ANNUAL REVIEWS
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Annu.Rev. Med. 1991.42:449-57 Copyright © 1991 by Annual Reviews Inc.All rights reserved
ANABOLIC STEROIDS Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
IN THE ATHLETE Richard H. Strauss, M.D.
Departments of Preventive Medicine and Internal Medicine, Ohio State University College of Medicine, Columbus, Ohio 43210 Charles E. Yesalis, Sc.D.
Departments of Health Policy and Administration and Exercise and Sport Science, Pcnnsylvania State University, University Park, Pennsylvania 16802 KEY
WORDS:
androgenic
hormones,
drug
testing,
gynecomastia,
sterility,
strength
ABSTRACT
Anabolic-androgenic steroid hormones can enhance muscular strength and size in athletes. However, deleterious side effects include transient sterility, gynecomastia, acne, balding, psychological changes, and possibly increased risks of heart disease and liver tumors. These drugs are banned by most sports organizations. INTRODUCTION
Anabolic steroids are derivatives of testosterone. They are exogenous male hormones taken by athletes in an attempt to make their muscles stronger and/or larger. These hormones are masculinizing (androgenic) but also have certain tissue building (anabolic) properties. A more complete name is anabolic-androgenic steroid hormones or simply androgens. PATTERNS OF USE
By 1935, androgenic steroids had been isolated and chemically char acterized, and the nature of their anabolic-androgenic effects was recog449 0066--4219/91/0401-0449$02.00
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
450
STRAUSS & YESALIS
nized (1). Anabolic steroids became available to physicians prior to World War II and were used in attempts to speed recovery from starvation, burns, and major surgery, as well as to treat depression (2, 3). They also have been tried as therapy for osteoporosis, the anemia of renal failure and alcoholic hepatitis. Currently, anabolic steroids are used therapeutically to replace deficient testosterone in ma1cs and to treat hereditary angioneu rotic edema. They are also given to transsexual females who wish to be masculinized. In 1939, Boje suggested that sex hormones, because of their physiologic action, might enhance physical performance (4). By 1944, data from studies of both animals and humans supported this notion (5). The first systematic use of anabolic steroids in sports has been attributed to a successful Soviet weightlifting team in the 1950s. Use of these drugs spread to other countries and, during the early 1960s, to other strength-intensive sports, from field events to football (5). Thereafter, use of steroids diffused to endurance sports such as long-distance running and swimming, as well as to rccre ational users attempting to "look good" -that is, look more muscular. Significant use of anabolic steroids has been reported among professional, collegiate (6), and even high-school athletes. In recent studies
of high-school seniors (not just athletes), 6.6% of males (7) and 1.3% of females (8) acknowledged prior use of anabolic steroids. Some of the anabolic steroids used by athletes are listed in Table 1. Anabolic steroids are generally used in "cycles"-that is, taken for a period such as eight weeks and then not used for several weeks or months or taken in lower Table 1
Trade names of commonly used anabolic steroids (20, 31, 34) Injectable anabolic steroids
Oral anabolic steroids Anadrol (oxymetholone)
Anatrofin (stenobolone)
Anavar (oxandrolone)
Bolfortan (testosterone nicotinate)
Dianabol (methandrostenolone)
Deca-Durabolin (nandrolone decanoate)
Maxibolin (ethylestrenol)
Delatestryl (testosterone enanthate)
Methyltestosterone
Depo-Testosterone (testosterone cypionate)
Primobolan (mcthenolone)
Dianabol (methandrostenolone)
Proviron (mesterolone)
Durabolin (nandrolone phenpropionate)
Winstrol (stanozolol)
Enoltestovis (hexoxymestrolum) Equipoise (boldenone-veterinary) Finajet (trenbolone) Primobolan (methenolone enanthate) Sustanon 250 (a mixture of testosterone esters) Therobolin Trophobolene Wintrol V (stanozolol-veterinary)
ANABOLIC STEROIDS
451
doses. Several types of anabolic steroids may be used simultaneously, a method called "stacking."
