The drive toward success in sports and the need for a cosmetically acceptable appearance have driven many adolescents to take a wide variety of so-called doping substances. The consumption of these chemicals in the hope and hype of improved sports performance, fueled by the easing of government restrictions on their proof of safety and efficacy, has resulted in an explosion of so-called ergogenic products available to our youth. Agents that have been used include anabolic steroids, anabolic-like agents, designer steroids, creatine, protein and amino acid supplements, minerals, antioxidants, stimulants, blood doping, erythropoietin, β-blockers, and others. The use of these agents has considerable potential to cause physical and psychological damage. Use and misuse of drugs in this sports doping process should be discouraged. This discussion reviews some of the agents that are currently being used. Clinicians providing sports medicine care to youth, whether through anticipatory guidance or direct sports medicine management, should educate their young patients about the hype and hyperbole of these products that may keep them out instead of in the game at considerable financial cost to the unwary consumer.
“He (it) cures most successfully in whom the people have the greatest confidence.”
( Galen, 180 ad )
For thousands of years, humans have sought the use of medicines, herbs, and other chemicals to improve their lives in various ways. Some scholars have interpreted the story of Adam and Eve in Genesis (chapter 3) as a story of the original humans seeking to be strong (wise) like God. Extensive pharmacopoeias have been developed in China and India over the past eons. The first classifier of medicinal herbs is noted by historians as the Chinese emperor Shen-Nung 2737 bc , and there is a classic recorded painting of him holding Ephedra (machuang) leaves. An early historical record of medical treatments is the Ebers Papyrus (1500 bc ), which lists more than 700 medicines of various origins (mineral, vegetable, and animal).
In recorded history, competitive athletes have used various mixtures of animal and plant origins, taken from known and unknown products, in attempts to improve their athletic performance and gain the perceived benefits of victory. For example, athletes during the Greek and Roman Games used wines, mushrooms, and opioids; stimulants (ie, strychnine) were popular at the beginning of the twentieth century. Galen, the famous Greek who became the physician to the gladiators of ancient Rome, observed the belief of athletes of his time (180 ad ) that consuming mushrooms and herbal teas was beneficial to their overall performance. In 1886, a cyclist died during a race in France because of a stimulant overdose. Such sports doping practices have continued in advocates of sport and others to the present age, even though such practices have been banned by sports officials. For example, the death of a British athlete at the Tour de France in 1967 was attributed to the use of amphetamines complicated by a state of dehydration, and 9 riders were ruled ineligible for the Tour de France in 2006 because of suspected sports doping.
Athletes of old and of today have been willing to take various chemicals even without any proof of their benefit, in hope of improving their general health or their sports performance. Over thousands of years, athletes have consulted experts from the ancient days of sorcery and alchemy to modern-day biochemistry and pharmacology to find effective yet safe performance-enhancing drugs. The milieu of “victory at any cost” that existed millennia ago continues to the present. In 1982, Goldman and colleagues asked 198 world-class athletes if they would take a chemical that would guarantee them success but would lead to their death in 5 years; in this survey, 52% reported they would take this chemical and this report remained at this level in repeat surveys between 1982 and 1995. Connor and Mazanov posed this Faustian bargain to members of the general public in Australia; they noted that only 2 of the 250 individuals surveyed agreed to take such a chemical. These sagacious members of the general public were not obsessed with victory at any cost.
As we enter a new millennium and century, it is sobering to realize that only a handful of the thousands of available herbal remedies of old or of modern chemistry have been shown to actually work as prescribed to better one’s health. Proof of improving sports performance with various chemicals (including herbs) is even more limited. Yet, today’s athletes are taking various products in ever-increasing numbers because they are driven to succeed to obtain the perceived glories of winning in contemporary society.
Agents that have been used in the hope of winning the game of sports and the game of life include anabolic steroids, anabolic-like agents, designer steroids, creatine, protein and amino acid supplements, minerals, antioxidants, stimulants, blood doping, erythropoietin, β-blockers, sodium bicarbonate and others Tables 1 and 2 . For example, a survey of 13,914 college athletes published in 1997 noted a significant intake of creatine (13%), amino acids (8%) and dehydroepiandrosterone (DHEA) (1%). Supplement use in athletes ranges between 40% and 60%. The teenage athlete should be carefully counseled that there are few substances (if any) that consistently and safely improve the performance of a well-trained individual. Also, the use of these agents has considerable potential to cause physical and psychological damage. Misuse of drugs in this manner (or the sports doping phenomenon as it is called) should be discouraged. This discussion reviews some of these agents that are used. Our sports youth live in a modern-day Faustian dilemma often with the encouragement of coaches, trainers, parents, the media, and other members of society obsessed with success at any price.
