Hormones and Sports Performance

WADA

The interactive network effects of the Endocrine system are key in producing effective adaptations to exercise. This in turn results in improved sport performance. Athletes are aware of the crucial role of the Endocrine system in sports performance. Therefore it is not surprising that, on the World Anti-Doping agency (WADA) banned list, the majority of prohibited substances both in and out of competition are hormones, mimetics and hormone and metabolic modulators. In 2013 hormones accounted for 75% of all adverse analytical findings. Use of such substances to enhance performance is not only illegal and against the spirit of sport, but also potentially harmful to the health of the athlete.

Considering some of these prohibited hormones, the usual suspects start with anabolic agents: anabolic androgenic steroids whether these be synthetic derivatives taken exogenously or molecular identical endogenous steroids, including metabolites and isomers, administered exogenously.  In a study recently published in the BJSM, female athletes with free testosterone levels in the highest tertile displayed better performance than those in lowest tertile of up to 4.5% in certain power/anaerobic events such as 400m, 800m, hammer and pole jump. This may be due to associated body composition with increased lean mass and “risk taking” behaviour. In 2015, the Court of Arbitration for Sport ruled that the IAAF should suspend the existing upper limit on female athlete testosterone, of 10nmol/l, because at the time there was insufficient evidence that such levels would improve performance in female athletes. In view of the results of this study, the situation may have to be reviewed. This is clearly an ethical dilemma regarding intersex athletes, whose hyerandrogenism is due to endogenous biological factors.

Next up there are peptide hormones/growth factors/mimetics. As previously discussed, growth hormone (GH) proved a challenging peptide hormone for which to develop a dope test. Firstly what are the “normal” ranges for elites athletes, seeing as exercise and sleep are the two major stimuli for GH release? Furthermore, elite athletes represent a subset of the population, for whom the normal range may differ. Secondly exogenous genetically engineered GH is to all intents and purposes identical to endogenous secreted GH, with a relatively short half life. Hence early on in development of a dope test we realised that downstream markers, particularly of bone turnover would have to be used. This brings the discussion to erythropoietin (EPO). In a similar way to GH and allied releasing factors, increases in key surrogate variables producing performance enhancement are measured. In the case of exogenous EPO these are changes in haemoglobin and haematocrit as recorded in an athletes’ biological passport. A recent study on amateur cyclists given EPO in a double blind randomised placebo controlled trial, reported no improvement in a submaximal field test. Although the effects in elite cyclists would arguably be more relevant, this is not possible for obvious ethical reasons. Nevertheless the effects on elite cyclists during maximal efforts, for example in an attack on a mountainous stage in the Tour de France, would not necessarily correlate to amateurs in submaximal conditions, where there may be other limiting factors to performance. In addition athletes may use supraphysiological dosing regimens (“stacking” or “pyramiding”), not necessarily comparable to those used in clinical studies. In my opinion, apart from potential ergogenic benefits, whatever the degree, the intention to “take a short cut” to improve performance is the issue, not to mention the adverse health sequelae, for example, the study noted a thrombotic tendency with EPO, even in modest doses.

Hormone and metabolic modulators have received attention following the fall from grace of Maria Sharapova. Meldonium which is licensed for use in Baltic countries has beneficial anti-ischaemic effects in cardiovascular, neurological and metabolic disease states. Apparently this drug was use amongst Soviet troops during the war in mountainous Afghanistan. Amongst athletes the intended purpose is to improve endurance exercise performance and recovery post exercise. This is an example where an unfortunate spin off from developing drugs to treat disease states, is that such drugs are also see by some athletes as a short cut to enhance sport performance.

Although thyroxine is not on the banned list, there are certainly arguments that exogenous thyroxine should not be given to athletes, unless there is definitive biochemical evidence that the athlete suffers with hypothyroidism: as defined by criteria for diagnosing this condition with consistently elevated thyroid stimulating hormone (TSH) above the normal range, with paired low T4. Thyroid autoantibodies may also provide extra clinical information. The effect of intense training on the hypothalamic-pituitary-thyroid axis is to slightly suppress both TSH and T4, whilst these remain in the normal range. In this instance medicating with exogenous thyroxine would be to support recovery from training, rather than to legitimately treat a proven medical condition. In a similar way a TUE is only justified for testosterone in pathological disorders of the hypothalamo-pituitary-testicular axis and not for suppressed testosterone as a result of training stress.

