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Question 4: Based Upon Your Understanding of the Scientific Literature, Are Steroids as Effective at Therapeutic Dosages Versus Higher Dosages? Return to TOC
Antonio: There is a dose-response relationship (i.e., the more you take, the greater your gains in muscle mass). This may or may not clearly translate into better performance (2). Interestingly, older men are as responsive as young men to synthetic testosterone's anabolic effects; a dose of synthetic testosterone as low as 125 mg taken once per week for 20 weeks was associated with high normal testosterone levels, low frequency of adverse events, and significant gains in fat-free mass and muscle strength (4).
Chetlin: My response to this would be no. What little peer-reviewed scientific literature is available clearly indicates that suprapharmacologic doses are more effective in terms of measurable change in strength, muscle size, and body composition. These results, however, have been derived only from men who are neither athletes nor regularly weight-trained. Suprapharmacologic doses of approximately 600 mg per week of testosterone esters, administered to these subjects over a period of at least 10 weeks, have resulted in significant increases in muscle strength, hypertrophy, and lean muscle mass (3–6, 34). Dosing regimens in the stated amount may raise mean serum testosterone concentration to 1,000 ng/dL or more (11). Given that the normal mean testosterone concentration is approximately 370 ng/dL (accumulated data from 816 independent labs using 14 different assays to measure total testosterone) (10), this would represent a 2.7-fold increase to actualize morphometric and performance enhancement. Current clinical hormone replacement intervention indicates a therapeutic dosage of 200 mg every 2 weeks by parenteral (i.e., intramuscular) injection with an ester of testosterone (i.e., testosterone enanthate) (14). Thus, a threshold supraphysiologic dose appears to be in the range of 6 times an accepted therapeutic one. When combined with weight training, the described effects were permissive and the extent of the noted improvement appears dose dependent (4, 6, 11).
Interestingly, a review of the clandestine literature of state-sponsored drug programs of the former German Democratic Republic reveals that athletes, both male and female, systematically took massive suprapharmacologic doses of AAS over several years, beginning in adolescence or earlier. Demonstrable performance improvements were meticulously noted in Olympic sporting events such as weight-lifting, swimming, track and field, and kayaking, to name but a few (12).
Hoffman: It appears that for AAS to be effective, they need to be taken in pharmacological doses. By providing AAS in physiological dosages (that which is normally produced by endogenous sources), it will simply cause the body to shut down its own supply of testosterone through a negative feedback mechanism. Thus, for any exogenously administered AAS to have any effect, they need to be taken in pharmacological or suprapharmacological dosages. A dose-response curve of the effect of AAS has been demonstrated, with the total dose of AAS having a logarithmic relationship to increases in lean body mass (11).
Kraemer, Vingren: First, AAS work. To argue against this hypothesis is foolhardy. From a scientific perspective, it has been difficult to demonstrate the efficacy per limitations in experimental designs and doses that can be administered. Thus, this leads to conflicting evidence regarding the effectiveness of AAS in promoting hypertrophy and increases in strength and power, leading some scientific panels and position stands in the 1970s to say AAS had no effect. The majority of studies have found that AAS supplementation with resistance training does not increase strength more than resistance training alone in non–testosterone-deficient populations (4, 5, 7, 9; for review, see 13). However, dose was most likely a major problem in these studies.
In a classic set of studies and as stated by Bhasin and colleagues (1) in one of their recent papers, “Supraphysiologic doses of testosterone, especially when combined with strength training, increase fat-free mass and muscle size and strength in normal men.” In that study, they used a dose of 600 mg weekly over 10 weeks. In a subsequent study (2), it was apparent to these investigators that
Although substantial gains in muscle mass and strength can be realized in older men with supraphysiological testosterone doses, these high doses are associated with a high frequency of adverse effects. The best trade-off was achieved with a testosterone dose (125 mg) that was associated with high normal testosterone levels, low frequency of adverse events, and significant gains in fat-free mass and muscle strength.
Therefore, the higher dose is associated with greater adverse effects, but potentially greater gains. Nevertheless, the evidence is very compelling that AAS do in fact work.
