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

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Performance Implications of RED-S (IOC statement 2014)

Introduction Relative Energy Deficiency in Sport (RED-S) has developed out of the concept of the Female Athlete Triad (menstrual dysfunction, disordered eating and decreased bone mineral density) as it has become apparent that low energy availability, ie not eating enough calories to support training levels, has more widespread adverse impacts on health consequently performance in athletes than previously recognised. RED-S can impact both male and female athletes of all ages – if you are a male athlete, please do not stop reading! Young developing athletes can be at particular risk of RED-S as this represents a time of growth and development, which entails many nutritional demands in addition to those to support training. This represents a time to set up the template for health into adulthood.

Why does RED-S occur? RED-S is particularly prevalent in sports where low body weight confers a performance advantage or for aesthetic reasons. For example: long distance running, triathlon, gymnastics, dance and cycle road racing. However, RED-S could also occur not as an intentional strategy to control body weight, but rather during cycles of increased training load where periodised nutrition has not been synchronised with the increased demand on the body.

What is RED-S? Fundamentally there is a mismatch between food intake (in terms of energy and micronutrients) and the demand for nutrition required to cover expenditure, both for training and for basic “housekeeping” tasks in the body. If there is insufficient energy availability, then the body switches into an energy saving mode. This “go slow” mode has implications for hormone production and metabolic processes, which impacts all systems throughout the body. The reason why RED-S was originally described as the Female Athlete Triad is that in women the “energy saving mode” involves menstrual periods being switched off: a pretty obvious external sign as all women of child bearing age should have periods (apart from when pregnant). Low oestrogen levels have an adverse effect on bone health, resulting in decrease in bone mineral density. This effectively renders young women at increased risk of both soft tissue and bone injury, as seen in post-menopausal women. As described in the IOC statement published 2014 in British Journal of Sports Medicine on RED-S, the Female Athlete Triad is now recognised as just the tip of the iceberg. Disruption of hormone levels does not only adversely impact menstrual periods and bone health. There are knock on effects impacting the immune system, cardiovascular system, muscles, nervous system, gut health and the list goes on. Importantly, this situation is also seen in male athletes: for example, whether or not a sport is weight bearing, which traditionally improves bone health, in RED-S the predominant effect of disrupted hormones is to decrease bone density, leading to increased fracture risk.

What is the significance of RED-S? Do these effects of RED-S matter? Yes: there is a detrimental effect on not only health, but on all elements of sports performance. These include an inability to improve as expected in response to training and increased risk of injury. In the long-term there are potential implications for health with inability to reach peak bone mass for young athletes and at the other end of the scale, irreversible bone loss being seen in retired athletes.

Here is a summary of the potential impact of RED-S:

• Endocrine dysfunction: decreased training response

• Metabolic disruption: decreased endurance performance

• Bone health: increased risk bone stress injuries

• Decreased functional immunity: prone to infection

• Gut malfunction: impaired absorption of nutrients

• Decreased neuromuscular co-ordination: injury risk

• Psychological impact: inability to recognise risk developing RED-S

As you can see, these adverse effects are all relevant to performance in endurance sport.

What to do if you are concerned you may have RED-S?

Health Considerations:

• Women: even if your adult weight is steady, if you are a female athlete of reproductive age whose periods have stopped, then do not ignore this! In the first instance, you need to exclude any other causes (for example polycystic ovary syndrome and other hormone issues) in conjunction with your doctor. Then take a look at how you are eating in line with your training load – see the nutritional considerations section below.

• Men: if you are a male athlete struggling to improve sport performance, then review both your training load and your periodised nutrition and recovery. If the cause is RED-S then do not wait until your sport performance drops or you get injured before taking action. You may also want to consider having your testosterone levels measured to check that these are in the normal range.

Nutritional Considerations: From colleague Jo Scott-Dalgleish BSc (Hons), mBANT, CNHC

• Ensure an adequate energy intake. Use My Fitness Pal or a similar app to track your food intake over the course of week. On any day when you train, if you are consuming fewer than 2500 calories as a male endurance athlete and 2000 calories as a female endurance athlete, your intake is likely to be inadequate as these are the guidelines for the general population. If you are taking in fewer than 2750 calories (male) or 2250 calories (female) on a day when you are training for two hours or more, you are likely to be at increased risk of RED-S. Use this data to learn more about appropriate food choices and serving sizes, and introduce some changes to increase your intake in line with your training load. But I do not suggest using apps like these on a long-term basis as they may encourage an unhealthy obsession with your food intake.

