response, drug response variability, manic symptoms, anabolic steroid use
- MeSH terms
- Adult, Affect, Aggression, Bipolar Disorder, Blood Pressure, Delayed-Action Preparations, Depressive Disorder, Dose-Response Relationship, Drug, Double-Blind Method, Follow-Up Studies, Humans, Injections, Intramuscular, Male, Middle Aged, Personality Inventory, Placebos, Psychiatric Status Rating Scales, Testis, Testosterone, Body Mass Index, Cross-Over Studies, Anabolic Agents
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