There are three reasons why athletes and sports people may take drugs:

1. As medication for disease: they are as entitled to treatment of a medical condition as anyone else but both the competitor and the doctor must be aware of the rules about banned substances. Failure to heed them can have serious consequences. An athlete could receive either a temporary or permanent ban from competing in that sport. If the doctor is at fault, there is potential for litigation irrespective of whether the individual is an amateur or professional competitor.
2. To enhance performance: in doing so this could give an unfair advantage. The GMC's stance on this is unequivocal:
   

   GMC Guidance Doctors who prescribe or collude in the provision of drugs or treatment with the intention of improperly enhancing an individual's performance in sport would be contravening the GMC's guidance, and such actions would usually raise a question of a doctor's continued registration. This does not preclude the provision of any care or treatment where the doctor's intention is to protect or improve the patient's health.

3. As recreational drugs: e.g. cannabis is a banned substance even though it is not considered a performance enhancing drug. The authorities say that it is necessary to take such steps as athletes and sports people are role models for young people and hence should not take illicit drugs. However, they do not suggest how young people would know that their heroes take drugs if they were not tested and positive results made public.

Drug testing

• All elite athletes competing at international level and professional sports people are likely to be routinely tested. However, testing may go down to much lower levels and include young competitors. Sometimes testing may be anticipated. It is common practice to test all who have won medals in major events but random drug testing can also take place. Elite athletes may also be visited by representatives from their governing body for out of season testing.
• Some drugs are permissible when not competing but not during competition. Others, such as anabolic steroids are banned at all times.
• Some drugs are banned in some sports but not others. Banned substances can include alcohol and caffeine above a certain level. Beta-blockers would impair performance of an endurance athlete but suppression of tremor gives unfair advantage in shooting events. It may be possible to get guidance from the sport's website. A number of useful sites are listed at the end of this article.
• Drug testing does not apply simply to sports such as athletics and football but may include snooker, bridge and chess played at the highest levels.

Therapeutic use exemption (TUE)

If a doctor believes that there is a good reason why his patient needs a banned substance, it is possible to issue a Therapeutic Use Exemption (TUE) certificate. An example of one to be used for football is found at the FIFA website listed at the end. They may be temporary for a single spell of illness or of longer duration. They must be issued in good faith, stating that alternative medication is inappropriate. For example, if a snooker player has hypertension, does he really need a beta-blocker?

Potential pitfalls

The problems faced by a doctor may be for relatively minor treatments such as decongestants, analgesics and medication for asthma. As mentioned above, some drugs are permissible in some sports and not others. Some are permissible out of competition but not whilst competing.

Doctors need to be aware of the possibility that patients may use an element of deceit to acquire prescriptions for substances that they know they should not have.

Analgesics

• Athletes often suffer injuries and analgesics may be appropriate. Non-steroidal anti-inflammatory drugs (NSAIDs) are the group of choice and are always permissible, as is paracetamol.
• Opiate-related analgesics are more problematic. Codeine is not on the World Anti-Doping Agency (WADA) list of banned substances and combinations such as co-codamol appear acceptable. It is the stronger narcotic agents that are banned. However, screening does not always differentiate adequately between the various narcotic or codeine related compounds and they are best avoided.
• Sometimes an athlete will ask the doctor to give an injection into an injured part to permit competition. Pain is an important warning that something is wrong and if a significant injury is pain-free this is a potentially dangerous situation. Steroid injections may also weaken ligaments and should not be given into tendons or ligaments.

Diuretics

The main reason for wishing to use diuretics is to produce more dilute urine so that illicit substances are not detected. For this reason they are banned. They may also be used in sports with weight categories such as judo and weight lifting. The competitor can dehydrate, make the weight at the weigh-in and then rehydrate before the competition as even mild dehydration can ebb fitness significantly. Jockeys have used diuretics for many years. Masking substances to hide the use of illicit drugs include probenecid and this is also banned.

