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

 

Addiction to Exercise

ExerciseAddiction

Health is not just the absence of illness, but rather the optimisation of all components of health: physical, mental and social. Exercise has numerous benefits on all these aspects. However, a recent article in the British Medical Journal described how exercise addiction can have detrimental physical, mental and social effects.

Dedication and determination are valuable qualities required to be successful in life, including achieving sporting prowess. Yet, there is a fine line between dedication and addiction.

To improve sports performance, cumulative training load has to be increased in a quantified fashion, to produce an overload and hence the desired physiological and Endocrine adaptive responses. Integrated periodisation of training, recovery and nutrition is required to ensure effective adaptation. Sufficient energy availability and quality of nutrition are essential to support health and desired adaptations. On the graph above the solid blue line represents a situation of energy balance, where the demands of increased training load are matched by a corresponding rise in energy availability. This can be challenging in sports where low body weight confers a performance or aesthetic advantage, where the risk of developing relative energy deficiency in sport (RED-S) has implications for Endocrine dysfunction, impacting all aspects of health and sports performance.

Among those participating in high volumes of exercise, what distinguishes a healthy level of commitment from exercise addiction? Physical factors alone are insufficient: all those engaging in high levels of training can experience overuse injuries and disruption in Endocrine, metabolic and immune systems. Equally, in all these exercising individuals, overtraining can result in underperformance.

Psychological factors are the key distinguishing features between the motivated athlete and the exercise addict. In exercise addiction unhealthy motivators and emotional connection to exercise can be identified as risk factors. In exercise addiction the motivation to exercise is driven by the obsession to comply with an exercise schedule, above all else. This can result in negative effects and conflict in social interactions, as well as negative emotional manifestations, such as anxiety and irritability if unable to exercise, including the perceived necessity to exercise even if fatigued or injured.

Two categories of exercise addiction have been described. Primary exercise addiction is the compulsion to follow an excessive training schedule. Without balancing energy intake, the physical consequence may be a relative energy deficiency, as indicated on the graph by the dashed blue line. In secondary exercise addiction, the situation is compounded by a desire specifically to control body weight. These individuals consciously limit energy intake, almost inevitably developing the full clinical syndrome described in RED-S, dragging them down to the position indicated by the dotted blue line on the chart. These situations of exercise addiction can lead to varying risk categories of RED-S.

As described at the start of this blog, there is a blurred boundary between the dedicated athlete and the exercise addict. In practice there is most likely a cross over. For example, an athlete may start with healthy motivators and positive emotional connection to exercise, which can become a primary addiction to adhere rigidly to a training schedule, rather than putting the emphasis on the outcome of such training. In the case of an athlete where low body weight is an advantage, it is easy to appreciate how this could become a secondary exercise addiction, where the motivation for exercising becomes more driven by the desire to control weight, rather than performance.

In order to support those with exercise addiction, discussion needs to focus on adopting a more flexible approach to exercise, by recognising that exercise addiction has detrimental effects on all aspects of current and long term health. Furthermore, in the case of athletes, a multi-disciplinary approach is desirable to help the individual refocus on the primary objective of training: to improve performance. In all situations, discussion should explore modifications to exercise and nutrition, in order to prevent the negative effects of RED-S on health and performance.

Exercise has numerous health benefits and is usually viewed as positive behaviour. However, the outcome of exercise is related to the amount of training, appropriate nutrition and motivation for exercising.

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

Addiction to Exercise British Medical Journal 2017

Clusters of Athletes British Association of Sport and Exercise Medicine 2017

Sport performance and relative energy deficiency in sport British Journal of Sport Medicine 2017

Balance of recovery and adaptation for sports performance British Association of Sport and Exercise Medicine 2017

Optimal Health for all athletes Part 4 Mechanisms of RED-S British Journal of Sport Medicine 2017

Sports Endocrinology – what does it have to do with performance? British Journal of Sport Medicine 2017

Inflammation: Why and How Much? British Association of Sport and Exercise Medicine 2017

Fatigue, Sport Performance and Hormones…

How do you feel on Monday morning, when the alarm wakes you at 7am with a day of work ahead after the weekend? A bit tired, slightly lethargic, sluggish, maybe a little bit down, perhaps a few regrets about somewhat too much alcohol/food over weekend, frustrated that the exercise training schedule didn’t go according to plan?sleep

There are many causes of fatigue and sport underperformance: Endocrine, immunological, infective, metabolic, haematological, nutritional, digestive, neoplastic….. The adrenal gland in the Endocrine system in particular has come in for some bad press recently.

Adrenal woes

Undoubtedly the adrenal glands have a case to answer. Situated above the kidneys these Endocrine glands produce glucocorticoids, mineralocorticoids, androgens from the adrenal cortex and from the adrenal medulla adrenaline. Glucocorticoids (e.g. cortisol) have a metabolic function to maintain energy homeostasis and an immune function to suppress inflammation. Mineralocorticoids (e.g. aldosterone) maintain electrolyte and water balance. As mineralocorticoids and glucocorticoids are similar biological steroid molecules, there is some degree of overlap in their actions.

