Drugs in sport

There are three reasons why athletes and sportspeople may take drugs:

• 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.

• To enhance performance: in doing so this could give an unfair advantage. The GMC's stance on this is unequivocal:

• As recreational drugs: many recreational drugs are banned by sports authorities, despite not being performance-enhancing. In some sports, such as horse racing, there is a rationale on safety grounds; competing under the influence of recreational drugs, including alcohol, could pose a threat to the competitor and others.² Elsewhere, the authorities' justification is that illegal recreational drug use 'brings the sport into disrepute', and that - as role models for others in society - athletes should not use illicit drugs.

  • These policies have been challenged, with some arguing that sportspeople found to be using recreational drugs should be offered counselling, rehabilitation, and monitoring, rather than receiving a competition ban.³

  • Policies on recreational drugs continue to evolve. For example, cannabis is legal in some jurisdictions and does not have performance-enhancing effects. The World Anti-Doping Agency (WADA) retains THC (the main psychoactive ingredient in cannabis) on its banned list - despite lobbying to remove it entirely - but downgraded the sanction in 2021 from a two-to-four year competition ban, to one-to-three months, if an athlete who tests positive for THC in-competition can demonstrate that they used it out-of-competition and that this was unrelated to sports performance.⁴

Drug testing⁵

• All elite athletes competing at international level and professional sportspeople 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 a sportsperson is not competing but not permissible during competition. Others, such as anabolic steroids are banned at all times.

• Some drugs are banned in some sports but not in 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 obtain guidance from the sport's website. Several 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

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 - eg, the one used for football is found at the FIFA website.⁶

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 in others.

Some are permissible out of competition but not whilst competing. The World Anti-Doping Agency (WADA) produces a full list of prohibited drugs every year.⁷

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 sustain 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 WADA list of banned substances and combinations such as co-codamol appear acceptable. It is the stronger narcotic agents that are banned; tramadol will also be banned in-competition from January 2024 onwards.⁸ 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 weightlifting.

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.

• Amphetamines are therefore on the list of banned substances. However, amphetamine prescriptions for recognised indications, such as ADHD, are increasing;⁹ athletes with ADHD may seek a TUE for stimulant use. WADA has released guidelines for physicians.¹⁰

• Sympathomimetic decongestants may also be used as performance-enhancing drugs. Pseudoephedrine is prohibited when the concentration in the urine is >150 micrograms per millilitre. Pseudoephedrine has been moved from the prohibited list to the monitoring program (ie it is one of several drugs which can be used during competition only but which WADA is monitoring for abuse). Ephedrine is prohibited when its concentration in urine is >10 micrograms per millilitre.⁷ This probably means that 0.5% ephedrine nasal drops are safe.

• Saline nasal 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. A TUE may be issued; this led to substantial controversy when Sir Bradley Wiggins was given TUEs over several years for intravenous triamcinolone to treat pollen allergies - something out of step with usual medical care.¹¹ Topical steroids are permitted.

Enhancement of oxygen transfer

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

• Training at altitude in a low PO₂ stimulates endogenous erythropoietin.

• Recombinant erythropoietin is effective, especially if combined with supplementary iron.

• Hypoxia-inducible factor-1 (HIF-1) acts as a transcription factor to facilitate erythropoietin production. Daprudostat was the first HIF-1 stabiliser to gain FDA approval (for treatment of renal anaemia) in February 2023;¹² however, HIF-1 stabilisers have been on WADA's banned list since 2011, suggesting they have been available illicitly for some time. Xenon gas also increases HIF-1a production, and was added to WADA's banned list in 2014; there were claims that some of the Russian Winter Olympics team used xenon at the Sochi Olympics in 2014.¹³

• 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 (autologous transfusion).

Of these techniques, only altitude training is legal. Substances to enhance oxygen uptake and haemoglobin substitutes are also banned.

Autologous transfusion is difficult to detect. At present, the only officially-sanctioned detection method is the Athlete Biological Passport, which measures changes in individual athletes' biometric data over time.¹⁴ Research on this and on other methods of detecting illicit methods of oxygen transfer enhancement are ongoing.^{15 16 17}

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.^{18 19} 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 occurs when an endogenous substance such as testosterone is taken. The ratio of testosterone to dehydroepiandrosterone (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.²⁰

• 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 premenstrual or menstruating during an important event. Their value as a contraceptive is also appreciated.

• Other banned substances include tibolone, which has some anabolic effect, and anti-oestrogens including the selective oestrogen receptor modulators (SERMs) and aromatase inhibitors. If there are genuine reasons to prescribe such drugs, a TUE can be issued.

• Anabolic steroid use is common amongst recreational athletes, with a global lifetime prevalence estimate of 18.4%.²¹ This may be higher than in professional athletes, as recreational athletes are often not subject to drug testing.

Other agents

New illicit performance-enhancing agents are being developed all the time. One of the most recent is peroxisome proliferator-activated receptor-delta agonists termed GW1516. It is a constant battle to develop analytical techniques which can detect these substances.

In the case of GW1516, mass spectrometry is being used for this purpose.²²

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.

• Corticotropins, including adrenocorticotropic hormone (ACTH).

• Human growth hormone (hGH), insulin-like growth factors and mechano growth factors.

• All the releasing factors of these listed hormones.

• Erythropoietin.

• Insulins.

Several techniques have been developed to detect peptide hormones and analogues.²³

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.²⁴

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.

Recombinant GH abuse remains a major challenge and isoform assays have been developed to detect this.²⁵

GH and insulin seem to work together to control blood glucose but the role of insulin is much more profound than just glucose homeostasis. Insulin may be used to counter the hyperglycaemic effects of GH but it is also abused by bodybuilders and there are reports of severe hypoglycaemia as a result.

Gene doping

In the future, this could potentially become a new possibility for abuse as a performance enhancer in sport. WADA 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.²⁶

Denying the charges

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

In terms of physiology, 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 supplements 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.²⁷

Eliminating drugs from 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. Yet, there remains an incentive to use any and all measures to enhance performance, especially in elite sport, where fine margins can make the difference between victory and finishing as a runner-up - which may also have major financial rewards. State-sponsored doping, once thought a relic of the Cold War, was exposed in Russia in 2015, ²⁸ leading to lengthy competition bans for athletes from that country. In many parts of the world, anti-doping testing rates are extremely low.²⁹

Accurately determining the prevalence of doping in sport is extremely challenging, and requires a synthesis of different methodologies and research teams. Existing studies report doping rates from 0% to 73%, with most falling below 5%.³⁰ Due to this difficulty in measurement, it is difficult to determine how effective anti-doping measures are. A survey-based study of German high-level cyclists and track and field athletes, however, found that they perceived effective diagnostic tests, competition bans, and a hypothetical criminal law against doping to be the most effective deterrents.³¹

Some have argued that doping should be allowed under medical supervision. Such an approach, it is argued, would allow performance-enhancing drugs to be studied more effectively, allowing clinicians to clearly identify 'safe' and 'unsafe' regimes. It is also true that anti-doping measures are increasingly expensive and arguably bringing diminishing returns, as doping strategies become more sophisticated.³² The prevailing counter-argument holds that allowing doping would always introduce additional health risks for athletes from the substances used, and that, in elite sport, doping would rapidly become mandatory for anyone wishing to be competitive.³³