Performance enhancing drugs

Ryan Shulman looks at anabolic steroids and other routes to chemically assisted athletic success

In 1993 the competitive bodybuilder Mohammed ‘Momo’ Benaziza died in his hotel room after the Holland Grand Prix contest. In 1996 another bodybuilder, Andreas Münzer, died 12 days after finishing sixth in the Arnold Schwarzenegger Classic. Doctors in Munich blamed his death on the abuse of anabolic-androgenic steroids (AAS), growth hormones and diuretics. According to several unofficial online body-building sources, Münzer apparently was taking a toxic cocktail of AAS as well as erythropoietin (EPO), insulin, aspirin and diuretics (see Table 1).

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Münzer may have been a professional bodybuilder, but his death demonstrates the dangers inherent in many of the substances commonly used by athletes for their performance-enhancing effects, as well as by non-athletes for improved aesthetics.

In this final part of our overview of the drugs athletes take, we look in depth at steroid abuse, as well as growth hormone, EPO, beta-blockers and amphetamines.

Anabolic androgenic steroids

(WADA Prohibited Substances List 2006)

AAS are synthesised derivatives of the human hormone testosterone. Just about every cell in the human body has receptors for testosterone: as the primary male sex hormone it affects all cells throughout the body. The effects depend on the type of cell, its location and any concomitant stimulus. To date it has proved impossible to manufacture a purely anabolic (growth-producing) steroid that doesn’t also deliver androgenic changes (increased male secondary sexual characteristics), such as deep voice, facial hair, balding or hair loss.

Studies have shown that between 1% and 6% of high school-age males and females are abusing AAS, with a worrying recent rise in use among girls(1). Figure 1 shows the trends in steroid use among 8th, 10th and 12th grade students in the US, taken from the Monitoring The Future (2)study of drug use among Americans. However, the graph shows a decline in use (male and female) over the past 12 to 18 months, which may be linked to a new targeted government anti-steroid campaign.

Effects of AAS

Since the early 1960s, when commercial AAS became available, several studies have been published on their effects. These studies are, however, limited in their efficacy. Most use a medically directed dose of a single agent, which fails to mimic trends in gymnasiums around the globe in which cycles of multiple agents are administered at doses far higher than the medically sanctioned levels. Accurate investigation of the effects of common regimes is almost certainly going to be precluded by ethical issues (3). Numerous studies have documented the increase in lean muscle mass that can be attributed to AAS. In humans this increased lean muscle mass seems not to correlate with a decrease in fat mass. Muscle changes are related on the whole to hypertrophy of individual fibres but also to development of new fibres(4). But researchers still don’t know the extent to which fast-twitch (Type I) versus slow-twitch (Type II) muscle fibres are affected, despite initial predictions that hyper-trophy would happen mainly in the larger Type I fibres.

It used to be thought that to make significant strength gains by taking AAS, the user would need already to be undertaking a serious strength training regimen. However, researchers have demonstrated changes in strength after intra-muscular testosterone injections (600mg/week), even where participants were not involved in any strength training(5). Methandrostenolone (Dianabol), one of the most commonly studied drugs, has been shown to improve strength, notably at levels of 10mg/day or higher, in power tasks (particularly upper body tasks such as the bench press).

Investigations into improved performance in endurance tasks have been limited, though animal studies(6)have shown benefits. Early medical uses of AAS included treatment of haematological disorders, which helped to improve haemoglobin levels. Based on these improvements, research was conducted into the possible role of AAS in increasing haemoglobin and thus improving performance in endurance type sports. Little improvement in haemoglobin count was noted in subjects who did not have blood disorders. The advent of EPO (see below) has superseded this line of investigation. Anecdotal claims by users that AAS help to significantly improve their recovery has not been backed up by research.

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Adverse effects of AAS

Because receptors for these hormones can be found throughout the body, their adverse effects are widespread, variable and drug/dose dependent.

AAS will affect the feedback mechanisms responsible for testosterone, sperm and semen production. Alterations in their levels are demonstrable even after 24 hours and will ultimately lead to testicular atrophy (shrinkage) and decreased sperm and semen production. Females will display masculinisation with deepening of the voice, facial hair, male pattern baldness and enlargement of the clitoris.

Androgens (including testosterone) are converted enzymatically in the body to oestrogens. Thus AAS use will eventually lead to increased blood oestrogen levels. High oestrogen levels are responsible for the development of gynaecomastia (breast tissue growth) in males, which may require surgical excision. Some abusers take Tamoxifen (one of many anti-oestrogen medications, which are all listed on the WADA Prohibited Substances List 2006) in an attempt to prevent gynaecomastia. Success of this treatment is variable and the medications have their own potential side effects.

