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Stay alert for performance-enhancing substance use
Jeffrey F. Jarvi, MS, PA-CMr. Jarvi practices at the Salem Pediatric Clinic, Salem, Ore. The author has indicated no relationships to disclose relating to the content of this article.Anabolic steroids. Testosterone precursors. Nutraceuticals. Designer drugs. The list of substances athletes may take to enhance performance is long, and growing longer. Before you can educate patients about the dangers of such use, you must educate yourself. Research into performance-enhancing substances has been increasing in the past 15 years, and none of the findings have been encouraging. Initial studies of androstenedione raise doubts about its performance-enhancing potential. Data on creatine do not support the claims made for the muscle-building effects of this substance. Erythropoietin (EPO) has positive effects in the appropriate medical setting, but it may be harmful or deadly when used to enhance endurance activity. The FDA has banned the sale of ephedra in dietary supplements because of its potentially dangerous and even lethal side effects. Despite the lack of proven benefits, recreational and professional athletes continue to use these and other substances to improve athletic performance. More than 1 million 12- to 17-year-old adolescents have taken potentially dangerous drugs and supplements, according to a survey completed in 2003.1 Most clinicians have not addressed this issue adequately. Fewer than 20% of school-age children reported that a medical professional had talked to them about the dangers of using anabolic steroids or other performance enhancing substances.2 To assist patients in making decisions about using these substances, clinicians should be knowledgeable and have informational resources available to offer patients. This article discusses the basic science of, research into, and health risks associated with the use of performance-enhancing substances. Anabolic steroidsThe history of synthetic testosterone is well documented. At a scientific meeting in 1889, Charles Edouard Brown-Séquard, an internationally recognized physician and scientist, reported that he had experienced increased strength and energy after injecting himself with testicle extract from dogs.3 The early 1900s were a period of experimentation with natural and synthetic androgens, which were used to treat a variety of conditions including senility, asthma, and menopause. Information on the effects of anabolic steroids on athletic performance has been largely anecdotal. Long-term studies have not been completed, although the dramatic success of the East German track team throughout the 1970s and 1980s has been described as the result of highly organized and systematic "doping."4 The ergogenic effects of steroids include increases in body weight, lean muscle mass, total muscle mass, and overall strength. Steroid users often take doses that are 10 to 100 times those used for legitimate medical indications, and androgen receptors are saturated at much lower doses than the ones athletes typically use. Steroids are given orally or by injection and are often taken in a practice known as stacking, which refers to the concomitant use of several types of androgens or anabolic steroids. Another method involves taking steroids for several weeks followed by several weeks off. This is known as cycling. The side effects of anabolic steroid use include increased aggressiveness, testicular atrophy, gynecomastia, elevated triglyceride levels, acne, premature closure of growth plates in the long bones of adolescents, and alteration of liver function. Athletes also report delayed healing after injury. Some of these side effects (closure of growth plates and testicular atrophy, for instance) are irreversible. Although the use of anabolic steroids is banned by athletic organizations, they remain available to athletes. One need only search the Internet to find them offered, usually for a high cost. A weight-training facility can also be a source of procurement of steroids if a supplier is available. Testosterone precursorsAndrostenedione is a naturally occurring precursor to testosterone, and dehydroepiandrosterone (DHEA) is a precursor to androstenedione. Both are available in OTC supplements that are taken orally. Androstenedione and DHEA purportedly increase circulating levels of testosterone, leading to enhanced athletic performance. Several recent studies have measured the effectiveness of androstenedione and DHEA. A randomized study using androstenedione, DHEA, and placebo in healthy men revealed no significant differences in strength or testosterone levels among the groups tested.5 A 1999 study reported a trial of androstenedione versus placebo in 30 healthy adult men.6 The subjects randomized to supplementation received 300 mg of androstenedione or a placebo over an 8-week period. All subjects completed a course in resistance training. No differences were found in fat-free mass, muscle fiber cross-sectional area, or knee extension strength between the two groups.6 The