Performance-Enhancing Substances in Adolescent Athletes

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Symposium on Adolescent Health -- February 2002

By Jorge E. Gomez, MD

Use of performance-enhancing substances is widespread among adolescents. Anabolic steroids, creatine, and androstenedione are currently among the most used ergogenic substances. In the past 10 years, the amount of data regarding these substances from well-designed clinical trials has increased dramatically. Anabolic steroids remain difficult to study because of their known harmful side effects. The vast amount of data on creatine and exercise performance does not support the dramatic claims of muscle building and power development by manufacturers. Androstenedione has been popularized by high-profile sports stars, but initial studies cast doubt about its performance-enhancing potential. The physician requires factual information about these substances to be able to counsel youth about their effects.

Introduction

For as long as historians have been writing about sports, athletes have attempted to enhance their performance using drugs and dietary supplements. The use of performance-enhancing substances is widespread among youth. Attributes of adolescents make them particularly prone to use performance-enhancing or ergogenic substances; they are struggling with issues of self-worth, sexual identity, and mastery, while at the same time are beginning to develop goal-directedness (ie, the appreciation for the future consequences of one's present actions). To assist youth in decision making about these substances, the practitioner should have some factual knowledge. Whether increased knowledge alone can dissuade a youngster from using a potentially harmful substance is debatable (1). A survey conducted many years ago asked young Olympic hopefuls if they would take a substance that would guarantee success even if they knew it would kill them in a year; most said yes.

Anabolic Steroids

An article in Scientific American written by Hoberman and Yesalis in 1995 chronicled the history of synthetic testosterone (2). On June 1, 1889, Dr Charles Edouard Brown-Sequard, at age 72 years, reported to his medical colleagues that he had experienced increased strength and energy by self-injecting with testicle extract from dogs. Over the next few decades, androgen-laden animal extracts underwent considerable experimentation. In the first half of the 20th century, natural and synthetic androgens were used to treat various conditions including senility, asthma, epilepsy, tuberculosis, menopause, and homosexuality. In the 1930s, pharmaceutical companies, seeing a potential boon, raced to formulate effective synthetic testosterone. The race was won by two chemists employed by Ciba, L. Ruzicka and A. Wettstein, who first patented a process for synthesizing testosterone.

By 1941, research was under way to study the effects of testosterone on muscle work. It has been speculated that in the late 1930s, the Nazis, under direct orders from Adolf Hitler, began administering testosterone to elite troops and infantry as well to increase aggressiveness. The use of testosterone in sports was not fully appreciated until the 1954 Olympics, at which use of testosterone by athletes was thought to be widespread (3).

Until recently, much of the scientific data on the effects of testosterone on athletic performance was largely anecdotal. Because of the known serious side effects (discussed below) of exogenous anabolic steroids, few prospective, randomized, placebo-controlled trials with healthy athletes from which to draw conclusions have been conducted. However, the anecdotal evidence regarding their desired and undesirable effects is convincing (1,2,4,5). Administration of exogenous anabolic steroids is known to increase muscle strength, muscle bulk, running power, and speed. Aggressiveness is increased, also. A recent study has verified that it can increase recovery from strenuous exercise, enabling the athlete to endure a greater amount and intensity of training (6).

Legitimate medical indications for using steroids include hypoandrogenism (eg, absent testicles), delayed puberty, micropenis, hereditary angioneurotic edema, some androgen-sensitive cancers, and muscle wasting associated with human immunodeficiency virus (2,7). The side effects of endogenous steroids are well known from both medical and anecdotal reports (1-5,7-9). These side effects are summarized in the Table . Unfortunately, some of these effects are not reversible with discontinuation of the hormone. In women, these permanent effects include hirsutism, deepening of the voice, and clitoromegaly. In men, the testicular atrophy and gynecomastia are often irreversible.

