REVIEW ARTICLE

Sports Medicine 12 (4): 250-265, 1991 0112.1642/91/0010-0250/$08.00/0 © Adis International Limited. All rights reserved. SP0152

Enhancement of Athletic Performance with Drugs An Overview Jon

C. Wagner

College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA

Contents 250 251 251 251 252 255 255 256 256 257 257 259 260 260 260 261 261 261 261 261 262 262

Summary

Summary 1. Drug Use in Athletes 1.1 Historical Perspective 1.2 Epidemiology 1.3 Classification of Drug Use in Athletes 2. Stimulants 2.1 Amphetamines 2.2 Caffeine 2.3 Cocaine 2.4 Other Sympathomimetic Drugs 3. Anabolic Steroids 4. Human Growth Hormone 5. Erythropoietin 6. Narcotic Analgesics 7. Alcohol 8. Marijuana 9. Tobacco 10. Miscellaneous Drugs 10.1 ,1-Blocking Agents 10.2 Diuretics 10.3 Nutritional Supplements 11. Conclusions

Drug use among athletes has become a recognised problem in sports. Athletes may use drugs for therapeutic indications, for recreational or social reasons, as ergogenic aids or to mask the presence of other drugs during drug testing. Stimulants were some of the first drugs used and studied as ergogenic aids. Amphetamines may increase time to exhaustion by masking the physiological response to fatigue. Caffeine may improve utilisation of fatty acids as a fuel source thereby sparing muscle glycogen. Cocaine and other sympathomimetic drugs have little or no effect on athletic performance. Anabolic steroids appear to have the potential to increase lean muscle mass and strength under certain conditions. Human growth hormone may also be used for an anabolic effect, but data on this effect are lacking. Erythropoietin may represent a pharmacological alternative to blood doping by increasing red blood cell mass. The use of narcotic analgesics is not necessarily ergogenic but can be harmful if used to allow participation of an athlete with a severe injury.

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251

According to the American College of Sports Medicine alcohol does not possess an ergogenic effect. However, it may be used to reduce anxiety or tremor prior to competition. Marijuana does not increase strength. Tobacco products may produce psychomotor effects or control appetite which may be beneficial to some athletes. Other drugs used by athletes include fJ-blocking agents, diuretics, and a variety of nutritional supplements. In addition, diuretics and probenecid may be taken to mask drug contents in the urine. Whether the ergogenic effects are real or perceived, the potential for adverse effects exists for all of these drugs. Potential health complications represent a serious risk to an otherwise healthy population. Further research on the long term health risks in athletes taking ergogenic drugs is needed.

For as long as humans have participated in sp6rts, athletes, coaches and trainers have searched for ways to improve performance. This has led to discoveries in optimal training methods. Unfortunately, the search has also led to experimentation with a wide variety of drugs. Today, the use and abuse of drugs in athletics has been implicated at virtually every level of competition. Once thought to be limited to only elite athletes, drug use has been reported in high school athletes and even noncompetitive individuals (Duda 1985; Murphy 1986). Public awareness of this type of drug misuse has been increased by the drug-related deaths of several well-known athletes and the intense media coverage of the disqualification of Canadian sprinter Ben Johnson at the 1988 Summer Olympics in Seoul. This awareness appears to be evolving into a public concern. This concern has been translated in the US into mass media attention on performance drugs, especially anabolic steroids, and tougher laws for the use and distribution of these drugs.

1. Drug Use in Athletes l.l Historical Perspective

Drug use in athletes is not a recent development. Ancient Greeks in the third century consumed herbs and mushrooms in an attempt to improve athletic performance (Murray 1983). In the late nineteenth century, European cyclists took substances to reduce fatigue during endurance events. Caffeine-based sugar cubes dipped in nitroglycerin (glyceryl trinitrate) were taken prior to

competition. Another popular concoction was a mixture of coca leaves and wine called vin mariani (Murray 1983). By the 19505 powerful drugs replaced these crude preparations. Amphetamine use was first suspected at both the Summer and Winter Olympics in 1952 (Murray 1983). Stimulant use became so widespread that later that same decade the American Medical Association established a special committee to investigate the effects of amphetamines on athletic performance (Karpovich 1959; Smith & Beecher 1959). At about this same time athletes from the Soviet Union and the United States began experimentation with anabolic steroids (Murray 1983). Despite the increased scrutiny from sports officials and medical researchers, drug use by athletes continued. Amphetamine use was linked to the deaths of 2 cyclists, one during the 1960 Summer Olympics in Rome and the other in the 1967 Tour de France (Murray 1983; Thomason 1982). As drug use became more common, the International Olympic Committee (IOC) in.stituted drug use control measures at the 1968 Olympic Games. During the 1980s athletes continued to make headlines for on and off the field drug exploits. At the 1983 Pan American Games in Caracas 19 athletes were disqualified for drug use. A number of other athletes withdrew from competition rather than risk being tested (Murray 1983). 1.2 Epidemiology Only recently has the epidemiology of drug misuse among athletes been examined. In 1984, re-