long-term effects of androstenedione and DHEA supplementation are unknown. The US Department of Health and Human Services has released a position statement regarding androstenedione saying that long-term use could produce adverse effects similar to those seen with anabolic steroids, and as of March 11, 2004, the FDA warned manufacturers to stop distributing such products.7 CreatineCreatine supplementation is a $100 million industry.8 The use of creatine supplements is intended to prolong the time to anaerobic metabolism. The regimen begins with an initial loading dose for a week followed by maintenance dosing. Peak levels are reached 60 to 90 minutes after oral ingestion. The usual cost of supplementation is between $15 and $30 per month. The effect of creatine at the muscular level is hypothesized to be related to its presence in a phosphorylated form, phosphocreatine. This assists in the production of ATP (adenosine triphosphate), the energy source for short-duration exercise. Creatine cannot work without strength training. It purportedly increases the athlete's ability to train.9 Studies have shown that the greatest benefit of creatine supplementation is in anaerobic activity such as power lifting rather than aerobic sports. Creatine supplementation does not appear to improve isometric or isotonic force production in older subjects.10 Reports of side effects are anecdotal, with abdominal cramping and dehydration said to be the most common. Susceptibility to heat illness may also be increased. Renal dysfunction has not been proven to occur. A recent study showed that the increase in serum creatinine in patients taking creatine supplements is the result of increased conversion of creatine to creatinine, not of decreased glomerular filtration function.11 No studies of the short- or long-term adverse effects of creatine on healthy men are currently available. Creatine is not currently listed as a banned substance. Human growth hormoneHuman growth hormone (HGH) is a polypeptide hormone, secreted by the pituitary gland, that serves to mediate metabolic and growth processes effecting lipid, carbohydrate, and protein metabolism. Somatropin is the recombinant human growth hormone (hGHr) developed by pharmaceutical companies. It is administered by injection, either IM or SC. Use of hGHr for performance enhancement can decrease body fat with a concomitant increase in lean body mass. It also enhances amino acid uptake and transport that increase the capacity for protein synthesis, which some athletes believe can increase strength development and muscle mass. However, HGH supplementation combined with resistance training in healthy younger and older men does not appear to augment muscle strength.12 The adverse effects of HGH are many and include acromegaly, behavioral changes, cardiovascular disease, diabetes, hypertension, and peripheral neuropathy. Designer supplementsSome companies have tried to develop supplements that provide users with an "edge" without producing positive results on the tests for banned substances that are routinely performed on competitive athletes. This fact was recently underscored by the discovery that elite track and field athletes were using tetrahydrogestrinone (THG), a so-called undetectable anabolic steroid. THG is purely synthetic. It has been represented as a dietary supplement, but the FDA has identified THG as an unapproved new drug that cannot legally be marketed without meeting the agency's standards of safety and efficacy. THG is closely related to the synthetic steroids gestrinone and trenbolone. As such, it carries the same side-effect profile as other anabolic steroids and is banned by the US Anti-Doping Agency (for more information, see www.usantidoping.org ).13 EphedraEphedra is a naturally occurring substance found in plants. The active ingredient is ephedrine, a sympathomimetic drug and CNS stimulant. Like an amphetamine, ephedra increases heart rate and BP and decreases appetite. Synthetic forms of ephedrine are regulated by the Federal Food, Drug, and Cosmetic Act and are used in OTC medications for the treatment of asthma and nasal congestion. In recent years, botanical sources of ephedra (Ma-Huang) have been combined with caffeine for use as a weight-loss aid and to enhance athletic performance. Studies of ephedrine and exercise performance have shown increased time to exhaustion on a cycle ergometer with no differences in oxygen consumption, carbon dioxide production, and minute ventilation when compared to placebo. Heart rate during exercise was increased with lower perceived levels of exertion.14 The side-effect profile of ephedra is well known and includes increased BP, heart palpitations, symptoms of hyperactivity of the autonomic nervous system, and stress to the circulatory system.15 The recent deaths of a National Football League lineman and a major-league baseball player have been directly linked to the use of ephedra. The FDA has banned the sale of dietary supplements containing ephedra. The final rule, published February 6, 2004, became effective April 12, 2004. See