Endocrine system – Dr Nicky Keay

Synergistic Interactions of Steroid Hormones

20 April 2018

The action of the sun on skin is the most effective way of making vitamin D. However, even walking around outside naked for 5 hours every day during UK winter months is not sufficient to make adequate vitamin D. Therefore, much to the relief of the audience at the recent BASEM Spring conference, this was not a strategy recommended by Dr Roger Wolman.

Vitamin D is a fat soluble steroid hormone. The majority of which is synthesised in the skin when exposed to ultraviolet B in sunlight, with a small contribution from dietary sources: this vitamin D3 molecule is then hydroxylated twice in the liver and then kidney to produce the metabolically active form of vitamin D. This activated steroid hormone binds to vitamin D receptors in various tissues to exert its influence on gene expression in these cells. The mono hydroxylated form of vitamin D is measured in the serum, as this has a long half life.

Does it matter having low levels of circulating vitamin D during winter months? What are the solutions if moving to warmer climates during the winter is (unfortunately) not feasible? What are the other hormones interact with vitamin D?

What are the beneficial effects of vitamin D, particularly in the athletic population?

Bone

Rickets and osteomalacia are conditions where vitamin D deficiency results in bone deformities and radiographic appearances are characterised by Looser zones, which in some ways are similar in appearance to stress fractures.

In a large prospective study of physically active adolescent girls, stress fracture incidence was found to have an inverse relationship with serum vitamin D concentrations. In adult female Navy recruits monitored during an 8 week training programme, those on vitamin D supplementation had a 20% reduction in stress fracture. However, oestrogen status was a more powerful risk factor at 91% in those recruits reporting amenorrhoea. Vitamin D is, itself, is a steroid hormone with range of systemic effects. As will be discussed below, its interaction with the sex steroid oestrogen has an important effect on bone turnover.

Immunity

Although sanatoriums, for those suffering with tuberculosis, were based on providing patients with fresh air, any beneficial effect was probably more due to vitamin D levels being boosted by exposure to sunlight. Certainly there are studies demonstrating the inhibitory effect of vitamin D on on slow growing mycobacteria, responsible for TB. What about the influence of vitamin D on other types of infection? In a recent publication, evidence was presented that supplementation with vitamin D prevented acute respiratory tract infections. This effect was marked in those with pre-existing low levels of vitamin D. In a study of athletes a concentration of 95 nmol/L was noted at the cut off point associated with more or less than one episode of illness. In another randomised controlled study of athletes, those supplemented with 5,000IU per day of vitamin D3 during winter displayed higher levels of serum vitamin D and had increased secretion of salivary IgA, which could improve immunity to respiratory infections.

Muscle

There is evidence that supplementing vitamin D3 at 4,000IU per day has a positive effect on skeletal muscle recovery in terms of repair and remodelling following a bout of eccentric exercise. In the longer term, dancers supplemented with 2,000IU over 4 months reported not only reduction in soft tissue injury, but an increase in quadriceps isometric strength of 18% and an increase of 7% in vertical jump height.

Synergistic actions of steroid hormones

No hormone can be considered in isolation. This is true for the network interaction effects between the steroid hormones vitamin D and oestrogen. In a study of professional dancers, there was found to be significant differences in serum vitamin D concentrations in dancers from winter to summer and associated reciprocal relationship with parathyroid hormone (PTH). In situations of vitamin D deficiency this can invoke secondary hypoparathyroidism. Although low levels of vitamin D were observed in the dancers, this was not a level to produce this condition. However, there was an increase in soft tissue injury during the winter months that could, in part, be linked to low vitamin D levels impacting muscle strength.

The novel finding of this study was that female dancers on the combined oral contraceptive pill (OCP) showed significant differences, relative to their eumenorrhoeic counterparts not on the OCP, in terms of higher levels of vitamin D and associated reductions of bone resorption markers and PTH. The potential mechanism could be the induction by the OCP of liver enzymes to increase binding proteins that alter the proportion of bound/bioactive vitamin D.

This interaction between steroid hormones oestrogen and vitamin D could be particularly significant in those in low oestrogen states such as postmenpoausal women and premenarchal girls. Menarche can be delayed in athletes, so is there a case for vitamin D supplementation in young non-menstruating athletes? What is the situation for men? Do testosterone and vitamin D have similar interactions and therefore implications for male athletes with RED-S, where testosterone can be low?

Vitamin D is not simply a vitamin. It is a steroid hormone with multi-system effects and interactions with other steroid hormones, such as sex steroids, which are of particular relevance to athletes.

References

BASEM Spring Conference 2018 “Health, Hormones and Human Performance”

BASEM Spring Conference 2018 Part 2 “Health, Hormones and Human Performance”

Calcium and Vitamin D Supplementation Decreases Incidence of Stress Fractures in Female Navy Recruits JBMR 2009

Vitamin D, Calcium, and Dairy Intakes and Stress Fractures Among Female Adolescents Arch Pediatr Adolesc Med 2012

A Single Dose of Vitamin D Enhances Immunity to Mycobacteria American Journal of Respiratory and Critical Care Medicine 2007

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data BMJ 2017

Influence of vitamin D status on respiratory infection incidence and immune function during 4 months of winter training in endurance sport athletes Exerc Immunol Rev. 2013

The effect of 14 weeks of vitamin D3 supplementation on antimicrobial peptides and proteins in athletes J Sports Sci. 2016

A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy American Journal of Physiology 2015

The influence of winter vitamin D supplementation on muscle function and injury occurrence in elite ballet dancers: A controlled study Journal of Science and Medicine in Sport 2014