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Tabla I. Substance abuse patterns in college student athletes

from 1985 to 1989. Adapted from Anderson and McKeag (1985, 1989) 1985

1989

Number of athletes surveyed 2049 Ergogenic drug use in previous year (%) Amphetamines 8 Anabolic steroids 4 Barbiturates 2 Major analgesics 28 Weight loss products n/a Social drug use in previous year (%) Alcohol 88 Caffeine 68 17 Cocaine/crack Psychedelics 4 Marijuana 36 Smokeless tobacco 20

2282

Abbreviation: n/a

3 5 2 34 5 89 64 5 4 28 28

= not assessed.

searchers at Michigan State University conducted a study looking at the substance abuse habits of collegiate athletes. The study, which was requested by the National Collegiate Athletic Association (NCAA), surveyed athletes from 5 men's and 5 women's sports, participating at all levels of competition. The results showed that student athletes abused a variety of ergogenic and recreational drugs and in most cases began drug use before entering college (Anderson & McKeag 1985). A follow-up study conducted in 1989 showed similar results (Anderson & McKeag 1989) [table I). Recent surveys on anabolic steroid use by high school students have revealed an apparent incidence of anabolic steroid use ranging from 6.6 to ILl % (Buckley et a1. 1988; Johnson et a1. 1989). Buckley and colleagues (1988) also found that nearly 40% of grade 12 male students who use or have used steroids reported first time use by the age of 15 years. In addition, 42.2% of respondents used these drugs for reasons unrelated to athletic performance. Reasons cited included (in order of prevalance) improving appearance, preventing or treating sports-related injuries and social use (Buckley et a1. 1988). In the study by Johnson et a1. (1989) which included female athletes, only 5 of914 women surveyed admitted to anabolic ster-

oid use. The results of these studies plus reports in the lay press suggest that athletes at an early age may consider the use of a number of drugs.

1.3 Classification of Drug uSe in Athletes The use of drugs by athletes can be divided into 4 categories: (a) therapeutic drug use; (b) recreational drug abuse; (c) performance-enhancing or ergogenic drug use; and (d) the use of drugs to mask the presence of other drugs in the urine. Individual drugs cannot be so easily categorised. For example, amphetamines, which are commonly referred to as a recreational drug, may be taken as a performance aid by some athletes. Some athletes may require drug therapy for a legitimate medical indication. Because of the overlap between therapeutic and ergogenic drugs, drug products must be carefully selected in athletes who compete at events where drug testing measures are in place. Drugs such as decongestants, which are common to many nonprescription cold and flu products, are included on some lists of banned drugs. For this reason coaches, trainers, medical staff and the athletes themselves should become familiar with any applicable list of banned substances. The lists of substances banned by the IOC and NCAA may be found in tables II and III. The use of non-performance-enhancing drugs or illicit drugs of abuse by athletes has also received public attention. Clearly, athletes are not exempt from the factors which contribute to drug abuse in the general population. In addition, factors unique to the athlete may place them at an increased risk for drug abuse. The elite or professional athlete's lifestyle of high visibility, high income, frequent travel and considerable amount of idle time have been cited as possible risk factors (Lombardo 1986; Wadler & Hainline 1989). For younger athletes, the added pressures of athletic success on top of academic and social demands could lead to drug abuse as a coping behaviour. The importance of athletic success in adolescents can lead to significant stress (Waitley et a1. 1983). The connection between athletics and alcohol promotion has also been mentioned as potentially

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Athletic Performance and Drugs

contributing to alcohol abuse among young athletes (Wadler & Hainline 1989). Ergogenic drug use or doping as it is often referred to, is defined by the IOC as the administra-

tion of or use by a competing athlete of any substance foreign to the body or of any physiological substance taken in abnormal quantity or taken by an abnormal route of entry into the body with the

Table II. Drugs banned by the International Olympic Committee - 1990 Stimulants

Narcotic analgesics

,/I-Blockers

Amlepramone

Alphaprodine

Acebutolol

Anileridine Buprenorphine Codeine

Alprenolol Atenolol Labetalol

Dextromoramide Dextropropoxyphen

Metoprolol Nadolol

Diamorphine (heroin) Dihydrocodeine

Oxprenolol Propranolol

Chlorphentermine

Dipipanone

Sotalol

Clobenzorex

Ethoheptazine

and related compounds

Clorprenaline

Ethylmorphine

Cocaine

Levorphanol Methadone

Diuretics Acetazolamide

Morphine Nalbuphine

Amiloride Bendrollumethiazide (bendrolluazide) Benzthiazide

(diethylpropion) Amletaminil Amiphenazole Amphetamine Benzphetamine Caffeine8 Cathine

Cropropamide Crothetamide Dimetamletamine Ephedrine Etaledrine Ethamivan Etilamletamine Fencamlamin Fenetylline Fenproporex Furfenorex Melenorex Methamphetamine Methoxypenamine Methylephedrine Methylphenidate Morazone Nikethamide Pemoline Pentetrazol (Ieptazol) Phendimetrazine Phentermine Phenylpropanolamine Pipradol Prolintane Propylhexedrine Pyrovalerone

Pentazocine Pethidine (meperidine) Phenazocine Trimeperidine and related compounds Anabolic steroids Bolasterone Bondenone Clostebol Dehydrochlormethyltestosterone Fluoxymesterone Mesterolone Methenolone Methyltestosterone Nandrolone Norethandrolone Oxandrolone Oxymesterone Oxymetholone Stanozolol Testosteroneb and related compounds

Strychnine and related compounds a

II urine concentration exceeds 12 mg/L.

b

II ratio 01 total urine concentration 01 testosterone to epitestosterone exceeds 6.