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
MECHANISMS OF ACTION
Testosterone is not effective when taken orally because much of that which is absorbed passes immediately through the liver and is metabolized. If testosterone is injected, it is also susceptible to relatively rapid breakdown by the liver. However, testosterone or other anabolic steroids can be altered so that the molecule resists metabolic breakdown. Most commonly, oral preparations are alkylated at the 17rt. position and injectible testosterone is esterified at the 17f3 position. Other structural changes to anabolic steroids and suspending them in oil for injection help them remain in the body for several weeks or even months. Anabolic steroids travel from the bloodstream, through cell walls, to cytoplasmic receptors for testosterone and related male hormones. The hormone receptor complexes interact with receptor sites on the chro
mosomes to elicit gene transcription and the subsequent synthesis of mes senger RNA. Ultimately, various enzyme, structural, or contractal proteins are produced (I, 2). The anabolic or androgenic response is determined by the location and type of cell, not by the essence of the steroid (2). In muscle cells, anabolic steroids stimlate the production of muscle protein (9). In other cells, male hormones stimulate secondary sex characteristics such as beard growth and thickening of the vocal cords. The huge doses of anabolic steroids currently in use may be ridiculously large (10). However, there appears to be a logarithmic relationship between anabolic steroid dose and lean mass gains in both man and animals (11). Anticatabolic effects also contribute to increases in lean mass, strength, and perhaps aerobic capacity (5). Anabolic steroids can reverse the cata bolic effects of natural corticosteroids that are released in times of physical or emotional stress and that can decrease endogenous androgen pro duction and action (I, 2). This anticatabolic effect is dependent upon intake of an adequate quality and quantity of protein. Both the increased aggression often associated with anabolic steroids and the placebo effect may lead to more strenuous physical training and thus add to the anabolic and anticatabolic effects described above. EFFECTS IN MEN
Do anabolic steroids help to increase muscle size and strength in men? The answer is "yes" -when the individual is performing strenuous strength training and is well nourished, with a sufficient protein intake. However,
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
452
STRAUSS & YESALIS
clinical observations and anecdotal accounts of athletes suggest a sig nificant variability in the body's response to anabolic steroids. Variation is probably due to genetic factors (12) as well as to diet and training. For references to the numerous papers both supporting and opposing this conclusion, the reader should consult the American College of Sports Medicine's Position Stand on "The Use of Anabolic-Androgenic Steroids in Sports" (13). Other reviews (5, 14, 15) also address this question. Although anabolic steroids may help to increase hemoglobin con centration, there is no clear evidence that they enhance aerobic capacity or endurance. However, animal studies suggest that such might be the case because of their anticatabolic effects (16). Do anabolic steroids affect health adversely? In the short term, the answer is clearly "yes," although these effects are considered minor by many users and are generally reversible (5, 17). Long-term effects are unclear. The incidence of fatal or serious long-term effects appears to be low (17). The use of anabolic steroids decreases production of tcstosteronc by the testes via negative feedback to the hypothalamus. Gonadotropin-releasing hormone levels drop, as do levels of luteinizing hormone and follicle stimulating hormone. Sperm production also falls (18). For this reason, anabolic steroids are being evaluated as a malc contraceptive (19) but have not been approved for such use. A decrease in the size and firmness of testes is observed with extended use of anabolic steroids. These effects appear to subside over several months after steroid use is stopped. Abnormal sperm may persist for months, so men planning to father a child would be wise to avoid anabolic steroids for a number of months beforehand. There are no reported cases of anabolic steroid use resulting in irreversible sterility in men with initially normal sperm counts (17). The effect of anabolic steroids on sex drive is highly variable. However, a common pattern is that sex drive increases when steroids are begun and may decrease to normal or below normal after several weeks of use (20). When steroids are stopped, sex drive usually falls below normal for several weeks or months until the testes resume production of testosterone. Some users notice no change in sex drive at any time, but some men have felt that their sex drive did not return to normal after prolonged steroid use. Human chorionic gonadotropin (HCG) is sometimes injected concurrently with anabolic steroids to prevent testicular atrophy or afterwards to pro mote quicker resumption of testosterone production by the testes (21). Gynecomastia develops in a minority of men who use anabolic steroids because a small amount of the androgens is metabolized to estrogens in fat cells and hepatic function may be altered (21). Gynecomastia appears as a small, firm, tender mass of breast tissue under one or both nipples.