Vitamin D status in professional ballet dancers: Winter vs. summer J Science and Medicine in Sport 2013

Health, Hormones and Human Performance Part 1

2 April 2018

How hormones determine health and athletic performance

Endocrine and Metabolic aspects of Sports and Exercise Medicine are crucial determinants of health and human performance, from reluctant exerciser through to elite athlete and professional dancer. This is what I set out to demonstrate as the chair of the recent British Association of Sport and Medicine conference, with insightful presentations from my colleagues whom I had invited to share their research and practical applications of their work. The audience comprised of doctors with interest in sport and exercise medicine, representatives from the dance world, research scientists, nutritionists, physiotherapists, coaches and trainers. In short, all were members of multi-disciplinary teams supporting aspiring athletes. The importance of the conference was reflected in CDP awards from FSEM, BASES, Royal College of Physicians (RCP), REP-S and endorsement for international education from BJSM and National Institute of Dance Medicine and Science (NIDMS).

Exercise is a crucial lifestyle factor in determining health and disease. Yet we see an increasing polarisation in the amount of exercise taken across the general population. At one end of the spectrum, the increasing training loads of elite athletes and professional dancers push the levels of human performance to greater heights. On the other side of the spectrum, rising levels of inactivity, in large swathes of the population, increase the risk of poor health and developing disease states. Which fundamental biological processes and systems link these groups with apparently dichotomous levels of exercise? What determines the outcome of the underlying Endocrine and metabolic network interactions? How can an understanding of these factors help prevent sports injuries and lead to more effective rehabilitation? How can we employ Endocrine markers to predict and provide guidance towards beneficial outcomes for health and human performance?

If you weren’t able to come and participate in the discussion, these are some topics presented. My opening presentation (see video below) set the scene, outlining why having an optimally functioning Endocrine system is fundamental to health and performance. Conversely, functional disruption of Endocrine networks occurs with non integrated periodisation of the three key lifestyle factors of exercise/training, nutrition and recovery/sleep, which can lead to adverse effects on health and athletic performance.

In the case of an imbalance in training load and nutrition, this can manifest as the female athlete triad, which has now evolved into relative energy deficiency in sports (RED-S) in recognition of the fact that Endocrine feedback loops are disrupted across many hormonal axes, not just the reproductive axis. And, significantly, acknowledging the fact that males athletes can also be impacted by insufficient energy availability to meet both training and “housekeeping” energy requirements. Why and how RED-S can affect male athletes, in particular male competitive road cyclists, was discussed, highlighting the need for further research to investigate practical and effective strategies to optimise health and therefore ultimately performance in competition.

A degree of overlap and interplay exists between RED-S (imbalance in nutrition and training load), non functional over-reaching and over-training syndrome (imbalances in training load and recovery). Indeed research evidence was presented suggesting that RED-S increases the risk of developing over-training syndrome. In these situations of functional disruption of the Endocrine networks, underlying Endocrine conditions per se should be excluded. Case studies demonstrated this principle in the diagnosis of RED-S. This is particularly important in the investigation of amenorrhoea. All women of reproductive age, whether athletes or not, should have regular menstruation (apart from when pregnant!), as a barometer of healthy hormones. Indeed, since hormones are essential to drive positive adaptations to exercise, healthy hormones are key in attaining full athletic potential in any athlete/dancer, whether male or female. Evidence was presented from research studies for the role of validated Endocrine markers and clinical menstrual status in females as objective and quantifiable measures of energy availability and hence injury risk in both male and female athletes.

Triumvirate of external factors impacting Endocrine system and hence performance

Alongside training metrics, if female athletes recorded menstrual pattern (as Gwen Jorgensen recently showed on her Training Peaks) and all athletes kept a biological passport of selected Endocrine markers; this could potentially identify at an early stage any imbalances in the triumvirate of training load, nutrition and recovery. Pre-empting development of RED-S or over-training syndrome, supports the maintenance of healthy hormones and hence optimal human performance.

Look out for presentations from speakers which will be uploaded on BASEM website shortly.

References

Video of presentation on the Endocrine and Metabolic Aspects of Sports and Exercise Medicine BASEM conference “Health, Hormones and Human Performance”

Study of hormones, body composition, bone mineral density and performance in competitive male road cyclists Investigation of effective and practical nutrition and off bike exercise interventions

Sports Endocrinology – what does it have to do with performance? Keay BJSM 2017

Cumulative Endocrine Dysfunction in Relative Energy Deficiency in Sport (RED-S)

31 December 2017

Screen Shot 2017-12-24 at 22.35.18

Unfortunately I continue to see athletes, both male and female, whose health and athletic performance is hampered due to Relative Energy Deficiency in Sports (RED-S). There have been some high profile athletes who have been very open about how RED-S has affected them, alerting younger athletes to potential pitfalls.

Does this issue warrant highlighting? Yes! The athletes I see and those that speak out are only just the tip of the iceberg. In a study of exercising females, half were found to have subtle menstrual hormone disruption such as luteal phase deficit or anovulation. A third were amenorrhoeic, with no periods at all. All women of reproductive age, whether an athlete or not, should have regular periods, otherwise there are potential serious health and performance sequaelae. However studies in both the USA and Australia have revealed that the majority of young exercising women are not aware of the link between menstrual disruption and deleterious, potentially irreversible effects on bone health.

The impact of non-integrated periodisation of training, nutrition and recovery has evolved since the early description of the female athlete triad. The constellation of amenorrhoea, disordered eating and osteoporosis is now considered to be a clinical spectrum. In turn the female athlete triad is part of a much broader picture of RED-S, which includes adverse multi-system effects beyond bone health and is also seen in male athletes.

