Western history first records myriad medical treatments in 1550 bc in the Ebers Papyrus, which is a 110-page scroll containing 700 formulas and remedies (animal, vegetable, and mineral) used by ancient Egyptian healers.1,2 Historical records from ancient China and India also reveal extensive herbal and plant-based pharmacopoeias.3 The attempt by athletes to improve their sports performance by taking various remedies and drugs has been observed for thousands of years. For example, athletes taking part in the ancient Greek and Roman games consumed various mixtures of mushrooms, figs, and opioids that contained stimulants such as strychnine, and other substances in attempts to seek victory over opponents in sports competition.4,5
Athletes in the 20th-century Olympics events also used strychnine to gain a competitive edge, even though it was known as a potential poison. Indeed, part of the 20th-century Olympic history is the discovery of various substances taken by some athletes in attempts to win and attempts by the Olympics Committees to find and stop these attempts.5 Athletes of all ages in the 21st century are willing to take a wide variety of drugs, concoctions, herbals, “health” foods, and others if they feel it will help “win” the game and sometimes even if they know deleterious effects may occur. Many athletes take various chemicals even without any evidence of their benefit or lack of safety. Very few of the thousands of herbal remedies now available have been shown to improve health or even sports performance. Despite this, billions of dollars are spent by athletes hoping for an edge in their sports competition.4–7
The United States Pure Food and Drug Act of 1906 was passed by the US Congress, which prevented adulterated or misbranded food and drugs from being manufactured, sold, or transported across the state lines.4 The 1938 Federal Food, Drug, and Cosmetic Act (FFDCA) then made it law that medications be tested for safety; however, it was not until 1962 that the Harris-Kefauver Amendment of the FFDCA was passed making it law that these drugs must be proven effective for their intended use prior to marketing.4
In order to avoid the close supervision provided to medications, intense lobbying convinced the US Congress to pass the 1994 Dietary Supplement Health and Education Act (DSHEA) in which “dietary supplements” were placed in a separate category. These chemicals were legally defined as substances that were mineral, vitamin, herb, other botanical substances, amino acid, or constituents of these products, metabolites, or even related concentrations, extractions, or combinations of these substances.8 The result is that makers of these products do not need to prove the safety or efficacy of their products. While they cannot claim to prevent, treat, or cure a specific disease, they can denote that the product will “maintain health or normal structure and function.”8
The unfortunate result of this 1994 law is that the public is inundated with a wide variety of products with a dietary supplement label and producing all types of claims for improved health. Athletes are also overwhelmed with a plethora of products claiming to help them become more successful sports participants who will perform better and be in improved health. In 1999, more than $12 billion was spent on “dietary supplements” and the public was bombarded with more than 89 supplement brands and 300 products competing for the attention of the public, including athletes, with unproven claims of improved health and improved sports performance.9 Since the implementation of the DSHEA in 1994, several ingredients have been found to be harmful by the FDA, and thus removed from the market.10 The first such agent to be removed was ephedrine alkaloids, in 2004, because of the cardiovascular effects it had.10 The most recent act is the 2006 Dietary Supplement and Nonprescription Drug Consumer Protection Act, which mandates that supplement and OTC manufacturers report serious adverse effects to the FDA within 2 weeks of the claim.10 While additional measures have been enacted to help protect athletes from adverse consequences, there is still the need of clinicians to educate athletes and their parents to what is known and not known about these substances.11
An ergogenic drug is one that presents with claims of improved sports performance, whether allowing one to run faster, jump higher, or whatever it takes to perform better in one’s chosen sports.4 “Ergogenic” comes from the Greek word, érgon (to work) and gennan (to produce) and when applied to a chemical or drug, implies that the consumer will be able to “work” better. If applied to sports, the claim will be the athlete can “work better” at his or her chosen sport.5 Substance-induced enhanced sports performance refers to improved sports results in the athlete. Reasons to use these products are listed in Table 7-1.