Steroid users usually use quantities of steroids on the order of 10 to 100 times that used for legitimate medical indications, despite the fact that androgen receptors are saturated at much lower doses (10). They often use both injectable and oral steroids, a practice known as "stacking." Another common practice is to cycle on and off the substances in an attempt to avoid unwanted side effects, a practice that is probably not effective. Another reason to "cycle-off" the steroids (otherwise known as a "holiday") is to avoid detection in settings where drug testing occurs predictably. During an "on" cycle, users often follow a pyramidal dosing scheme, starting with low doses, building up, and then tapering.

The results of increased power and speed in athletes on steroids has in no case been illustrated better than in the dramatic success of East German athletes through the 1970s and 1980s. In his book, Faust's Gold , sports historian and psychologist Steven Ungerleider describes the highly organized and systematic "doping" of hundreds of East German Olympic hopefuls during this period (11). The results were miraculous: unprecedented numbers of gold medals in Olympic and other international competitions as well as world records, often by large margins over previous records. The bottom line is that steroids work. Unfortunately, the price may be high. In addition to the side effects shown in the Table, heavy steroid use has been linked to cardiomyopathy, myocardial ischemia, liver failure, and certain types of cancer (11,12). Many of the athletes who were the victims of the East German doping scheme have sought legal retribution for illnesses linked to heavy steroid use.

In the United States, use of anabolic and androgenic steroids is widespread, ranging from 4% to 12% among male adolescents and from 0.5% to 2% among female adolescents (13-17). Faigenbaum et al reported that 2.7% of middle school students reported using anabolic steroids (18). Students most likely to use steroids were those in sports that required power, especially football and wrestling (13). Interestingly, up to one third of teenage users in one survey were nonathletes; these youngsters were presumably using the steroids to enhance their physical appearance through increased muscularity (19). A study by Windsor and Dumitru done in San Antonio, in which they surveyed high school athletes throughout the city, found that anabolic steroid use was prevalent in the higher income areas but much less so in low-income areas (20). Steroids are expensive but can be easily obtained, often through gyms. In Texas, most anabolic steroids used illicitly are believed to be veterinary-grade hormones brought in from Mexico.

A couple of recent studies have provided further insight into the psychological makeup of young steroid users. Kindlundh et al reported that use in adolescents was significantly associated with strength training, tobacco use, heavy alcohol consumption, use of cannabis, lysergic acid diethylamide, amphetamines, and opioids (21). Not surprisingly, young anabolic steroid users often have low self-esteem and unrealistic expectations of athletic and sexual prowess. Gruber et al found that anabolic steroid use in young females was significantly associated with hypomanic and depressive symptoms, rigid dietary practices, nontraditional gender roles, and a chronic dissatisfaction with their physiques (22).

Creatine

Unlike anabolic steroids, on which few clinic trials have been published, we have seen an explosion of legitimate scientific data on the effects of oral creatine supplementation on athletic performance. In contrast to anabolic steroids, creatine is a nonregulated dietary supplement. Creatine is relatively inexpensive, widely available, and thought to have few if any serious side effects. Most studies of the effects of creatine on athletic performance have appeared in the last 10 years (23).

Creatine is a naturally occurring compound found primarily in skeletal muscle but also in the liver, brain, and cardiac muscle. The average man who weighs 70 kg has approximately 120 g of creatine. The average daily dietary requirement for creatine is about 2 g, an amount found in about 0.5 kg of lean red meat (24). Creatine's main metabolic function is to combine with inorganic phosphate to form phosphocreatine, a high-energy substrate. In the muscle, phosphocreatine serves as a reservoir to drive anaerobic muscle contraction. Muscle stores of phosphocreatine are probably consumed during the first 5 to 10 seconds of high-intensity exercise and, therefore, must be regenerated, a process that requires only a few minutes.

Some clinical evidence suggests that creatine supplementation may attenuate age-related loss of muscle endurance and strength, and may enhance skeletal muscle function during exercise in patients with heart failure (25). Supplementation of patients with Duchenne muscular dystrophy has resulted in improved muscle function (26).

Because of creatine's role in muscle contraction, increasing muscle stores of creatine is thought to result in increased phosphocreatine and, therefore, in increased energy to perform physical work. Manufacturers and proponents of creatine maintain that exogenous creatine supplementation will result in increased strength, power, and muscle bulk and, therefore, increased speed and explosiveness. Supplementation with creatine is also thought to improve recovery between bouts of exercise and to allow an increase in the total training load. Review of the available randomized, placebo-controlled trials reveals little evidence to support these claims (24,27-31).