Although an athlete may appear healthy, what are the underlying Endocrine disruptions occurring in RED-S that ultimately will impede both optimal health and performance to full potential? In general, female exercisers are more susceptible to internal and external perturbations as the female Endocrine system is more finely balanced than in males. Nevertheless, in a study of male athletes, in the short time period after completing a training session, bone turnover was adversely affected, with an increase in markers of resorption relative to formation, if an athlete did not refuel rapidly with protein and carbohydrate. In the now classic research by Loucks, 5 days of manipulated energy restricted availability, via dietary intake and exercise output, caused disruption in LH pulsatility in previously eumenorrhoeic women. From this research and subsequent studies, not only is the reproductive axis disrupted with reduced energy availability, in addition hypothalamus-pituitary-thyroid (decreased T3) and adrenal axes (increased cortisol) and decreased IGF1 due to relative GH resistance are all disrupted. These interactive hormonal dysfunctions occur even before reduction in sex steroids. A recent study demonstrated that beyond the average energy availability over a 24 hour time window, within day energy deficits in terms of duration and magnitude are associated with a greater degree of disruption of Endocrine and metabolic markers, in particular decreased oestradiol and increased cortisol. So consistency of nutrition, not only during a training season but from day to day is vital.

Although energy availability is the crucial factor in the pathophysiology of RED-S, measuring this is not practical for all athletes in terms of accuracy and cost. Clinical menstrual status in female athletes and basic Endocrine markers are proposed as being more reliable and accessible. The Endocrine system is very sensitive to internal and external perturbations, as described above, and presages performance consequences of RED-S, such as injury. An important starting point is for all female athletes is to ask themselves: are my periods regular? This is also a vital question that coaches and parents need to consider for athletes in their care. If the answer is no, then this needs to be assessed, ideally by those with experience in Sports Endocrinology.

Why are these clinical and biochemical markers of Endocrine dysfunction important for athletes? Essentially there are significant health and performance implications for athletes. As outlined in the stories of female athletes, by the time career limiting stress fractures become obvious, typically in early twenties, the Endocrine system has been in disarray for a significant time. Long term, irreversible poor bone health and adverse body composition have been established.

In my opinion, emphasis should be placed on the positive outcome of integrating periodised training, nutrition and recovery to support a functional Endocrine system and therefore optimal health and ability to reach full athletic potential. For example for female athletes, competing in sports where low body mass confers a performance advantage, such as ballet, gymnastics and road cycling, finely tuned neuromuscular skills are essential to reach maximal potential and minimise injury risk. Yet these are the athletes most at risk of developing RED-S, with consequential adverse effects on menstrual cycles, endogenous oestrogen secretion and neuromuscular function.

Rather than reading headlines about the concerning health issues amongst athletes, more guidance for athletes and those working with them, on the warning signs and how to combat RED-S are needed so that athletes can reach their full potential and the headlines become about athlete achievements.

For more discussion on the Endocrine and Metabolic aspects of Sport and Exercise Medicine, all members of multi-disciplinary team working with athletes, including athletes and coaches are welcome to the BASEM Spring Conference

BAsem2018_SpringConf_BJSM

References

Relative Energy Deficiency in Sports (RED-S) Practical considerations for endurance athletes

British middle-distance runner Bobby Clay is struggling with osteoporosis but wants her experience to act as a lesson for fellow young athletes Athletics Weekly 2017

In a special AW report, former English Schools champion Jen Walsh reveals the devastation that the female athlete triad can wreak Athletics Weekly 2017

Optimal Health: Especially Young Athletes! Part 3 – Consequences of Relative Energy Deficiency in Sports BASEM 2017

Prevalence High prevalence of subtle and severe menstrual disturbances in exercising women: confirmation using daily hormone measures. Human Repro 2010

Energy deficiency, menstrual disturbances, and low bone mass: what do exercising Australian women know about the female athlete triad? Int J Sport Nutr Exerc Metab. 2012

Female adolescent athletes’ awareness of the connection between menstrual status and bone health J Pediatr Adolesc Gynecol. 2011

Optimal health: including female athletes! Part 1 Bones BJSM 2017

Optimal Health: For All Athletes! Part 4 – Mechanisms BASEM 2017

Sports Endocrinology – what does it have to do with performance? BJSM 2017

The Effect of Postexercise Carbohydrate and Protein Ingestion on Bone Metabolism Translational Journal of the American College of Sports Medicine 2017

Luteinizing hormone pulsatility is disrupted at a threshold of energy availability in regularly menstruating women JCEM 2003

Within-day energy deficiency and reproductive function in female endurance athletes Scandinavian Journal of Science and medicine in Sports 2017

Low Energy Availability is Difficult to Assess But Outcomes Have Large Impact on Bone Injury Rates in Elite Distance Athletes Sports Nutrition and Exercise Metabolism 2017

Body Composition for Health and Sports Performance

Reduced Neuromuscular Performance in Amenorrheic Elite Endurance Athletes Medicine & Science in Sports & Exercise 2017

Internal Biological Clocks and Sport Performance

5 October 2017

A Nobel Prize was awarded this week to researchers who uncovered the molecular mechanisms controlling circadian rhythm: our internal biological clock.

PastedGraphic-2 — Circadian Hormone Release

These mechanisms rely on negative feedback loops found in many biological systems where periodicity of gene expression is key, such as the Endocrine system. Internal biological clocks allow for anticipation of the requirements from body systems at different times of the day and the ability to adapt to changes in external lifestyle factors. What is the clinical significance of biochronometers?