| Serve as an energy source |
| Decrease fatigue in sports events |
| Increase lean body mass and strength |
| Decrease adipose tissue |
| Alter weight in desirable directions |
| Improve aerobic capacity |
| Enhance motor capacity |
| Improve appearance |
| Enhance overall sports performance |
| α-Lipoic acid |
| Anabolic steroids (DHEA, androstenedione) |
| Antioxidants (vitamin C, vitamin E, β-carotene) |
| Amphetamines |
| Bee pollen |
| β-blockers (ie, propranolol) |
| β-Hydroxy-β-methylbutyrate |
| Blood |
| Caffeine |
| Calcium |
| Carnitine |
| Choline |
| Chrysin |
| Chromium |
| Clenbuterol |
| Coenzyme Q 10 |
| Creatine |
| DSMO |
| Diuretics (furosemide, spironolactone, hydrochlorothiazide) |
| Engineered dietary supplements |
| Ephedrine |
| EPO |
| Folic acid |
| Ginkgo biloba |
| Ginseng |
| Glycerol |
| hGH |
| Inosine |
| IGF-I |
| Iron |
| Minerals: Boron Chromium Vanadium Iron Selenium Zinc |
| Niacin |
| Nicotine |
| Nonsteroidal antiinflammatory drugs (ibuprofen, mefenamic acid, naproxen, others) |
| Omega-3 fatty acids |
| Oxygen |
| Pantothenic acid |
| Phosphorus |
| Pyridoxine (vitamin B 6 ) |
| Plant steroids (phytosteroids; γ-oryzanol; ferulic acid [FRAC]) |
| Protein supplements |
| Riboflavin |
| Sodium bicarbonate |
| Sport drinks |
| Thiamin (vitamin B 1 ) |
| Tribulus terrestris |
| Vitamin supplements |
| Vitamin B 12 (cyanocobalamin) |
| Vitamin B 15 (dimethylglycine) |
| Yohimbine (yohimbe) |
| Others |
| Various illicit drugs Alcohol. marijuana, tobacco, methamphetamine, cocaine, GHB; GBL Hallucinogens (lysergic acid diethylamide and phencyclidine·HCl) Barbiturates, opiate narcotics, inhalants (volatile solvents, nitrous oxide, nitrites) |
Protection for consumers
Some progress was made in the twentieth century to help consumers understand whether or not the medications or chemical agents they take are beneficial and safe. In 1906, the Pure Food and Drug Act required foods and drugs, which were sent between various states, to be provided with accurate labels. It was not required that medications be tested for safety until the 1938 Federal Food, Drug and Cosmetic Act (FFDCA). It was also not required that these drugs be proven effective for their intended use until the 1962 Harris-Kefauver Amendment of the FFDCA. However, the 1994 Dietary Supplement Health and Education Act (DSHEA) reversed some of these gains acquired over the previous 88 years. DSHEA allowed products classified as dietary supplements to avoid the scrutiny applied to drugs or medications. Thus, manufacturers of dietary supplements (defined as a vitamin, mineral, herb, other botanic, amino acid, metabolites of these products, related metabolites, related concentrations, or extracts or combinations) do not need to prove safety or efficacy of their products. All that is needed is to note that their products “maintain health or normal structure and function.”
This has opened up the commercial floodgates to various agents used by athletes in the hope that the products they use are ergogenic (see Table 1 ). It is important for physicians and medical educators to be aware of these various products and to be willing to provide education to society and their patients about what is known and not known about these products. With the legal floodgates open and the continuing drive for success in sports at any cost that permeates society in the United States and the world, Americans spent more than US$12 billion on dietary supplements in 1999.
Research on these products remains limited and athletes rely on word of mouth from fellow sports enthusiasts, coaches, nutrition store personnel, advertisements, and other unscientific sources for information on what drugs, herbs, or other available agents will help them improve their athletic performance or their lives in general. Most research has been done on adult men, who are involved in competitive athletics and not on teenage athletes. The potency and purity of nutritional agents are not known and the long-term effects of these various substances are also unknown at present. However, the use of ergogenic agents remains popular, and more than 30,000 individual commercial products are available throughout the world. Unproven claims (see Table 1 ) remain while the hope of victory burns strong in athletes of all ages whether competing at the high school (or below) level or at the Olympic level of competition.