Anecdotal and some survey data indicate that the doses of AAS actually taken by athletes are much higher than those used in most controlled human studies, and that these higher doses are effective in increasing muscle mass and strength. In addition, the effect of long-term use (years) of AAS on strength and how long such potential effects may last after AAS use is stopped have not been directly determined experimentally in humans. The lack of positive findings for AAS as ergogenic aids is due most likely to the restriction in the maximal dose allowed in human studies by many institutional review boards and ethics committees. It appears that if such data were to be collected, it would need to be under highly supervised clinical scenarios (as has been done), and even then, side effects would cause dropouts (1, 2). Nevertheless, studies with doses higher than 600 mg per week probably will never be conducted, due to the potential for side effects; the only recourse would be to study these questions indirectly by following athletes who already use AAS. However, the major problems with self-reported studies are the actual content and type of AAS used, due to untested black market and Internet sources.
Question 5: To What Degree Can Performance Really Be Enhanced by the Administration of Anabolic Steroids? Return to TOC
Antonio: Performance is dependent on many factors. Certainly in sports that put a premium on strength and power, it is clear that AAS self-administration can enhance performance. However, AAS use can assist athletes in recovery, which can be of value to endurance athletes.
Chetlin: The answer to this question is also left to some speculation. There is virtually universal agreement that AAS improve athletic performance, but to what degree? Because there are no controlled studies that have specifically examined this question, we are reduced to informed conjecture regarding the magnitude of performance enhancement one might expect to realize in a given sport. Though institutionally protected mechanisms greatly limit even the possibility of facilitating studies to examine AAS-induced performance improvement in otherwise healthy humans (e.g., athletes), the furtive literature left in the wake of past Eastern European regimes reveals specific, predicted advancement in various athletic disciplines. Specific drug protocols lasting several years were associated, for example, with the following forecasted gains: men's shot put 2.5–4 m; women's shot put 4.5–5 m; men's discus throw 10–12 m; women's discus throw 11–20 m; women's hammer throw 6–10 m; women's javelin throw 8–15 m; women's 400-m run 4–5 seconds; women's 800-m run 5–10 seconds; and women's 1,500-m run 7–10 seconds. Across genders and various sports, these illicit state-sponsored programs produced performance gains of approximately 3–20% (12), remarkable gains considering that among groups of homogeneous elite athletes an improvement of 1–2% may mean the difference between winning a gold medal or no medal at all. Exercise scientists employed in these now-defunct governmental programs determined that women derive the greatest AAS-driven improvements in performance, with the most profound enhancements observed in junior athletes after the initial bout of anabolic administration (12).
Given the response variation to AAS, the extent of functional improvement is likely due to a combination of intervening factors, including
Drug dosage—Higher doses may translate into greater performance gains (3, 6, 11).
Drug number—The practice of stacking appears to enhance AAS effects in a permissive fashion (12, 15).
Androgen receptor sensitivity—AR-mediated AAS use may promote up-regulation of these specific receptors (25, 38).
Training status—Younger, less-experienced individuals (especially women) may respond in a more pronounced fashion to AAS effects (12).
Athletic discipline—Sporting endeavors that emphasize speed, strength, power, and aggression (i.e., shorter-duration, higher-intensity efforts) may derive the most benefit from AAS supplementation. This is strictly a comparative assessment; improvement in many sports, with varying degrees of functional and metabolic requirements, may be enhanced with this class of drugs (12).
Genetics—This is an inescapable component; transcriptional and translational expression of specific drug effects probably varies greatly from one individual to the next.
Hoffman: This is an interesting question, due to the fact that a huge mistake was made in study methodology (e.g., use of physiological dosages versus pharmacological dosages typically used by athletes, mode of exercise assessment different from the training stimulus, and the use of novice resistance-trained subjects) during the early research examining the efficacy of AAS use. Early studies were unable to see any significant differences in strength or body mass gains (10, 12, 14, 18, 28). As a result, scientific and medical communities at the time suggested that AAS had little influence on athletic performance. This was contrary to anecdotal evidence emanating from gyms and spreading among competitive athletes, and it created a credibility gap between researchers/medical community and athletes.