The importance of integration of lifestyle factors, such as timing of eating, activity and sleep with our internal biological clocks is revealed in situations of circadian misalignment that lead to suboptimal health and disease states in the longer term.

Consideration of our biochronometers is especially important for athletes in order to synchronise periodised training, nutrition and recovery and thus optimise health and sports performance.

Athletic Performance Performance in a cycle time trial was found to be better in the evening, rather than the morning, proposed to be due to a more favourable endogenous hormonal and metabolic internal milieu. Certainly there were some disgruntled swimmers at an international event, when the usual pattern of morning heats and evenings finals was switched, to accommodate television viewing spectators.

Female athletes: menstrual cycle/training season Women have an extra layer of endogenous biological periodicity in the form of the menstrual cycle controlled by temporal changes of hormone release in the hypothamalmus-pituitary-ovarian Endocrine axis. Changes in external factors of training load, nutrition and recovery are detected by the neuroendocrine gatekeeper, the hypothalamus, which produces an appropriate change in frequency and amplitude of GnRH (gonadotrophin releasing hormone), which in turn impacts the pulsatility of LH (lutenising hormone) release from the pituitary and hence the phases of the menstrual cycle, in particular ovulation. Even short term reduction of energy availability in eumenorrhoeic female athletes can inhibit LH pulsatility frequency and release of other hormones such as IGF1. Disrupted release of sex steroids and IGF1 has a negative effect on bone turnover: increased resorption and decreased formation. Active females have been found more susceptible to reduction in energy availability impacting bone metabolism than their male counterparts.

Another consequence of the phasic nature of the menstrual cycle relating to external factors such as exercise, is that injury risk could be linked to changes in the expression of receptors for for sex steroids oestrogen and progesterone in skeletal muscle. Certainly during pregnancy and the post partum period, relaxin hormone increases the laxity of soft tissues, such as ligaments, and hence maintenance stretching, rather than seeking to increase flexibility, is recommended to prevent injury, .

In order to produce desired temporal adaptive changes in response to exercise training, signalling pathways mediated by reactive oxidative species and inflammatory markers are stimulated in the short term, with supportive Endocrine interactions in the longer term. However, an over-response can impair adaptive changes and impact other biological systems such as the immune system. This maladaptive response could occur as a result of non-integrated periodisation of training, nutrition and recovery in athletes and, in the case of female athletes, oral contraceptive pill use has been implicated, as this effectively imposes a medical menopause, preventing the phasic release of endogenous hormones.

Considering a longer time scale, such as a training season, female athletes were found to have a more significant fall ferritin during than male athletes. Low normal iron does not necessarily correlate to iron deficiency anaemia, but low levels in athletes can impact bone health. Supplementation with vitamin C to improve absorption may help, although iron overload can have deleterious effects. As training intensity increases as the season progresses, six monthly haematological reviews for female athletes were recommended in this study.

Changes in set point feedback Feedback control of the Endocrine system, for example the hypothalamic-pituitary-thyroid axis is dynamic: both anticipatory and adaptive, depending on internal and external inputs. However, presentation of a prolonged stimulus can result in maladaptation in the longer term. For example, disruption of signalling pathways leading to hyperinsulinaemia results in insulin resistance, which represents the underlying pathophysiological mechanism of obesity and the metabolic syndrome. In other words a situation of tachyphylaxis, where prolonged, repeated stimulus over time results in insensitivity to the original stimulus. This also applies to the nature of exercise training over a training season and diets that exclude a major food type: temporal variety is key.

Lifespan (prematurity, ageing) Changes during the lifespan represent an important biochronometer. Premature and small-for-dates babies are at risk of long term metabolic and Endocrine dysfunction, potentially due to intrauterine reprogramming of the hypothalamic-pituitary axis. At the other end of the biological time scale, with advancing age, DNA methylation and changes in epigenetic expression occur. It has been suggested that this age related methylation drift could be delayed with calorie restriction. Melatonin, a key player in intrinsic biological time keeping has been proposed to attenuate bone resorption by reducing relative oxidative stress. This would potentially explain why shift workers with disrupted sleep patterns are reported to be at risk not only of metabolic dysfunction, but also impaired bone health. Disrupted sleep patterns are a concern for athletes, especially those whose training and competition schedule involve frequent international travel across time zones.

In summary, respecting your internal biological clocks and integrating your lifestyle and your training, nutrition and recovery with these intrinsic pacemakers in mind will optimise health and performance.

For further discussion BASEM annual conference 22/3/18: Health, Hormones and Human Performance

Presentations

References

The Nobel Prize in Physiology or Medicine 2017

Circadian clock control of endocrine factors Nat. Rev. Endocrinol

Temporal considerations in Endocrine/Metabolic interactions Part 1 Dr N. Keay, British Journal of Sports Medicine 2017

Temporal considerations in Endocrine/Metabolic interactions Part 2 Dr N. Keay, British Journal of Sports Medicine 2017

Athletic Fatigue: Part 2 Dr N. Keay 2017

Effect of Time of Day on Performance, Hormonal and Metabolic Response during a 1000-M Cycling Time Trial Plos One 2017

Optimal Health: For All Athletes! Part 4 – Mechanisms Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Effects of reduced energy availability on bone metabolism in women and men Bone 2017

Expression of sex steroid hormone receptors in human skeletal muscle during the menstrual cycle Acta Physiol (Oxf). 2017

Endocrine system: balance and interplay in response to exercise training

Kynurenic acid is reduced in females and oral contraceptive users: Implications for depression Science Direct 2017