Definitions
The term doping is derived from the Dutch word “dop” in reference to the practice of providing race horses with an opium mixture to act as a stimulant and enhance victory of the competing animal. Sports doping refers to the attempt of improvement or stimulation of sports performance in Homo sapiens in the eternal quest for victory at any cost. The promise of having a drug that is a true sports doping chemical often belies an eternal quest for the product having an ergogenic quality, and this term is derived from the Greek words érgon (to work) and gennan (to produce).
Definitions
The term doping is derived from the Dutch word “dop” in reference to the practice of providing race horses with an opium mixture to act as a stimulant and enhance victory of the competing animal. Sports doping refers to the attempt of improvement or stimulation of sports performance in Homo sapiens in the eternal quest for victory at any cost. The promise of having a drug that is a true sports doping chemical often belies an eternal quest for the product having an ergogenic quality, and this term is derived from the Greek words érgon (to work) and gennan (to produce).
Anabolic steroids
Anabolic steroids or anabolic-androgenic steroids (AAS ) are a class of chemicals that are synthetic derivatives of testosterone and represent a drug class often abused by adolescent and adult athletes. The roots of their use can be traced over 6 millennia ago when ancient farmers noted the quieting or passive effects that castration had on animals. Testosterone was isolated in 1935 and developed to improve metabolism; it was used by athletes to gain strength as early as the 1940s. Concern over the use of anabolic steroids by athletes led to an inaugural definition of sports doping by the International Olympic Committee (IOC) in 1964, the banning of these drugs by the IOC, the start of antidoping programs by the IOC in 1967, and the first official testing for these chemicals at the 1976 Montreal Olympic Games.
The term anabolic refers to the stimulation of protein synthesis, whereas androgenic implies the stimulation of male secondary sex characteristics. The terms steroids or steroid hormones refer to chemicals that are derived from cholesterol and include corticosteroids and sex hormones (ie, testosterone, estrogen, and progesterone). Anabolic steroids stimulate several receptors: androgen, estrogen, progestin, and glucocorticoid. Some examples of oral and injectable anabolic steroids are listed in Table 3 . The US Food and Drug Administration (FDA) has classified these chemicals as Schedule II drugs since 1990. Dianabol has been discontinued because of the high level of abuse noted by athletes. Adequate training and protein intake are necessary for maximal effect on protein synthesis in muscle tissue and the individual response is variable. Anabolic steroids have become the sine qua non of the Faustian bargain awaiting our youth.
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Epidemiology
It is clear that many youth try anabolic steroids including one-third who are not athletes. Various studies over the past few decades confirm that 5% to 11% of high school boys and 0.5 to 2.5% of high school girls in the United States have tried anabolic steroids; of these, 50% used these chemicals before 16 years of age and 33% of these youth were not athletes. Approximately 80% of male bodybuilders and 40% of female body builders use these drugs in contrast to 20% of college athletes; 38% of users try the injectable forms. The mean start age is about 14 years with a range of 8 to 17 years. One study looked at 1881 high school students in Georgia and noted that 5.3% of ninth grade boys and 1.5% of ninth grade girls claimed they use or had used anabolic steroids. A 1988 study of 3403 high school seniors nationally indicated that 6.6% responded they were or had used these chemicals; 38.3% were less than 16 years of age; of these, 47.1% indicated that the main reason for using these drugs was to improve their sports performance. The 2008 Monitor the Future Study noted the annual prevalence rates had dropped; for boys in the 8th, 10th, and 12th grades, it was 1.2%,1.9%, and 2.7%, respectively versus 0.6%, 0.5%, and 0.7% for girls. Several decades of research suggests a lifetime prevalence of 4% to 6% with teenage boys and 1.5% to 3% for teenage girls.
These youth have limited knowledge of the dangers of these drugs. Abuse of these chemicals may be increased in the nonathletic population versus the athletic adolescent population. Adolescents who take anabolic steroids may also be involved in other high-risk behaviors, including illicit drug use such as cocaine, alcohol, cigarettes, marijuana, smokeless tobacco, and various injectable drugs. Adolescents obtain these drugs from many sources, even from veterinary suppliers. Unless they have been banned (as in Olympic competition) and drug testing is in force, anabolic steroids are popular with all athletes. Although abuse of anabolic steroids by American professional athletes has decreased somewhat in recent years, the use of these and other drugs by famous athletes has long encouraged teenagers to try these substances. Youth often believe that these chemicals are natural hormones and are endorsed by their sports heros. Many teenagers are convinced that these drugs are valuable and worth any risk, even in very high doses.