In studies administering AAS in dosages that are commonly used by experienced resistance-trained athletes, results appear to confirm the anecdotal claims of superior performance and size improvements. The majority of studies examining AAS administration on experienced resistance-trained athletes has reported significant strength and body-mass gains (1, 2, 6, 15, 21, 27, 29, 30). In experienced resistance-trained athletes, strength gains are generally small in comparison with novice lifters. However, when these athletes are given AAS, their strength gains appear to be 2- to 3-fold higher, compared with athletes at a similar level who are not supplementing with AAS (6, 15, 30). Recent research also has demonstrated a 3-fold difference in lean body mass accretion (29). Thus, the evidence is quite convincing that AAS administration in conjunction with a resistance training program and an adequate diet will increase both strength and lean body mass.
Lively: There should no longer be a question as to whether or not AAS are ergogenic. Well-controlled studies (3, 4, 7, 12, 15, 16) have demonstrated that administration of AAS produces both an increase in muscle mass and strength. The literature demonstrates strength improvements in the range of 5–20% over baseline levels, depending on the administered dose and regimen (
. Studies do show that the anabolic effects of AAS are dose dependent (4, 15) and that the combination of strength training and AAS administration leads to larger increases in muscle size and strength than are achieved with either intervention alone (3). In view of the evidence on dose dependence, it is also possible that the literature underestimates the anabolic effects, because it is difficult for a study to mimic the large doses, multiple drugs, and training regimens that are actually used by most AAS users.
Question 6: What Are the Health Consequences of Steroid Use (i.e., in Women, Men, and Adolescents)? Return to TOC
Antonio: We wrote a review article on this topic several years ago (
. First, let me address the issue of androgen use in men. It has been estimated that 1–3 million male and female athletes in the United States have used androgens. Androgen or AAS use has been associated purportedly with liver dysfunction, altered blood lipids, infertility, musculotendinous injury, and psychological abnormalities. Yet, androgens have been available to athletes for more than 50 years and there is little evidence to show that their use will cause any long-term detriment; furthermore, the use of moderate doses of certain AAS (e.g., testosterone enanthate, nandrolone decanoate) results in side effects that are largely benign and reversible. It is our contention that the incidence of serious health problems associated with the use of androgens by athletes has been exaggerated (
. This is an area where there is perhaps more myth and misinformation (with creatine misinformation coming in a close second) than any other topic. The mainstream press reports of “roid rage,” yet this is more media creation than actual scientific fact (9).
The issue of women and children, of course, is different. Women clearly can become masculinized if they take sufficient doses of AAS. Children, of course, should not be taking AAS due to the potentially detrimental effects on their growth plates. However, there are clinical applications for androgens in children. For instance, one study determined whether oxandrolone administration for 1 year after a burn reverses muscle and bone catabolism in hypermetabolic pediatric burn patients. They discovered that long-term administration of oxandrolone safely improves lean body mass, as well as bone mineral content and density, in severely burned children (7).
Chetlin: This question necessitates a multifactorial answer, based upon length of use, dosage, polydrug practice, and predisposition of the user to diseases exacerbated by AAS. According to my objective review of the literature, otherwise healthy males taking pharmacologic or suprapharmacologic doses of a single AAS, under controlled short-term conditions, apparently may not experience irreversible side effects (3, 4, 11, 31, 32). Please notice that I have made a very qualified comment and have italicized some operative words. Having made this statement, it must be noted that medically established and self-reported adverse effects of individuals abusing AAS are numerous, which may or may not prove reversible. These include hypertension, altered lipoproteins (increased LDLs, decreased HDLs), libido changes (increased or decreased), myocardial arrhythmias, myocardial hypertrophy, thrombosis, hepatotoxicity, hepatic neoplasm, acne, cutaneous striae, alopecia, male-pattern baldness, schizophrenia, and affective disorder (i.e., mania, depression) (11, 16, 23, 27, 28, 33, 36, 39). Gender-specific effects also have been reported in both men (e.g., testicular atrophy, impotence, prostate hypertrophy, gynecomastia) and women (e.g., hirsutism, masculinization, menstrual cessation, clitoral hypertrophy, voice changes) (11,12,15,16). Though some long-term effects in men may prove reversible, side effects associated with androgenization in women may not be reversible or may be only partially reversible with androgen antagonists. Children given AAS may experience premature epiphyseal closure of the long bones, precocious puberty, severe acne, and, in the case of prepubescent girls, various gynecological disorders (e.g., amenorrhea, ovarian cysts) (11, 12). Overall, long-term health risks associated with suprapharmacologic AAS usage are not well established, although there is some evidence to indicate that chronic AAS users, including those who administer more than one drug concurrently (i.e., polydrug practice), may have increased risk for cardiovascular disease and an incidence of mortality 5 times higher than normal (26, 27).