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
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Rarely, a small amount of clear fluid is secreted. After steroids are stopped, the breast tissue usually becomes less prominent but does not disappear entirely. Some steroid users have taken antiestrogen compounds such as tamoxifen in an attempt to minimize gynecomastia, but it is not clear that this is effective. Occasionally, breast tissue is removed surgically for cosmetic reasons, but scarring may be visible. Acne commonly appears or is made worse with steroid use. Loss of scalp hair and balding are accelerated in men who have inherited a tendency for baldness (I, 2). Increased aggressiveness and irritability are common with steroid use. Some athletes consider this an advantage because they "attack the weights" more aggressively. However, problems with interpersonal relationships sometimes occur, such as altercations with friends or other athletes ('roid rage) (3). Cases of hypomania, schizophrenia, and psychotic episodes have been noted among anabolic steroid users (22). When anabolic steroids are discontinued, depression sometimes results. The potential for physical
and psychological dependence has been observed (23, 24). Generally, the behavioral effects are variable and transient. With estimates of a million or more users in the US, only a small fraction experience mental disturbances requiring treatment (3). Based on the results of studies with animals, the frequency of musculo tendinous injury is thought by some to increase with steroid use (5). These effects could be exacerbated in athletes because muscle strength and motivation increase faster than the strength of the associated tendons and connective tissue. However, some athletes contend that their incidence of injury is less while using the drugs. The effects of anabolic steroids on immune responses are unclear at present. Kopera concluded that anabolic steroids favorably influence anti body formation, immune status in general, and resistance to infection (1). However, others have demonstrated reductions in both humoral and cell mediated immune responses in both humans and animals, which gives cause for concern (25). Little or no attention has been directed to the impact of anabolic steroids on the actual incidence and prevalence of infectious disease. When oral anabolic steroids are used, HDL-cholesterol decreases in plasma and low-density lipoproteins sometimes increase, which suggests that steroid users are at greater risk for cardiovascular disease (5, 20, 26). Steroid use also appears to exacerbate high blood pressure in individuals with hypertensive tendencies. Acute thrombotic risk has been linked to steroid use in case reports of nonfatal myocardial infarction and stroke in several athletes (27, 28). Liver tumors, both benign and malignant, have been linked with the
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
454
STRAUSS & YESALIS
administration of anabolic steroids as therapy for patients with serious diseases such as aplastic anemia (29). The 17o:-alkylated (oral) anabolic steroids, in particular, were implicated. Peliosis hepatis, in which liver tissue dies and is replaced by blood-filled cysts, also was observed (30). In healthy young athletes who used steroids, two deaths from liver tumors, one of which was malignant, have been reported (17). In addition, two deaths have occurred from malignant kidney tumors (Wilms' tumor) in bodybuilders, at least one of which was associated with steroid use (5). Moderate elevations of the common liver function tests SGOT and SGPT do not necessarily indicate liver disease in persons who are training with heavy weights. Small amounts of these enzymes are released naturally from the stressed skeletal muscles; this results in blood levels moderately higher than normal that may be misinterpreted as reftecting liver damage by anabolic steroids (20). Other liver function tests appear to be reliable; that is, muscular exercise alone does not cause them to be elevated (17). AIDS and HIV infections associated with the sharing of needles for injecting anabolic steroids have been reported in bodybuilders (5). Needle sharing would also increase the transmission of hepatitis B. EFFECTS IN WOMEN
Many of the differences in secondary sexual characteristics between men and women are determined by testosterone. Therefore, it is not surprising that women who take anabolic-androgenic steroid hormones gradually develop masculine secondary sexual characteristics, including larger, stronger muscles. In contrast, women who train with weights but do not take steroids can increase their strength significantly (although probably not as much as with the drugs) without noticeably increasing muscle size. Side effects of anabolic steroids in women include growth of facial hair, increased body hair, deepening of the voice, enlargement of the clitoris, and coarsening of the skin (I, 2, 31). These effects appear to be permanent. Effects that apparently return to normal after the male hormones are stopped include menstrual cessation or irregularity, increased libido, increased aggressiveness, and acne. Menopause may be reached sooner in women who have a long history of anabolic steroid use. As with men, women's responses to anabolic steroids vary. The health risks discussed above for men also apply to women. In general, the extent to which women athletes use anabolic steroids has not been well studied. A few women take high doses of anabolic steroids, equal to those used by men (31). Like men though, most women use steroids in low to moderate doses, primarily for their anticatabolic effect, in sports such as running and swimming. It appears that the majority of
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women athletes do not wish to experience the masculinizing effects of anabolic steroids and thus do not use them.