www.fda.gov/oc/initiatives/ephedra/december2003 for more information. ErythropoietinEPO is a naturally occurring hormone that stimulates an increase in hemoglobin. This subsequently increases the oxygen-carrying capacity of the blood. Synthetic EPO (recombinant or rEPO) became commercially available in 1985. Injections of rEPO given to patients with kidney failure requiring dialysis can improve physical performance to near-normal levels. This can be attributed to the increase in hemoglobin and hematocrit. The use of rEPO by endurance athletes gained popularity in the late 1980s, but using the substance to improve athletic performance is not legal. Several studies have been completed regarding the ergogenic potential of rEPO. These studies show increases of hematocrit and Vo2max (Vo2max is the maximum volume of oxygen consumed by the body each minute during exercise, while breathing air at sea level).16 The results are similar to those seen in studies of blood doping (the autologous transfusion of previously donated blood).17 The artificial increases in hematocrit and hemoglobin can have disastrous consequences. The increase in RBC mass will in turn increase the viscosity of the blood, which can be further enhanced by dehydration during endurance activity. The heart must work harder in the setting of hypovolemic hyperviscosity, which elevates the risk of hypertension, myocardial infarction, and stroke. These outcomes have been reported in cyclists who have supplemented with rEPO.18 Prescription drugsNumerous prescription drugs have been used as performance-enhancing substances. Some have been banned by international sporting organizations and many have restrictions on their use, but others continue to be used. ß-Agonist use increased dramatically in the 1996 Olympics, with as many as 60% of the athletes carrying a diagnosis of exercise-induced asthma. ß-Agonists (eg, albuterol) are considered anabolic and stimulating and have been banned in competition without a medical indication. ß-Blockers are used to control anxiety to aid competitors in sports such as range shooting, archery, and the biathlon. Athletes take diuretics to shed weight for competition and define muscle in such activities as bodybuilding. Caffeine has long been considered an ergogenic aid because as a stimulant, it can enhance the ability to complete endurance activity. Herbal supplementsHerbal medicines have been used for centuries to improve physical performance. The ancient Greeks, Andean Indians, and Australian Aborigines used various supplements, including sesame seeds and coca leaves, to decrease fatigue. At present, many herbs are classified as dietary supplements and are found in numerous products including health bars and drinks. Common uses are to increase energy, promote weight loss, and increase muscle development. The formulations of herbal supplements vary from manufacturer to manufacturer, which makes standardization difficult. Currently, the United States Pharmacopeia ( www.usp.org ) is establishing standards for certain botanical products. If standards are met, manufacturers can place an official NF (National Formulary) on their labels. Two of the most commonly used supplements are ginkgo biloba and ginseng. Ginkgo biloba has been found to improve blood flow (microcirculation), which can improve memory performance and may be ergogenic for aerobic-endurance athletes. Studies have shown improved exercise performance in patients with peripheral artery disease who take ginkgo, but no evidence indicates that similar effects occur in healthy men.19 Although ginseng has historically been used to treat many disorders, current studies have focused on its cardiovascular effects. Claims of increased aerobic endurance have been made for ginseng, but research does not support these claims in the active population.20 Office assessment of athletesThe first challenge for clinicians is to identify the user or potential user of performance-enhancing substances. Asking direct questions during a routine physical exam can elicit an exercise profile and provide additional clues into use of supplements.
These questions are just a beginning. A yes answer to any of them may give the clinician a motivation for substance use and help direct further discussion. For example, an adolescent athlete's attempts to gain weight can lead to questions about calorie intake and supplements for gains of muscle mass. During the physical examination, the clinician should remember the side-effect profiles of commonly used agents. Routine BP checks may help in identifying stimulant use if a patient suddenly develops hypertension. An unusual or unexpected weight gain should also arouse suspicion since it may mean the patient is using anabolic steroids, creatine, or DHEA. The adolescent athlete is at high risk for supplement use and abuse. Societal pressures to win and achieve athletic prowess make adolescents particularly susceptible. Remember that they are struggling with issues of self-worth and sexual identity as well. Clinicians should be prepared to provide factual information and advice (see "Web resources").