Bumetanide Canrenone Chlormerodrin Chlorthalidone Diclolenamide Ethacrynic acid Furosemide (Irusemide) Hydrochlorothiazide Mersalyl Spironolactone Triamterene and related compounds Peptide honnones and analogues Chorionic gonadotrophin Corticotrophin Growth hormone Erythropoietin

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Table III. Drugs banned by the National Collegiate Athletic Association - 1989-1990

Psychomotor and eNS stimulants Amfepramone (diethylpropion) Amiphenazole Amphetamine Bemigride Benzphetamine Caffeine 8 Chlorphentermine Cocaine Cropropamide Crothetamide Dimethylamphetamine Doxapram Ethamivan Ethylamphetamine Fencamfamine Meclofenoxate Methamphetamine Methylphenidate Nikethamide Pemoline Pentetrazol (Ieptazol) Phendimetrazine Phenmetrazine Phentermine Picrotoxine Pipradol Prolintane Strychnine and related compounds a b c

Anabolic steroids Boldenone Clostebol Dehydrochlormethyltestosterone Fluoxymesterone Mesterolone Methenolone Methandienone Nandrolone Norethandrolone Oxandrolone Oxymesterone Oxymetholone Stanozolol Testosterone b and related compounds Substances banned for specific sports

Diuretics Acetazolamide Bendroflumethiazide (bendrofluazide) Benzthiazide Bumetanide Chlorothiazide Chlorthalidone Ethacrynic acid Flumethiazide Furosemide (frusemide) Hydrochlorothiazide Hydroflumethiazide Methylclothiazide Metolazone Polythiazide Quinethazone Spironolactone Triamterene Trichlormethiazide and related compounds

Rifle

Alcohol Atenolol Metoprolol Nadolol Pindolol Timolol

Street drugs Heroin MarijuanaC

and related compounds

THC (tetrahydrocannabinol)C

Propranolol

If urine concentration exceeds 15 mg/L. If ratio of total urine concentration of testosterone to epitestosterone exceeds 6. If urine concentration of the metabolite exceeds 25 I"g/L.

sole intention of increasing in an artificial manner his/her performance in competition (United States Olympic Committee 1988). This definition not only prohibits use of drugs believed to enhance athletic performance but also includes methods such as blood doping. The procedure of blood doping involves removing an athlete's red blood cells and transferring them back into the athlete prior to competition. The resultant rise in red blood cell mass is thought to improve oxygen consumption and ultimately endurance (Ekblom 1987). Depending upon the desired effect, athletes may

use an ergogenic drug as part of a training regimen or during competition. Drugs such as anabolic steroids which are used to increase muscle mass and strength may be taken well before competition and not even exist in detectable amounts in the athlete's body during competition, whereas drugs such as amphetamines may be taken immediately prior to competition to provide a short duration of strength or speed. Whether drugs can produce meaningful changes in performance is often debated. Because performance in sport may also be the result of factors such

Athletic Performance and Drugs

as skill level, opponent's skill level, playing conditions and psyche, concluding that drugs produce a definite cause-and-effect relationship to overall performance is difficult (Lombardo 1986). Ergogenic drugs, however, may potentially effect individual physiological components of performance. Muscle mass, strength, speed and aerobic capacity are measurable. Changes in these components could impact overall performance. This would suggest that athletes participating in individual I-dimensional sports such as running, throwing and lifting events may benefit more from ergogenic drugs than athletes in multidimensional team sports. However, based on the widespread nature of ergogenic drug use, athletes from a variety of sports must sense a real or perceived effect. The most recent addition to the classifications of drug use in athletics is masking agents. With the increasing use of drug testing at athletic events, athletes have begun searching for ways to avoid detection. Diuretics may be used to reduce the concentration of othet drugs in the urine by increasing the rate of excretion by the kidneys (United States Olympic Committee 1988). Probenecid, a drug used to treat gout, is thought to block renal elimination of anabolic steroids in the same manner as it delays excretion of penicillins. In response to these attempts to modifY urine contents, athletic organisations have added diuretics and probenecid to their lists of banned drugs (Wagner 1989). The ergogenic potentials and adverse reaction profiles are discussed below.