Oxidative Stress in Female Athletes Using Combined Oral Contraceptives Sports Medicine

Iron monitoring of male and female rugby sevens players over an international season J Sports Med Phys Fitness. 2017

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming Frontiers in Endocrinology 2017

Stress- and allostasis-induced brain plasticity Annu Rev Med

Optimising Health and Athletic Performance Dr N. Keay 2017

Long-term metabolic risk among children born premature or small for gestational age Nature Reviews Endocrinology 2017

Caloric restriction delays age-related methylation drift Nature Communications 2017

Melatonin at pharmacological concentrations suppresses osteoclastogenesis via the attenuation of intracellular ROS Osteoporosis International 2017

Sleep for health and sports performance Dr N. Keay, British Journal of Sports Medicine 2017

Metabolic and Endocrine System Networks

24 July 2017

EndoMetaNetworks

What are the most effective strategies to optimise health and performance? There are ever more emerging possibilities, permutations and combinations to chose from.

The simple answer is that the most effective option will depend on your starting point and what you are trying to achieve. In all cases exercise and activity levels are the fundamental basis for health and performance. Regarding nutritional strategies to support effective exercise adaptations, no single component of your dietary intake can be considered in isolation. After all, the metabolic pathways and Endocrine axes in your body work as an interactive network, with an important temporal dimension.

Emerging evidence implicates resistance to the anabolic pancreatic hormone, insulin, as the underlying pathological process in the development of metabolic syndrome. What type of diet might drive or conversely counter this process involving metabolism and the Endocrine system? The standard approach, of calorie restriction and aggressive pharmacological treatment of raised lipids, does not produce the anticipated reduction in cardiovascular mortality. Rather the synergistic effect of a diet high in both fat and carbohydrate induces hypothalamic inflammation and dysfunction in the control system of energy metabolism. The hypothalamus is the neuroendocrine gatekeeper providing the crucial link between internal and external stimuli and homeostasis of the internal milieu through integrated Endocrine responses. Intriguingly there is as an inflammatory component to the pathogenesis of cardiovascular disease.

The interaction between metabolic, Endocrine and inflammatory networks is seen in polycystic ovary syndrome (PCOS). The clinical diagnosis of PCOS relies on two of three diagnostic criteria (menstrual disturbance, hyperandrogenism, ovarian morphology). However, the underlying metabolic disruption for all phenotypes of the condition, from overweight to slim, is insulin resistance. The link between adverse body composition, metabolic and Endocrine dysfunction has recently been described. Adipokines, a class of cytokine, including adiponectin and resistin are produced by adipose tissue and exert an effect on metabolism, including insulin sensitivity and inflammation. Changes in plasma concentrations and/or expression of adipokines are seen in metabolic dysfunction and potentially have direct and indirect effects on the hypothalmic-pituitary-gonadal axis in PCOS.

Further evidence of the crucial interaction between metabolic and Endocrine systems and health was found in a longitudinal study of children, quantifying heart rate variability and the energy and inflammatory related biomarkers leptin (atherogenic) and adiponectin (anti-atherogenic) as potential predictive markers in cardiovascular screening/prevention.

Exogenous hormones impact not only the endogenous Endocrine system, but have metabolic effects. The intended purpose of the combined oral contraceptive pill (OCP) is to suppress ovulation. Another effect on the Endocrine system is to increase production of sex hormone-binding globulin (SHBG), which binds free testosterone. This has a therapeutic effect in the treatment of PCOS to lower elevated testosterone, however this may not be such a desirable effect in female athletes, where higher range testosterone levels as associated with performance advantages in certain power events. In the case of female athletes with relative energy deficiency in sports (RED-S), use of the OCP masks underlying hypothalamic amenorrhoea and is not effective in bone health protection. Further areas where Endocrine manipulation impacts metabolism are an increase in oxidative stress with OCP use and alterations in nutritional requirements due to alteration of absorption of vitamins and minerals such as vitamin B complex and magnesium, which are vital for enzymic processes involved in energy production. Yet an elevation of ferritin as an acute phase reactant is seen. These interactions of Endocrine and metabolic networks are particularly important considerations for the female athlete.

There is no single elixir for health and performance. We are individuals with subtle differences in our genetic and epigenetic make up, including the diversity of our microbiome. Furthermore, the Endocrine and metabolic milieu changes during our lifespan. Personalised health and performance strategies must take account of the complex, intricate interactions between the Endocrine and metabolic networks.

For further discussion on Health, Hormones and Human Performance, come to the BASEM annual conference

References

One road to Rome: Metabolic Syndrome, Athletes, Exercise Dr N.Keay

Endocrine system: balance and interplay in response to exercise training Dr N. Keay

Dietary sugars, not lipids, drive hypothalamic inflammation Molecular Metabolism June 2017

Saturated fat does not clog the arteries: coronary heart disease is a chronic inflammatory condition, the risk of which can be effectively reduced from healthy lifestyle interventions British Journal of Sport and Exercise Medicine

Adiponectin and resistin: potential metabolic signals affecting hypothalamo-pituitary gonadal axis in females and males of different species Reproduction: Journal for the Society of Reproduction and Fertility 2017

Longitudinal Associations of Leptin and Adiponectin with Heart Rate Variability in Children Front. Physiol 2017

AKR1C3-mediated adipose androgen generation drives lipotoxicity in women with polycystic ovary syndrome J Clin Endocrinol Metab 2017

Hormones and Sports Performance Dr N. Keay

Mechanisms for optimal health…for all athletes! Dr N. Keay, British Journal of Sport and Exercise Medicine

Oxidative Stress in Female Athletes Using Combined Oral Contraceptives Sports Medicine – Open

Oral contraceptives and changes in nutritional requirements European Review for Medical and Pharmacological Sciences

Inflammation: Why and How Much? Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Hormones and Sports Performance

15 July 2017

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

Endocrine system: balance and interplay in response to exercise training

12 June 2017

The process of homeostasis maintains a steady internal milieu. So how is it possible for adaptations to occur? What are the internal mechanisms that determine a good outcome versus a negative one?