• Focus on nutrient density. Make good quality food choices to help you get enough vitamins and minerals as well as carbohydrates, protein, fat and fibre. Try to eat fresh, minimally processed foods rather than too much packaged food, including 3-5 servings of vegetables and 2-3 pieces of fresh fruit each day.

• Avoid excluding foods, whole food groups or following ‘fad diets’. Unless you have a genuine allergy or a diagnosed medical condition such as coeliac disease or lactose intolerance. Or you have been advised to avoid certain foods by a dietician or other well-qualified nutrition practitioner to help manage a health condition such as Irritable Bowel Syndrome. If you are vegetarian or vegan, see Jo’s blog here for tips on ensuring a well-balanced approach.

• Periodise your carbohydrate intake in line with your training. Increase your intake of starches and sugars (including vegetables and fruit) on your heavier training days. A low daily carbohydrate intake might be in the range of 2-4 g/kg of body weight. This is OK for lower volume training days, but should be increased to 5-8 g/kg when training for 2-3 hours or more in a single day. Again, use an app like My Fitness Pal for a week to help you assess your carbohydrate intake. If you are experiencing RED-S, avoid following approaches like fasted training or low carb-high fat diets (LCHF) due to potential adverse effects on hormones.

• Pay attention to your recovery nutrition. Consuming 15-25g of protein and 45-75g of carbohydrate in the hour after exercise, whether as a snack or as part of a meal will help you to each your energy intake goals, restock your glycogen stores for your next training session and protect lean muscle mass.

Jo Scott-Dalgleish BSc (Hons), mBANT, CNHC, is a registered nutritional therapist specialising in nutrition for endurance sport, based in London. She works with triathletes, distance runners and cyclists to help optimise both their performance and their health through the creation of an individual nutritional plan. For more details, please visit www.endurancesportsnutritionist.co.uk.

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

References

Optimal health: including female athletes! Part 1 Bones Dr N. Keay, British Journal of Sport Medicine 2017

Optimal health: including male athletes! Part 2 Relative Energy Deficiency in sports Dr N. Keay, British Journal of Sport Medicine 2017

Optimal Health: Especially Young Athletes! Part 3 – Consequences of Relative Energy Deficiency in Sports Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Mechanisms for optimal health…for all athletes! Dr N. Keay, British Journal of Sport Medicine 2017

The IOC consensus statement: beyond the Female Athlete Triad—Relative Energy Deficiency in Sport (RED-S) British Journal of Sports Medicine 2014

Nutritional considerations for vegetarian endurance athletes Jo Scott-Dalgleish, Endurance Sports Nutrition 2017

 

Athletic Fatigue: Part 2

A degree of athletic fatigue following a training session, as described in part 1, is required to set in motion mechanisms to drive beneficial adaptations to exercise. At what point does this process of functional over-reaching tip into non-functional over-reaching denoted by failure to improve sports performance? Or further still along the spectrum and time scale, the chronic situation of overtraining and decrease in performance? Is this a matter of time scale, or degree, or both?

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Integrated Periodisation of Training Load, Nutrition and Recovery keeps an individual on the green plateau, avoiding descent into the red zone, due to an excess or deficiency

Determining the tipping point between these fatigue situations is important for health and performance. A first step is always to exclude underlying organic disease states, be these of Endocrine, systemic inflammatory or infective aetiologies. Thereafter the crucial step is to assess whether the periodisation of training, nutrition and recovery are integrated over a training block and in the longer term over a training season.

What about the application of Endocrine markers to monitor training load? Although the recent studies described below are more applicable to research scenarios, they give some interesting insights into the interactive networks effects of the Endocrine system and the multifactorial nature of fatigue amongst individual athletes.

In the short term, during a 2 day rowing competition, increases in wakening salivary cortisol were noted followed by return towards baseline in subsequent 2 day recovery. Despite individual variability with salivary cortisol measurement, this does at least offer a noninvasive way to adjust training loads around competition time for elite athletes.