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
EFFECTS IN BOYS
Teen-age boys often want to gain strength or weight. For example, a high school football player may try to gain 20 pounds of muscle over the summer to improve his chances of playing on the first-string team. The boy who tries anabolic steroids during training may indeed increase his strength or weight, in part because he accelerates his rate of maturation. He fills out and reaches a level of muscularity that he may well have reached eventually anyway. However, the continued use of steroids may further enhance his strength and muscularity beyond that which he would have achieved naturally. The major drawback is that if the boy has not reached his full height, he may stunt his growth. In our society, height is an advantage, and most boys do not wish to jeopardize their potential height. Anabolic steroids tend to close the growth plates at the ends of bones sooner than normal, and thereby preclude further growth (I). This would be most likely with prolonged, high doses of the drugs. Recent evidence suggests that low doses of testosterone used to treat constitutional delay in growth and development in adolescent boys does not adversely affect final adult height (32). DRUG CONTROL AND TESTING
It is generally considered unethical for physicians to prescribe anabolic steroids for the purpose of enhancing athletic performance. In some states the practice is illegal. Thus, most anabolic steroids are purchased on the black market. Sources include drugs diverted from US manufacturers or smuggled across the borders from other countries. Fake anabolic steroids are increasingly sold on the black market as legal restrictions become tighter. Most sports organizations ban the use of anabolic steroids and some test for its presence in urine at certain competitions or at unannounced times. Most of the oral anabolic steroids are undetectable after two or three weeks but some oil-based injectables can be detected in urine up to one year later. The detection of anabolic steroids is technically difficult, requiring analy sis with a gas chromatograph-mass spectrometer (33). The cost of analysis, approximately $100 per sample, is a limiting factor. Testing for anabolic steroids is performed at the Olympic Games and at various international
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
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STRAUSS & YESALIS
and national events. The National Collegiate Athletic Association and the National Football League perform testing at unannounced as well as specified times. Patients who tell their physicans that they are using anabolic steroids should be given a careful physical examination and blood tests to assess liver function and lipid profile. Scare tactics usually are ineffective, but the harmful effects of anabolic steroids should be discussed and the patient encouraged to stop using the drugs. ACKNOWLEDGMENT This paper was adapted m part from the authors' chapter "Drugs in Sports in Sports Medicine, edited by R. H. Strauss. Philadelphia: Saun ders (1991). 2nd edition. "
Literature Cited
1. Kochakian, C, ed. 1976. Anabolic
Androgenic Steroids. New Vork: Sprin ger-Verlag 2. Kruskemper, H. 1968. Anabolic Steroids. New York: Academic 3. Bahrke, M., Vesalis, C, Wright,J. 1990. Psychological and behavioral effects of endogenous testosterone levels and anabolic-androgenic steroids among males. Sports Med. 10(5): 303-37 4. Bojc,O. 1939. Doping. Bull. Hlth. Org. League of Nations 8: 439-69 5. Yesalis, C, Wright, J., Lombardo, J. 1989. Anabolic-androgenic steroids: A synthesis of existing data and recom mendations for future research. Clin. Sports Med. I: 109-34 6. Anderson, W., McKeag, D. 1989. Rep lication of the national study of substance use and abuse habits of college student athletes, final report. Mission, Kansas: Natl. Collegiate Athletic Assoc. 7. Buckley, W., Vesalis, C, Friedl, K., Anderson, Streit, A., Wright, 1. 1988. Estimated prevalence of anabolic steroid use among male high school seniors. J. Am. Med. Assoc. 260(23):
W.,
3441-45 8. Johnston,
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R. 1990. Monitoring the fUlUre: A continuing study of the lifestyles and values of youth. Ann Arbor: Univ. Mich. Inst. for Soc. Res. Snochowski, M. et al. 1981. Androgen and glucocorticoid receptors in human skeletal muscle cytosol. J. Steroid Biochem. 14: 765-71 Wilson,J. 1988. Androgen abuse by ath letes. Endocr. Rev. 9(2): 181-99
II. Forbes, G. 1985. The effect of anabolic steroids on lean body mass: The dose response curve. Metabolism 34(6): 571-
73 12. Bardin,
W.,
Catterall, J., Jane, 0. 1990. The androgen induced phenotype. In Anabolic Steroid Abuse, ed. L. Erinoff. NIDA Res. Monogr. Rockville, MD: Nat. Inst. on Drug Abuse. In press 13. American College of Sports Medicine. 1984. Position stand on the use of anabolic-androgenic steroids in sports. Sports Med. Bull. 19: 13-18 14. Haupt, H., Rovere, G. 1984. Anabolic steroids: A review of the literature. Am. J. Sports Med. 6: 469-84 IS. Wright, J. E. 1980. Anabolic steroids and athletics. Exercise Sport Sci. Rev. 8:
149-202 16. Dahlmann, 8., Widjaja, A., Reinauer, H. 1981. Antagonistic effects of endur
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ance training and testosterone on alka line proteolytic activity in rat skeletal m uscle. Eur. J. Appl. Physiol. 46: 229-35 Friedl, K. 1990. Reappraisal of the health risks associated with the use of high doses of oral and injectable andro genic steroids. See Ref. 12 Holma, P., Aldercreutz, H. 1976. Effect of an anabolic steroid (methandienone) on plasma LH-FSH and testosterone and on the response to intravenous administration of LRH. Acta Endocri nol. 83: 856--6 4 Holma, P. 1977. Effects of an anabolic steroid (methandienone) on spermatogenesis. Contraception 15: 151-
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20. Strauss, R. H., Wright, J. E., Finerman, G. A. M., C atlin , D. H. 1983. Side eiTects
of anabolic steroids in weight-trained men. Physician Sportsmed. 11(12): 87-
95
21. Friedl, K., Yesalis, C. 1989. Gyne comastia in body builders self-admin istering androgens and human chorionic gonadotropin. Physician Sportsmed
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17(3): 67-79
22. Pope, H., Katz, D. 1988. Affective and psychotic symptoms associated wi th anabolic steroid use. Am. J. Psychiatry I45(4); 487-90 23. Yesalis, c., Streit, A., Vicary, J., Friedl,
K., Brannon, D., Buckley, W. 1989. Anabolic steroid use: Indications of habituation among adolescents. J. Drug Educ. 19(2): 103-16 24. Brower, K., Blow, F., Beresford, T., Fuelling, C. 1989. Anabolic-androgenic steroid dependence. J. Clin. Psychiatry
50(1); 31 33
25.