2. Stimulants 2.1 Amphetamines As previously mentioned, ergogenic drug use in the modem era of athletics began with amphetamines. The first reported use of amphetamines to enhance performance had a military rather than athletic application. During World War II, studies in German soldiers showed that amphetamines delayed fatigue (Laties & Weiss 1981). Smith and Beecher (1959) conducted the first indepth research on the effects of amphetamines on athletic performance. Swimming, running and weight-

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throwing performance in trained athletes was measured in the presence of amphetamines and placebo. The subjects were given 14 mg/70kg of bodyweight 2 to 3 hours prior to measuring performance. Improvements in performance were seen in 67 to 93% of swimmers, 73% of runners and 85% of weight-throwers. Weight-throwers showed the greatest degree of improvement (3 to 4%). Runners improved by approximately 1.5% followed by swimmers at 0.5 to 1.16%. These improvements, although small, could account for the difference between victory and defeat. Although considered a classic study on the effect of drugs on athletic performance, the results have been criticised for not addressing factors such as judgement, timing and eye-hand coordination. Conflicting results were observed in a study by Karpovich (1959). Athletes were given an amphetamine dose of 10 or 20mg or placebo and then tested in various swimming and running events. Amphetamines produced negative or no effect in 50 of 54 subjects. Of the 4 with improved performance, I improved in the presence of placebo. Nearly 20 years after these initial studies, Chandler and Blair (1980) investigated the effect ofamphetamines on individual physiological components rather than a measurement of competitive performance. Six male subjects were given either placebo or amphetamine 15 mg/70kg of bodyweight in a double-blind manner. Subjects showed significant improvements in strength, acceleration and anaerobic capacity following administration of amphetamines. Slight increases were seen in muscular power and aerobic power whereas no improvement in sprinting speed was demonstrated. The time to exhaustion and maximal heart rate was also increased by amphetamines. In spite of an increase in time to exhaustion, lactic acid concentrations rose and V02max was unchanged. This suggests that the performance effects seen with amphetamines may be the result of masking the symptoms of fatigue rather than any physiological mechanism. The available data suggest that amphetamines can improve performance in some individuals.

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Sports where speed, power and endurance are essential may be most affected. Amphetamines can produce numerous adverse reactions, many of which are related to the drug's effect on the central nervous system (CNS). Restlessness, insomnia, instability and agitation have all been reported. More serious behavioural effects include confusion, agitation, paranoia and vivid hallucinations (Schuster & Fischman 1975; Weiner 1985). Convulsions, coma and death may result from excessive amphetamine doses (Langston & Langston 1986). Long term exposure to amphetamines can result in dyskinesias, primarily involving facial and masticatory muscles. Side effects are not limited to the central nervous system. Cardiac complications include hypertension, angina and arrhythmias. Vomiting, gastrointestinal discomfort, weight loss, necrotising vasculitis and subarachnoid haemorrhage have all been reported secondary to use of amphetamines. Abrupt discontinuation of the drug can result in chronic fatigue, lethargy and depression (Weiner 1985). 2.2 Caffeine Caffeine is a methylxanthine derivative related to theophylline and theobromine. Caffeine is widely consumed as an ingredient in coffee, soft drinks and many nonprescription drug products and has been taken by athletes as an ergogenic aid (Delbeke & Debackere 1984). Athletic endurance may be improved in the presence of caffeine. The drug blocks adenosine receptors in the CNS. This blockade reduces the inhibition of the release of neurotransmitters (RaIl 1985). The resultant stimulation of the CNS may increase alertness and reduce the perception of fatigue. Caffeine's ability to increase circulating levels of free fatty acids reduces the body's dependence on muscle glycogen as a fuel source during prolonged exercise. This potential effect on endurance has been shown at doses of 250mg taken 1 hour prior to exercise and again immediately before exercise (Costill et al. 1978). Athletic endeavours requiring fine motor coordination and steadiness may not be

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enhanced by caffeine consumption. Standing steadiness, hand-arm steadiness and reaction time appear to be unaffected or adversely affected by caffeine (Franks et al. 1975; Ivy et al. 1979). Caffeine is banned by both the IOC and NCAA (National Collegiate Athletic Association 1989; United States Olympic Committee 1990). A urinary caffeine concentration of 12 mgfL is considered a positive result under IOC standards. The NCAA cut-off point is 15 mgfL. Since caffeine consumption is so common, a concern of many athletes is that they may unintentionally consume enough caffeine to produce a positive test result. A recent study demonstrated that, when administered in the form of coffee, tea or soft drink, caffeine doses in excess of 12 mgfkg were needed to produce a urinary level above 15 mgfL (maximum dose 17.53 mgfkg). Approximately eight 150ml (50z) servings of strongly brewed coffee would have to be consumed to reach these caffeine values (van der Merwe et al. 1988). Adverse reactions to caffeine may be the result of acute or chronic ingestion. CNS stimulation can produce nervousness, instability and insomnia at a variety of doses. Excess.ive doses have been reported to cause delirium, seizures, coma and death. Hypertension, arrhythmias and cholesterol abnormalities have also been linked to caffeine consumption (RaIl 1985). 2.3 Cocaine Despite the media reports of cocaine use among athletes there is very little evidence that the drug possesses any ergogenic effect. Anecdotal reports would suggest cocaine is used more for social reasons than to enhance athletic performance. Cocaine does not increase muscle strength (Ritchie Green 1985), but little else is known about its effects on performance. Nonetheless, athletes report taking the drug for perceived ergogenic reasons (Puffer 1986). The toxicity of cocaine is well known. Sudden death has been reported in the general population as well as in highly conditioned athletes (Duda 1986; Weiss 1986). The drug's cardiac effects in-

