Synergistic Interactions of Steroid Hormones

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

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

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

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

Bone

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

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

Immunity

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

Muscle

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

Synergistic actions of steroid hormones

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

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

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

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

References

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

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

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

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

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

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

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

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

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

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

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

Health, Hormones and Human Performance Part 2

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 the recent BASEM spring conference set out to demonstrate. The previous blog described functional disruption of Endocrine networks caused by non-integrated periodisation of the three key lifestyle factors of exercise/training, nutrition and recovery/sleep, can lead to adverse effects on health and athletic performance.

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Integrated periodisation of exercise, nutrition, recovery for optimisation of health and performance (Keay BJSM 2017)

Grace, aesthetic line and ethereal quality belie the athletic prowess required in ballet. What are the Endocrine, metabolic and bone health consequences for this unique group of athletes? Dr Roger Wolman (Medical Advisor to National Institute for Dance Medicine and Science) returned to the important topic of insufficient energy availability in sport/dance where being lightweight confers a performance advantage, resulting in dysfunction in multiple endocrine axes. Dr Wolman discussed his recent research studies in dancers revealing an intriguing synergistic action between oestrogen and vitamin D, which is itself a steroid hormone. Evidence was presented to demonstrate how being replete in vitamin D has beneficial effects on bone, immunity and muscle function. Thus it is key in preventing injury and supporting health in athletes, with particular relevance in premenarchal and postmenopausal women, who are in relative oestrogen deficient states. This presentation will certainly change my clinical practice and, I am sure, that of many in the audience, in ensuring that athletes/patients are vitamin D replete. This may have to be achieved in the form of strategic use of sports informed vitamin D supplementation, given that even walking naked for 5 hours a day outside during UK winter, would not stimulate enough vitamin D production. Therefore, to the relief of many in the audience, Dr Wolman did not recommend this strategy.

Dr Kate Ackerman (member of RED-S IOC working group) explained why we should all tap into our inner endocrinologist. Sport and Exercise Medicine (SEM) goes far beyond diagnosing and treating injury. Is there any underlying endocrine cause for suboptimal health, performance or injury? Be this an endocrine diagnosis that should not be missed, or a functional endocrine dysfunction due to relative energy deficiency in sports (RED-S). Dr Ackerman explained the importance of the multidisciplinary team in both identifying and supporting an athlete experiencing the consequences of RED-S. New research from Dr Ackerman’s group was presented indicating the effects of RED-S on both health and athletic performance.

Females now have combative roles alongside their male counterparts. What are the implications of this type of intensive exercise training? Dr Julie Greaves (Research Director of the ministerial women in ground close combat research programme) presented insightful research revealing that differences in the geometry of bone in men and women can predispose towards bone stress injury and account for increased incidence in this type of injury in female recruits.

Lunchtime discussion and debate was focused on the determinants of athletic gender, lead by Dr Joanna Harper and Professor Yannis Pitsiladis (International Federation of Sports Medicine). Rather than relying on genetic sex, testosterone concentration was proposed as the criteria for determining whether an athlete competes in male or female events. That testosterone concentration is linked to performance was demonstrated in a study published last year in the BMJ where female athletes in the upper tertile of testosterone were shown to have a performance advantage in certain strength based track and field disciplines. This could potentially be an objective, functional metric used to determine sporting categories for transgender and intersex athletes. The only current uncertainty is how previously high levels of testosterone seen in male, or intersex athletes would have already had an impact on physiology, if this athlete then wished to compete as female and therefore lower testosterone levels with medication.

Nutrition is a key component in optimising health and performance through the Endocrine system. Dr Sophie Killer (English Institute of Sport) explained practical implications for athletes. In a study stimulating a training camp, there were distinct differences between athletes on different regimes of carbohydrate intake in terms of endocrine markers and psychological effects. Those athletes on restricted carbohydrate intake fared worse.

Insulin insensitivity is the underlying pathological process in developing type 2 diabetes mellitus (T2DM) and metabolic syndrome. What is the crucial lifestyle intervention to combat this? Dr Richard Bracken (Swansea University) presented the science behind why and how exercise improves blood glucose control and therefore ultimately risk of developing the macro and microvascular complications of diabetes. T2DM is an increasing health issue in the population, which has to be addressed beyond reaching for the prescription pad for medication. Dr Bracken outlined some effective strategies to encourage the reluctant exerciser to become more active. Having worked myself in NHS diabetic clinics over many years, this was a key presentation at the conference to demonstrate that SEM goes far beyond a relatively small group of elite athletes. Highlighting the crucial role of physical activity in supporting health and performance through optimisation of endocrine networks: uniting the elite athlete and the reluctant exerciser.

