Growing Concern...

Performance-Enhancing Drugs and Today’s Athlete: A Growing Concern

By Seth A. Cheatham, MD; Robert G. Hosey, MD; Darren L. Johnson, MD
ORTHOPEDICS 2008; 31:1014

October 2008

The use of anabolic steroids in professional athletes has been a concern for a long time; however, the rise in use by younger athletes is especially troubling. Physician-guided education is vital to the creation of an effective intervention program.

As athletic competition continues to intensify, athletes strive to higher levels of performance to achieve success. There appears to be a “win at all costs” mentality, not only among many of today’s athletes, but also among their coaches and parents. It is this same mentality that fuels many athletes to seek performance-enhancing substances such as anabolic steroids and other drugs. However, no longer is this just a problem of the elite athlete; today, the perception that anabolic steroids correlate with athletic success can be found among collegiate and scholastic athletes as well.

Epidemiology
In the United States, an estimated 1 to 3 million people have used anabolic steroids.1 Many of these are young adults. An estimated 4% to 12% of US high school boys and up to 3.3% of high school girls have used anabolic steroids.2 A study by Buckley et al3 found that 6.6% of male high school seniors had tried steroids, with 67% initiating use by 16 years and 40% using multiple cycles. These findings were later confirmed in studies of Indiana high school football players, as well as a 2003 Centers for Disease Control report. Prevalence studies extend to middle school populations as well. A 1993 study of Modesto, California, seventh graders reported an overall use rate of 3.8%.4 These findings correlated with a later study out of Massachusetts that found a usage rate of 2.7% in students between 9 and 13 years.4

In a recent study of substance abuse by the National Collegiate Athletic Association (NCAA), an overall usage rate of 1.1% was found across all 3 of its divisions. In regard to reasons for use, 47% reported that the main reason was performance enhancement, while 53% reported it was to recover from an injury. While the relative numbers of this study may be surprisingly low, the availability of anabolic steroids is concerning. Only 0.7% of those surveyed reported that a reason not to use or to have stopped using was that the steroids were hard to get.5 Furthermore, the survey inquired about the use of other substances. Although dehydroepiandrosterone (DHEA), with a usage rate of 0.6%, was the only testosterone precursor specifically questioned, another 10.4% revealed they had used other supplement products.

Metabolic/Physiologic Effects
There is an enlarging body of evidence regarding the anabolic “tissue-building” effects of anabolic steroids and other testosterone precursors on skeletal muscle. It has been shown that these drugs can influence lean body mass, muscle size and strength, protein metabolism, bone metabolism, and collagen synthesis.6 Many of these effects have been shown to occur with or without exercise.7 The most profound effects are noted when supraphysiologic doses accompany a training program and are used in conjunction with a diet adequate in protein and calories.

Testosterone-induced muscle hypertrophy and increases in muscle strength are the result of increases in the cross-sectional area of muscle fibers.8 Research suggests that the anabolic effects are mediated by testosterone-influenced increases in muscle protein synthesis.6 Androgen receptors in skeletal muscle regulate the transcription of the target genes that control the accumulation of DNA needed for muscle growth. Complementary effects include glucocorticoid antagonism, which minimizes its catabolic actions, and stimulation of the growth hormone insulin-like growth factors.6

Dosage and Patterns of Use
Anabolic steroids may be taken orally, injected intramuscularly, or applied transdermally. They are divided into 3 main classes.6 Testosterone esters are injected compounds and constitute class I. Class II agents include the nortestosterone derivatives such as nandrolone decanoate and nandrolone phenpropionate. These 2 classes exert their effects on androgen and estrogen receptors by way of aromatization of estradiol. The third and final class of anabolic steroids includes those alkylated at C-17 and are orally administered. The alkylation slows the hepatic metabolism of these agents.2

A typical pattern of use involves both oral and injectable forms of anabolic steroids taken over 6- to 12-week cycles.1 Of note, injectable forms tend to be favored because they are less hepatotoxic than oral forms. However, oral forms are favored when testing is anticipated, due to the fact that they are cleared from the system more quickly. The simultaneous use of multiple steroids is referred to as “stacking.” A pattern of increasing a dose through a cycle is called “pyramiding.” By stacking and pyramiding, the user hopes to maximize steroid receptor binding, thereby reducing toxic side effects.1 Some users also use accessory medications such as clomiphene and human chorionic gonadotropin (HCG) to minimize the side effects.6

Testosterone Precursors
Tetrahydrogestrinone (THG), or “the clear,” is classified as a designer steroid and was revealed by the US Anti-Doping Agency in 2003. It was initially developed to avoid detection by all testing protocols at that time. The discovery of THG was serendipitous because a used syringe containing a substance purported to be an undetectable steroid was sent to the US Anti-Doping Agency by an unnamed track and field coach.9 This drug has received significant media attention in the past few years because of scandals involving professional and Olympic athletes. Chemically related to 2 other banned steroids, tenbolone and gestrinone, THG is used like other anabolic steroids. It is known to be more hepatotoxic, with highly potent androgenic and progestin properties.10 The substance is banned from marketing in the United States, so there are no long-term studies on its effectiveness or side effect profile.