Athletic Performance and Drugs

clude myocardial infarction, arrhythmias and coronary artery vasoconstriction (Cantwell & Rose 1986). Cocaine can also produce adverse CNS reactions such as seizures, visual scotoma, blindness and optic neuropathy (Cregler & Mark 1986; Lowenstein et al. 1987; Newman et al. 1988). Behavioural changes include insomnia, euphoria, dysphoria, confusion, paranoia and hallucinations (Cregler & Mark 1986; Jaffe 1985). An interesting hypothesis by Giammarco (1987) suggests that highly conditioned sprint athletes may be at a particular risk for cocaine-related mortality. Because of the muscle composition of these athletes, a dose large enough to produce a seizure may also result in a lethal amount of heat and lactic acid causing cardiac shut down. 2.4 Other Sympathomimetic Drugs Phenylpropanolamine and ephedrine are structurally related to amphetamines. At high enough doses phenylpropanolamine produces CNS effects similar to amphetamines (Weiner 1985). Studies with ephedrine have demonstrated no objective or subjective effect on athletic performance (Sidney & Lefcoe 1977). The potential for abuse by athletes probably is related more to the easy availability of these drugs as nonprescription products than to evidence of ergogenic' effects. This easy availability also may put an athlete at risk for unintentionally testing positive during a urine drug test. As with the other stimulants previously discussed, the majority of the adverse reactions to phenylpropanolamine and ephedrine are related to stimulation of the CNS. Less serious side effects include nervousness, irritability, insomnia and headaches. More severe reactions such as agitation, confusion, paranoia, hypertension and arrhythmias have also been reported (PenteI1984; Weiner 1985).

3. Anabolic Steroids Anabolic steroids are synthetic derivatives of the male sex hormone testosterone. These drugs were developed in an attempt to create purely anabolic

257

compounds without the androgenic effects of testosterone. Since no steroid has been produced which is 100% anabolic, the drugs should actually be referred to as anabolic-androgenic steroids. Since the initial use of anabolic steroids in athletics, a debate has been waged as to whether these drugs can improve performance. Much of the scientific evidence in this regard was either poorly designed or employed doses substantially lower than those actually used by athletes. Further research is also hampered by ethical concerns over giving such supratherapeutic doses in a relatively healthy population, as well as the difficulty of blinding subjects from the effects of anabolic steroids on mood. Numerous studies on the ability of anabolic steroids to increase muscle mass and strength have produced conflicting data (Crist et al. 1983; Fahey & Brown 1973; Freed et al. 1975; Hervey et al. 1976). Absolute conclusions are difficult to come by. In a review of the literature by Ryan (1981), the conclusion was made that these drugs do not produce significant improvements in muscle mass or strength. Conversely, Haupt and Rovere (1984) concluded that anabolic steroids were effective if certain conditions were met. First, the athlete must intensively train in weightlifting before and during the anabolic steroid regimen. Secondly, the athlete must consume a high-protein diet. Thirdly, any changes in muscle strength should be measured by single-repetition, maximal weight techniques which are familiar to the athlete. The reported widespread use of anabolic steroids by athletes indicates either a real or perceived ergogenic benefit. Several possible mechanisms of action have been put forth. First, anabolic steroids occupy receptors located in muscle cells which stimulate RNA leading to increased synthesis of protein (Murad & Haynes 1985; Rogozkin 1979). Second, protein utilisation is improved by positively affecting nitrogen balance (Murad & Haynes 1985). Lastly, the drugs are not inherently anabolic, but the euphoria, aggressiveness and decreased fatigue allow longer and more intense workouts (Freed et al. 1975; Hervey 1976; Lamb 1984). Interestingly, experienced weightlifters improved

258

their performance when given a placebo claimed to be methandrostenolone (Ariel & Saville 1972). The one area of anabolic steroid research where the ergogenic data appear unequivocable is the lack of effect of anabolic steroids on endurance. Beneficial improvements in aerobic metabolism or V02max have not been demonstrated with use of anabolic steroids (Fahay & Brown 1973; Hervey et al. 1976; Johnson et al. 1975). Anabolic steroids have the potential to produce a wide array of adverse effects. Much of what is known about the toxicity of these products involves diseased patients receiving therapeutic doses. Athletes may consume doses up to 100 times that of the recommended therapeutic dose. Whether this fact is offset by the athlete's age, health status and duration of exposure to anabolic steroids is not known. Data specific for the athlete population are compiled from a limited number of studies and case reports. Several recent reviews of the adverse reactions related to anabolic steroid use are available (Hickson et al. 1989; Kibble & Ross 1987). The adverse effects range from minor to severe, and affect an assortment of body systems. Complications involving the liver include peliosis hepatis, hepatic tumours and nonspecific changes in liver function tests (Freed et al. 1975; Hagerman et al. 1983; Haupt & Rovere 1984; Lamb 1984; O'Shea 1970; O'Shea & Winkler 1970; Windsor & Dumitru 1984). Peliosis hepatis is a condition where blood-filled sacs form in the liver. This disease has been noted in patients with aplastic anaemia and other medical indications who were given anabolic steroids in therapeutic doses for an extended duration (Wilson & Griffin 1980). Peliosis hepatis has not yet been reported in athletes using anabolic steroids. Hepatocellular carcinoma has been seen secondary to anabolic steroid use both in the general population and in athletes (Creagh et al. 1988; Goldman 1985; Hickson et al. 1989; Overly et al. 1984). Elevations in liver function tests can be seen in athletes taking anabolic steroids. However, intensive physical training can raise those liver enzymes also found in muscle tissue without the