One road to Rome
One Road to Rome (BJSM Keay 2017)

Motivate2Move initiative aims to shift the emphasis from treating disease, to preventing disease. Dr Brian Johnson presented the excellent resource for healthcare professionals to encourage, motivate and educate patients in order to consider exercise as an effective and enjoyable way to improve health.

Hormones play a key role in health and human performance, applicable to all levels of exerciser from reluctant exerciser to elite athlete.

FactorsWordCloud4

References

Health, Hormones and Human Performance BASEM Spring Conference

Video of presentation on Endocrine and Metabolic aspects of Sport and Exercise Medicine from BASEM Spring Conference

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

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

One road to Rome: Exercise Keay, BJSM 2017

 

 

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.

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Triumvirate of external factors impacting Endocrine system and hence performance

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

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

References

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

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

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

 

 

 

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?

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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. 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.

References

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

 

 

 

Health and Performance during Lifespan: latest research

LifeSeasonDay

Your lifespan depends on genetic and key lifestyle choices

Lifespan is dependent on a range of genetic factors combined with lifestyle choices. For example a recent study reported that an increase in one body mass index unit reduced lifespan by 7 months, whilst 1 year of education increased lifespan by 11 months. Physical activity was shown to be a particularly important lifestyle factor through its action on preventing age-related telomere shortening and thus reducing of cellular ageing by 9 years. Nevertheless, even though males and females have essentially identical genomes, genetic expression differs. This results in different disease susceptibilities and evolutionary selection pressures. More studies involving female participants are required!

Circadian clock

Much evidence is emerging about the importance of paying respect to our internal biological clocks when considering the timing of lifestyle factors such as eating, activity and sleep. For example intermittent fasting, especially during the night, and time restricted eating during the day enables metabolic flexibility. In other words, eating within a daylight time window will support favourable metabolism and body composition. No midnight snacks!

For athletes, even more care needs be given to timing of nutrition to support athletic performance. In the short term there is evidence that rapid refuelling after training with a combination of carbohydrate and protein favours a positive balance of bone turnover that supports bone health and prevents injury in the longer term. Periodised nutrition over a training season, integrated with exercise and recovery, is important in order to benefit from training adaptations and optimise athletic performance.

Protein intake in athletes and non athletes

Recovering from injury can be a frustrating time and some athletes may be tempted to reduce food intake to compensate for reduced training. However, recommendations are to maintain and even increase protein consumption to prevent a loss of lean mass and disruption of metabolic signalling. In the case of combined lifestyle interventions, such as nutrition and exercise aimed at reducing body weight, these should be directed at improving body composition. Adequate protein intake alongside exercise will maintain lean mass in order to minimise the risk of sarcopenia and associated bone loss which can occur during hypocaloric regimes. Good protein intake is important for bone health to support bone mineral density and reduce the risk of osteoporosis and fracture.

Adolescent Athlete

In the young athlete, integrated periodisation of training, nutrition and recovery is of particular importance, not only to support health and performance, but as an injury prevention strategy.  Sufficient sleep and nutrition to match training demands are key.

Differences between circadian phenotype and performance in athletes

For everyone, whether athlete or reluctant exerciser, balancing and timing key lifestyle choices of exercise, nutrition and sleep are key for optimising health and performance. However there are individual differences when it comes to the best time for athletes to perform, according to circadian phenotype/chronotype. In other words personal biological clocks which run on biological time. An individual’s performance can vary by as much as 26% depending on the time of day relative to one’s entrained waking time.

Later in Life

Ageing can be can be confused with loss of fitness and ability to perform activities of daily living. Although a degree of loss of fitness does occur with increasing age, this can be prevented to a certain degree and certainly delayed with physical activity. Exercise attenuates sarcopenia, which supports bone mineral density with the added benefit of improved proprioception, helping to reduce risk of falls and potential fracture; not to mention the psychological benefits of exercise.

 

For more discussion on Health Hormones and Human Performance come to British Association of Sport and Exercise Medicine Spring Conference 

BAsem2018_SpringConf_BJSM

References

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity Nature Communications 2017

Physical activity and telomere length in U.S. men and women: An NHANES investigation Preventive Medicine 2017

The landscape of sex-differential transcriptome and its consequent selection in human adults BMC Biology 2017

Temporal considerations in Endocrine/Metabolic interactions Part 1 British Journal of Sport and Exercise Medicine, October 2017

Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting Obesity 2017

Temporal considerations in Endocrine/Metabolic interactions Part 2 British Journal of Sport and Exercise Medicine, October 2017

Time-restricted eating may yield moderate weight loss in obesity Endocrine Today 2017