Stimulants

• The problem of stimulants in sport reached public attention in 1960 when the Danish cyclist Knut Jenson died in the Rome Olympics and it transpired that he had been taking amphetamines.
• The problem for doctors is not usually with amphetamines, as these now have few indications, but with decongestants that may be requested or bought over the counter to clear the airways of an athlete with a cold.
• Substances containing phenylephedrine and pseudoephedrine should be avoided. Ephedrine is prohibited when its concentration in urine is > 10 micrograms per millilitre.¹ This probably means that 0.5% ephedrine nose drops are safe.
• Saline nose drops are certainly safe and allowed but less effective. If a pharmacological agent is required, an anticholinergic such as ipratropium spray may be used.
• Beta-2 agonists are banned substances but they may be used if delivered by inhaler to a patient with asthma and a TUE is issued.
• Corticosteroids are also banned but if anyone needs them, whether they are otherwise fit to compete at top level needs to be questioned. A TUE may be issued. Topical steroids are permitted.

Enhancement of oxygen transfer

For endurance events, a high haematocrit enhances performance. There are 3 ways to achieve this:

• Training at altitude in a low PO₂ stimulates endogenous erythropoietin.
• Recombinant erythropoietin is effective, especially if combined with supplementary iron.
• Blood doping means removal of a unit of blood, perhaps 4 to 6 weeks before competition, the body replaces the lost blood and shortly before competition the blood is transfused.

Of these 3 techniques, only altitude training is legal. There is no satisfactory way of detecting blood doping by autologous transfusion.² Techniques are being developed to detect recombinant EPO and may already be used.^3,4 Substances to enhance oxygen uptake and haemoglobin substitutes are also banned.

Anabolic steroids

• Anabolic steroids are a generic term for male hormones. The idea behind their abuse in sport is that they promote muscle growth and protein synthesis. However, abuse also has side effects such as cardiomyopathy, atherosclerosis, hypercoagulopathy, hepatic dysfunction and psychiatric and behavioural disturbances.⁵ They may be used for hypogonadism or diseases such as aplastic anaemia but such people are unlikely to compete at an elite level.
• In the 1970s athletes would take synthetic androgens such as nandrolone and these are easy to detect without any controversy. A much more difficult problem is when an endogenous substance such as testosterone is taken. The ratio of testosterone to dihydroepiandrosterone (DHEA) is usually about 1:1 or 2:1. A similar ratio is expected in women. If it is over 4:1 then exogenous testosterone is likely. Some men appear to have naturally high ratios but a radiocarbon test can detect synthetic testosterone. New ways are being developed to detect metabolites of androstenedione, testosterone and dihydrotestosterone abuse.⁶
• Female hormones also have anabolic effects, although not as marked as male hormones. Athletes who return to training after pregnancy often find that they are stronger than they were before. Oral contraceptives are permitted substances and may well be desirable. They tend to reduce menstrual loss and hence any tendency to iron deficiency. As well as making menstruation more tolerable, they can be used to adjust its timing so that the competitor is not pre-menstrual or menstruating during an important event. Their value as a contraceptive is also appreciated.
• Other banned substances include tibolone, which has some anabolic effects, and anti-oestrogens including the SERMs and aromatase inhibitors. If there are genuine reasons to prescribe such drugs, a TUE can be issued.

New trends in hormone abuse

The chemicals that we tend to think of as anabolic (the male hormones described above) are not the only ones with anabolic properties and hence other hormones may also be abused. In 1989 the Medical Commission of the International Olympic Committee (IOC) introduced the new doping class of peptide hormones and analogues. This includes:

• Human chorionic gonadotrophin (hCG) and related compounds
• Corticotrophins, including adrenocorticotrophic hormone (ACTH)
• Human growth hormone (hGH), Insulin-like Growth Factors and Mechano Growth Factors
• All of the releasing factors of these listed hormones
• Erythropoietin (Epo)
• Insulins

Both hCG and luteinising hormone (LH) may also be used to enhance the endogenous production of testosterone by artificial means and are prohibited in males.^7,8

In the past 20 years, growth hormone (GH) has been considered as a performance-enhancing drug in the world of sport. A blood test for hGH was first introduced at the 2004 Summer Olympic Games in Athens, Greece. Further tests are being developed to enhance the detection window for hGH abuse.
Because resting or random measurements of plasma GH concentrations per se are meaningless, new methods have been devised to evaluate plasma levels of GH-sensitive substances that are more stable, and hence detectable, than the hormone itself.⁹

Growth hormone and insulin seem to work together to control blood glucose but the role of insulin is much more profound than just glucose homeostasis.¹⁰ Insulin may be used to counter the hyperglycaemic effects of GH but it is also abused by body builders¹¹ and there are reports of severe hypoglycaemia as a result. The legal classification of insulin has been changed from P (for sale in pharmacies) to PoM (prescription only medicine).