Unfortunately supplements are a source of preventable anti-doping rule violations (ADRV) representing up to half of the total ADRVs. Either such supplements have not listed all the contents, or contamination has occurred during manufacture. If an athlete wishes to take supplements, certainly it is advisable only to take reliably tested products. Nevertheless even if an athlete unintentionally ingests prohibited substances, then ultimately they are still liable. If claims of the benefits of such supplements sound too good to be true, they probably are. Ultimately supplements will not win races and there is no substitute for periodised training, nutrition and recovery.

Effectively there is an arms race between would-be doper and medical expertise in Sports Endocrinology. However, freezing samples for potential re-analysis with emerging understanding and technology in the future is an added deterrent for athletes whose intention is to take a short cut to improving sport performance.

For further discussion on Endocrine and Metabolic aspects of SEM come to the BASEM annual conference 22/3/18: Health, Hormones and Human Performance

References

Endocrine system: balance and interplay in response to exercise training

Sports Endocrinology – what does it have to do with performance? Dr N. Keay, British Journal of Sports Medicine 2017

Enhancing Sport Performance: Part 1 Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Keay N, Logobardi S, Ehrnborg C, Cittadini A, Rosen T, Healy ML, Dall R, Bassett E, Pentecost C, Powrie J, Boroujerdi M, Jorgensen JOL, Sacca L. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sport: a double blind, placebo controlled study. Journal of Clinical Endocrinology and Metabolism. 85 (4) 1505-1512. 2000.

From population based norms to personalised medicine: Health, Fitness, Sports Performance  Dr N. Keay, British Journal of Sports Medicine 2017

Enabling Sport Performance: part 2

Enhancing Sports Performance: part 3

World Anti-Doping Agency

Serum androgen levels and their relation to performance in track and field: mass spectrometry results from 2127 observations in male and female elite athletes British Journal of Sports Medicine

Doping Status of DHEA Treatment for Female Athletes with Adrenal Insufficiency Clinical Journal of Sports Medicine 2017

Testosterone treatment and risk of venous thromboembolism: population based case-control study British Medical Journal 2016

Effects of erythropoietin on cycling performance of well trained cyclists: a double-blind, randomised, placebo-controlled trial The Lancet, Haematology 2017

Meldonium use by athletes at the Baku 2015 European Games. Adding data to Ms Maria Sharapova’s failed drug test case British Journal of Sports Medicine 2016

Fatigue, sport performance and hormones..more on the endocrine system  Dr N. Keay, British Journal of Sports Medicine 2017

Australian Sport Anti-Doping Authority

 

Enhancing Sports Performance: part 3

Amateur and recreational athletes

Recently the World Anti-Doping Agency WADA released details for the 2017 Prohibited List, which will come into effect on 1 January 2017. If you have read part 1 and part 2 of this series of blogs, you might be thinking that illegal doping to enhance sports performance is only of relevance to elite sport. Equally that the discussion of TUEs is only related to elite athletes. Well this blog will explore whether that is the case…

I am writing from a medical perspective based on my experience of working on the international medical research team that investigated the development of dope test for growth hormone GH, supported by the IOC.

The list issued by UK Anti-Doping UKAD of athletes banned from competition due to taking illegal performance enhancing drugs dispels the assumption that doping is confined to elite athletes. Indeed it is concerning that the list is substantial and includes a range of athletes from teenagers to age groupers across a variety of sports. Consider that this only shows results from sports where drug testing takes place.

As discussed in a recent article in British Medical Journal BMJ, there are an estimated 3 million anabolic steroid users in Europe alone. These users may not necessarily be involved in sports where drug testing takes place. From a medical point of view there is the concern of long term, irreversible adverse effects on health: cardiac, hepatic, psychiatric and reproductive complications.