Excessive androgens are also responsible in part for the acceleration of baldness in those susceptible, as well as acne, prostate enlargement and possible increased risk of prostate cancer. Insulin resistance and thus poor intrinsic control of blood sugar levels in AAS users(7)may be a predictor of diabetes mellitus or contribute to the development of coronary artery disease.

Orally administered AAS must pass through the liver before reaching the blood- stream, so are more damaging to the liver than equivalent intravenous doses. Most studies have shown increased levels of markers of liver damage in AAS users. Similar increased levels of biochemical markers of cholestatic jaundice (blockage of the bile duct – another documented side-effect of AAS) have been demonstrated. An increased incidence of liver tumours (mostly benign) has also been recorded.

Almost all types of AAS adversely alter lipid levels. While the extent of change varies by drug, steroid users will experience a drop of up to 50% in HDL cholesterol (the ‘good’ cardioprotective cholesterol) and a rise in LDL (‘bad’ atherogenic cholesterol) of up to 30%(8). Users are thus at an increased risk of accelerated vascular disease, including coronary artery disease, which could lead to heart attacks at an early age. Research has found that lipid levels can remain elevated even after AAS use has ceased(9).

Other well documented psychological issues include increased aggression, dependence, depression, eating disorders and altered body image disorder.

Oral steroidals

(WADA Prohibited Substances List 2006)

Androstenedione (street name ‘Andro’) and Dehydroepiandrosterone (DHEA), which are precursors to testosterone as well as oestrodiol and oestrone, are available as supplements. They are far weaker than AAS, but are able to increase blood testosterone levels, albeit transiently. Evidence for an increase in strength from ‘Andro’ use is lacking and some studies show evidence of increased protein breakdown. Other claims such as DHEA’s anti-obesity properties are based largely on animal research, and studies have shown significant androgenic effects. There is no data available on the long-term adverse effects of these products.

Somatotropin (human growth hormone)

(WADA Prohibited Substances List 2006) Human growth hormone (HGH) is secreted naturally from the pituitary gland and causes growth in all tissues of the body. It is thought that HGH causes retention of nitrogen, increased protein synthesis leading to increased muscle mass, mobilisation of fat and increased use of fat for energy, which spares muscle glycogen. These effects have been shown in men over the age of 60 (there are few studies of its effects in the younger population) and, as a consequence, HGH has been hyped at a commercial level as an ‘anti-aging miracle’. One trial, which compared HGH and placebo treatment of endurance athletes, showed a net increase in anabolic activity at rest, during and after exercise in the treatment group(10).

It is a common misconception that HGH can be successfully taken in oral form, rather than as an injected drug. The large molecule is broken down if taken orally. Many over-the-counter supplements use the ‘HGH’ acronym in their names in an attempt to take advantage of this poor understanding. Others claim to contain HGH, but in such minute amounts that there could be no observable effects(11). Authentic HGH is expensive, up to $5,000 a month, depending on the illegal source, demand etc.

When used in adults without a medically proven HGH deficiency, the side effects include acromegaly (enlarged hands/feet, brow and lower jaw protrusion), diabetes, osteoporosis, carpal tunnel syndrome and leukaemia. Until HGH was produced synthetically there was a risk of Creutzfeldt-Jakob Disease as the hormone was removed from cadaveric pituitary glands. Black-market HGH may still be pituitary derived.

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Insulin-like growth factor 1 (IGF-1)

(WADA Prohibited Substances List 2006)

IGF-1 is a polypeptide produced by the liver and is partly under the control of growth hormone. Many of the touted anabolic effects of HGH are in fact attributable to the actions of IGF-1. As with HGH, over-the-counter preparations claiming to include IGF-1 usually contain precursors that have not been shown to be ergogenic. The side effects include jaw pain, obesity and shortness of breath.

Erythropoietin (EPO)

(WADA Prohibited Substances List 2006)

EPO is clearly an ergogenic substance, normally produced by the kidneys to stimulate red blood cell production. Levels above those normally produced by the kidneys will increase the oxygen-carrying capacity of the blood and thus improve outcomes for endurance athletes. Audran et al(12)showed an increase in VO2max of 9% and increased power output of 7%. EPO is potentially dangerous as it augments the red cell numbers in the blood and thus increases viscosity, leading to potentially lethal thrombus (clot) formation.