Gene doping

In the future, this could potentially become a new possibility for abuse as a performance enhancer in sport. The World Anti-Doping Agency describes gene doping as 'the non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance'. The potential for gene doping would be to inject 'normal' genes into the body to increase the functioning of a 'normal' cell. For example, genes producing insulin growth factor 1 to help muscles grow and repair.¹²

Denying the charges

Sometimes when an athlete is found to have taken a banned substance, he or she admits to the fault but very often they deny ever knowingly having taken a banned substance. Cynics are unsurprised but often the athletes seem very genuine.

Elite athletes are not "normal" people and so reference ranges for physiological substances need to be determined on their peers. A cyclist who may be burning 9,000 calories a day during competition is not a normal subject. Sprinters tend to be very muscular and have a low body fat content. Fat is important in the metabolism of steroid hormones. The people who set such standards are sufficiently well versed in sports medicine and exercise physiology that they set their standards by the normal for the group that they examine. Nevertheless, if they say that their reference range will include 99% of all those active athletes who are not taking banned substances, then 1 in 100 will fall outside that range.

Most top athletes use dietary supplements¹³ and the contents of these may not be as vigorously controlled as may be hoped. Contaminants that have been identified include a variety of anabolic androgenic steroids including testosterone and nandrolone as well as the pro-hormones of these compounds, ephedrine and caffeine. This contamination may be the result of poor manufacturing practice, but there is some evidence of deliberate adulteration of products. The principle of strict liability that applies in sport means that innocent ingestion of prohibited substances is not an acceptable excuse, and athletes testing positive are liable to penalties. Although it is undoubtedly the case that some athletes are guilty of deliberate cheating, some positive tests are likely to be the result of inadvertent ingestion of prohibited substances present in otherwise innocuous dietary supplements.^14,15

The beneficial effects of creatine have been shown in a number of studies.¹⁶ It is thought to offer potential gains in body mass and muscle strength.¹⁷ Creatine, ginseng and a number of other substances raise the question of when does a dietary supplement become a drug? Some people like to use herbal products in the belief that they are beneficial but not pharmacological. Some may even have been contaminated with pharmaceutical products as with the contamination of chinese treatments for eczema with corticosteroids.¹⁸

Ethical considerations

The position of the GMC with regard to a doctor aiding and abetting drug abuse in sport is clear. However, a doctor may be faced by a patient who admits to using anabolic steroids. He does not enter competitions and so is not tested. He wants the doctor to monitor his liver function as an early warning of any damage. What is the position? He will continue to take the steroids whether the doctor cooperates or not. Would it be reasonable to warn him of the dangers and to check liver function and lipids? This would not be endorsing his action any more than a needle exchange encourages intravenous drug abuse. He may also benefit from the needle exchange. Is it a damage limitation exercise that can be justified?

Getting drugs out of sport

There is a constant battle between those seeking new techniques to detect illicit use of performance enhancing substances and those who wish to circumvent the rules. Testing is vigorous and can be unannounced and the penalties for being discovered are severe. Nevertheless there are, and always will be, those who attempt to use illicit ways of enhancing performance to get the necessary slight edge that is required to win. From time to time illegal substances are discovered. In british sport this should not be seen as evidence of widespread abuse of drugs but evidence that a vigorous and effective system of monitoring is in place.

Some would argue that the only way to get a "level playing field" is to lift all bans on drugs and let us push human endurance to the limit. Records have tumbled with new technologies going back to spikes and starting blocks and including modern running shoes and fibreglass poles for vaulting. Should we encourage the same with pharmacological technology? This is a false argument as the banned substances are not without significant risk. It cannot even be argued that the athlete is free to make his own choice because if the opposition use drugs to gain advantage, he will have to do the same to be able to compete.