Creatine users often load with a dose of creatine monohydrate ranging from 10 to 30 g, followed by anywhere from 2 to 20 g daily. Studies of muscle biopsies in subjects ingesting creatine have shown the greatest change in muscle creatine stores after 2 days of supplementation (24). One study showed that doses of 3 g of creatine taken daily for 28 days caused the same increase in muscle creatine as did doses of 20 g taken daily for 6 days (32). That more than 3 g of creatine taken daily will result in any further increase in muscle stores appears unlikely. Most randomized, placebo-controlled trials have used from 20 to 30 g of creatine per day over 5 to 7 days.

The potential for creatine supplementation to increase muscle strength and bulk has generated great interest. Of 34 placebo-controlled, randomized trials, 18 showed an increase in muscle strength. The typical mode of exercise in these trials was the 1-repetition or 3-repetition maximum, or the maximum weight that could be lifted a maximum of 1 time or 3 times. One of the most impressive studies was conducted by Becque et al with 23 young male lifters, who showed an increase of 28% in the 1-repetition maximum biceps curl after creatine supplementation of 20 g per day for 7 days (33). With almost as many trials showing no increase in strength as those that did, arguing for a consistent increase in muscle strength with creatine would be difficult. In 8 studies looking specifically at the bench press, 3 studies showed an improvement. Regarding muscle bulk, 11 of 17 methodologically rigorous studies showed an increase in body mass after short-term creatine supplementation. However, in the 12 studies that also examined body composition, only 5 studies showed an increase in muscle mass. Some experts have concluded that the increase in body mass after short-term supplementation is primarily water weight.

Most high-quality studies done on creatine and exercise have been studies with athletes performing exercise on a stationary cycle. Creatine has been shown most consistently to provide an ergogenic effect with this type of exercise. In a review of 35 studies using cycle work as the mode of exercise, 21 studies showed an increase in performance, and 14 studies showed no difference. In most of these studies, short bouts of high-intensity cycling (against high resistance) are done with short rest periods (30 seconds to 2 minutes) in between. The increase in cycling performance has consisted usually of a smaller decrement in power output over repeated cycling bouts when subjects are compared with controls. These results suggest that creatine not only may increase total power output during repeated bouts of cycling but also may enhance recovery between bouts. Possible mechanisms for the increase in cycling performance include increased rate of phosphocreatine resynthesis, higher corticotropin and cortisol levels (increased carbohydrate utilization), decreased hydrogen ion buildup, and, consequently, decreased lactic acid production (24,34).

Results of studies using more sports-specific exercise modes have been even less impressive. In 6 studies of sprint running over distances ranging from 10 to 100 meters, only 1 study showed improvement in sprint speed. Only 3 of 9 studies of creatine and sprint swimming performance showed improvement. In contrast, none of the 5 creatine studies of swim bouts lasting 30 to 150 seconds showed an improvement. In 1 study, swimmers on creatine actually got slower, an effect directly attributed to increased body mass. Regarding vertical jumping, only 3 of 6 studies showed increased jump performance in subjects on creatine. In 6 studies of running lasting from 30 to 150 seconds, only 2 studies showed improved running speed. Finally, in 6 other studies using a variety of exercise modes, 4 studies showed improvement in activities including sprint skating, 274-meter shuttle run, and rowing.

Across exercise modes, the odds that creatine supplementation would increase performance appear to be no better than 50-50. One possible explanation for the disparate results among equally well-conceived studies is that the increase in muscle creatine with a standard supplementation regimen varies highly among people. Not surprisingly, persons with lower starting levels of muscle creatine have larger increases with supplementation. Vegetarians fall into this category. Creatine uptake from the gastrointestinal tract is also highly variable. Exercise and simultaneous ingestion of creatine with carbohydrate appear to enhance muscle uptake (35,36). At this time, we have no way to predict who will respond to creatine supplementation and who will not.