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In 1963, the Council of Europe developed a definition of sports doping as “the administration or use of substances in any form alien to the body or of physiological substances in abnormal amounts and with abnormal methods by healthy persons with the exclusive aim of attaining an artificial and unfair increase in performance in competition.”12 The word “doping” comes from the Dutch word, dop, referring to a mixture of opium given to stimulate racing horses.5 Agents that have been used in attempts to improve sports performance include anabolic steroids, testosterone, creatinine, oxygen, amphetamines, ephedrine, iron, blood, and others as listed in Table 7-2.4–7,9,12–20
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The claims listed in Table 7-1, as outrageous as they seem, are powerful enough to entice thousands of athletes to try them. Encouragement to buy these agents can come from coaches, trainers, fellow athletes, “nutrition” store employees, magazine advertisements, professional athletes, and others. Since much of the known research has been performed on adult males involved in competitive sports, the actual short-term and long-term effects on children and adolescents are practically unknown. Even though the purity and even actual chemical that are found in these products is not clear, sports doping remains a very popular phenomenon among all ages of athletes. Anabolic steroids and creatine are among the most popular sports doping agents.4–7,9,12–20
Prevalence rates vary among studies and depend on several demographic factors including age, athlete or nonathlete, and the type of sports participation. Studies have noted that 5% to 11% of high school males and 0.5% to 2.5% of high school females experiment with anabolic steroids (see next section).4 Approximately half of those who use anabolic steroids start are younger than 16 years and approximately one-third are not athletes. The Monitoring the Future Study has assessed the annual prevalence rates of anabolic steroid use among the US high school students from 1989 to 2006. In the 2006 Monitoring the Future Study, the annual prevalence rates for steroid use were 1.2%, 1.9%, and 2.7% among males and 0.6%, 0.5%, and 0.7% in females in the 8th, 10th, and 12th grades, respectively.21 The Centers for Disease Control and Prevention’s 2005 Youth Risk Behavioral Surveillance (YRBS) examined the annual prevalence rates of anabolic steroid use among the US high school students from 1991 through 2005. This study noted a lifetime steroid prevalence use of 4.8% among high school males and 3.2% among high school females.22 The rates were consistently higher in males than females throughout the study period but the gender gap has narrowed in recent years. More than 300,000 high school students have used anabolic steroids and it is estimated that 3% to 7% of adolescents use these drugs.6 Studies indicate that anabolic steroid use is more common in athletes than in nonathletes.23–25 Among athletes, football players are commonly implicated but use has also been demonstrated in other sports such as gymnastics, weight training, basketball and baseball.23,24 Reasons cited for steroid use include improving athletic capability and increasing strength among athletes to improving appearance and enhancing overall well-being in nonathletes.23,25
Creatine has gained popularity as a performance-enhancing substance among adolescents. Creatine is an essential amino acid that helps supply energy to muscles and has been touted to decrease muscle fatigue and improve muscle performance. One study by Smith and Dahm surveyed 328 high school athletes between the ages of 14 and 18 years and found that 8.2% of male athletes used creatine as a supplement and the use increased with age.26 Most of those who used creatine learned of its use from a friend and purchased it in a health food store.26 In another study, more than 1000 middle and high school athletes were surveyed with 5.6% of respondents reporting use of creatine and use also increased with age.27 Studies continue to support the widespread use of supplements by athletes of all ages.28–30
Anabolic steroids or androgenic anabolic steroids, listed by the FDA since 1990 as Schedule III controlled drugs, are synthetic testosterone derivatives that are well-known in the athletic community.4–6,31,32 Testosterone was isolated in 1935 as a chemical to provide a positive effect on overall metabolism. Anabolic steroids interact with a wide variety of receptors, including glucocorticoid, progestin, estrogen, and androgen. Anabolic steroids have been used since the 1940s to improve strength in body builders and others. “Anabolic” refers to its ability to stimulate protein synthesis and “androgenic” refers to its stimulation of male secondary sex characteristics. The term “steroid hormones” or “steroids” refers to the fact that these chemicals are derived from cholesterol and are in a class that includes corticosteroids and sex hormones (i.e., progesterone, estrogen, and testosterone). Table 7-3 lists various anabolic steroids. Dianabol® was removed from the official market because of the high level of abuse associated with it.