Calabrese, L., Kleiner, S., Barn a B., Skib inski , C., Kirken dall, D. et al. 1989. The effec ts of anabolic steroids and ,
strength training on the human immune response. Med . . Sci. Sports Exercise
21(4); 3S6--92
26. Friedl, K., Jones, R., Hannan, C., Ply mate, S. 1989. The administration of pharmacological doses of testosterone
or 19-nortestosterone to normal men is not associated with increased insulin secretion or impaired glucose tolerance.
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27. Frankie, M., Eichber g, R., Zachariah, S. 1988. Anabolic-androgenic steroids and a stroke in an athlete; Case report. Arch. Phys. Med. Rehabil. 69: 632-
33 28. McNutt, R., Ferenchick, G., Kirlin, P., Hamlin, N. 1988. Acute myocardial
infarction in a 22-year-old world class weight lifter using anabolic steroids. Am. J. Cardiol. 62: 164 29. Johnson, F. L. 1975. The association of oral androgenic-anabolic steroids and life threatening disease. Med Sci. Sports
7; 284-86 30. Bagheri, S. A., Boyer, J. L. 1974. Peliosis
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hepatis associated with androgenic anabolic steroid therapy. Ann. Intern. Med. 81: 610-18 Strauss, R. H., Liggett, M. T, Lanese, R. R. 198 5 . Anabolic steroid use and perceived effects in ten weight-trained women athletes. J. Am. Med. Assoc. 253:
2871-73 32. R ichman, R., Kirsch, L. 1988. Tcs tosterone treatment in adolescent boys with constitutional delay in growth and development. N. Engl. J. Med. 319:
1563-67 33. Catlin, D., Kammerer, R., Hatton, C.
et al. 1987. Analytical chemistry of the games of the XXIII Olympiad in Los Angeles, 1984. Clin. Chem. 33(2): 319-
27 34. Perry, P. J., Andersen, K. H., Yates, W. R. 1990. Illicit anabolic steroid use in athletes. Am. J. Sports Med. 18: 422 28 -
Further
Quick links to online content
Annu.Rev. Med. 1991.42:449-57 Copyright © 1991 by Annual Reviews Inc.All rights reserved
ANABOLIC STEROIDS Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
IN THE ATHLETE Richard H. Strauss, M.D.
Departments of Preventive Medicine and Internal Medicine, Ohio State University College of Medicine, Columbus, Ohio 43210 Charles E. Yesalis, Sc.D.