Separating the creatine studies into those involving elite athletes and those involving normal subjects reveals another interesting result: 26 of 48 studies involving normally active subjects showed improvement in exercise performance, whereas only 13 of 39 studies involving elite athletes showed improvement. Normally active subjects appear to be more likely to realize performance enhancement from creatine than elite athletes. One possible explanation is that elite athletes are already at such a high performance level that other changes in their training are likely to result in only small improvements.

The current available evidence indicates that oral creatine supplementation is relatively safe. The most common adverse effects are minor gastrointestinal disturbances (primarily abdominal pain, cramping, and diarrhea), which are purported to be transient with continued use (37). Concerns over suspected nephrotoxicity of creatine have been put to rest by a recent study showing that the increase in serum creatinine on creatine supplementation is the result of increased conversion of creatine to creatinine, not of decreased glomerular filtration function (38,39). Another study showed that creatine use and resistance training did not affect blood lipids (40). One recent paper theorized that excess creatine in the body may be converted to formaldehyde, which is cytotoxic (41). No data yet support this hypothesis.

Androstenedione and Dehydroepiandrosterone

Androstenedione (andro) is a naturally occurring precursor to testosterone, and dehydroepiandrosterone (DHEA) is a precursor to androstenedione. Both compounds may be converted to testosterone, or may be aromatized to estrone. Both andro and DHEA are available as over-the-counter oral supplements. Use of these compounds is alleged to increase circulating testosterone and, thus, to have anabolic effects. Use of andro to enhance athletic performance has been popularized recently by high-profile professional athletes.

So far, few randomized, placebo-controlled trials of andro and DHEA and exercise performance have been conducted. Before 1999, only 3 reports had been published, 1 that boasted from 4-fold to 7-fold increases in testosterone in women (N = 2), and 2 other studies that showed no effect (42). The scientists who conducted the study with 2 women worked for a German pharmaceutical company and did not divulge details of their methods.

In 1999, King et al reported a trial of andro versus placebo testing in 30 healthy adult men (42). Those subjects randomized to supplementation received 300 mg of andro per day over an 8-week period during which they engaged in resistance training. The subjects receiving placebo performed the same resistance training. At the end of 8 weeks, no difference was found in fat-free mass, fat mass, muscle fiber cross-sectional area, or knee extension strength between the two groups. Neither were any differences in circulating levels of testosterone seen. However, the group receiving andro had significantly lower levels of high-density lipoprotein cholesterol and significantly higher levels of estradiol and estrone compared with baseline.

Three other well-done studies with andro have been conducted. Wallace et al randomized 40 healthy men to take andro, DHEA, or placebo for 3 months (43). After strength training, no significant differences were found in strength or testosterone levels among the three groups. Brown et al had andro and placebo groups undergo 8 weeks of resistance training (44). Both groups significantly increased strength over baseline, but at the end of the trial, no significant differences were seen in strength, fat-free mass, or testosterone between the groups. This study did not show an increase in estrogen compounds in the andro group. A crossover study by Ballantyne et al, using 200 mg of andro per day for 2 days versus placebo, showed from 2-fold to 3-fold increases in androstenedione, 70% increase in leuteinizing hormone, and significant increase in estradiol in the subjects taking andro after heavy resistance exercise (45). Testosterone levels and strength were no different between subjects on and off andro. Another study using different doses of andro (100 mg per day and 300 mg per day) and a placebo showed no increase in testosterone in the group taking 100 mg per day but a 34% increase in the group taking 300 mg per day (46). Both groups on andro had significantly elevated estradiol levels compared with the placebo group. Broeder et al reported lack of enhancement of adaptation to resistance training but consistently elevated estradiol in middle-aged men supplemented with andro (47). Another study with middle-aged men showed some improvement in strength with long-term andro supplementation (48).