Addison’s disease and Cushing’s disease are serious medical conditions, corresponding respectively to under or over production by the adrenal glands of steroid hormones. Someone presenting in Addisonian crisis is a medical emergency requiring resuscitation with intravenous hydrocortisone and fluids. Conversely those with Cushing’s can present with hypertension and elevated blood glucose. Yet, apart from in the extremes of these disease states, cortisol metrics do not correlate with clinical symptoms. This is one reason why it is unwise and potentially dangerous to stimulate cortisol production based on clinical symptoms. Inappropriate exogenous steroid intake can suppress normal endogenous production and reduce the ability to respond normally to “stress” situations, such as infection. This is why the prescription of steroids, for example to reduce inflammation in autoimmune disease, is always given in a course of reducing dose and a steroid alert card has to be carried. Athletes should also be aware that exogenous steroid intake is a doping offence.

However, what is the “normal” concentration for cortisol? Well, for a start, it depends what time of day a sample is taken, as cortisol is produced in a circadian rhythm, with highest values in the morning on waking and lowest levels about 2/3am. Nor is this temporal periodicity of production the only variable, there are considerations such as tissue responsiveness and metabolism (break down) of the hormone. On top of these variables there are other inputs to the feedback control mechanism, which can in turn influence these variables. In other words, focusing on the steroid hormone production of the adrenal gland in isolation, could overlook underlying hypothamalmic-pituitary-adrenal (H-P-A) axis dysfunction and indeed wider issues.

Much maligned thyroid

That is not end of the possible causes of fatigue and sport underperformance: the H-P-A axis is just one of many interrelated, interacting Endocrine systems. There are many neuroendocrine inputs to the hypothalamus, the gate keeper of the control of the Endocrine system. Furthermore there are network interaction effects between the various Endocrine control feedback loops. For example cortisol towards the top end of “normal” range can impede the conversion at the tissue level of thyroxine (T4) to the more active triiodothyronine (T3) by enzymes which require selenium to function. Rather T4 can be converted to reverse T3 which is biologically inactive, but blocks the receptors for T3 and thus impair its action. This in turn can interfere with the feedback loop controlling thyroid function (hypothalamic-pituitary-thyroid axis). The physiological ratio of T4 to T3 is 14:1, which is why supplementation with desiccated thyroid is not advisable with ratio of 4:1. There are other processes which can crucially interfere with this peripheral conversion of T4 to T3, such as inflammation and gut dysbiosis, which can occur as result of strenuous exercise training. So what might appear to be a primary thyroid dysfunction can have an apparently unrelated underlying cause. Indeed amongst highly trained athletes thyroid function can show an unusual pattern, with both thyroid stimulating hormone (TSH) and T4 at low end of the “normal “range, thought to be due to resetting of the hypothalamic-pituitary control signalling system. This highlights that the “normal” range for many hormones comprises subsets of the population and in the case of TSH, the “normal” range is not age adjusted, despite TSH increasing with age. As described by Dr Boelaert at recent conferences, there is certainly no medical justification for reports of some athletes in the USA being given thyroxine with TSH>2 (when the normal range is 0.5-5mU/l). Although thyroxine is not on the banned list for athletes, it could have potentially serious implications for health due to its impact on the Endocrine system as a whole.

Endocrine system interactions

SportsEndocrinologyWordCloud

Symptoms of fatigue are common to many clinical conditions, not just dysfunction in an Endocrine control axis in isolation, nor even the network interactive effects of the Endocrine system in isolation. For example, the impact of nutrition relative to training load produces a spectrum of clinical pictures and Endocrine disturbances seen in Relative Energy Deficiency in Sport (RED-S) in terms of health and sport performance.

Underlying mechanisms of Endocrine dysfunction

There may be predisposing factors in developing any clinical syndrome, the usual suspects being inflammation: whether infective, dysbioses, autoimmune; nutritional status linked with endocrine status;  training load with inadequate periodised recovery to name a few….

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

From population based norms to personalised medicine: Health, Fitness, Sports Performance British Journal of Sport Medicine 2017

Sports Endocrinology – what does it have to do with performance? British Journal of Sport Medicine 2017

Advanced Medicine Conference, Royal College of Physicians, London 13-16 February 2017, Endocrine session: Dr Kristien Boelaert, Dr Helen Simpson, Professor Rebecca Reynolds

Subclinical hypothydroidism in athletes. Lecture by Dr Kristeien Boelaert, British Association of Sport and Exercise Medicine Spring Conference 2014. The Fatigued Athlete

Sport Performance and RED-S, insights from recent Annual Sport and Exercise Medicine and Innovations in Sport and Exercise Nutrition Conferences British Journal of Sport Medicine 2017

Relative Energy Deficiency in Sport CPD module British Association of Sport and Exercise Medicine 2017

Sleep for health and sports performance British Journal of Sport Medicine 2017

Inflammation: why and how much? British Association of Sport and Exercise Medicine 2017

Clusters of athletes British Association of Sport and Exercise Medicine 2017

Enhancing Sport Performance: Part 1 British Association of Sport and Exercise Medicine 2017

Balance of recovery and adaptation for sports performance British Association of Sport and Exercise Medicine 2017

Annual Sport and Exercise Medicine Conference, London 8/3/17 Gut Dysbiosis, Dr Ese Stacey

Adrenal fatigue does not exist: a systematic review BMC Endocrine Disorders. 2016; 16(1): 48.

A Controversy Continues: Combination Treatment for Hypothyroidism Endocrine News, Endocrine Society April 2017