National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Anabolic Steroid Abuse 1U.S. Department of Health0 and Human Services • Public Health2 Service • National Institutes of Health Anabolic Steroid Abuse Editors: Geraline C. Lin, Ph.D. Division of Preclinical Research National Institute on Drug Abuse Lynda Erinoff, Ph.D. Division of Preclinical Research National Institute on Drug Abuse Research Monograph 102 1990 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, D.C. 20402 Anabolic Steroid Abuse ACKNOWLEDGMENT This monograph is based on the papers and discussion from a technical review on “Anabolic Steroid Abuse” held on March 6 and 7, 1989, in Rockville, MD. The review meeting was sponsored by the Office of Science and the Division of Preclinical Research, National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required, All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company. Trade, proprietary, or company names appearing in this publication are used only because they are considered essential in the context of the studies reported herein. DHHS publication number (ADM)90-1720 Printed 1990 NIDA Research Monographs are indexed in the Index Medicus. They are selectively included in the coverage of American Statistics Index, Biosciences Information Service, Chemical Abstracts, Current Contents, Psychological Abstracts, and Psychopharmacology Abstracts. iv Contents Page Preface vii Geraline C. Lin and Lynda Erinoff Abuse Liability of Anabolic Steroids and Their Possible Role in the Abuse of Alcohol, Morphine, and Other Substances 1 Theodore J. Cicero and Lynn H. O’Connor History of Anabolic-Androgenic Steroids 29 Charles D. Kochakian Anabolic-Androgenic Steroids 60 John A. Lombardo Anabolic Steroids: An Ethnographic Approach 74 Paul J. Goldstein Incidence of the Nonmedical Use of Anabolic-Androgenic Steroids 97 Charles E. Yesalis, William A. Anderson, William E. Buckley, and James E. Wright Androgens: Endocrine Physiology and Pharmacology 113 Stephen J. Winters v Page The Androgen-Induced Phenotype 131 C. Wayne Bardin, James F. Catterall, and Olli A. Jänne Reappraisal of the Health Risks Associated With the Use of High Doses of Oral and Injectable Androgenic Steroids 142 Karl E. Friedl Androgen Interaction Through Multiple Steroid Receptors 178 Olli A. Jänne Anabolic-Androgenic Steroids Profoundly Affect Growth at Puberty in Boys 187 Alan D. Rogol, Paul M. Martha, Jr., and Robert M. Blizzard Indications of Psychological Dependence Among Anabolic-Androgenic Steroid Abusers 196 C.E. Yesalis, J.R. Vicary, W.E. Buckley, A.L. Streit, D.L. Katz, and J.E. Wright Anabolic-Androgenic Steroid-Induced Mental Status Changes 215 David L. Katz and Harrison G. Pope, Jr. Anabolic Steroids and Behavior: A Preclinical Research Prospectus 224 Bruce B. Svare List of NIDA Research Monographs 242 vi Preface The incidence and prevalence of anabolic steroid abuse, especially by ado- lescents, carries with it significant social as well as health-risk concerns. There are a number of questions regarding this misuse that need to be addressed. Do results from well-controlled studies support the efficacy of anabolic steroids in increasing muscle mass and augmenting performance? What information is available on the health consequences of misuse of ana- bolic steroids at suprapharmacological doses over extended periods of time? Do steroids have the potential for development of tolerance and dependence, and do they meet the criteria for abuse potential as defined in strict pharma- cological terms? Are adolescents at particular risk? These are among the questions that prompted the National Institute on Drug Abuse to undertake this review on anabolic steroid abuse in an effort to understand the extent and scope of the problem and to identify research priorities in this area. The contents of this monograph encompass a wide range of topics begin- ning with the important question of whether anabolic steroids possess abuse potential and whether they play a role in the abuse of other substances. There follows an historical overview of the discovery and development of anabolic steroids, a critical evaluation of the performance-enhancing effects of anabolic steroids, and an ethnographic study of anabolic steroid abuse in New York City. Next is a summary of the epidemiological evidence on the incidence and prevalence of steroid use. To better understand the health consequences of abuse, the normal endocrine physiology and pharmacology, as well as molecular and receptor mechanisms underlying the actions of anabolic steroids, are presented, followed by an appraisal of the health risks associated with abuse. Since adolescents are of special concern, a detailed account of the endocrinological effects of anabolic steroids in this special population is included. Finally, this review is completed with a discussion of the behavioral aspects of anabolic steroid use including indications of psychological dependence and evidence for steroid-induced mental status changes and aggressive behavior. This monograph represents a “state-of-the-art” information resource concern- ing anabolic steroid abuse and suggests future directions for research. It is vii hoped that this monograph will serve to stimulate further research in this area. The monograph should be valuable to members of the scientific com- munity who are involved in drug abuse research; to those interested in the field of anabolic steroids, including professionals in sports medicine, endo- crinology, psychiatry, and education; and to government agencies with regu- latory responsibility, drug enforcement responsibility, or both. The editors would like to express their thanks to the authors of the chapters in this monograph and to all the participants in the technical review on which this monograph is based. We would especially like to thank Dr. Marvin Snyder, Director, Division of Preclinical Research, for his role in initiating and supporting this effort. Geraline C. Lin, Ph.D. Lynda Erinoff, Ph.D. Division of Preclinical Research National Institute on Drug Abuse viii Abuse Liability of Anabolic Steroids and Their Possible Role in the Abuse of Alcohol, Morphine, and Other Substances1 Theodore J. Cicero and Lynn H. O’Connor INTRODUCTION The purpose of this chapter is to discuss the possible abuse potential of anabolic steroids in man and animals. A second major goal is to provide an overview of the relevant literature concerning the possible involvement of steroids in the acute and chronic actions of more commonly abused drugs, such as opiates and alcohol. At the outset, several considerations should be borne in mind. First, there seems to be little doubt that steroids are misused and that such use has significant adverse effects, particularly when steroids are used by prepubertal and pubertal adolescents, who are unusually susceptible to the disruptive effects of steroids (Haupt and Rovere 1984; Lombardo, this volume; Taylor 1987; Wilson 1988). However, the issue of whether these compounds have abuse liability in the classical, pharmacological sense of that term remains a matter of debate and will be the primary focus of this chapter. Second, there is a paucity of data relevant to the abuse potential of anabolic steroids in humans, and even less information is at hand utilizing animal models. Moreover, the absence of well-controlled, double-blind studies util- izing placebo controls severely limits the conclusions that can be drawn. Specifically, as will be elaborated below, it is virtually impossible to distin- guish between “expectancy” effects of steroid use and the immediate rein- forcing properties of the drugs from the studies currently available. Finally, steroid abusers rarely if ever abuse only a single steroid. Rather, taking a number of steroids, other illicit and prescription drugs, and hormones (growth hormone), a practice often referred to as “stacking,” 1 appears to be the normal pattern of use (Taylor 1987; Wilson 1988). Com- pounding this problem, the patterns of steroid use by regular users, includ- ing doses and frequency of administration, are highly variable, which makes well-controlled studies in an experimental situation difficult at best and, per- haps, of somewhat limited value vis-à-vis an examination of “normal” ster- oid misuse in humans, Moreover, since these compounds are generally obtained illicitly on the black market, their purity is frequently suspect, which makes self-reported estimates of the doses and types of compounds administered