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

Periodized Nutrition for Athletes Sports Medicine 2017

Internal Biological Clocks and Sport Performance British Journal of Sport and Exercise Medicine, October 2017

Nutritional support for injuries requiring reduced activity Sports in Science Exchange 2017

Balance fat and muscle to keep bones healthy, study suggests NTU October 2017

Dietary Protein Intake above the Current RDA and Bone Health: A Systematic Review and Meta-Analysis Journal of the American College of Nutrition 2017

Too little sleep and an unhealthy diet could increase the risk of sustaining a new injury in adolescent elite athletes Scandinavian Journal of Medicine & Science in Sports

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

The impact of circadian phenotype and time since awakening on diurnal performance in athletes Current Biology

Successful Ageing British Association of Sport and Exercise Medicine 2017

Focus on physical activity can help avoid unnecessary social care BMJ October 2017

Biochemical Pathways of Sarcopenia and Their Modulation by Physical Exercise: A Narrative Review Frontiers in Medicine 2017

 

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

Conferences in Sport/Dance, Exercise Science and Medicine 2018

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

 

Temporal considerations in Endocrine/Metabolic interactions Part 1

LifeSeasonDay

It is not a simple question of what, but when we eat, sleep and exercise.

The Endocrine system displays temporal variation in release of hormones. Integrating external lifestyle factors with this internal, intrinsic temporal dimension is crucial for supporting metabolic and Endocrine health.

Amplitude and frequency of hormonal secretion display a variety of temporal patterns:

  • Diurnal variation, synchronised with external light/dark. Orchestrated by a specific area of the hypothalamus, the neuroendocrine gatekeeper.
  • Circadian rhythm, roughly 24-25 hours which can vary with season according to duration of release of melatonin from the pineal gland.
  • Infradian rhythms longer than a day, for example lunar month seen in patterns of hypothalamic-pituitary-ovarian axis hormone release during the menstrual cycle.
  • Further changes in these temporal release and feedback patterns occur over a longer timescale during the lifespan.

Hormones influence gene expression and hence protein synthesis over varying timescales outlined above. The control system for hormone release is based on interactive feedback loops. The hypothalamus is the neuroendocrine gatekeeper, which integrates external inputs and internal feedback.  The net result is to maintain intrinsic biological clocks, whilst orchestrating adaptations to internal perturbations stimulated by external factors such as sleep pattern, nutrition and exercise.

Circadian alignment refers to consistent temporal patterns of sleep, nutrition and physical activity. Circadian misalignment affects sleep-architecture and subsequently disturbs the interaction of metabolic and Endocrine health. This includes gut-peptides, glucose-insulin interaction, substrate oxidation, leptin & ghrelin concentrations and hypothalamic-pituitary-adrenal/gonadal-axes. The main stimuli for growth hormone release are sleep and exercise. Growth hormone is essential for supporting favourable body composition. These integrated patterns of environmental factors may have a more pronounced effect on those with a genetic predisposition or during crucial stages of lifespan. For example curtailed sleep during puberty can impact epigenetic factors such as telomere length and thus may predispose to metabolic disruption in later life. Regarding activity levels, there are strong relationships between time spent looking at screens and markers, such as insulin resistance, for risk of developing type 2 diabetes mellitus in children aged 9 to 10 years.

In addition to adverse metabolic effects set in motion by circadian misalignment, bone turnover has also shown to be impacted. Circadian disruption in young men resulted in uncoupling of bone turnover, with decreased formation and unchanged bone resorption as shown by monitoring bone markers. In other words a net negative effect on bone health, which was most pronounced in younger adult males compared with their older counterparts. These examples underline the importance of taking into account changes in endogenous temporal patterns during the lifespan and hence differing responses to external lifestyle changes.

For male and female athletes, integrated periodised training, nutrition and recovery has to be carefully planned over training seasons to support optimal adaptations in Endocrine and metabolic networks to improve performance. Training plans that do not balance these all these elements can result in underperformance, potentially relative energy deficiency in sport and consequences for health in both short and long term.

Part 2 will consider the longer term consequences and interactions of these temporal patterns of lifestyle factors, including seasonal training patterns in male and female athletes, on the intrinsic biochronometry controlling the Endocrine and metabolic networks during lifespan.

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

References

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

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

Metabolic and Endocrine System Networks Dr N. Keay

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

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

Factors Impacting Bone Development Dr N. Keay

Sleep, circadian rhythm and body weight: parallel developments Proc Nutr Soc

Sleep Duration and Telomere Length in Children Journal of Paediatrics 2017

Screen time is associated with adiposity and insulin resistance in children Archives of Disease in Childhood

Circadian disruption may lead to bone loss in healthy men Endocrine today 2017

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

Optimal Health: For All Athletes! Part 4 – Mechanisms 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

Medically young, older athletes

Spot the differences?