Departments of Health Policy and Administration and Exercise and Sport Science, Pcnnsylvania State University, University Park, Pennsylvania 16802 KEY
WORDS:
androgenic
hormones,
drug
testing,
gynecomastia,
sterility,
strength
ABSTRACT
Anabolic-androgenic steroid hormones can enhance muscular strength and size in athletes. However, deleterious side effects include transient sterility, gynecomastia, acne, balding, psychological changes, and possibly increased risks of heart disease and liver tumors. These drugs are banned by most sports organizations. INTRODUCTION
Anabolic steroids are derivatives of testosterone. They are exogenous male hormones taken by athletes in an attempt to make their muscles stronger and/or larger. These hormones are masculinizing (androgenic) but also have certain tissue building (anabolic) properties. A more complete name is anabolic-androgenic steroid hormones or simply androgens. PATTERNS OF USE
By 1935, androgenic steroids had been isolated and chemically char acterized, and the nature of their anabolic-androgenic effects was recog449 0066--4219/91/0401-0449$02.00
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
450
STRAUSS & YESALIS
nized (1). Anabolic steroids became available to physicians prior to World War II and were used in attempts to speed recovery from starvation, burns, and major surgery, as well as to treat depression (2, 3). They also have been tried as therapy for osteoporosis, the anemia of renal failure and alcoholic hepatitis. Currently, anabolic steroids are used therapeutically to replace deficient testosterone in ma1cs and to treat hereditary angioneu rotic edema. They are also given to transsexual females who wish to be masculinized. In 1939, Boje suggested that sex hormones, because of their physiologic action, might enhance physical performance (4). By 1944, data from studies of both animals and humans supported this notion (5). The first systematic use of anabolic steroids in sports has been attributed to a successful Soviet weightlifting team in the 1950s. Use of these drugs spread to other countries and, during the early 1960s, to other strength-intensive sports, from field events to football (5). Thereafter, use of steroids diffused to endurance sports such as long-distance running and swimming, as well as to rccre ational users attempting to "look good" -that is, look more muscular. Significant use of anabolic steroids has been reported among professional, collegiate (6), and even high-school athletes. In recent studies
of high-school seniors (not just athletes), 6.6% of males (7) and 1.3% of females (8) acknowledged prior use of anabolic steroids. Some of the anabolic steroids used by athletes are listed in Table 1. Anabolic steroids are generally used in "cycles"-that is, taken for a period such as eight weeks and then not used for several weeks or months or taken in lower Table 1
Trade names of commonly used anabolic steroids (20, 31, 34) Injectable anabolic steroids
Oral anabolic steroids Anadrol (oxymetholone)
Anatrofin (stenobolone)
Anavar (oxandrolone)
Bolfortan (testosterone nicotinate)
Dianabol (methandrostenolone)
Deca-Durabolin (nandrolone decanoate)
Maxibolin (ethylestrenol)
Delatestryl (testosterone enanthate)
Methyltestosterone
Depo-Testosterone (testosterone cypionate)
Primobolan (mcthenolone)
Dianabol (methandrostenolone)
Proviron (mesterolone)
Durabolin (nandrolone phenpropionate)
Winstrol (stanozolol)
Enoltestovis (hexoxymestrolum) Equipoise (boldenone-veterinary) Finajet (trenbolone) Primobolan (methenolone enanthate) Sustanon 250 (a mixture of testosterone esters) Therobolin Trophobolene Wintrol V (stanozolol-veterinary)
ANABOLIC STEROIDS
451
doses. Several types of anabolic steroids may be used simultaneously, a method called "stacking."
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
MECHANISMS OF ACTION
Testosterone is not effective when taken orally because much of that which is absorbed passes immediately through the liver and is metabolized. If testosterone is injected, it is also susceptible to relatively rapid breakdown by the liver. However, testosterone or other anabolic steroids can be altered so that the molecule resists metabolic breakdown. Most commonly, oral preparations are alkylated at the 17rt. position and injectible testosterone is esterified at the 17f3 position. Other structural changes to anabolic steroids and suspending them in oil for injection help them remain in the body for several weeks or even months. Anabolic steroids travel from the bloodstream, through cell walls, to cytoplasmic receptors for testosterone and related male hormones. The hormone receptor complexes interact with receptor sites on the chro
mosomes to elicit gene transcription and the subsequent synthesis of mes senger RNA. Ultimately, various enzyme, structural, or contractal proteins are produced (I, 2). The anabolic or androgenic response is determined by the location and type of cell, not by the essence of the steroid (2). In muscle cells, anabolic steroids stimlate the production of muscle protein (9). In other cells, male hormones stimulate secondary sex characteristics such as beard growth and thickening of the vocal cords. The huge doses of anabolic steroids currently in use may be ridiculously large (10). However, there appears to be a logarithmic relationship between anabolic steroid dose and lean mass gains in both man and animals (11). Anticatabolic effects also contribute to increases in lean mass, strength, and perhaps aerobic capacity (5). Anabolic steroids can reverse the cata bolic effects of natural corticosteroids that are released in times of physical or emotional stress and that can decrease endogenous androgen pro duction and action (I, 2). This anticatabolic effect is dependent upon intake of an adequate quality and quantity of protein. Both the increased aggression often associated with anabolic steroids and the placebo effect may lead to more strenuous physical training and thus add to the anabolic and anticatabolic effects described above. EFFECTS IN MEN
Do anabolic steroids help to increase muscle size and strength in men? The answer is "yes" -when the individual is performing strenuous strength training and is well nourished, with a sufficient protein intake. However,
Annu. Rev. Med. 1991.42:449-457. Downloaded from www.annualreviews.org Access provided by University of Manchester - John Rylands Library on 01/24/15. For personal use only.
