Anabolic-Androgenic Steroids for Athletes: Adverse Effects

By Dónal P. O’Mathúna, PhD

How many athletes use or have used testosterone and other anabolic-androgenic steroids (AAS) is difficult to determine, but estimates range from between 1 and 3 million Americans.1 Up to 11% of high school males have used AAS, one-third of whom were not active in school sports.2 Use of AAS among professional bodybuilders and baseball players is widespread, and use by recreational weightlifters is growing. In Britain, 9% of weightlifters use AAS, but some gyms have no users, while in other gyms, almost half the athletes use.3

Strict regulations have made AAS (like those in the Table) available only by prescription—or on the black market. In response, many products claim to be natural "testosterone boosters" available as dietary supplements. The most popular, androstenedione and DHEA (dehydroepiandrosterone), have been reviewed previously in Alternative Medicine Alert. Studies have found that these are neither effective performance enhancing agents nor do they increase serum testosterone levels. Therefore, they would not be expected to have the same adverse effects as AAS discussed here, although they do raise estrogen levels and lower HDL levels.

As testosterone replacement therapy becomes more popular, questions surrounding the adverse effects reported by athletes will become more common. All health care professionals should have some knowledge of AAS effects.

Mechanism of Action

AAS include natural and synthetic steroids that are similar to testosterone (see Figure), with anabolic and androgenic effects. Anabolic effects are manifested primarily by the growth of non-reproductive tissues. Athletes seek anabolic effects like increased muscle mass and decreased fat mass. Androgenic effects are those that promote development of male sexual characteristics and reproduction. More than 1,000 steroids have been manufactured in attempts to increase anabolic effects while minimizing androgenic effects. Common oral and injection AAS are listed in the Table.

Common Usage

For many years, the medical community combated AAS use by denying its effectiveness for promoting lean body mass.2 Early studies were flawed and did not reflect the way AAS are used. Athletes actually "cycle" on and off compounds, switching from one to another to avoid developing tolerance. They "stack" AAS, taking several different steroids at the same time to lower the dose of each and activate different steroid receptors. The scientific basis for stacking is highly questionable and has not been proven.2

Clinical Trials

AAS are generally accepted as having the desired anabolic effects, provided athletes also consume adequate protein and exercise intensely. In a randomized controlled trial, those taking 600 mg testosterone intramuscular (IM) injections weekly for 10 weeks had significantly increased muscle mass, muscle strength, and fat-free mass compared to placebo (P < 0.05).4 However, not all studies have found such strength gains.5

Athletes use many different steroids in different doses and varying regimens. Many take AAS at doses of 40-100 times the therapeutic recommendations.2 So, even if AAS work, what harm might accompany the benefits?

Adverse Effects

Most professional and collegiate sports organization ban AAS. Even Major League Baseball agreed to start testing in 2003 because of claims that steroid use is running rampant among players.6 The concerns are over the example given to younger players and the side effects. For example, Major League Baseball physicians report that serious muscle and tendon injuries occur 4-5 times more frequently since the use of steroids increased dramatically.6

Any examination of adverse effects is difficult because much AAS use is illegal. AAS use often is clandestine, with athletes often not telling their wives—even while attending infertility clinics.7 Major League Baseball injury reports also are anecdotal, leading others to claim the adverse effects "have been historically over-stated"2 and "exaggerated."1 A review of all adverse effects reported between 1966 and 1996 concluded that most reports were anecdotal and the side effects were minor, and many were reversible as soon as AAS use ceased.1 Many of the adverse effects are never reported outside the locker room.

Cardiac Effects

The direct effects of AAS on cardiac tissue in humans has not been examined, although several deaths of athletes using AAS have been associated with cardiac damage.8 In the first study of its kind, mice given testosterone for three weeks had their exercise-induced development of cardiac capillaries inhibited. Control mice showed normal exercise-induced capillarization.9

The first controlled study examining the cardiovascular effects of AAS on bodybuilders was published in 2001.10 Adult male volunteers were divided into three groups of 10: bodybuilders using AAS for 6.6 years on average; bodybuilders who had never used AAS; and men who never were bodybuilders or AAS users. HDL levels were significantly lower in the steroid using group compared to the other bodybuilders (0.6 vs. 1.4 mmol/L; P < 0.001). The left ventricular mass was significantly higher (P = 0.04), though not the left ventricular volume. Blood pressure and endothelial function showed no differences between the groups.

Endothelial function is an early indicator of future risk of atherosclerosis and is measured by flow-mediated vasodilatation (FMD). Healthy arteries give higher FMD values as measured by ultrasound. Twenty male bodybuilding AAS users were matched to six non-users.11 Athletes trained for eight weeks without AAS, for 8-12 weeks using AAS, and then for eight more weeks without AAS. Athletes selected and self-administered a wide variety of AAS, with testosterone esters commonly used. When AAS use commenced, HDL levels dropped dramatically (P < 0.01), but were no longer statistically different at the study’s end. FMD levels were significantly lower in the bodybuilders at all stages of the study (P < 0.01).