Over an 11 day stimulated training camp and recovery during the sport specific preparatory phase of the training season, blood metabolic and Endocrine markers were measured. In the case of an endurance based training camp in cyclists, a significant increase in urea (due to protein breakdown associated with high energy demand training) and decrease in insulin-like growth factor 1 (IGF1) from baseline were noted. Whereas for the strength-based athletes for ball sports, an increase in creatine kinase (CK) was seen, as a result of muscle damage. This study demonstrates how different markers of fatigue are specific to sport discipline and mode of training. Large inter-individual variability existed between the degree of change in markers and degree of fatigue.

In the longer term, for the case of overtraining syndrome potential Endocrine markers have been reviewed. Whilst basal levels of most measured hormones remained stable, a blunted submaximal exercise response of growth hormone (GH), prolactin and ACTH could be indicative of developing overtraining syndrome. Whilst this review is interesting, dynamic testing is not a practical approach and these findings are not specific to over training. Rather this blunted dynamic exercise response would indicate relative suppression of the neuroendocrine hypothalamic-pituitary axis which could potentially involve other stressors such as inadequate sleep or poor nutrition. Although basal levels may lie “within the normal range”, if both pituitary derived stimulating hormone and end endocrine gland hormone concentrations fall in the lower end of the normal ranges (eg low end of range TSH and T4) this is consistent with mild hypothalamic suppression observed over the range of training and fatigue conditions (functional/non-functional and overtraining) and/or Relative Energy Deficiency in Sports (RED-S).

Although the studies above are of research interest, non invasive monitoring, specific to an athlete is more practical for monitoring the effects of training. Several useful easily measurable metrics can give clues: resting heart rate, heart rate variability, power output. Tools on Strava and Training Peaks provide practical insights in monitoring training effectiveness via these metrics. A range of mobile apps makes it ever easier to augment a personal training log to include these training metrics, along with feel, sleep and nutrition. Such a log provides feedback on health and fitness for the individual athlete, in order to personalise training plans. Certainly adding the results from any standard basal blood tests will also help add to the picture, along the lines of building a longitudinal personal biological passport. After all, “normal ranges” are based on the general population, of which top level athletes may represent a subgroup. The more personalised the metics recorded over a long time scale, the more sensitive and useful the process to guide improvement in sport performance.

Context is key when considering athletic fatigue: temporal considerations and individual variation. Certainly the interactive network effects of the Endocrine system are important in determining the degree of adaptation to exercise and therefore sports performance. However the Endocrine system acts in conjunction with many other systems (metabolic, immune and inflammatory), in determining the effectiveness of training in improving sports performance. So it is not surprising that one metric or marker in isolation is not predictive of fatigue status in individual athletes.

For more discussion on Health, Hormones and Human Performance come to the British Association of Sport and Exercise Medicine annual conference

References

Athletic Fatigue: Part 1

Endocrine system: balance and interplay in response to exercise training

Temporal considerations in Endocrine/Metabolic interactions Part 1

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

Capturing effort and recovery: reactive and recuperative cortisol responses to competition in well-trained rowers British Journal of Sports Medicine

Blood-Borne Markers of Fatigue in Competitive Athletes – Results from Simulated Training Camps Plos One

Hormonal aspects of overtraining syndrome: a systematic review BMC Sports Science, Medicine and Rehabilitation 2017

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 2017

Strava Fitness and Freshness Science4Performance 2017

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

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

Athletic Fatigue: Part 1

Interpreting athletic fatigue is not easy. Consideration has to be given to context and time scale. What are the markers and metrics that can help identify where an athlete lies in the optimal balance between training, recovery and nutrition which support beneficial adaptations to exercise whilst avoiding the pitfalls of fatigue and maladaptation? This blog will discuss the mechanisms of athletic fatigue in the short term.