Sports Medicine 12 (4) 1991

presence of anabolic steroids. Because of this, anabolic steroid use should be followed by monitoring alkaline phosphatase and the liver-specific isoenzyme of lactate dehydrogenase (Haupt & Rovere 1984). Elevated liver function tests usually return to baseline following discontinuation of the drug (Haupt & Rovere 1984). The selection of anabolic steroid compound can impact the risk of liver complications. Orally active anabolic steroids, which are modified at the C17a position, are associated with more hepatotoxicity than injectable drugs (Farrell et al. 1975). Similar hepatic side effects have been seen with oral contraceptives having the same molecular modification (Mays & Christopherson 1984). The use of anabolic steroids results in a reduction in circulating testosterone. The hypothalamus of the brain signals the pituitary to produce less luteinising hormone and follicle-stimulating hormone. These reduced hormone levels result in a decrease in sperm production and testicular size (Hervey et al. 1981; Shephard et al. 1977; Strauss et al. 1982; Stromme et al. 1974; Ulrich et al. 1989). Sex drive may also be affected. The effect is variable but often involves an enhat;lced sex drive early in the course of steroid use which then decreases to normal or below normal as the drugs are continued (Strauss et al. 1983). Some anabolic steroid users take human chorionic gonadotrophin to counteract testicular atrophy and/or diminished sex drive (Strauss et al. 1983). In some men, gynaecomastia develops when excess androgen is converted to estrogen. This condition of increased breast tissue may be the result of high doses of anabolic steroids. Tamoxifen, an antiestrogen, is taken by some steroid users to reverse the gynaecomastia (Friedl & Yesalis 1989; Strauss 1987). The breast tissue usually returns to normal once anabolic steroid use is stopped (Strauss 1987). Women taking anabolic steroids develop masculine characteristics. Deepening of the voice, malepatterned baldness, decreased breast size and enlarged clitoris have been reported (Strauss et al. 1985). Adolescents taking anabolic steroids may experience premature epiphyseal closure of the long

259

Athletic Performance and Drugs

bones resulting in short stature (Haupt & Rovere 1984; Lamb 1984). Anabolic steroids can have a negative effect on lipoprotein profiles. The drugs can significantly decrease high density lipoprotein (HDL) cholesterol and increase low density lipoprotein (LDL) cholesterol (Alen et al. 1985; Alen & Rahkila 1984; Hurley et al. 1984; Kleiner et al. 1989; McKillop & Ballantyne 1987). This altered HDL/LDL ratio has been identified as a risk factor for cardiovascular disease (Lipids Research Oinics Program 1984). Although lipid levels return to baseline upon discontinuing anabolic steroids, the risk to athletes is at present unknown. Hypertension, cardiac enlargement, myocardial hypertrophy and stroke have all been reported among anabolic steroid users (FrankIe et al. 1988; Hickson et al. 1989; Kibble & Ross 1987; McNutt et al. 1988). Emerging data suggest that anabolic steroids can cause serious psychiatric reactions. Pope and Katz (1988) surveyed 41 known users of anabolic steroids and reported that 9 (22%) met the criteria for a manic or depressive episode while on steroids or during withdrawal. Case reports describing steroidinduced psychiatric symptoms include euphoria, irritability, hyperactivity, persistent delusions, acute schizophrenia, increased aggressiveness, violent behaviour and thoughts of suicide (Annitto & layman 1980; Brower et al. 1989; Freed et al. 1975; Freinhar & Alvarez 1985; Haupt & Rovere 1984; Kibble & Ross 1987; Lamb 1984; Pope & Katz 1987, 1990; Tennant et al. 1988; Wilson et al. 1974). A recent review of the physiological and behavioural effects of anabolic steroids in men concluded that the reactions are variable, transient upon discontinuation and appear to occur more frequently with 17a-alkylated compounds (Bahrke et al. 1990). The notion that anabolic steroids are addictive has been raised by Kashkin and Kleber (1989). This claim has led to an effort in the United States to reclassify anabolic steroids as controlled substances (Cowart 1987a,b; Taylor 1987). Several states have enacted such legislation, with similar bills currently under consideration in other states. Recently, the Federal government passed a bill

which added anabolic steroids to Schedule III of the Controlled Substances Act. This law makes the distribution of these drugs without a prescription a felony punishable by up to 5 years' imprisonment and a fine of up to $250 000. Possession without a prescription would be a misdemeanour. Other adverse reactions with anabolic steroids include a diminished glucose tolerance and acquired immune deficiency syndrome (AIDS) [from needle sharing] and connective tissue abnormalities (Laseter & Russell 1991) [Cohen & Hickman 1987; SkIarek et al. 1984].