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You don’t have to be a Radiologist to see that there are some differences between the two X-rays above. Both are from adults of the same age 51 years. Female on left as you look at screen and male on right. In both cases, these adults would be described as “medically young”. Always physically active and reasonably accomplished as athletes in their respective sport disciplines. Never smoked, never overweight, good nutrition.

As discussed at the recent conference at the Royal Society of Medicine (RSM) on “Sports Injuries and Sports Orthopaedics” in the session on the “Ageing Athlete”, there are challenges for athletes in Masters’ age groups, including mechanical joint issues associated with increasing age.

Looking at the male X-ray on right there is small gap between femoral head (ball-like structure) and acetabulum (socket in which femoral head lies). This gap is where the articular cartilage reduces friction between articulating surfaces of this ball and socket joint. In contrast in female X-ray on left of screen, this gap is reduced as cartilage has been worn away so that on right hip (left as you look at screen) bone is grinding on bone. Ouch!

Look again at the femoral heads (ball like structures). In the male these have smooth contours and are symmetrical on both sides. In contrast, in the female there is marked asymmetry with squashed appearance on right side (left of screen) of the femoral head with honeycomb appearance suggesting that there is cyst formation and impaction into socket of joint. This results in shorter leg and weakness of the bone architecture so more likely to compress further. Strangely the blood supply to femoral head is retrograde, meaning it flows backwards from origin of supplying blood vessel to provide vital nutrients to bone, which is a living tissue. If this blood supply is disrupted then the bone dies (avascular necrosis) and become more fragile. The femoral neck (slim area below femoral head) where blood supply courses, has been telescoped down and looks stubby compared to opposite side in female.

Although in the female, the right hip aches and is stiff, it is actually the left hip (right as you look at screen) that hurts more, both at rest and when trying to exercise. Why? If you look carefully on the upper boarder of acetabulum (socket) you will see small cysts. I imagine that pain is caused when the synovial fluid (lubricating fluid) in joint is forced into exposed bone, in hydraulic action especially when moving the hip joint.

So what to do? Total hip replacement (THR) is the only feasible option for the female above, due to extensive damage to the hip joints. Why are some people more prone to this type of joint damage? Apart from underlying medical pathologies that damage joints, the nature of some types of exercise can contribute. For example Ballet is demanding on the hip joint in terms of range of movement and load bearing. The individual can also be predisposed in biomechanical terms to joint issues: in the female X-ray above the femoral head is more exposed than the male.

Although the perception is that THR is more for the elderly wishing to be able to walk to the shops, with improvements in materials and technology used in hip protheses, there are examples of young athletes successfully returning to previous pre-operative levels of exercise training without pain. Recently a 28 year old male soloist dancer of the Paris Opera Ballet had a THR and returned to professional dancing. The medically young athlete will probably have the required motivation and physical ability to rehab effectively. A house in the south of France with private pool and climate for rehab outside would certainly add to motivation. Nevertheless, return to dancing at a professional level in a top level Ballet company after THR is remarkable as classical dance requires a unique combination of outstanding strength, control, proprioception and flexibility. At the conference at the RSM, during the lecture on “Can I run after my hip replacement?” hip replacements in the medically young, active population were reported to have good success rate with athletes able to return to previous level of sport with predicted lifespan of replacement of up to 25 years. Of course every individual athlete should weigh up the pros and cons. Taking up a new impact sport would probably not be sensible. Delaying surgery too long, apart from increasing pain, can compromise biomechanics and therefore replacement outcome. On the other hand, any operation carries a risk, however small and THR requires extensive rehabilitation in order to return to sport.

Deciding on the timing of THR in medically young, older athlete is not straight forward, especially if considering your own hips. Ultimately in such a person, the decision to go for surgery is based on quality of life and limitation to current sport activity, combined with the desire to return to previous level of activity, without the pain. What would you do?

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

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

Conference: Sports Injuries and Sports Orthopaedics, Royal Society of Medicine, 18/1/17, Session “The Ageing athlete”. Including lectures on: “Can I run after my hip replacement? Current recommendations for impact exercise following joint replacement” Mr Konan and “Managing acute injuries in worn joints” Mr Oussedik

 

 

 

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 bone mineral density) and relative energy deficiency in sport (RED-S) with multi-system effects. In this situation there is a mismatch between dietary energy intake (including diet quality) and energy expenditure through training. The net result is a shift to an energy saving mode in the Endocrine system, which impedes both improvement in sport performance and health. RED-S should certainly be considered among the potential causes of sport underperformance, suboptimal health and recurrent injury,  with appropriate medical support being provided.
  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.