Changes in the external environment, such as exercise training, challenge homeostasis, producing spatial and temporal responses in the internal environment. These cause interactions between muscle, bone and gut, modulated by the Endocrine system. The degree and nature of these responses dictate whether a positive adaptation occurs. An excessive response, or a response not in tune with the networks of the Endocrine system, can hinder adaptation or produce a maladaptive response. The balance and interplay of internal responses are crucial in determining the outcome to exercise training in the individual.

F=MA

Local responses in exercising tissues

Exercising tissues release exerkines (metabolites, nucleic acids, peptides) which are packaged in exosomes and microvesicles. The content of these vesicle packages increases with intensity of endurance exercise in a dose-dependent manner. These exerkines have autocrine and paracrine effects, which modulate systemic adaptations to endurance exercise in the tissues themselves and those in the vicinity.

The range of these molecular responses from exercising tissues has been identified applying multi-omics (epigenomic, transcriptomic and proteomic analyses). Furthermore variance in trainability has been shown to be correlated with the integrated responses of tissue molecular signalling pathways to endurance exercise.

In a similar manner, the degree of inflammatory response and production of reactive oxygen and nitrogen species (RONS) to exercise mediate favourable adaptations. Inter-individual variations in redox status has been shown to determine the ability to adapt to exercise training. However, unlimited increase in response does not necessarily produce a better outcome. An over response to exercise in these signalling pathways, hinders adaptation.

Exercise promotes bone adaptation in terms of bone material, structure and muscle action. Paracrine crosstalk occurs between muscle and bone. Muscle myokines and insulin like growth factor 1 (IGF1) favour bone formation, whilst inflammatory molecules, such as interleukin 6 (Il-6) released during muscle contractions, favour bone reabsorption. The balance between these opposing processes determines whether bone remodelling is effective, or whether bone stress reactions occur over a pathological continuum. These responses and adaptations occur on the background of lifespan Endocrine environment, which impacts the outcome.

Gut microbiota

The gut microbiota support the regulation of inflammation at the local and systemic level. Furthermore the communication between the gut microbiota and mitochondria has been described as an important interaction in facilitating adaptive responses to exercise. Mitochondria are organelles crucial for production of ATP, as well as RONS. The gut microbiota are involved in mitochondrial biogenesis by regulating key mitochondrial transcriptional factors and enzymes . Furthermore, the metabolites of the gut microbiota such as short chain fatty acids, modulate the inflammatory effects of mitochondrial oxidative stress. Conversely genetic variants in the mitochondrial genome could impact mitochondrial function and thus the gut microbiota in terms of composition and activity.

The gut microbiota have a role in regulating intestinal permeability. Leaky gut is where epithelial integrity is lost at the tight junctions between cells in the gut lining. Leaky gut can occur in gut dysbiosis and also following endurance exercise where re-perfusion injury produces acute hyper-permeability. In these instances, increased gut permeability augments the antigen load and causes increased systemic inflammation and potentially can trigger autoimmune disease. This demonstrates that an excessive inflammatory response to exercise can hinder positive adaptation

Metabolic adaptations

Metabolic flexibility, the ability to respond and adapt to changes in metabolic demand, is enhanced with exercise training through these autocrine, paracrine and Endocrine mechanisms. Metabolic flexibility supports energy availability and fuel selection during exercise. Exercise mimetics, such as artificial metabolic modulators, have been reported to up-regulate gene expression to shift metabolism to fat oxidation in exercising muscle. This would potentially extend the limit of endurance exercise. However this “short cut” to adaptation favouring improved sport performance is illegal, with such molecular ligands on the World Anti-Doping Agency (WADA) banned list.

Hierarchy of control

There is a hierarchy of control in modulating multi-system adaptations to exercise. The Endocrine system is key. Exercise per se produces an Endocrine response, for example exercise is a key stimulus for growth hormone release via the hypothalamus, the neuroendocrine gatekeeper. Growth hormone supports the anabolic response to exercise. In addition, the Endocrine milieu during the lifespan has an impact on response and adaptations to exercise. Any disruption in the Endocrine system hinders adaptive changes. Endocrine dysfunction may occur as a result of non-integrated periodisation of exercise/nutrition and recovery as seen in relative energy deficiency in sports (RED-S). Dysfunction can also occur due to an Endocrine pathology.

Conclusion

Changes in external stimuli, such as exercise and nutrition, produce internal responses on autocrine, paracrine and Endocrine levels. These molecular signalling pathways drive adaptive changes through integrated, network effects. However any imbalances in these interactive responses can hinder desired adaptive changes and even result in negative maladaptive outcomes to exercise training.

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

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.