Androstenedione, or andro, is a precursor to the hormone testosterone, produced in the adrenals and gonads. In 1996, androstenedione became available to the public as an over-the-counter supplement. Marketing claims for androstenedione include increased strength, greater fat-free mass, and improved libido. It was commonly used in Major League Baseball during the 1990s by such notable players as Mark McGwire. At high doses, androstenedione has been shown to increase levels of testosterone. However, levels of estradiol were also shown to increase after use. A 2006 review11 summarized several studies that examined the effect of androstenedione on strength training. At dosages of 50 or 100 mg per day, androstenedione had no effect on muscle strength or size, or on body fat levels. One study used a daily dosage of 300 mg of androstenedione combined with several other supplements, and also found no increase in strength when compared to a control group that did not take the supplements. The review authors speculated that sufficiently high doses may lead to increased muscle size and strength.11 However, due to the federal ban on androstenedione supplements, it is difficult to carry out new research on its positive and negative effects.

Like androstenedione, DHEA is a testosterone precursor, made in the body by the adrenal glands with weak androgenic properties. It is marketed to increase muscle mass and promote weight loss. Dehydroepiandrosterone is used by athletes to increase testosterone levels and theoretically increase muscle bulk. However, investigations into these ergogenic claims reveal no changes in lean mass or muscular strength following supplementation.12 There is also concern about virilization in women and gynecomastia in men following DHEA use.

Risk Factors
As clinicians and team physicians, we need to watch out for the risk factors associated with performance-enhancing drug use. Many studies have attempted to create a profile of the typical user, which may be helpful in situations such as sport physicals. Generally, the relative risk for anabolic steroid use is 2 to 3 times higher in men.6 The impact of factors such as age, race, and ethnicity is unclear. Furthermore, there may be some association between performance-enhancing drug use and academic performance. DuRant et al13 reported a significantly higher usage rate among athletes with a below-average academic record. Anabolic steroid users are also more likely than non-users to participate in school-sponsored athletic programs. More specifically, sports such as football, wrestling, baseball, and track and field, which require muscular strength and power, are more closely associated with anabolic steroid use. However, it is important to realize that 30% to 40% of anabolic steroid users do not participate in a school-sponsored sport. More likely, these users participate in bodybuilding or weightlifting.3

Adverse Effects
The adverse effects of anabolic steroids can be divided into 5 categories: hepatic, cardiovascular, reproductive/endocrine, dermatological, and psychiatric.2

Numerous studies have correlated elevations in liver function tests with the use of anabolic steroids. The C-17 alkylated oral preparations are most often associated with liver toxicity. Other hepatic abnormalities include cholestasis and hepatocellular adenomas.6 Anabolic steroids can also have dramatic effects on one’s lipid profile. Potential changes include increases in low-density lipoprotein and decreases in high-density lipoprotein.2,6 Once again, the C-17 alkylated oral agents seem to exert the greatest effect.

Hypertension is not uncommon secondary to fluid retention and blood volume increases. It is therefore not surprising that there is an increased risk of myocardial infarction, cardiomyopathy, and sudden cardiac death.

Steroid use over time provides feedback inhibition of luteinizing hormones and follicle-stimulating hormone, which in turn leads to testicular atrophy and decrea androstenedione, dehydroepiandrosterone sed spermatogenesis.6 In men, it is not uncommon for anabolic steroids to undergo peripheral aromatization to estrogens, which can cause feminizing changes such as a high-pitched voice or gynecomastia. In women, anabolic steroids can cause hirsutism, deepening of the voice, decreased menstruation, and clitoral hypertrophy.

Dermatologically, severe cases of acne and even premature baldness have been noted; and psychologically, anabolic steroid use has been associated with changes in mood and behavior such as mania, hypomania, depression, and aggressive behavior.14 Studies have shown that these effects are variable and short-lived on discontinuation, and seem to be related to the type and dosage of anabolic steroid.

Children seem to be most susceptible to the adverse effects of anabolic steroid use. In addition to the aforementioned side effects, children and adolescents experience accelerated maturation associated with changes in physique and earlier development of secondary sexual characteristics. An additional concern with adolescents is premature closure of growth plates in long bones.15 This is likely due to aromatization of estrogens. With adolescents, some of the effects may become irreversible with chronic use, particularly the virilizing effects in young women.

Conclusion
Our society equates success with winning. The desire to succeed among athletes of all ages is a powerful stimulus to obtain and use performance-enhancing drugs to achieve their goals. The use of anabolic steroids in professional athletes has been a concern for a long time; however, the rise in use by younger athletes is especially troubling. It is therefore important for health-care professionals to have a thorough understanding of the physiology and risks of these drugs.

Educational programs addressing the social, media, and peer influences that perpetuate adolescent use of anabolic steroids and other performance-enhancing drugs have shown promise. Such educational programs need to be directed toward middle and high school classrooms to decrease the rate of first-time use in these age groups. Physician-guided education in schools and to athletes, parents, and coaches is vital to the creation of an effective intervention program. With effective education, team physicians will be able to discourage the use of anabolic steroids and convince patients that there is no substitute for good nutrition and a sensible strength training program.

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Authors
Drs Cheatham, Hosey, and Johnson are from the Department of Orthopedic Surgery and Sports Medicine, University of Kentucky, Lexington, Kentucky.

Drs Cheatham, Hosey, and Johnson have no relevant financial relationships to disclose.

Correspondence should be addressed to: Seth A. Cheatham, MD, Department of Orthopedic Surgery and Sports Medicine, University of Kentucky, 740 S Limestone, Ste K415, Lexington, KY 40536-0284.