4. Human Growth Hormone When released from the pituitary, growth hormone produces acute and delayed effects. The effects result in the natural growth and development of nearly every body system including skeletal and muscle mass. Physiological stimuli such as exercise and stress can increase growth hormone secretion (Macintyre 1987). In addition, a number of hormones and neurotransmitters can also boost secretion of growth hormone (Frohman 1987). This has led athletes to use propranolol, vasopressin, clonidine and levodopa as exogenous stimulants of growth hormone (Macintyre 1987). Synthetic human growth hormone is also available and has been reportedly used by athletes. No research supports the use of human growth hormone as an ergogenic aid (Cowart 1988). Animal studies have demonstrated an increase in the size and strength of atrophied muscles, but no effect on normal muscles (Macintyre 1987). How these data apply to healthy humans is not known. The potential toxicity of human growth hormone is theorised from the known effects of growth hormone hypersecretion. Acromegaly is the most common feature of growth hormone excess. Aside from the overgrowth of bone and soft tissue, peripheral neuropathy, coronary artery disease and cardiomyopathy are frequent complications. Acromegaly and its complications may be irreversible even after growth hormone levels are restored to normal (Frohman 1987). Other potential adverse effects include diabetes, hypothyroidism and arth-

260

ritis (Haupt 1989; Macintyre 1987). Synthetic human growth hormone is banned by the IOC and NCAA although no urine test is available for detection.

Sports Medicine 12 (4) 1991

banned substances for the NCAA and some professional sports' organisations under the classification of street drug (National Collegiate Athletic Association 1989).

5. Erythropoietin 7. Alcohol As previously mentioned, the process of blood doping has been used by athletes to improve endurance. Human recombinant erythropoietin (epoetin), which is now available, has the potential to produce erythrocythaemia similar to or greater than blood doping. The drug's effects on red blood cell mass have been demonstrated in patients with anaemia associated with chronic renal failure (Eschbach et al. 1987). Unpublished work by Ekblom et al. (1989) has shown that erythropoietin produced increases in haemoglobin and haematocrit with a resultant increase in maximum aerobic power and physical performance. The media have reported several deaths in world class athletes known to be taking erythropoietin. Although the deaths have not been conclusively linked to erythropoietin use, the possibility of serious complications does exist. The resultant polycythaemia can lead to hypertension, congestive heart failure and stroke (Wadler & Hainline 1989). Despite difficulties in detecting exogenous from endogenous erythropoietin, the drug is banned by both the IOC and NCAA (National Collegiate Athletic Association 1989; United States Olympic Committee 1990).

6. Narcotic Analgesics Although not considered ergogenic aids, narcotic analgesics have the potential for misuse in athletics. Treatment of serious pain which allows an athlete to participate may lead to further injury which may threaten the athlete's career. For this reason, the IOC has banned narcotic analgesics while allowing use of aspirin and nonsteroidal antiinflammatory agents for the treatment of less serious pain (United States Olympic Committee 1990). Narcotic analgesics are not restricted by the NCAA. Heroin is, however, included on the list of

The American Society of Sports Medicine (1982) has concluded that alcohol does not benefit athletic performance. Athletes may still believe that alcohol can serve as a caloric source or reduce anxiety before competition. A common misconception is that beer and other alcohol-containing beverages are rich in carbohydrates. Alcohol is not a particularly good source of carbohydrates (Clark 1989). Athletes would be better served to consume fruit juices or even soft drinks as part of any precompetition carbohydrate loading. Despite claims to the contrary, alcohol is not a good source of any vitamins or minerals. Alcohol consumption decreases anaerobic strength and does not affect endurance as measured by V02max and oxygen consumption (Bond et al. 1983; Nelson 1959). This is evidenced by the neutral or negative results seen in sprint and middledistance runners given enough alcohol to produce a blood alcohol concentration between 0 and 100 mgfdl (McNaughton & Preece 1982). On the other hand, alcohol in low doses may possess anxiolytic properties. In precision events, alcohol may improve performance by reducing essential tremor (Koller & Biary 1984). Because of this, alcohol is banned in riflery events by the IOC and NCAA. Even though alcohol can produce psychomotor changes in balance, reaction time, motor coordination, visual tracking and information processing which potentially are deleterious to athletic performance, alcohol abuse by athletes may not always manifest itself by poor performance (Clark 1987). Chronic alcohol abuse can lead to an array of serious health complications whose discussion is beyond this review.

