Health, Hormones and Human Performance Part 1

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.


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




Male Athletes: the Bare Bones of Cyclists

Chris Boardman is an Olympic gold medal winner and world record breaking cyclist. However, he explains in his biography that he retired in his early thirties with weak bones and low testosterone. At the time he was treated with medication aimed at improving his bone strength, but this severely impacted his performance on the bike.

What was the cause of this superlative male athlete’s unhealthy condition that ultimately lead to his retirement? Is this still an issue for male cyclists today? Is it limited to elite professional riders?

Periodisation of key training factors support the Endocrine system to optimise performance

In 2014 the IOC published a description of relative energy deficiency in sports (RED-S), where nutrition intake is insufficient to cover training demands and the basic “housekeeping” activities of the body. This induces an energy-saving mode that impacts health and therefore athletic performance. The female athlete triad had been previously described as the combination of disordered eating, menstrual disruption and impaired bone health. RED-S goes beyond the female athlete triad to include a broader range of  impacts on systems other than just the bones and female hormone production. Significantly RED-S includes male athletes. Today, Chris Boardman would be diagnosed with RED-S.

Has this new information improved the identification and support of male athletes at risk of RED-S? In a recent pilot study, 5 out of 10 competitive amateur riders (Category 2 and above) were in the lowest age-matched percentile of body fat and 9 out 10 where in the lowest 6% relative to the population of similar age. Significantly, 7 out of 10 riders had below-average for age bone mineral density (BMD) in the lumbar spine, with two males having bone densities that would be low for an 85 year old.

Why is poor bone health a particular risk for competitive male cyclists? Depending on the type of exercise, beneficial adaptations include mechanical strengthening of specific parts of the skeletal system. For example, assuming good nutrition, runners tend to have strong hips, whereas rowers have more robust spines in terms of BMD and bone microarchitecture. Conversely the non-weight-bearing nature of cycling and the generally lower level of upper-body musculature reduce the mechanical loading forces though the spine: low osteogenic (bone building) stimuli. Although similar to swimming, in the sense that body weight is supported in the water, the major difference between these two forms of exercise is that in cycling, particularly for climbing, low body mass confers a performance advantage. This brings in the additional factor for bone health of potential inadequacies in nutrition and therefore consequences on hormone production.

An optimal balance of training, nutrition and recovery drives beneficial adaptations to exercise throughout the body. The body’s Endocrine system releases hormones that stimulate positive changes, such as the process of improving the efficiency of delivering and utilising oxygen and nutrients to exercising tissues, including the skeletal system. Any imbalances in periodisation between the three inputs of training, nutrition and recovery will compromise health and athletic performance.

Cyclists are at particular risk of insufficient fuelling. This may be an intentional attempt to maintain low body weight, which can lead to healthy eating becoming an unhealthy orthorexic pattern, where vital food groups for endurance sport, such as carbohydrates are excluded. There is also a practical element to fuelling adequately during long rides and refuelling afterwards. Consistency of nutrition throughout the day has been highlighted in a recent study of male endurance athletes where although an average 24 hour intake may be sufficient, if there are any significant deficits during this time, then this is reflected in increased adverse impact on catabolic Endocrine makers. In another study of male athletes if refuelling with carbohydrate and protein after training did not occur promptly, this lead to an increase in bone resorption over formation markers.

Recovery is an essential part of a training schedule, because the adaptations to exercise occur during rest. Sleep, in particular, is a major stimulus for growth hormone release, which drives positive adaptive changes in terms of body composition and bone turnover. Conversely, insufficient recovery time due to a packed schedule of training and work, places extra stresses on the Endocrine system. Getting to bed half an hour earlier than usual every day quickly adds up to an extra night’s sleep.

Does it matter if some areas of the skeleton are weaker than others? Yes, because this increases your risk of fracture, not just if you come off your bike, but also with relatively low force impacts. In the case of runners and triathletes, bone stress injuries are more likely to occur as an early warning sign of impaired bone health due to RED-S. Since low impact forces are absent in cycling, it may take a crash to reveal the strength of a rider’s bones. Studying the list of injuries in elite cyclists there are many fractures, with longer recovery time for vertebral fractures. So potentially cyclists can develop more severe bone health issues than other athletes, before becoming aware of the situation.

If you are a male cyclist, what can you do to prevent issues of bone health and risk of developing RED-S and suboptimal performance on the bike? Watch this space! A study is planned to investigate practical and effective strategies to optimise health and performance on the bike. In meantime there will be more discussion on “Health, Hormones and Human Performance” at the BASEM conference 22 March. All welcome, including athletes and coaches, alongside healthcare professional working with athletes.