Beta-blockers

(WADA Prohibited Substances List 2006 – in competition, selected sports only)

Beta-blockers are used medically to treat cardiac conditions and hypertension. They are abused by athletes in sports involving accuracy and concentration, such as shooting, darts, archery, golf etc. They act to block the action of adrenalin and noradrenalin on the heart and are thus used to reduce anxiety and steady the arms and hands. Potential side effects include hypotension, cardiac arrhythmias, sexual dysfunction and acute exacerbation of asthma.

Methamphetamine (‘Speed’)

(WADA Prohibited Substances List 2006)

Methamphetamine is another synthetic street drug that stimulates the sympathetic nervous system. Its effects are similar to that of cocaine (see SIB 58), except that they tend to last longer. It can be swallowed, smoked or injected. It is included in the pharmacologic class known as amphetamines, which have been used medicinally in nasal decongestants, appetite suppressants and, during the Second World War, to increase stamina and decrease fatigue in soldiers. Other stimulants with similar properties that are banned from competition include: Dexedrine, Benzadrine, ephedrine, and psuedoephedrine hydrochloride (Sudafed).

The side effects of speed are in line with cocaine and ecstasy, including difficulties with temperature regulation and energy metabolism as well as the cardiovascular side effects described in SIB 58. Impaired concentration and poor sleep will adversely affect performance.

Speed and other similar amphetamines are drugs taken to improve performance in competition rather than regularly throughout training, as regular use can lead to tolerance. Lab tests using Dexedrine have shown significant improvements in knee extension strength, acceleration, anaerobic capacity, time to exhaustion, and pre-exercise and maximum heart rates(13). These effects can clearly provide performance bonuses; however, the risks involved in terms of added stresses on the body are considerable.

Conclusion

The pressures of attaining peak performance placed on athletes by fans, coaches and themselves can drive them towards the lure of illegal ergogenic substances. The potential benefits should be tempered by improved knowledge of the serious health implications as well as the potential economic and social implications of being caught.

References

1. Bahrke MS, Yesalis CE, ‘Abuse of anabolic androgenic steroids and related substances in sport and exercise.’ Current Opinion in Pharmacology4:614-620 (2004)

2 .www.monitoringthefuture.org

3.Hartgens F, Kuipers H, ‘Effects of Androgenic- Anabolic Steroids in Athletes.’ Sports Med34 (8): 513-554 (2004)

4.Kadi F, ‘Adaptation of human skeletal muscle to training and anabolic steroids’. Acta Physiol Scand Suppl646: 1-52 (2000)

5.Bhasin S, Storer TW et al, ‘The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men’. N Engl J Med 335: 1-7 (1996)

6.Tamaki T, Uchiyama S et al, ’Anabolic steroids increase exercise tolerance’. Am J Physiol Endocrinol Metab280 (6): E973-81 (2001)

7.Cohen JC, Hickerman R, ‘Insulin resistance and diminished glucose tolerance in power lifters ingesting anabolic steroids’. J Clin Endocrinol Metab64; 960-3 (1987)

8.Lenehan P, Anabolic Steroids and other performance enhancing drugs. London: Taylor & Francis (2003)

9.Hartgens F, Rietjens G et al ‘Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a)’. Br J Sports Med38:253-259 (2004)

10.Healy ML et al, ‘High dose growth hormone exerts an anabolic effect at rest and during exercise in endurance-trained athletes’. J Clin Endocrinol Metab88(11):5221-6 (2003)

11.Juhn M, ‘Popular sports supplements and ergogenic aids’. Sports Med 33 (12): 921-939 (2003)

12.Audran M Gareau R et al. ‘Effects of erythropoietin administration in training athletes and possible indirect detection in doping control’. Med Sci Sports Exerc31 (5): 639- 45 (1999)

13.Chandler JV, Blair SN. ‘The effect of amphetamines on selected physiological components related to athletic success’. Med Sci Sports Exerc 12(1):65-9 (1980)

14. Hartgens F, Kuipers H, ‘Effects of Androgenic- Anabolic Steroids in Athletes’. Sports Med34 (8): 513-554 (2004)

15.www.monitoringthefuture.org/data/ 05data/fig05_15.pdf

16. Adapted from data www.bodybuildingpro.com/ andreasmunzercocktail.html 17.Adapted from

www.nida.nih.gov/ResearchReports/Steroids/ anabolicsteroids2.html#scope