A study with females using testosterone found negative cardiac effects.12 Twelve female-to-male transsexuals were matched with 12 normal females. The transsexual subjects all took testosterone, two as IM injections and 10 as testosterone depots (200-800 mg). Significantly lower HDL levels were found in those using testosterone (1.2 vs. 1.6 mmol/L; P < 0.001), as was decreased arterial vasodilator response (P = 0.01).

Hepatic Effects

AAS are almost exclusively metabolized by the liver. Although liver damage can be detected by raised liver enzyme levels, intense weightlifting alone can raise these levels.1 Such changes have been detected in athletes using AAS, but return to normal soon after AAS use is stopped. Five AAS-using weightlifters avoided steroids for eight weeks and then used increasing amounts of testosterone and other AAS for 26 weeks.13 Liver enzyme levels were significantly higher in the AAS group than the controls (six weightlifters) when AAS consumption began and ended (P < 0.05), but not 12-16 weeks later. Enzyme levels remained within the normal range, leading the researchers to conclude that liver impairment was slight and reversible after 12, but not eight, weeks.

A controlled study randomly divided 26 experienced bodybuilders into three groups.14 One group self-administered AAS; the second group participated in an eight-week double-blind study of nandrolone injections or placebo; the third group participated in a 12-week double-blind cross-over study of nandrolone. At the end of the study no significant differences existed in liver-function enzyme levels.

A more serious adverse effect of AAS on the liver is peliosis hepatitis. Cystic blood-filled spaces in hepatic lobules can rupture leading to liver damage and liver failure. Only one case of peliosis hepatitis has been reported in an athlete using AAS;1 otherwise, it may be HIV-associated.

Psychological Effects

Some claim AAS improve performance by increasing athletes’ aggressiveness, called "roid rage."1 Uncontrollable aggression from AAS use has been used in criminal cases as a legal defense called the "dumbbell defense."15 In a controlled study, two behavioral assessment tools were given to male weightlifters: 30 current AAS users, 23 previous users, and 40 nonusers.15 For aggression/hostility and tension/anxiety indicators, no statistically significant differences were found between the three groups, or in comparison with population norms. The only significant difference was that current AAS users had higher "guilt" scores compared to the two other groups.

Fertility Effects

Endogenous AAS lead to reduced serum testosterone levels that can influence spermatogenesis. In-depth interviews with 110 AAS users revealed that 56% of the males reported testicular atrophy; 62% of the females had menstrual irregularities.3 A World Health Organization randomized controlled trial reported that testosterone (200 mg weekly IM injection) was an effective, reversible male contraceptive with few short-term side-effects.16 A 20-year-old male bodybuilder and father began using AAS and was azoospermic 10 months later.17 Five months after ceasing AAS he was oligospermic, and after 10 months his sperm count was normal.

However, cases have been reported where infertility persisted up to three years after AAS cessation.7 In one assessment of the duration of AAS’ effect, teenage boys predicted to grow excessively tall were administered 500 mg testosterone IM for one year.18 Ten years later, the men were compared to a control group and had significantly more maldescended testes and varioceles, and lower sperm motility, along with non-significantly reduced sperm count, concentration, and normal morphology. Overall fertility was not negatively impacted.

Effects in Female Users

Use of AAS by female athletes has grown recently. Nine female weightlifters using various AAS, including testosterone, were compared to nine non-AAS using female weightlifters.19 Those using AAS had markedly elevated serum testosterone (average, 48 mmol/L vs. 1 mmol/L). Seven AAS-using women exceeded normal male testosterone levels. All these women exhibited hirsuitism, male patterns of muscle development, acne, clitoromegaly, and menstrual disturbances. Serum HDL levels were 39% lower than in controls (average, 0.9 mmol/L; P < 0.05). LDL levels were increased, but not significantly (P < 0.06).

Conclusion

Female AAS users experience serious adverse effects from AAS that warrant immediate discontinuation. Among males, the durability of the adverse effects may not be as detrimental as once suspected, although controlled studies have demonstrated lowered HDL levels, some liver impairment, and infertility. These effects appear to be generally reversible, although in some cases the damage may have contributed to some newsworthy fatalities. The alleged negative psychological effects of AAS administration have not been borne out in controlled studies.

The use of AAS is banned in the Olympics and by the NFL, NBA, NCAA, and high schools. Obtaining and using these drugs is illegal except by prescription for "medically necessary" purposes. Many within the athletic community continue to view their use as inherently unethical and a form of cheating.

Recommendation

Athletes put their health at risk when taking AAS and should be actively discouraged from doing so. The willingness of athletes to risk their health and a criminal record stems from underlying societal values. The American College of Sports Medicine claims this willingness arises from "our societal fixations on winning and physical appearance."20 The pressures are enormous. Ken Caminiti, former baseball MVP, stated that if he didn’t use steroids, "the guy next to you is . . . going to take your job and make the money."6 Given that mentality, physicians should remain alert for the most common adverse effects of AAS when caring for athletes. v

Dr. O’Mathúna is Professor of Bioethics and Chemistry at Mount Carmel College of Nursing, Columbus, OH.

References

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