Although professional dance can be viewed as an art form, rather than a sport, the increased technical requirements together with extended rehearsal and performance schedules place high physical and psychological demands on dancers, similar to elite athletes. In a recent article in the Dance Gazette there is discussion of “performance enhancement in dance being more about survival than competitive edge”.  Unlike sport, in classical dance there is a difference between female dancers who might dope in order to reduce body weight and male dancers looking for means to improve muscle strength.

The show must go on but the aim should be to strive for clean sport and to safeguard the health of athletes.

For further discussion on Endocrine and Metabolic aspects of SEM come to the BASEM annual conference 22/3/18: Health, Hormones and Human Performance

References

Enhancing sport performance: part 1 British Association of Sport and Exercise Medicine

Enabling Sport Performance: part 2

WADA

UKAD

BMJ 2016;353:i5023

Dance Gazette issue 3 2016 p.50-53

Enabling Sport Performance: part 2

Medical perspective on Therapeutic Use Exemptions: TUEs

As described in part 1 of this series of blogs I was on the international medical research team investigating the development of a test for identifying athletes doping with growth hormone. This experience helped form my view on the interaction of medicine and sport performance.

Over the next few days the results of anti-doping study will be presented at the International Federation Forum, with one of the discussions being “Medication Abuse in Elite Sport: the Epidemic!”

As doctors, our primary objective is to treat medical conditions in the most effective manner. It would not be ethical to withhold treatment to certain groups of patients, such as elite athletes. Therefore, where the prescribed medication for the treatment of a legitimate medical condition is on the prohibited list issued by the World Anti-Doping Agency (WADA), a TUE should be sought. After all elite athletes are just as likely to become ill as the general population, if not more so with functional immunosuppression due to training loads and possible energy deficient states.

In my opinion, the use of TUEs in the case of preventative treatment appears to be where the main discussion is centred. The athlete might not be acutely unwell, but may have a chronic condition, which can flare in an acute manner especially where there are known triggers. For example in the general population it is better medical practice to offer prophylactic treatment to a known asthmatic in order to decrease the risk of having an acute asthma attack, rather than waiting to treat an acute attack. Following on this argument, there is a case for offering elite athletes preventative treatment, rather than running the risk of an acute exacerbation requiring urgent treatment in difficult circumstances, for example in the middle of a race where access to required urgent treatment might be problematic. A view has been expressed that athletes with severe asthma have no place in performance sport and the paralympics would be more appropriate. Maybe this view is too extreme, after all exercise is recommended as a supportive strategy for asthma. Successful swimmers such as Thorpedo (Ian Thorpe) overcame both asthma and a reported allergy to chlorine to win Olympic and World titles.

In my opinion, the concept of TUEs for prevention of acute exacerbations of documented chronic conditions is valid. However, the issue seems to be the exact nature of such prophylatic treatment. Ideally the minimum dose of a medcation with the least potential performance enhancing qualities should be preferred. This has to be balanced against the most effective treatment for the specific documented medical condition of the individual athlete. Ultimately the athlete should be at neither disadvantage nor advantage due to a chronic, treatable medical condition.

Canadian law professor and sports lawyer Dr Richard Mc Laren (who conducted investigation into Russian state-sponsored doping) suggested that to investigate potential abuse of TUE system, frequency of certain medications being used in specific sports would need to be quantified.

In the meantime this vexed issued is being discussed at the Association of Summer Olympic International Federations (ASOIF) 9-11 November.

For further discussion on Endocrine and Metabolic aspects of SEM come to the BASEM annual conference 22/3/18: Health, Hormones and Human Performance

References

Enhancing sport performance: part 1 Dr N. Keay, British Association of Sport and Exercise Medicine

Relative Energy Deficiency in Sport Dr N. Keay, British Association of Sport and Exercise Medicine

WADA World Anti-Doping Agency

UKAD UK Anti-Doping

Enhancing Sport Performance: part 1

The good, the bad and the ugly

A medical perspective on clean athletes, dopers and abuse of the system

When I worked with the international medical research team investigating a method for detecting athletes doping with growth hormone (GH), I was struck by the co-operation of the medical teams and the athletes supporting this research in various countries. This project was supported by the International Olympic Committee and the drug companies manufacturing growth hormone who did not want to see this product mis-used.

growthhormone

Why would athletes seek to dope with GH? GH alters body composition by increasing lean mass and decreasing fat mass, a potential advantage for power sports. In addition to this anabolic effect, GH is potentially advantageous to physiology and metabolism in endurance sport by increasing use of lipid over glycogen as a substrate. However there are serious side effects of elevated GH levels as seen in patients suffering with acromegaly: including increased risk of diabetes mellitus, hypertension and cancer.