Sport Endocrinology presentations

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

Balance of recovery and adaptation for sports performance Dr N.Keay, British Association of Sport and Exercise Medicine

Inflammation: Why and How Much? Dr N.Keay, British Association of Sport and Exercise Medicine

Clusters of Athletes – A follow on from RED-S blog series to put forward impact of RED-S on athlete underperformance Dr N.Keay, British Association of Sport and Exercise Medicine

Optimal Health: For All Athletes! Part 4 – Mechanisms Dr N.Keay, British Association of Sport and Exercise Medicine

The potential of endurance exercise-derived exosomes to treat metabolic diseases Nature Reviews Endocrinology

Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise Cold Spring Harbor Perspectives in Medicine

Genomic and transcriptomic predictors of response levels to endurance exercise training
Journal of Physiology

Adaptations to endurance training depend on exercise-induced oxidative stress: exploiting redox inter-individual variability Acta Physiologica

Mechanical basis of bone strength: influence of bone material, bone structure and muscle action Journal of Musculoskeletal and Neuronal Interactions

The Crosstalk between the Gut Microbiota and Mitochondria during Exercise Frontiers in Physiology

Leaky Gut As a Danger Signal for Autoimmune Diseases Frontiers in Immunology

Metabolic Flexibility in Health and Disease Cell Metabolism

Hormones and Sports Performance

PPARδ Promotes Running Endurance by Preserving Glucose Cell Metabolism

Fatigue, Sport Performance and Hormones…

2 May 2017

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

Clusters of Athletes

2 April 2017

At some time, most athletes experience periods of underperformance. What are the potential causes and contributing factors?

classification

Effective training improves sports performance through a process of adaptation that occurs, at both the cellular and system levels, during the recovery phase. Training overload must be balanced with sufficient subsequent recovery. A long-term improvement in form is expected, following a temporary dip in performance, due to short-term fatigue.

However, when an athlete experiences a stagnation of performance, what are the potential underlying causes? How should these be addressed to prevent an acute situation developing into a more chronic spiral of decreasing performance?

Depending on clinical presentation, the first step is to exclude medical conditions. Potential infective causes include Epstein Barr virus (particularly in young athletes), Lyme disease and Weil’s disease. Systemic inflammatory conditions should be considered. Endocrine and metabolic causes include pituitary, gonadal, adrenal, thyroid dysfunction, blood sugar control, and malabsorption.

If medical conditions are excluded, attention should turn to the athlete’s energy balance in the context of adherence to the current training plan. Potential causes of underperformance, the inability to improve in training and competition, are illustrated in the diagram above.

Athletes in the upper right quadrant fail to live up to performance expectations, in spite of maintaining a good energy balance while adhering to the prescribed training plan. However, they may represent non-functional overreaching, where overload is not balanced with sufficient recovery. In other words, the periodisation of training and recovery is not optimised. The balance between chronic training load (fitness) and acute training load (fatigue) provides a useful metric for assessing form. Heart rate variability (HRV) can be another potentially useful measure in detecting aerobic, endurance fatigue. If the training plan is not producing the expected improvements, then this plan needs revising. Don’t forget that sleep is essential to facilitate endocrine driven adaptations to exercise training.

Athletes in the lower right quadrant are of more concern. Inadequate energy balance, especially during periods of increased training load or intentional weight loss, can be a cause of underperformance, despite the athlete being able to adhere to the training plan. This would correspond to being at risk of developing relative energy deficiency in sport (RED-S) on the amber warning in the risk stratification laid out by the International Olympic Committee.

Both of these groups are able to adhere to a training plan, but suboptimal training and recovery periodisation and/or insufficient energy intake can produce a situation of underperformance. Intervention is required to prevent them moving into the clusters on the left, representing a more chronic underperformance scenarios that are therefore more difficult to rectify.

Athletes in the upper left quadrant exhibit overtraining syndrome: a prolonged maladaptation process accompanied by a decrease in performance (not merely stagnation) and inability to adhere to training plan. The metric of decreased HRV and inability of heart rate to accelerate in response to exercise have been suggested as markers of overtraining.

Those athletes in the lower left quadrant fall into the RED-S category, where multiple interacting Endocrine networks are impacted by an energy deficient state. RED-S not only impairs sports performance, but impacts both current and future health. For example low endogenous levels of sex steroids and insulin-like growth factor 1 (IGF1) disrupt formation of bone microarchitecture and bone mineralisation, resulting in increased risk of recurrent stress fracture in addition to potentially irreversible bone loss in the longer term. In cases of recurrent injury and underperformance amongst athletes it is imperative to exclude Endocrine dysfunction and then consider whether RED-S is the fundamental cause.

There are many potential causes of underperformance in athletes. Once medical conditions have been excluded, the main aim should be to prevent acute situations becoming chronic and therefore more difficult to resolve.

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

Sport Endocrinology Dr N. Keay, British Journal of Sport Medicine 2017

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

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

Optimal Health: For All Athletes! Part 4 – Mechanisms, Dr N. Keay, British Association of Sport and Exercise Medicine

Balance of recovery and adaptation for sports performance Dr N. Keay, British Association of Sport and Exercise Medicine

Sleep for health and sports performance Dr N. Keay, British Journal of Sport Medicine

Optimal health: including female athletes! Part 1 Bones Dr N.Keay, British Journal of Sport Medicine

Inflammation: why and how much? Dr N. Keay, British Association of Sport and Exercise Medicine

Fatigue, Sport Performance and Hormones… Dr N.Keay, British Journal of Sport Medicine

Part 3: Training Stress Balance—So What? Joe Friel

Heart Rate Variability (HRV) Science for Sport

Relative Energy Deficiency in sport (REDs) Lecture by Professor Jorum Sundgot-Borgen, IOC working group on female athlete triad and IOC working group on body composition, health and performance. BAEM Spring Conference 2015.