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Anabolic steroids are taken in various regimens, typically in prolonged and very high (supraphysiologic) doses in attempts to achieve optimal pharmacologic effects. One method is called “stacking” that involves cycles of 6 to 12 weeks of high dose use and then no use, followed by more cycles of heavy use.4,7 Many use a “pyramiding” plan in which oral and injectable doses are increased over time from 10 to 100 times a physiologic or therapeutic dose and typically obtained from veterinary supplies.31 A therapeutic oral dose is one used for management of various medical illnesses, and is often 2 to 20 mg, depending on the specific steroid being prescribed. Athletes often take several agents together with doses up to 200 mg/d.
The intended purpose is to increase lean body mass and strength while some only want to improve overall appearance. Research does show that high doses of anabolic and androgenic steroids in association with adequate training and protein intake does lead to an increase in water retention, lean body mass, muscle mass, and overall body weight.4–7 These effects may be very beneficial to some athletes and are noted only if involved in intensive training regimens; otherwise the athlete may gain weight but not increase overall strength. The exact impact on the athlete’s performance based on doping with anabolic steroids is controversial and not predictable. However, the publicized use by some professional and college athletes has led many adolescents to conclude they should take them, especially those involved in wrestling, football, body building, sprinting, shot putting, discus throwing, and weight lifting.
Side effects of anabolic steroids are complex, numerous, and potentially very serious, as noted in Table 7-4.4–6,31–33 Female athletes seek to take doses of steroids that will increase muscle mass and strength but not cause masculinization. These include hirsutism and clitoromegaly that may be permanent and deepening of the voice that is permanent. Female athletes may also develop amenorrhea, skin coarseness, and male-pattern baldness. Severe acne and hair loss can be seen in both males and females.
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Gynecomastia may be seen in some males and is partly irreversible. Prostate hyperplasia can occur with possible heightened risk for the development of prostate cancer. Also noted in males are reduced levels of FSH and LH, testosterone levels, and testicular size. The reduction in testicular size is reversible, though abnormalities in germinal elements can continue for several months after stopping anabolic steroid use.
Of particular concern in the adolescent is the effect of anabolic steroids on bone growth. Early in puberty, androgens are responsible for bone growth and towards the end of puberty they are responsible for epiphyseal closure.34 As a result of the premature closure, a reduction can be observed in adult height.34 Adolescents are also at an increased risk for muscle strains or ruptures with more intense training.34
Adverse events associated with anabolic steroids include effects on the liver and range from mild to severe with the incidence varying with dosage, length of use, and agent chosen.34 The oral 17-alpha alkyated anabolic steroids have been associated with much of the hepatoxicity as noted in Table 7-4.35 Injectable anabolic steroids increase the risk for hepatitis (B and C), HIV/AIDS, and other complications from the use of nonsterile needles. There may be increased platelet aggregation, cardiac hypertrophy, myocardial infarction, and sudden death with anabolic steroid use.
The response of physicians who care for young athletes should be to educate them to the real and unacceptable dangers that anabolic steroids present, dangers that far outweigh any potential benefit to weight or strength gain.36 Anabolic steroids have been banned by the National Collegiate Athletic Association (NCAA), International Olympic Committee, and various professional sporting associations. Young adolescents who are still developing cognitive skills may not be able to appreciate the dangers of drugs taken now that will cause serious medical damage later in life. Even older athletes with “adult” thinking skills may choose the risks of such drugs for the potential of “winning at any cost” philosophy. Even coaches and trainers may be drawn into allowing harm to their athletes if it leads to a winning season while some parents may condone use of these drugs if parents conclude it will lead to a college sports scholarship or a “successful” professional sports career. Thus, society must be clearly educated to these dangers and though some of these steroids are used to treat management of wasting caused by HIV/AIDS or chronic renal failure, these drugs should not be used by athletes to improve sports performance.
Athletes who take anabolic steroids may take additional drugs to boost the anabolic effects of steroids, including androstenedione, human growth hormone (hGH), DHEA (dehydroepiandrosterone), methamphetamine, and clenbuterol.4–6 Diuretics are taken to reduce fluid retention or dilute urine in attempts to prevent a positive sports doping test. These diuretics include spironolactone, furosemide, and hydrochlorothiazide. Tamoxifen is an antiestrogen taken by athletes abusing anabolic steroids in attempts to avoid feminization effects. hCG and clomiphene are taken after the end of an anabolic steroid cycle to reduce hypogonadotrophic hypogonadism and to reduce testicular atrophy and infertility.34 ACTH (corticotrophin) is taken to increase endogenous corticosteroids to induce euphoria, while various narcotics and other illicit drugs are also abused for their euphoric effects. Additional drugs abused include stimulants, analgesics (such as oxycodone, meperidine, morphine, hydrocodone, others), antibiotics, and corticosteroids.