Oral anabolic steroids are 17α-alkylation chemicals that slow liver inactivation and cause much of the liver side effects of these drugs. The injectable forms are from 19β-esterification processes and pose infectious disease risks, including hepatitis (B and C) and human immunodeficiency virus (HIV)/AIDS. The therapeutic doses of such drugs as used for treatment of various medical disorders are 8 to 30 mg depending on the particular drug being used. Because teenage athletes are often not afraid (nor informed) of risks, they may use prolonged and heavy (supraphysiologic) doses. They may use these drugs in various combinations in a method called stacking, that is, cycles of 6 to 12 weeks on and then off. In 1 study, 18.2% used only 1 cycle, whereas 38.1% used oral and injectable anabolic steroids. Increasing a drug dose in a cycle is called pyramiding, and doses may be 10 to more than 40 times the usual therapeutic doses. While taking several drugs together (ie, stacking), some athletes use up to 200 mg per day. These athletes may not have any fear of side effects in their quest for ergogenic qualities or even in attempts to simply improve appearance.
Effects
Athletes use anabolic steroids in the hope of increasing lean body mass, strength, and/or aggressiveness; as noted, some only wish to improve appearance. Athletes at particular risk for the use of anabolic steroids include those engaged in sports such as weight lifting, shot putting, discus throwing, bodybuilding, sprinting, football, and wrestling. If athletes take high doses of anabolic steroids while undergoing heavy resistance training, there may be an increase in body weight (with increased water retention) and lean muscle mass. One controlled study looked at adult men taking 600 mg of intramuscular testosterone and noted that they gained significant size and strength. However, not all studies agree and the exact effects of anabolic steroids are complex and not fully defined. The effect of training is important because healthy volunteers who take these drugs without training show no increase in muscle strength or muscle size. Some experiments have noted that inexperienced weight lifters who take anabolic steroids may experience an increase in body weight but not strength. Whether or not athletes get a significant increase in athletic performance remains controversial, and individualized results are the norm.
Adverse Effects
Side effects of anabolic steroids are legion and reviewed in Table 4 . Addiction to anabolic steroids may occur. One study of 164 steroid users identified 28% as being dependent on these drugs. The maturation process may be accelerated in growing athletes with possible early closure of epiphyses and shortened ultimate adult height. An increase in tendon injuries has also been reported in teenagers on anabolic steroids. Liver complications are many and are related to the oral alkylated forms; these adverse effects include increase in liver function tests, peliosis hepatitis, cholestasis, hepatic failure, and hepatic neoplasms (benign and malignant). Risks for cardiovascular disorders occur, including hypertension, reports of cardiomyopathy, and various thrombogenic phenomena such as myocardial infarctions, cerebrovascular accidents, and sudden death.
| Fluid retention |
| Masculinization of females Hirsutism Clitoromegaly Alopecia (males also) Voice deepening |
| Other changes for females Amenorrhea Skin coarseness Acne (both sexes; can be severe) |
| Growing athletes: Acceleration of maturation Early epiphyseal closure Shortened ultimate adult height Increase in tendon injuries |
| Psychological changes See increase in: Aggressiveness Irritability Depression |
| Gastric ulcers |
| Liver complications Increase in liver function tests Cholestasis Peliosis hepatitis Liver failure Benign liver neoplasm Malignant liver tumor (hepatocellular carcinoma) |
| Hyperglycemia (hyperinsulinemia) |
| Prostatic enlargement (possible increase risk for prostatic cancer) |
| Decrease in glycoproteins (follicle-stimulating hormone and luteinizing hormone) with: Decreased spermatozoa Decreased testosterone levels Reduction in testicular size |
| Increase in tendon injuries |
| Reduction in high density lipoprotein, increased total cholesterol |
| Increased platelet aggregation, potential rise in cardiovascular disorders |
| Wilms tumor (at least 1 case report) |
Masculinization of females may occur with changes such as hirsutism and clitoromegaly, both of which may be permanent; deepening of the voice is an irreversible effect of anabolic steroids in females. Amenorrhea, male-pattern baldness, and skin coarseness may also be seen in women; the skin changes may be permanent. Female athletes try to get a high enough dose to get the expected or desired results on muscle mass, but low enough to prevent unwanted side effects such as masculinization. Hair loss and severe acne may be seen in both sexes. Males may develop gynecomastia (partly irreversible) and prostatic enlargement (with possible increased risk for prostatic cancer). The reduction in testicular size is reversible, but abnormalities of germinal elements can persist for several weeks after cessation of anabolic steroids.