With the upcoming 2012 olympics in the UK, there is a call to toughen the UK's stance on doping in sport. Various suggestions have been made including the possibility of trialling a doping passport to be carried by all athletes. This would record the results of doping tests and natural concentrations of hormones such as erythropoietin during their careers, the idea being that this would make it easier to detect any substance abuse.

World Anti-Doping Agency

The World Anti-Doping Agency (WADA) was founded with the belief that 'athletes have a fundamental right to participate in doping-free sport and that doping endangers athlete health and the integrity of sport.' It serves as the independent international body responsible for coordinating and monitoring the global fight against doping in sport. The website link can be found below.

Document references

1. The World Anti-Doping Code, the Prohibited List International Standard, World Anti-Doping Agency
2. Ekblom BT; Blood boosting and sport. Baillieres Best Pract Res Clin Endocrinol Metab. 2000 Mar;14(1):89-98. [abstract]
3. Gore CJ, Parisotto R, Ashenden MJ, et al; Second-generation blood tests to detect erythropoietin abuse by athletes. Haematologica. 2003 Mar;88(3):333-44. [abstract]
4. Delanghe JR, Bollen M, Beullens M; Testing for recombinant erythropoietin. Am J Hematol. 2008 Mar;83(3):237-41. [abstract]
5. Kam PC, Yarrow M; Anabolic steroid abuse: physiological and anaesthetic considerations. Anaesthesia. 2005 Jul;60(7):685-92. [abstract]
6. Cawley AT, Hine ER, Trout GJ, et al; Searching for new markers of endogenous steroid administration in athletes: "looking outside the metabolic box". Forensic Sci Int. 2004 Jul 16;143(2-3):103-14. [abstract]
7. Kicman AT, Cowan DA; Peptide hormones and sport: misuse and detection. Br Med Bull. 1992 Jul;48(3):496-517. [abstract]
8. Handelsman DJ; Clinical review: The rationale for banning human chorionic gonadotropin and estrogen blockers in sport. J Clin Endocrinol Metab. 2006 May;91(5):1646-53. Epub 2006 Feb 14. [abstract]
9. Rigamonti AE, Cella SG, Marazzi N, et al; Growth hormone abuse: methods of detection. Trends Endocrinol Metab. 2005 May-Jun;16(4):160-6. [abstract]
10. Sonksen PH; Insulin, growth hormone and sport. J Endocrinol. 2001 Jul;170(1):13-25. [abstract]
11. Evans PJ, Lynch RM; Insulin as a drug of abuse in body building. Br J Sports Med. 2003 Aug;37(4):356-7. [abstract]
12. Play True. Gene Doping. Issue 1 - 2005, The World Anti-Doping Agency
13. Beltz SD, Doering PL; Efficacy of nutritional supplements used by athletes. Clin Pharm. 1993 Dec;12(12):900-8. [abstract]
14. Maughan RJ; Contamination of dietary supplements and positive drug tests in sport. J Sports Sci. 2005 Sep;23(9):883-9. [abstract]
15. Parr MK, Geyer H, Hoffmann B, et al; High amounts of 17-methylated anabolic-androgenic steroids in effervescent tablets on the dietary supplement market. Biomed Chromatogr. 2007 Feb;21(2):164-8. [abstract]
16. Okudan N, Gokbel H; The effects of creatine supplementation on performance during the repeated bouts of supramaximal exercise. J Sports Med Phys Fitness. 2005 Dec;45(4):507-11. [abstract]
17. Calfee R, Fadale P; Popular ergogenic drugs and supplements in young athletes. Pediatrics. 2006 Mar;117(3):e577-89. [abstract]
18. Ernst E; Adverse effects of herbal drugs in dermatology. Br J Dermatol. 2000 Nov;143(5):923-9. [abstract]

Internet and further reading

• Therapeutic Use Exemptions, the FA.com
• The World Anti-Doping Code, the Prohibited List International Standard, World Anti-Doping Agency
• World Anti-Doping Agency

Acknowledgements