One of the challenges we encountered in developing a dope test for GH was that endogenously secreted growth hormone was virtually identical to the manufactured product. In addition, this peptide hormone is released episodically in a pulsatile manner and has a short plasma half life. So early on it was realised that direct measurement of growth hormone was not a reliable option, rather quantification of indirect plasma markers would be required. In turn that meant investigating the pharmacokinetic properties of these markers in exercising people.

So far so good. However what are the “normal” ranges for growth hormone and these secondary markers in elite athletes? The ranges used in the usual clinical hospital setting may not be accurate as exercise is a major stimulus for growth hormone release. Part of the reason elite athletes are better than amateur athletes is that they may have slightly different physiology and/or genetically determined physiology that responds more rapidly to training than the rest of us. So the first step was establishing what normal ranges are for growth hormone and its associated markers in elite athletes. Cue trips to Manchester velodrome with portable centrifuges, taking blood from Olympic medal winning rowers at the British Olympic Park and numerous evenings performing VO2 max tests on athletes.

Throughout this research I was struck by the desire of the elite athletes to participate in a study that would identify cheats, allowing them, as clean athletes, to compete on a level playing field. This gave those of us in medical research team extra incentive to come up with the most reliable and robust test possible. Nevertheless, we were aware that an arms race was taking place, with the dopers trying equally hard to cheat our test. Ultimately, however scientifically robust a test may be, it will not succeed if there is manipulation of the samples provided. This is what makes the alleged systemic abuse of the process so ugly.

For further discussion on Endocrine and Metabolic aspects of SEM come to the BASEM annual conference 22/3/18: Health, Hormones and Human Performance

References

Sports Endocrinology – what does it have to do with performance? Dr N. Keay, British Journal of Sports Medicine

From population based norms to personalised medicine: Health, Fitness, Sports Performance Dr N.Keay, British Journal of Sport Medicine 22/2/17

Keay N, Logobardi S, Ehrnborg C, Cittadini A, Rosen T, Healy ML, Dall R, Bassett E, Pentecost C, Powrie J, Boroujerdi M, Jorgensen JOL, Sacca L. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sport: a double blind, placebo controlled study. Journal of Endocrinology and Metabolism. 85 (4) 1505-1512. 2000.

Wallace J, Cuneo R, Keay N, Sonksen P. Responses of markers of bone and collagen turover to exercise, growth hormone (GH) administration and GH withdrawal in trained adult males. Journal of Endocrinology and Metabolism 2000. 85 (1): 124-33

Keay N. The effects of growth hormone misuse/abuse. Use and abuse of hormonal agents: Sport 1999. Vol 7, no 3, 11-12

Wallace J, Cuneo R, Baxter R, Orskov H, Keay N, Sonksen P. Responses of the growth hormone (GH) and insulin-like factor axis to exercise,GH administration and GH withdrawal in trained adult males: a potential test for GH abuse in sport. Journal of Endocrinology and Metabolism 1999. 84 (10): 3591-601

Keay N, Logobardi S, Ehrnborg C, Cittadini A, Rosen T, Healy ML, Dall R, Bassett E, Pentecost C, Powrie J, Boroujerdi M, Jorgensen JOL, Sacca L. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential usefulness as in the detection of GH abuse in sport: a double blind, placebo controlled study. Endocrine Society Conference 1999

Wallace J, Cuneo R, Keay N. Bone markers and growth hormone abuse in athletes. Growth hormone and IGF Research, vol 8: 4: 348

Cuneo R, Wallace J, Keay N. Use of bone markers to detect growth hormone abuse in sport. Proceedings of Annual Scientific Meeting, Endocrine Society of Australia. August 1998, vol 41, p55

Enabling Sport Performance: part 2

Enhancing sports performance: part 3