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Proposed causes of fatigue dependent on duration and intensity of training session

In the short term, during an endurance training session or race, the temporal sequence of athletic fatigue depends on duration and intensity. It is proposed that below lactate threshold (LT1), a central mechanism governs: increasing central motor drive is required to maintain skeletal muscular power output until neuromuscular fatigue cannot be overcome. From lactate threshold (LT1) to lactate turn point (LT2), a combination of central and peripheral factors (such as glycogen depletion) are thought to underpin fatigue. During high intensity efforts, above LT2 (which correspond to efforts at critical power), accumulation of peripheral metabolites and inability to restore homeostasis predominate in causing fatigue and ultimately inability to continue, leading to “task failure”. Of course there is a continuum and interaction of the mechanisms determining this power-duration relationship. As glycogen stores deplete this impacts muscle contractility by impairing release of calcium from the sarcoplasmic reticulum in skeletal muscle. Accumulation of metabolites could stimulate inhibitory afferent feedback to central motor drive for muscle contraction, combined with decrease in blood glucose impacting central nervous system (CNS) function.

Even if you are a keen athlete, it may not be possible to perform a lactate tolerance or VO2 max test under lab conditions. However a range of metrics, such as heart rate and power output, can be readily collected using personalised monitoring devices and then analysed. These metrics are related to physiological markers. For example heart rate and power output are surrogate markers of plasma lactate concentration and thus can be used to determine training zones.

A training session needs to provoke a degree of training stress, reflected by some short term fatigue, to set in motion adaptations to exercise. At a cellular level this includes oxidative stress and exerkines released by exercising tissues, backed up by Endocrine responses that continue to take effect after completing training during recovery and sleep. Repeated bouts of exercise training, followed by adequate recovery, result in a stepwise increase in fitness. Adequate periodised nutrition to match variations in demand from training also need to be factored in to prevent the Endocrine system dysfunction seen in Relative Energy Deficiency in Sports (RED-S), which impairs Endocrine response to training and sports performance. Integrated periodisation of training/recovery/nutrition is essential to support beneficial multi-system adaptations to exercise on a day to day time scale, over successive training blocks and encompassing the whole training and competition season. Psychological aspects cannot be underestimated. At what point does motivation become obsession?

In Part 2 the causes of athletic fatigue over a longer time scale will be discussed, from training blocks to encompassing whole season.

For more discussion on Health, Hormones and Human Performance come to the British Association of Sport and Exercise Medicine annual conference

References

Endocrine system: balance and interplay in response to exercise training

Power–duration relationship: Physiology, fatigue, and the limits of human performance European Journal of Sport Science 2016

Strava Ride Statistics Science4Performance 2017

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

Relative Energy Deficiency in Sports (RED-S) Practical Considerations for Endurance Athletes

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

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

Addiction to Exercise – what distinguishes a healthy level of commitment from exercise addiction? Dr N Keay, British Journal of Sports Medicine 2017

 

 

Temporal considerations in Endocrine/Metabolic interactions Part 2

LifeSeasonDay

As discussed in the first part of this blog series, the Endocrine system displays temporal variation in release of hormones. Amplitude and frequency of hormonal secretion display a variety of time-related patterns. Integrating external lifestyle factors with this internal, intrinsic temporal dimension is crucial for supporting metabolic and Endocrine health and sport performance.

Circadian misalignment and sedentary lifestyle has been implicated in the increased incidence of metabolic syndrome driven by insulin resistance and associated metabolic inflexibility and decrease in fat oxidation. However, a recent study of overweight individuals, found that increases in fat oxidation from lifestyle intervention, corresponded to different clinical outcomes. Both those who maintained weight loss and those who regained weight displayed increased fat oxidation compared to baseline. How could this be? Increased fat oxidation is only part of the equation in overall fat balance. What adaptations in the metabolic and Endocrine networks were occurring during rest periods? In the case of those that maintained weight loss, increased fat oxidation was reflected in biochemical and physiological adaptations to enable this process. Whereas for those that regained weight in the long term, increased fat oxidation was enabled by increased availability of lipids, indicating increased fat synthesis over degradation.

Clearly there is individual variation in long-term Endocrine and metabolic responses to external factors. Focusing on optimising a single aspect of metabolism in the short term, will not necessarily produce the expected, or desired clinical outcome over a sustained period of time. As previously discussed the single most effective lifestyle change that induces synchronised, beneficial sustained Endocrine and metabolic adaptations is exercise.

It will come as no surprise that focusing on maximising use of a single substrate in metabolism, without integration into a seasonal training plan and consideration of impacts on internal control networks, has not produced the desired outcome of improved performance amongst athletes. Theoretically, increasing fat oxidation will benefit endurance athletes by sparing glycogen use for high intensity efforts. Nutritional ketosis can be endogenous (carbohydrate restricted intake) or exogenous (ingestion of ketone esters and carbohydrate). Low carbohydrate/high fat diets have been shown in numerous studies to increase fat oxidation, however, this was at the expense of effective glucose metabolism required during high intensity efforts. Potentially there could be adverse effects of low carbohydrate intake on gut microbiota and immunity.