Mechanisms for optimal health…for all athletes! BJSM 2017

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

Optimal health: including male athletes! Part 2 Relative Energy Deficiency in sports BJSM 2017

Lifestyle Choices for optimising health: exercise, nutrition, sleep BJSM 2017

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

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

Within-day Energy Deficiency and Metabolic Perturbation in Male Endurance Athletes International Journal of Sport Nutrition and Exercise Metabolism 2018

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

Sleep for health and sports performance BJSM 2017




Ubiquitous Microbiome: impact on health, sport performance and disease

Microbiome Mitochondria Feedback

The gut microbiome plays a key role in regulating the optimal degree of response to exercise required to stimulate desired adaptive changes.

We have at least as many bacterial cells as human cells in our bodies. We are all familiar with the effects of disturbing the balance of beneficial microbes in our gut. Beyond this, the gut microbiome (the range of microbes, their genetic material and metabolites) is essential for health. An interactive feedback exists between gut microbiota and functional immunity, inflammation, metabolism and neurological function

Sports performance: endurance exercise increases metabolic, oxidative and inflammatory stress, signalled by the release of exerkines from exercising tissue. This signalling network induces adaptive responses mediated via the Endocrine system. Maladaptation to exercise can be due either to an undesirable over-response or an insufficient response.

Intricate interactive feedback links exist between mitochondria and the gut microbiota. In addition to being the power generators of all metabolically active cells, mitochondria produce reactive oxygen species (ROS) and reactive nitrogen species during high intensity exercise. These oxidative stress signals not only mediate adaptive responses to exercise during recovery, but influence gut microbiota by regulating intestinal barrier function and mucosal immune response. Mitochondrial genetic variation could influence mitochondrial function and thus gut microbiota composition and function. Equally, the gut microbiota and its metabolites, such as short chain fatty acids, impact mitochondrial biogenesis, energy production and regulate immune and inflammatory responses in the gut to mitochondrial derived oxidative species. So nutritional strategies to support favourable gut microbiota would potentially support the beneficial effects of the interactions described above to optimise sport performance in athletes.

Conversely, disruption to favourable diversity of the gut microbiota, dysbiosis, is associated with increase in both inflammation and oxidative stress. Not a good situation for either health or sport performance. Alteration to the integrity of the intestinal wall increasing permeability can also be a factor in disrupting the composition of the gut microbiota. The resultant increased antigen load due to bacterial translocation across the gut wall is linked to increased inflammation, oxidative stress and metabolic dysfunction. “Leaky gut” can occur in high level endurance exercise where splanchnic blood flow is diverted away from the gut to exercising tissues for long periods of time, resulting in relative hypo-perfusion and an effective re-perfusion injury on stopping exercise. In the longer term the increased levels of inflammation, oxidative stress and antigen load impair adaptation to exercise and are associated with endocrine dysfunction in chronic disease states, for example autoimmune conditions, metabolic syndrome (type 2 diabetes mellitus, obesity) and depression.

Evidence links the composition of the gut microbiota to changes in circulating metabolites and obesity. For example, low abundance of certain species of gut microbiota reduces levels of circulating amino acid glutamine, which acts as a neurotransmitter precursor. Bariatric surgery is associated with changes in the release of gut hormones regulating food intake behaviour and energy homeostasis. In addition, beneficial changes are seen in the gut microbiota which could directly or indirectly support weight loss, via action on gut hormones.

Metformin is frequency used to improve insulin sensitivity in both type 2 diabetes mellitus and polycystic ovary syndrome. However, the mechanism is poorly understood. There is now evidence that the effect of metformin is mediated via changes in gut microbiota diversity. Transfer of stool from those treated with metformin improves insulin sensitivity in mice. In addition metformin regulates genes in some gut microbiota species that encode metalloproteins or metal transporters, which are know to be effective ligands. The pathophysiology of metabolic syndrome and obesity involves an inflammatory component which is triggered by gut dysbiosis and bacterial translocation, with increased generation of oxidative species. Probiotics have a potential role in regulating the redox status of the host via their metal ion chelating ability and metabolite production, which has an impact on the production of ROS and associated signalling pathways. Prebiotics found in dietary polyphenols promote these actions of favourable gut microbiota, which is of benefit in metabolic syndrome.

Recently it has been postulated that the gut microbiome, apart from playing a crucial role in health and pathogenesis of disease states, also impacts brain development, maturation, function and cognitive processes.

Understanding the role of the gut microbiome on metabolism, inflammation and redox status is very relevant to athletes where an optimal response to exercise training supports adaptations to improve performance, whereas an over or under response in these pathways results in maladaptive responses.