Athletic Performance and Drugs

8. Marijuana As with alcohol, marijuana produces effects which would impair athletic performance. In addition, chronic use may lead to the controversial subject of antimotivational syndrome. The characteristics of this syndrome of apathy, impaired judgement and loss of ambition are potentially detrimental to virtually any athletic endeavour (Wadler & Hainline 1989). Studies of marijuana's physiological effects show increases in resting heart rate and blood pressure and no effect on vital capacity and hand grip strength (Steadward & Singh 1975). Anecdotal reports by athletes indicate the drug's only performance attributes may be to produce a loose, relaxed feeling before and during competition (Wagner 1989a). Marijuana is not banned by the IOC (United States Olympic Committee 1990). The NCAA and several other sports organisations include the drug as a banned substance (National Collegiate Athletic Association 1989).

9. Tobacco

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movement time and total response time showed no improvements in the user group (Edwards et al. 1987). Animal studies suggest nicotine may produce a calming effect (Morrison 1967). Following administration of nicotine swimming mechanics in rats is improved (Battig I 970), but endurance is decreased (Bhagat & Wheeler 1973). The effect of smoking tobacco on physiological parameters related to performance has been studied. Smoking negatively affects oxygen cost ofventilation, heart rate and V02max (Klausen et al. 1983). No effect on aerobic power was seen in smokers (Maskud & Baron I 980). Most athletes who use nicotine in the form of smokeless tobacco indicate an awareness of the potential health risk (Ernster et al. 1990). This awareness has produced a decrease in the amount of television broadcast time during game 5 of the World Series where players are seen using smokeless tobacco products from 24 minutes in 1986 to 3.8 minutes in 1988 (Jones 1987; Sussman & Barovich 1989).

10. Miscellaneous Drugs 10.1 {3- Blocking Agents

The association between tobacco and athletics principally involves smokeless tobacco. Smokeless tobacco usually takes one of 2 forms. Snuff is a finely shredded product which is placed between the lower lip or cheek and the gum. Chewing tobacco is a more coarse product which is put in the cheek pouch. The use of smokeless tobacco seems to be a popular ritual among many baseball players. Surveys of major and minor league baseball players in the United States have demonstrated an incidence of current use ranging from 34 to 39% (Connolly et al. 1988; Ernster et al. 1990). Leucoplakia and localised peridontal disease were frequent findings in the smokeless tobacco group of athletes (Ernster et al. 1990). According to Lombardo (1987), athletes may use nicotine for the following reasons: (a) stimulatory effect; (b) calming effect; (c) appetite control; and (d) use unrelated to performance. Studies on the effect of smokeless tobacco on reaction time,

P-Blockade adversely affects physical performance as measured by anaerobic endurance, V02max and time to fatigue. Muscle strength appears to be unaffected in the presence of l3-blockers (Kaiser 1984). These drugs can reduce tremor and improve hand/arm steadiness which can aid athletes in precision events. In a study involving world-class pistol marksmen, metoprolol improved shooting scores in 22 of 33 subjects (Kruse et al. 1986). 13Blockers are banned in shooting events by the IOC and NCAA (National Collegiate Athletic Association 1989; United States Olympic Committee 1990). 10.2 Diuretics The use of diuretics as a means to avoid drug testing detection has been previously mentioned. Diuretics are also used by athletes such as jockeys, boxers and wrestlers to achieve rapid weight loss

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to make a particular weight classification. Diuretics have been shown to result in a mean weight loss of 4.1 % over a 24-hour period, but also decreased ~02max, workload in maximal exercise and blood lactate concentrations (Caldwell et al. 1984). 10.3 Nutritional Supplements Consumption of vitamins and minerals is widespread among athletes in the belief that they are ergogenic aids (Percy 1982). However, studies have not demonstrated any performance benefits associated with vitamin and mineral supplements (Weight 1988). Presently, chromium has been promoted as a safe alternative to anabolic steroids. The proposed anabolic effect is the result of increased insulin activity which stimulates intracellular uptake of amino acids. These anabolic claims need to be confirmed in larger study populations and should address chromium deficiencies in the diet. Use of chromium, although relatively nontoxic, may signal an athlete at risk for more potent ergogenic aids such as anabolic steroid (Wagner 1989b). Individual amino acids may be taken by athletes in an attempt to stimulate production of growth hormone. Whether amino acid supplemen-

tation in conjunction with weight-training produces anabolic gains greater than with weighttraining alone is unclear (Jacobson 1990). Further studies are needed to determine the efficiency and health risk of amino acid supplementation, especially in high doses.

11. Conclusions The use of ergogenic aids in athletics appears to be relatively commonplace in a wide variety of sports at virtually all levels of competition. Substances used by athletes as ergogenic aids range from the commonplace to the exotic. Evidence of the effects of these drugs on athletic performance is often sparse and controversial. Future studies designed to more accurately define real performance benefits may be difficult due to ethical issues. Even if these studies were to find unequivocal

scientific evidence that drugs cannot improve performance, athletes may still use drugs based on anecdotal information of perceived effects. Therefore, efforts to discourage ergogenic drug use among athletes should focus on ethical and health issues. Attitudes toward ergogenic drug use, long term health risks and the effect of drug testing and education are several areas of potential research.

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Correspondence and reprints: Dr Jon C. Wagner, Assistant Dean for Student and Professional Affairs, College of Pharmacy, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, NE 68198-6000, USA.