This effect was observed even in a study on a short timescale using a blinded, placebo-controlled exogenous ketogenic intervention during a bicycle test, where glycogen was available as a substrate. The proposed mechanism is that although ketogenic diets promote fat oxidation, this down-regulates glucose use, as a respiratory substrate. In addition, fat oxidation carries a higher oxygen demand for a lower yield of ATP, compared to glucose as a substrate in oxidative phosphorylation.

Metabolic flexibility the ability to use a range of substrates according to requirement, is key for health and sport performance. For example, during high intensity phases of an endurance race, carbohydrate will need to be taken on board, so rehearsing what types/timing of such nutrition works best for an individual athlete in some training sessions is important. Equally, some low intensity training sessions with low carbohydrate intake could encourage metabolic flexibility. However, in a recent study “training low” or periodised carbohydrate intake failed to confer a performance advantage. I would suggest that the four week study time frame, which was not integrated into the overall training season plan, is not conclusive as to whether favourable long term Endocrine and metabolic adaptations would occur. A review highlighted seasonal variations in male and female athletes in terms of energy requirements for different training loads and body composition required for phases of training blocks and cycles over a full training season.

Essentially an integrated periodisation of training, nutrition and recovery over a full training season will optimise the desired Endocrine and metabolic adaptations for improved sport-specific performance. The emphasis will vary over the lifespan of the individual. The intricately synchronised sequential Endocrine control of the female menstrual cycle is particularly sensitive to external perturbations of nutrition, exercise and recovery. Unfortunately the majority of research studies focus on male subjects.

In all scenarios, the same fundamental temporal mechanisms are in play. The body seeks to maintain homeostasis: status quo of the internal milieu is the rule. Any external lifestyle factors provoke short term internal responses, which are regulated by longer term Endocrine network responses to result in metabolic and physiological adaptations.

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

References

Temporal considerations in Endocrine/Metabolic interactions Part 1 Dr N. Keay

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

Sedentary behaviour is a key determinant of metabolic inflexibility Journal of Physiology 2017

Influence of maximal fat oxidation on long-term weight loss maintenance in humans Journal of Applied Physiology 2017

One road to Rome: Metabolic Syndrome, Athletes, Exercise Dr N.Keay 2017

Metabolic and Endocrine System NetworksDr N. Keay 2017

Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males Applied Physiology, Nutrition, and Metabolism 2017

Endocrine system: balance and interplay in response to exercise training Dr N. Keay 2017

No Superior Adaptations to Carbohydrate Periodization in Elite Endurance Athletes Medicine & Science in Sports & Exercise 2017

Total Energy Expenditure, Energy Intake, and Body Composition in Endurance Athletes Across the Training Season: A Systematic Review Sports Medicine – Open 2017

Successful Ageing Dr N. Keay, British Association of Sport and Exercise Medicine 2017

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

 

 

 

Metabolic and Endocrine System Networks

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

 

 

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

Clusters of Athletes

 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

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?

  1. 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.
  2. 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 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.
  3. 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.
  4. 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.

Optimal health: for all athletes! Part 4 Mechanisms

As described in previous blogs, the female athlete triad (disordered eating, amenorrhoea, low bone mineral density) is part of Relative Energy Deficiency in sports (RED-S). RED-S has multi-system effects and can affect both female and male athletes together with young athletes. The fundamental issue is a mismatch of energy availability and energy expenditure through exercise training. As described in previous blogs this situation leads to a range of adverse effects on both health and sports performance. I have tried to unravel the mechanisms involved. Please note the diagram below is simplified view: I have only included selected major neuroendocrine control systems.

REDs

Low energy availability is an example of a metabolic stressor. Other sources of stress in an athlete will be training load and possibly inadequate sleep. These physiological and psychological stressors input into the neuroendocrine system via the hypothalamus. Low plasma glucose concentrations stimulates release of glucagon and suppression of the antagonist hormone insulin from the pancreas. This causes mobilisation of glycogen stores and fat deposits. Feedback of this metabolic situation to the hypothalamus, in the short term is via low blood glucose and insulin levels and in longer term via low levels of leptin from reduced fat reserves.