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



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

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

The Crosstalk between the Gut Microbiota and Mitochondria during Exercise Front Physiol. 2017

Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities Psychother Psychosom 2017

Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention Nature Medicine 2017

Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug Nature Medicine 2017

L’altération de la perméabilité intestinale : chaînon manquant entre dysbiose et inflammation au cours de l’obésité ? Med Sci (Paris)

Antioxidant Properties of Probiotic Bacteria  Nutrients 2017

The Impact of Gut Microbiota on Gender-Specific Differences in Immunity Front. Immunol 2017

Commentary: Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome Front. Immunol., 27 July 2017

Gut microbial communities modulating brain development and function Gut Microbes



Successful Ageing

As I am discovering, ageing is an inevitable process. However what can you do to keep as healthy as possible in order to get the most out of life?

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If you are a Masters athlete, you will know that moving into these age groups means it is advisable to change training emphasis in order to prevent injury and compete successfully. As discussed at the recent conference Royal Society of Medicine on Sports Injuries and Sports Orthopaedics, during the session on “The Ageing Athlete”, older athletes need a longer dynamic warm up with controlled mobilisation and muscle activation, together with strength and conditioning sessions to prevent injury. Moving into next age group every five years gives the opportunity to assess and modify training accordingly.

Childhood development has an impact on long term adult health. Essentially the most rapid changes and potential peaks attained during childhood and adolescence reflect optimal physical and cognitive functioning in later life. The evidence from population cohort studies was presented by Professor Diana Kuh, director of MRC Unit for Lifelong Health and Ageing, at the recent conference at the Royal Society of Medicine. Up to 66% of the decline in functional ability in ageing adults is related to childhood development. In the case of pubertal timing, Professor Kuh described that delay causes 20% reduction of volumetric trabecular bone accrual. In my 3 year longitudinal study of 87 pre and post pubertal girls, high levels of training delayed menarche and blunted attainment of peak bone mass (PBM). Conversely an optimal level of training did not delay menarche and improved bone mineral density compared to age marched sedentary controls. A similar long term effect is seen in older female athletes who have experienced amenorrhoea of more than 6 months duration. Even after retirement and resumption of menses pre-menopause, irreversible loss of bone mineral density (BMD) is seen. Professor Kuh argued for specific and personalised recommendations to individuals to support successful ageing.

From a personalised medical perspective, what about hormonal changes associated with ageing? Although in men testosterone levels decline with age, nevertheless the change is more dramatic in women at menopause where the ovaries stop producing oestrogen and progesterone. This results in increased risk after the menopause of osteoporosis, cardiovascular disease and stroke, together with other vasomotor symptoms and mood changes. With increased life expectancy comes an increasing number of women with menopausal symptoms and health issues which can negatively impact on quality of life. What about hormone replacement therapy (HRT)? HRT improves menopausal symptoms and reduces the risk of post menopausal long term health problems, provided HRT is started within ten years after the menopause. After this window of opportunity replacement oestrogen can actually accelerate cell damage. As with any medical treatment there will be those for whom HRT is contra-indicated. Otherwise the risk:benefit ratio for each individual has to be weighed up so that women can arrive at an informed decision. Regarding the risk of breast cancer, this is increased by 4 cases per 1,000 women aged 50-59 years on combined HRT. This compares to an additional 24 cases in women who have body mass index (BMI)>30 and are not on HRT. This underlines the important of lifestyle which is crucial in all areas of preventative medicine.

What type of HRT has the most favourable risk:benefit ratio? Oral preparations undergo first pass metabolism in the liver, so other routes of delivery such as transdermal may be preferred. There is also an argument that hormones with identical molecular structure are preferable to bio-similar hormones. What functional effect could a slight difference in sex steroid structure have? For example no methyl group and a side chain with hydroxyl group (C-OH) rather than a carbonyl group (C=O)? That is the difference between oestradiol and  testosterone.


In the case of hormones with identical molecular structure to those produced endogenously, there are no potential unwanted side effects or immunogenic issues as the molecule is identical to that produced by the body. Although the oestradiol component in most HRT preparations in the UK has an identical molecular structure to endogenous oestradiol, there is only one licensed micronised progesterone preparation that is has an identical molecular structure. Synthetic, bio-similar progestins have additional glucocorticoid and androgenic effects compared to molecular identical progesterone which exerts a mild anti-mineralocorticoid (diuretic) effect.

Norethisterone (synthetic progestin)

With an increasing ageing population and increase in life expectancy, it is important to support successful ageing and quality of life with a personalised and specific approach.

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


Conference Royal Society of Medicine 17/1/17 “Sports Injuries and Sports Orthopaedics” Session on “The Ageing Athlete”

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

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

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

Bio-identical hormone replacement therapy course. Marion Gluck Training Academy 27/1/17

The British Menopause Society

Royal College of Obstetricians and Gynaecologists 

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.