Use of Additional or Concomitant Doping Agents
Users of AAS may use other drugs as well. For example, they may use human growth hormone (hGH), methamphenamine, or clenbuterol (see later discussion) to augment the anabolic effects of AAS. Human chorionic gonadotropin (HCG) may be added to raise testosterone synthesis and counter the anabolic steroid-induced effect of testicular atrophy. Diuretics (eg, furosemide, spironolactone, hydrochlorothiazide) may be used to reduce fluid retention, produce the desired rippled look, or dilute urine to subvert a drug-screening regimen. The use of diuretics to lose weight quickly is not an unusual plan of wrestlers. The use of such medications can result in increased weakness such that a wrestler can be injured by competing against a stronger opponent. Electrolyte dysfunction and other medical side effects of diuretics may complicate the picture. Pulmonary embolism has been reported in a high school wrestler using such a regimen.
Stimulants may be taken along with AAS to increase the drive for exercise and competition, whereas anti-acne medications are used to deal with the anabolic steroid-induced acne. Antiestrogens (as tamoxifen or clomiphene) may be used to prevent male feminization effects (ie, gynecomastia) of anabolic steroids. These athletes may use other drugs as well in the course of their training, such as antibiotics, corticosteroids (ie, prednisone), and analgesics (eg, morphine, propoxyphene, meperidine, oxycodone, and others). Narcotics and other illicit drugs are abused for their pleasure-granting effects as well. Corticotrophin (ACTH) is used to raise levels of internally produced corticosteroids and to produce a sense of euphoria.
Prevention
The use of anabolic steroids poses significant risks to the user/abuser and these chemicals have been banned by the (IOC), the National Collegiate Athletic Association (NCAA), the National Football League (NFL), and many other sporting associations. However, it is often difficult for the adolescent user to stop because many young people have difficulty understanding the consequences of their actions (concrete thinking) and have difficulty avoiding the win-at-all-cost attitude prevalent in the global sports milieu. It is important to educate youth about these sports doping agents. Parents and coaches must be taught about these chemicals and they should not encourage the use of such potentially dangerous chemicals under the guise of “Winning is Everything!” Goldberg and colleagues have introduced the ATLAS model or the Adolescent Training and Learning to Avoid Steroids Program with some success.
Although there may be some medical indications for these drugs (ie, treatment of HIV-associated wasting or chronic renal failure), seeking to improve sports performance should not be one of the medical indications to use these drugs. Guidelines for following athletes who insist on taking anabolic steroids are provided by Blue and Lombardo. The effort to ban anabolic steroids has now been complicated with the appearance of designer steroids, the first of which was norbolethone that was initially detected by a laboratory in Los Angeles in 2002. Other identified designer steroids include madol (desoxy-methyl testosterone) and tetrahydrogestrinone. Unfortunately, experts and amateurs in the biochemistry industry continue to produce such drugs, and the cat and mouse game between sports dopers and sports officials will continue in perpetuum.
Other Anabolic-like Agents
DHEA
DHEA is a mildly androgenic hormone naturally produced in the adrenal glands and testes. It is the precursor to testosterone (as well as dihydrotestosterone) and estrogen. Although DHEA is banned by the FDA and has no proven ergogenic effects, it is used by athletic teens and adults as an alternative to anabolic steroids. The ergogenic attempt is based on a hope and hype that DHEA will increase testosterone and an anabolic insulin-like growth factor (IGF-I). Despite animal studies having shown some DHEA-induced liver toxicity, it is marketed to adults (middle-aged and older) as an over-the-counter alternative to anabolic steroids with additional unproven claims of promoting euphoria, enhancing libido, delaying cardiovascular disease, preventing cancer, and boosting one’s immunity. Research is limited on DHEA. One study evaluated men (average age 24 years) who used 1600 mg per day for 4 weeks; serum testosterone levels were not altered. Another study called the Andro Project also noted no ergogenic qualities of DHEA.
DHEA is given at a dose of 50 to 100 mg per day for 6 to 12 months in oral or injectable forms, up to 1600 mg. Side effects may occur as with ingestion of sex hormones. At doses of more than 100 mg/day, gynecomastia (irreversible) in men and hirsutism in women can occur; cancer (prostate or endometrial) may be worsened. DHEA should be considered as an anabolic steroid and teenagers should be advised not to use it. The FDA has ruled it has no medical usage, and it has been banned by the National Hockey League, the IOC, the NFL, among others ( Tables 5 and 6 ).