Identifying the User

A major challenge for the primary care physician is to identify the user of performance-enhancing substances. The anabolic steroid user is the most easily identified. Many of these youngsters are brought to the attention of health care providers because of behavioral changes, which include bursts of rage, emotional lability, extreme aggressiveness, and uncharacteristic lascivious or risk-taking behavior. Female anabolic steroid users are less likely to have problems with rage but may be volatile, seem depressed, or be intensely preoccupied with their physique, or exhibit sexually inappropriate behavior. Youngsters will often deny using steroids. At the same time, they may boast of their strength, athletic achievements, or sexual prowess. Admission of other drug use, especially alcohol, stimulants, or cannabis, may be a red flag of concomitant steroid use (49).

The physical examination may provide additional clues. Gynecomastia or testicular involution in the male; deepened voice, hirsutism, and clitoromegaly in the female; or worsened acne or the appearance of striae in either gender may indicate androgen excess. Note that a significant proportion of adolescent steroid users are not athletes or may have a completely normal phenotype. Therefore, all adolescents must be screened for steroid or other performance-enhancing substance use when being screened for other high-risk behavior.

Little information is available on the profile of adolescent creatine users. A study by Smith and Dahm found that 8.2% of high school athletes reported using creatine (50). These creatine users were more likely to be older, to be football players, and to use other supplements than nonusers. Creatine use in the age group appears haphazard (78% of users did not know how much they were taking).

What We Can Tell Youngsters About Ergogenic Substances

Anabolic Steroids
Steroids are related to the male hormone testosterone. Taken orally or injected, when combined with resistance training, steroids result in supranormal strength and power gains. Some of their side effects are not reversible. They are dangerous drugs; the more severe side effects are heart disease and liver failure, which may result in death. Anabolic steroids taken by skeletally immature youth may result in premature closure of the growth plates and, thus, short adult height. Steroids have also been known to cause drastic personality changes and psychological problems, including depression, rage, and psychotic symptoms (51), and some athletes have been driven to suicide while using steroids (52). They are illegal and banned by nearly all major athletic governing bodies.

Creatine
Creatine is a naturally occurring compound. It is not illegal, not considered a banned substance, and readily available over the counter. The claims of increased muscle bulk, strength, power, speed, and endurance are inflated and not based on the current available science. The sudden weight gain after starting creatine supplementation is probably water weight. Creatine compounds are relatively safe when used on a short-term basis, most often causing minor gastrointestinal disturbances. However, the safety of long-term creatine use has not been studied.

Androstenedione and Dehydroepiandrosterone
These compounds are precursors of testosterone and estradiol. They are taken to increase circulating testosterone and, therefore, to increase muscle strength and bulk. We have few scientific studies on the effect of andro or DHEA and muscle performance. The data that are available indicate that supplementation with andro or DHEA does not result in increased levels of testosterone, except perhaps with large doses. Studies in young men have shown no increases in strength. These supplements have consistently produced increases in the female hormones estrone and estradiol. They have also caused a decrease in high-density lipoprotein cholesterol, which may increase the risk of heart disease.

C onclusion

Recent, well-designed scientific studies have provided evidence regarding the safety and efficacy of the commonly used ergogenic substances. It is unlikely that increasing adolescents' knowledge of these substances will by itself change use patterns (53). Our society's drive to win at all costs must change before significant reductions in the use of performance-enhancing substances will be seen.

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Dr Gomez, associate professor and director, Pediatric Sports Medicine & Fitness Clinic, Department of Pediatrics, The University of Texas Health Science Center at San Antonio. Send reprint requests to Jorge E. Gomez, MD, Department of Pediatrics, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229-3900; or e-mail gomezje@uthscsa.edu .

Table. Side Effects of Anabolic Steroids (1,2,4,5).

 

System

Side Effects

Cardiovascular

Decreased HDL-C
Hypertension
Myocardial ischemia
Cardiomyopathy

Musculoskeletal

Premature physeal closure
Tendinopathy

Genitourinary (males)

Testicular atrophy
Infertility
Gynecomastia

Dermatologic

Acne
Striae
Hirsutism (females)

Psychiatric/behavioral

 

Hypomania
Depression
Aggression
Emotional lability
Increased libido

Other (females)

Deepening of the voice

HDL-C = high-density lipoprotein cholesterol

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