The influence of professional athletes and pop culture provide the impetus for performance-enhancing drug use. If we can keep lines of communication open with patients, we can help them to make more knowledgeable choices. REFERENCES 1. Parker J, Thomson A. Blue Cross and Blue Shield Association survey projects 1.1 million teens have used potentially dangerous sports supplements and drugs. The Healthy Competition Campaign. Available at: http://www.healthycompetition.org/hc/news/adult_survey_103103.html . Accessed October 8, 2004. 2. Koch JJ. Performance-enhancing substances and their use among adolescent athletes. Pediatr Rev. 2002;23:310-317. 3. Hoberman JM, Yesalis CE. The history of synthetic testosterone. Sci Am. February 1995;272:76-81. 4. Ungerleider S. Faust's Gold: Inside the East German Doping Machine. New York, NY: Thomas Dunne Books/St Martin's Press; 2001. 5. Wallace MB, Lim J, Cutler A, Bucci L. Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Med Sci Sports Exerc. 1999;31: 1788-1792. 6. King DS, Sharp RL, Vukovich MD, et al. Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial. JAMA. 1999;281:2020-2028. 7. US Department of Health and Human Services [Web site]. HHS launches crackdown on products containing andro. Available at: http://www.fda.gov/bbs/topics/news/2004/hhs_031104.html . Accessed October 8, 2004. 8. Chorley JN. Dietary supplements as ergogenic aids. Adolescent Health Update. October 2000;13 9. American College of Sports Medicine position stand on the use of anabolic-androgenic steroids in sports. Med Sci Sports Exerc. 1987;19:534-539. 10. Branch JD, Williams MH. Creatine as an ergogenic supplement. In: Bahrke MS, Yesalis CE, eds. Performance-Enhancing Substances in Sport and Exercise. Champaign, Ill: Human Kinetics; 2002:175-195. 11. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999;31:1108-1110. 12. Healy ML, Russell-Jones D. Growth hormone and sport: abuse, potential benefits, and difficulties in detection. Br J Sports Med. December 1997;31:267-268. 13. US Food and Drug Administration [Web site]. FDA statement on THG. October 28, 2003. Available at: http://www.fda.gov/bbs/topics/NEWS/2003/NEW00967.html . Accessed October 8, 2004. 14. Bell DG, Jacobs I. Combined caffeine and ephedrine ingestion improves run times of Canadian Forces Warrior Test. Aviat Space Environ Med. 1999;70:325-329. 15. Rados C. Ephedra ban: no shortage of reasons. March-April 2004. FDA Consumer. Available at: http://www.fda.gov/fdac/features/2004/204_ephedra.html . Accessed November 12, 2004. 16. Birkeland KI, Stray-Gundersen J, Hemmersbach P, et al. Effect of rhEPO administration on serum levels of sTfR and cycling performance. Med Sci Sports Exerc. 2000;32:1238-1243. 17. Williams MH, Branch JD. Ergogenic aids for improved performance. In: Garrett WE Jr, Kirkendall DT, eds. Exercise and Sport Science. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000:373-384. 18. Tokish JM, Kocher MS, Hawkins RJ. Ergogenic aids: a review of basic science, performance, side effects, and status in sports. Am J Sports Med. 2004;32:1543-1553. 19. Blume J, Kieser M, Holscher U. Placebo-controlled double-blind study of the effectiveness of Ginko biloba special extract EGb 761 in trained patients with intermittent claudication [in German]. Vasa. 1996;25(3):265-274. 20. Allen JD, McLung J, Nelson AG, Welsch M. Ginseng supplementation does not enhance healthy young adults' peak aerobic exercise performance. J Am Coll Nutr. 1998;17:462-466.
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