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


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

Optimal health: especially young athletes! Part 3 Consequences of Relative Energy Deficiency in sports

In my previous blogs I have described the adverse effects of Relative Energy Deficiency in sports (RED-S) in both female and male athletes both in terms of current health and sport performance and potential long term health problems. What about young aspiring athletes? There is concern that early sport specialisation, imbalances in training not covering the full range of the components of fitness, together with reduced sleep, all combine to increase injury risk. Young athletes are particularly vulnerable to developing RED-S during a period of growth and development accompanied by a high training load.

Sufficient energy availability and diet quality, including micronutrients, is especially important in young athletes. To investigate further I undertook a three year longitudinal study involving 87 pre- and post-pubertal girls, spread across control pupils at day school together with students in vocational training in both musical theatre and ballet streams. There was a gradation in hours of physical exercise training per week ranging from controls with least, followed by musical theatre, through to ballet stream with the most.

In all girls dietary, training and menstrual history were recorded and collected every six months. At the same visit anthropometric measurements were performed by an experienced Paediatric nurse and bloods were taken for Endocrine markers of bone metabolism and leptin. Annual DEXA scans measured body composition, total body bone mineral density (BMD) and BMD at lumbar spine (including volumetric) and BMD at femoral neck.

The key findings included a correlation between hours of training and the age of menarche and subsequent frequency of periods. In turn, any menstrual dysfunction was associated with low age-matched (Z score) BMD at the lumbar spine. There were significant differences between groups for age-matched (Z score) of BMD at lumbar spine, with musical theatre students having the highest and ballet students the lowest. There were no significant differences in dietary intake between the three groups of students, yet the energy expenditure from training would be very different. In other words, if there is balance between energy availability and energy expenditure from training, resulting in concurrent normal menstrual function, then such a level of exercise has a beneficial effect on BMD accrual in young athletes, as demonstrated in musical theatre students. Conversely if there is a mismatch between energy intake and output due to high training volume, this leads to menstrual dysfunction, which in turn adversely impacts BMD accrual, as shown in the ballet students.

I was fortunate to have two sets of identical twins in my study. One girl in each twin pair in the ballet stream at vocational school had a twin at a non-dance school. So in each twin set, there would be identical genetic programming for age of menarche and accumulation of peak bone mass (PBM). However the environmental influence of training had the dominant effect, as shown by a much later age of menarche and decreased final BMD at the lumbar spine in the ballet dancing girl in each identical twin pair.

After stratification for months either side of menarche, the peak rate of change for BMD at the lumbar spine was found to be just before menarche, declining rapidly to no change by 60 months post menarche. These findings suggest that optimal PBM and hence optimal adult BMD would not be attained if menarche is delayed due to environmental factors such as low energy density diet. If young athletes such as these go on to enter professional companies, or become professional athletes then optimal, age-matched BMD may never be attained as continued low energy density diet and menstrual dysfunction associated with RED-S may persist. Associated low levels of vital hormones such as insulin like growth factor 1 (IGF-1) and sex steroids impair bone microarchitecture and mineralisation. Thus increasing risk of injury such as stress fracture and other long term health problems. The crucial importance of attaining peak potential during childhood and puberty was described at a recent conference at the Royal Society of Medicine based on life course studies. For example, delay in puberty results in 20% reduction of bone mass.


It is concerning that RED-S continues to occur in young athletes, with potential current and long term adverse consequences for health. Young people should certainly be encouraged to exercise but with guidance to avoid any potential pitfalls where at all possible. In my next blog I will delve into the Endocrine mechanisms involved in RED-S: the aetiology and the outcomes.

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


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

Keay N. The modifiable factors affecting bone mineral accumulation in girls: the paradoxical effect of exercise on bone. Nutrition Bulletin 2000, vol 25, no 3. 219-222.

Keay N The effects of exercise training on bone mineral accumulation in adolescent girls. Journal of Bone and Mineral Research. Vol 15, suppl 1 2000.

Keay N, Frost M, Blake G, Patel R, Fogelman I. Study of the factors influencing the accumulation of bone mineral density in girls. Osteoporosis International. 2000 vol 11, suppl 1. S31.

New S, Samuel A, Lowe S, Keay N. Nutrient intake and bone health in ballet dancers and healthy age matched controls: preliminary findings from a longitudinal study on peak bone mass development in adolescent females, Proceedings of the Nutrition Society, 1998

Keay N, Dancing through adolescence. Editorial, British Journal of Sports Medicine, vol 32 no 3 196-7, September 1998.

Bone health and fractures in children. National Osteoporosis Society

Lifetime influences on musculoskeletal ageing and body composition. Lecture by Professor Diana Kuh, Director of MRC Unit for Lifelong Healthy Ageing, at Royal Society of Medicine, conference on Sports Injuries and sports orthopaedics. 17/1/17

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.

Health and fitness in young people