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clinical observations and anecdotal accounts of athletes suggest a sig nificant variability in the body's response to anabolic steroids. Variation is probably due to genetic factors (12) as well as to diet and training. For references to the numerous papers both supporting and opposing this conclusion, the reader should consult the American College of Sports Medicine's Position Stand on "The Use of Anabolic-Androgenic Steroids in Sports" (13). Other reviews (5, 14, 15) also address this question. Although anabolic steroids may help to increase hemoglobin con centration, there is no clear evidence that they enhance aerobic capacity or endurance. However, animal studies suggest that such might be the case because of their anticatabolic effects (16). Do anabolic steroids affect health adversely? In the short term, the answer is clearly "yes," although these effects are considered minor by many users and are generally reversible (5, 17). Long-term effects are unclear. The incidence of fatal or serious long-term effects appears to be low (17). The use of anabolic steroids decreases production of tcstosteronc by the testes via negative feedback to the hypothalamus. Gonadotropin-releasing hormone levels drop, as do levels of luteinizing hormone and follicle stimulating hormone. Sperm production also falls (18). For this reason, anabolic steroids are being evaluated as a malc contraceptive (19) but have not been approved for such use. A decrease in the size and firmness of testes is observed with extended use of anabolic steroids. These effects appear to subside over several months after steroid use is stopped. Abnormal sperm may persist for months, so men planning to father a child would be wise to avoid anabolic steroids for a number of months beforehand. There are no reported cases of anabolic steroid use resulting in irreversible sterility in men with initially normal sperm counts (17). The effect of anabolic steroids on sex drive is highly variable. However, a common pattern is that sex drive increases when steroids are begun and may decrease to normal or below normal after several weeks of use (20). When steroids are stopped, sex drive usually falls below normal for several weeks or months until the testes resume production of testosterone. Some users notice no change in sex drive at any time, but some men have felt that their sex drive did not return to normal after prolonged steroid use. Human chorionic gonadotropin (HCG) is sometimes injected concurrently with anabolic steroids to prevent testicular atrophy or afterwards to pro mote quicker resumption of testosterone production by the testes (21). Gynecomastia develops in a minority of men who use anabolic steroids because a small amount of the androgens is metabolized to estrogens in fat cells and hepatic function may be altered (21). Gynecomastia appears as a small, firm, tender mass of breast tissue under one or both nipples.
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Rarely, a small amount of clear fluid is secreted. After steroids are stopped, the breast tissue usually becomes less prominent but does not disappear entirely. Some steroid users have taken antiestrogen compounds such as tamoxifen in an attempt to minimize gynecomastia, but it is not clear that this is effective. Occasionally, breast tissue is removed surgically for cosmetic reasons, but scarring may be visible. Acne commonly appears or is made worse with steroid use. Loss of scalp hair and balding are accelerated in men who have inherited a tendency for baldness (I, 2). Increased aggressiveness and irritability are common with steroid use. Some athletes consider this an advantage because they "attack the weights" more aggressively. However, problems with interpersonal relationships sometimes occur, such as altercations with friends or other athletes ('roid rage) (3). Cases of hypomania, schizophrenia, and psychotic episodes have been noted among anabolic steroid users (22). When anabolic steroids are discontinued, depression sometimes results. The potential for physical
and psychological dependence has been observed (23, 24). Generally, the behavioral effects are variable and transient. With estimates of a million or more users in the US, only a small fraction experience mental disturbances requiring treatment (3). Based on the results of studies with animals, the frequency of musculo tendinous injury is thought by some to increase with steroid use (5). These effects could be exacerbated in athletes because muscle strength and motivation increase faster than the strength of the associated tendons and connective tissue. However, some athletes contend that their incidence of injury is less while using the drugs. The effects of anabolic steroids on immune responses are unclear at present. Kopera concluded that anabolic steroids favorably influence anti body formation, immune status in general, and resistance to infection (1). However, others have demonstrated reductions in both humoral and cell mediated immune responses in both humans and animals, which gives cause for concern (25). Little or no attention has been directed to the impact of anabolic steroids on the actual incidence and prevalence of infectious disease. When oral anabolic steroids are used, HDL-cholesterol decreases in plasma and low-density lipoproteins sometimes increase, which suggests that steroid users are at greater risk for cardiovascular disease (5, 20, 26). Steroid use also appears to exacerbate high blood pressure in individuals with hypertensive tendencies. Acute thrombotic risk has been linked to steroid use in case reports of nonfatal myocardial infarction and stroke in several athletes (27, 28). Liver tumors, both benign and malignant, have been linked with the