Hoffman: The clinical examination of AAS usage is quite limited. Much of the problem is related to an inability to study this drug in a nonclinical population due to the unwillingness of institutional review boards to approve such studies. As a result, most of the investigations on medical issues associated with AAS use have been performed on athletes self-administering the AAS. Most of the adverse events appear to be seen in athletes who have been using AAS for several years. In addition, anecdotally, there appears to be a disproportionate amount of adverse events seen in bodybuilders compared with strength/power athletes.
Some of the cardiovascular effects associated with AAS use are decreased HDL, increased cholesterol, increased triglycerides, elevated blood pressure, and increased risk of thrombosis. The magnitude of the effect may differ depending upon the AAS used. Of interest is that these effects appear to be reversible when the athlete cycles off the steroid. In regard to left ventricular function, studies suggest that highly strength-trained athletes, with no history of anabolic steroid use, exhibit a high incidence of waveform abnormalities, but athletes self-administering AAS exhibit a higher percentage of waveform abnormalities. In addition, a study on rats has shown that synthetic testosterone administration for 8 weeks will increase left ventricle stiffness and will cause decreases in stroke volume and cardiac performance (17). It was hypothesized by the researchers that increased stiffness may be related to formation of cross-links of adjacent collagen molecules within the heart. AAS administration also may predispose an individual to thrombosis due to AAS-stimulated platelet aggregation. Some evidence exists that shows that anabolic AAS reduce the endothelial nitric oxide dilator system, causing coronary artery occlusion (19). However, this may depend upon the AAS compound used. Generally, issues related to thrombosis have been reported in case studies of bodybuilders with a number of years of steroid use.
Other adverse events generally associated with AAS use include acne, male-pattern baldness, gynecomastia, decreased sperm count, testicular atrophy, impotence, and transient infertility. In addition, increases in the risk of liver tumors and liver damage are often discussed as a consequence of AAS use. This is likely due to the liver being the primary site of steroid clearance. However, the relationship between AAS use and hepatic disease appears to be exaggerated. Dickerman et al. (7) has shown that the blood chemistry of bodybuilders self-administering AAS shows elevations in aspartate aminotransferase (AST), alanine aminotransferases (ALT) and creatine kinase (CK), but no change in gamma-glutamyl-transpeptidase (GGT). This chemistry panel is not suggestive of hepatic dysfunction, but of possible muscle damage. These researchers suggested that AAS-induced hepatotoxicity may be overstated. In another study by that research team (23), surveys were sent to physicians, asking them to provide a differential diagnosis for a 28-year-old AAS-using bodybuilder with an abnormal serum chemistry profile (elevations in AST, ALT, and CK, but with a normal GGT). The majority of physicians (56%) failed to mention muscle damage or muscle disease as a potential diagnosis. The majority of physicians (63%) indicated liver disease as primary diagnosis. If prior reports of hepatic disease and anabolic steroid usage had been based upon increased aminotransferases, the authors concluded that the medical community may have overemphasized AAS-induced hepatotoxicity. In regards to hepatic cancer, it appears that such isolated cases have been reported in nonathletic populations being treated with testosterone for aplastic anemia. Many of these individuals were treated with oral AAS (17a-alkylated) for years of continued use. No cysts or tumors have been reported in athletes using 17b-alkylated AAS. Thus, there does appear to be evidence that the risk of hepatic disease from anabolic steroid use is not as great as the medical community had thought originally.