DHEA is a hormone produced in the adrenal glands and testicles and is converted to androstenedione or androstenediol. These are subsequently converted to testosterone and testosterone and androstenedione can further be aromatized to estrone and estradiol.37 DHEA became available in 1996 as an OTC nutritional supplement and is used by some athletes as an alternative to anabolic steroids.38 It is proposed that DHEA can increase testosterone and insulinlike growth factor (IGF-1) which have anabolic properties. DHEA has been touted to reduce fat, promote muscle mass, increase strength, and improve sexual performance, and a wide range of doses have been used, from 50 to 100 mg/d up to 1600 mg a day.4,38 Studies have not supported these claims including a study by Broeder and colleagues deemed the “Andro Project.”39 Patients took androstenedione, androstenediol (200 mg daily), or placebo along with a high-intensity resistance-training program for 12 weeks.39 The authors found that testosterone levels increased transiently but returned to baseline by 12 weeks and neither agent improved lean body mass or increased muscle strength when compared to placebo.39 They also noted that estrone and estradiol levels were significantly elevated.39 Side effects are not well known owing to few long-term studies. DHEA has been associated with irreversible virilization in women and gynecomastia in men.38 Theoretically, high doses could lead to excessive androgen levels and produce the same side effects as anabolic-androgenic steroids.38 DHEA is banned by many sporting organizations.
Androstenedione is an androgen that is a precursor of testosterone, dihydrotestosterone, estrone, and estradiol and is produced in the adrenal glands and testes.4,7 It was legally available until 2004 when the Anabolic Steroid Control Act was enacted. Because of the potential for serious health adverse events of androstenedione that were similar to anabolic-androgenic steroids, androstenedione was placed into scheduled III controlled substance.38–40 DHEA was not added because of claims by the lobbyists that it was effective as an antiaging substance and had minimal risks.38–40 Androstenedione is taken as a “T-booster” and used to raise testosterone (“T”) levels and increase muscle mass using high doses such as 100 to 300 mg/d and also used 60 minutes before a sports event.
Androstenedione is taken in a pill form in the US and nasal form in Europe, often in combination with different anabolic steroids in various cycling patterns. As with DHEA, androstenedione does not effectively raise testosterone levels nor increase lean body mass, muscle strength or improve performance.38 Androstenedione has a similar side effect profile compared to anabolic steroids. It is banned by most sporting organizations and should not be taken by growing individuals or those at risk for breast cancer and prostate cancer.4,7 Despite the fact that androstenedione can no longer be produced as a dietary supplement, it remains a popular sports doping drug, though use among high school students in the United States has dropped since 2001.121
Growth hormone is secreted from the pituitary gland in a pulsatile fashion that varies with gender and age.40,41 Concentrations are higher in neonates and during puberty and are positively influenced during slow wave sleep, exercise, hypoglycemia, amino acid intake (leucine and arginine), increased temperature, and stress.40,42 Growth hormone leads to the production of IGF-1, which mediates the anabolic actions of growth hormone.40 This results in increased total body protein turnover and muscle mass.40 Despite a lack of evidence to support, hGH is claimed to have anabolic effects that increase lean body mass and decrease fat mass.40 It is also purported to enhance performance within endurance and power sports.40,43 As a doping agent, hGH is often used in combination with anabolic steroids in power sports or with erythropoietin in endurance sports because of their theoretical synergistic effect.44 The use of chronic, high doses by athletes has the potential to lead to significant side effects ranging from infection (caused by nonsterile needles) to hypertension, insulin resistance, osteoarthritis, and visceromegaly to name a few.40,45,46 hGH is difficult to detect in those using it, and hGH bought from the black market may contain growth hormone obtained from human pituitary glands and increases the risk for disease transmission.40 Its exorbitant cost, at $3000 or more per month, still does not prevent its widespread illegal use.4,7
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