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administration of anabolic steroids as therapy for patients with serious diseases such as aplastic anemia (29). The 17o:-alkylated (oral) anabolic steroids, in particular, were implicated. Peliosis hepatis, in which liver tissue dies and is replaced by blood-filled cysts, also was observed (30). In healthy young athletes who used steroids, two deaths from liver tumors, one of which was malignant, have been reported (17). In addition, two deaths have occurred from malignant kidney tumors (Wilms' tumor) in bodybuilders, at least one of which was associated with steroid use (5). Moderate elevations of the common liver function tests SGOT and SGPT do not necessarily indicate liver disease in persons who are training with heavy weights. Small amounts of these enzymes are released naturally from the stressed skeletal muscles; this results in blood levels moderately higher than normal that may be misinterpreted as reftecting liver damage by anabolic steroids (20). Other liver function tests appear to be reliable; that is, muscular exercise alone does not cause them to be elevated (17). AIDS and HIV infections associated with the sharing of needles for injecting anabolic steroids have been reported in bodybuilders (5). Needle sharing would also increase the transmission of hepatitis B. EFFECTS IN WOMEN
Many of the differences in secondary sexual characteristics between men and women are determined by testosterone. Therefore, it is not surprising that women who take anabolic-androgenic steroid hormones gradually develop masculine secondary sexual characteristics, including larger, stronger muscles. In contrast, women who train with weights but do not take steroids can increase their strength significantly (although probably not as much as with the drugs) without noticeably increasing muscle size. Side effects of anabolic steroids in women include growth of facial hair, increased body hair, deepening of the voice, enlargement of the clitoris, and coarsening of the skin (I, 2, 31). These effects appear to be permanent. Effects that apparently return to normal after the male hormones are stopped include menstrual cessation or irregularity, increased libido, increased aggressiveness, and acne. Menopause may be reached sooner in women who have a long history of anabolic steroid use. As with men, women's responses to anabolic steroids vary. The health risks discussed above for men also apply to women. In general, the extent to which women athletes use anabolic steroids has not been well studied. A few women take high doses of anabolic steroids, equal to those used by men (31). Like men though, most women use steroids in low to moderate doses, primarily for their anticatabolic effect, in sports such as running and swimming. It appears that the majority of
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women athletes do not wish to experience the masculinizing effects of anabolic steroids and thus do not use them.
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EFFECTS IN BOYS
Teen-age boys often want to gain strength or weight. For example, a high school football player may try to gain 20 pounds of muscle over the summer to improve his chances of playing on the first-string team. The boy who tries anabolic steroids during training may indeed increase his strength or weight, in part because he accelerates his rate of maturation. He fills out and reaches a level of muscularity that he may well have reached eventually anyway. However, the continued use of steroids may further enhance his strength and muscularity beyond that which he would have achieved naturally. The major drawback is that if the boy has not reached his full height, he may stunt his growth. In our society, height is an advantage, and most boys do not wish to jeopardize their potential height. Anabolic steroids tend to close the growth plates at the ends of bones sooner than normal, and thereby preclude further growth (I). This would be most likely with prolonged, high doses of the drugs. Recent evidence suggests that low doses of testosterone used to treat constitutional delay in growth and development in adolescent boys does not adversely affect final adult height (32). DRUG CONTROL AND TESTING
It is generally considered unethical for physicians to prescribe anabolic steroids for the purpose of enhancing athletic performance. In some states the practice is illegal. Thus, most anabolic steroids are purchased on the black market. Sources include drugs diverted from US manufacturers or smuggled across the borders from other countries. Fake anabolic steroids are increasingly sold on the black market as legal restrictions become tighter. Most sports organizations ban the use of anabolic steroids and some test for its presence in urine at certain competitions or at unannounced times. Most of the oral anabolic steroids are undetectable after two or three weeks but some oil-based injectables can be detected in urine up to one year later. The detection of anabolic steroids is technically difficult, requiring analy sis with a gas chromatograph-mass spectrometer (33). The cost of analysis, approximately $100 per sample, is a limiting factor. Testing for anabolic steroids is performed at the Olympic Games and at various international
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and national events. The National Collegiate Athletic Association and the National Football League perform testing at unannounced as well as specified times. Patients who tell their physicans that they are using anabolic steroids should be given a careful physical examination and blood tests to assess liver function and lipid profile. Scare tactics usually are ineffective, but the harmful effects of anabolic steroids should be discussed and the patient encouraged to stop using the drugs. ACKNOWLEDGMENT This paper was adapted m part from the authors' chapter "Drugs in Sports in Sports Medicine, edited by R. H. Strauss. Philadelphia: Saun ders (1991). 2nd edition. "
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