A critical body weight and threshold body fat percentage was proposed as a requirement for menarche and subsequent regular menstruation by Rose Frisch in 1984. To explain the mechanism behind this observation, a peptide hormone leptin is secreted by adipose tissue which acts on the hypothalamus. Leptin is one of the hormones responsible for enabling the episodic, pulsatile release of gonadotrophin releasing hormone (GnRH) which is key in the onset of puberty, menarche in girls and subsequent menstrual cycles. In my 3 year longitudinal study of 87 pre and post-pubertal girls, those in the Ballet stream had lowest body fat and leptin levels associated with delayed menarche and low bone mineral density (BMD) compared to musical theatre and control girls. Other elements of body composition also play a part as athletes tend to have higher lean mass to fat mass ratio than non-active population and energy intake of 45 KCal/Kg lean mass is thought to be required for regular menstruation.

Suppression of GnRH pulsatility, results in low secretion rates of pituitary trophic factors LH and FSH which are responsible for regulation of sex steroid production by the gonads. In the case of females this manifests as menstrual disruption with associated anovulation resulting in low levels of oestradiol. In males this suppression of the hypothamlamic-pituitary-gonadal axis results in low testosterone production. In males testosterone is aromatised to oestradiol which acts on bone to stimulate bone mineralisation. Low energy availability is an independent factor of impaired bone health due to decreased insulin like growth factor 1 (IGF-1) concentrations. Low body weight was found to be an independent predictor of BMD in my study of 57 retired pre-menopausal professional dancers. Hence low BMD is seen in both male and female athletes with RED-S. Low age matched BMD in athletes is of concern as this increases risk of stress fracture.  In long term suboptimal BMD is irrecoverable even if normal function of hypothamlamic-pituitary-gonadal function is restored, as demonstrated in my study of retired professional dancers. In young athletes RED-S could result in suboptimal peak bone mass (PBM) and associated impaired bone microstructure. Not an ideal situation if RED-S continues into adulthood.

Another consequence of metabolic, physiological and psychological stressor input to the hypothalamus is suppression of the secretion of thyroid hormones, including the tissue conversion of T4 to the more active T3. Athletes may display a variation of “non-thyroidal illness/sick euthyroid” where both TSH and T4 and T3 are in low normal range. Thyroid hormone receptors are expressed in virtually all tissues which explains the extensive effects of suboptimal levels of T4 and T3 in RED-S including on physiology and metabolism.

In contrast, a neuroendocrine control axis that is activated in RED-S is the hypothalamic-pituitary-adrenal axis. In this axis, stressors increase the amplitude of the pulsatile secretion of CRH, which in turn increases the release of ACTH and consequently cortisol secretion from the adrenal cortex. Elevated cortisol suppresses immunity and increases risk of infection. Long term cortisol elevation also impairs the other hormone axes: growth hormone, thyroid and reproductive. In other words the stress response in RED-S amplifies the suppression of key hormones both directly and indirectly via endocrine network interactions.

The original female athlete triad is part of RED-S which can involve male and female athletes of all ages. There are a range of interacting endocrine systems responsible for the multi-system effects seen in RED-S. These effects can impact on current and future health and sports 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

Teaching module on RED-S for BASEM as CPD for Sports Physicians

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

Optimal health: including male athletes! Part 2 Relative Energy Deficiency in sports 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

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.

Jenkins P, Taylor L, Keay N. Decreased serum leptin levels in females dancers are affected by menstrual status. Annual Meeting of the Endocrine Society. June 1998.

Keay N, Dancing through adolescence. Editorial, British Journal of Sports Medicine, vol 32 no 3 196-7, September 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.

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.

Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, Meyer N, Sherman R, Steffen K, Budgett R, Ljungqvist A. The IOC consensus statement: beyond the Female Athlete Triad-Relative Energy Deficiency in Sport (RED-S).Br J Sports Med. 2014 Apr;48(7):491-7.

“Subclinical hypothydroidism in athletes”. Lecture by Dr Kristeien Boelaert at BASEM Spring Conference 2014 on the Fatigued Athlete

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