Prevention, Diagnosis, and Treatment of the Overtraining Syndrome: Joint Consensus Statement of the European College of Sport Science and the American College of
Sports Medicine. Joint Consensus Statement. Medicine & Science in Sports & Exercise 2012

Sports Endocrinology

25 March 2017

SportsEndocrinologyWordCloud

The Endocrine system comprises various glands distributed throughout the body that secrete hormones to circulate in the blood stream. These chemical messengers, have effects on a vast range of tissue types, organs and therefore regulate metabolic and physiological processes occurring in systems throughout the body.

The various hormones produced by the Endocrine system do not work in isolation; they have interactive network effects. The magnitude of influence of a hormone is largely determined by its circulating concentration. This in turn is regulated by feedback loops. For example, too much circulating hormone will have negative feedback effect causing the control-releasing system to down regulate, which will in turn bring the level of the circulating hormone back into range. Ovulation in the menstrual cycle is a rare example of a process induced by positive hormonal feedback.

In the control system of hormone release, there are interactions with other inputs in addition to the circulating concentration of the hormone. The hypothalamus (gland in the brain) is a key gateway in the neuro-endocrine system, coordinating inputs from many sources to regulate output of the pituitary gland, which produces the major stimulating hormones to act on the Endocrine glands throughout the body.

growthhormone

The Endocrine system displays complex dynamics. There are temporal variations in secretion of hormones both in the long term during an individual’s lifetime and on shorter timescales, as seen in the diurnal variation of some hormones such as cortisol, displaying a circadian rhythm of secretion. The most fascinating and complex control system is found in the hypothalamic-pituitary-ovarian axis. Variation in both frequency and amplitude of gonadotrophin releasing factor (GnRH) secretion from the hypothalamus dictates initiation of menarche and the subsequent distinct pattern of cyclical patterns of the sex steroids, oestrogen and progesterone.

So what have the Endocrine system and hormone production got to do with athletes and sport performance?

Exercise training stimulates release of certain hormones that support favourable adaptive changes. For example, exercise is a major stimulus of growth hormone, whose action positively affects body composition in terms of lean mass, bone density and reduction of visceral fat.
Disruption of hormones secreted from the Endocrine system can impair sport performance and have potential long term adverse health risks for athletes. This picture is seen in the female athlete triad (disordered eating, amenorrhoea and low bone mineral density) and relative energy deficiency in sport (RED-S) with multi-system effects. In this situation there is a mismatch between dietary energy intake (including diet quality) and energy expenditure through training. The net result is a shift to an energy saving mode in the Endocrine system, which impedes both improvement in sport performance and health. RED-S should certainly be considered among the potential causes of sport underperformance, suboptimal health and recurrent injury, with appropriate medical support being provided.
Caution! Athletic hypothalamic amenorrhoea, as seen in female athletes (in female athlete triad and RED-S) is a diagnosis of exclusion. Other causes of secondary amenorrhoea (cessation of periods >6 months) should be excluded such as pregnancy, polycystic ovary syndrome (PCOS), prolactinoma, ovarian failure and primary thyroid dysfunction.
Unfortunately the beneficial effects of some hormones on sport performance are misused in the case of doping with growth hormone, erythropoeitin (EPO) and anabolic steroids. Excess administered exogenous hormones not only disrupt the normal control feedback loops, but have very serious health risks, which are seen in disease states of excess endogenous hormone secretion.

So the Endocrine system and the circulating hormones are key players not only in supporting health, but in determining sport performance in 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

Sport Performance and RED-S, insights from recent Annual Sport and Exercise Medicine and Innovations in Sport and Exercise Nutrition Conferences Dr N. Keay, British Journal of Sports Medicine 17/3/17

Teaching module on RED-S for British Association of Sport and Exercise Medicine as CPD for Sports Physicians

Optimal Health: Including Female Athletes! Part 1 – Bones Dr N. Keay, British Journal of Sport Medicine 26/3/17

Optimal Health: Including Male Athletes! Part 2 – REDs Dr N. Keay, British Journal of Sport Medicine 4/4/17

Optimal health: especially young athletes! Part 3 Consequences of Relative Energy Deficiency in sports Dr N. Keay, British Association of Sport and Exercise Medicine 13/4/17

Optimal health: for all athletes! Part 4 Mechanisms Dr N. Keay, British Association of Sport and Exercise Medicine 13/4/17

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

Enhancing sports performance: part 3

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

Sleep for health and sports performance Dr N. Keay, British Journal of Sport Medicine

Balance of recovery and adaptation for sports performance Dr N. Keay, British Association of Sport and Exercise Medicine

Clusters of athletes Dr N. Keay, British Association of Sport and Exercise Medicine

Inflammation: why and how much? Dr N. Keay, British Association of Sport and Exercise Medicine

Fatigue, Sport Performance and Hormones…Dr N. Keay, British Journal of Sport Medicine

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.

Keay N, Fogelman I, Blake G. Effects of dance training on development,endocrine status and bone mineral density in young girls.Current Research in Osteoporosis and bone mineral measurement 103, June 1998.

Keay N, Effects of dance training on development, endocrine status and bone mineral density in young girls, Journal of Endocrinology, November 1997, vol 155, OC15.

Keay N, Fogelman I, Blake G. Bone mineral density in professional female dancers. British Journal of Sports Medicine, vol 31 no2, 143-7, June 1997.

Keay N. Bone mineral density in professional female dancers. IOC World Congress on Sports Sciences. October 1997.

Keay N, Bone Mineral Density in Professional Female Dancers, Journal of Endocrinology, November 1996, volume 151, supplement p5.