What’s so good about menstrual cycles?

Menstrual periods are a barometer of healthy hormones. The evolutionary purpose of ovulation is to reproduce. Furthermore the carefully biologically choreographed variation of hormones that occurs during an ovulatory menstrual cycle is crucial to health and athletic performance.

Why? Hormones are chemical messengers that have far reaching effects throughout the body and drive the beneficial adaptations to exercise. In the case of menstrual cycles, the fluctuations of oestrogen and progesterone are key to this process. The effects of these sex steroids go far beyond reproduction. These hormones play important roles in bone strength, cardiovascular health, optimal lipid profile and production of neurotransmitters to regulate mood. The effects of low levels of oestrogen and progesterone are well documented in menopausal women who experience loss in bone mass, risk of osteoporosis and fracture, together with an increase risk of cardiovascular disease.

Some definitions

Amenorrhoea=lack of menstrual cycles

Menarche= start of menstrual cycles

According to the Royal College of Obstetrics and Gynaecology

Primary Amenorrhoea: no onset of menstrual cycles by age 16 years.

Secondary amenorrhoea: cessation of menstrual cycles in a previously regularly menstruating woman for > 6months

Oligomenorrhoea: < 9 menstrual cycles per calendar year

Any form of amenorrhoea requires medical investigation to exclude an underlying medical condition. The most common medical causes of amenorrhoea are polycystic ovary syndrome (PCOS), prolactinoma, thyroid conditions and other endocrine conditions. Functional hypothalamic amenorrhoea (FHA) is a diagnosis of exclusion. In other words before arriving at a diagnosis of FHA [1], medical conditions that could potentially cause amenorrhoea have to be ruled out.

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Relative energy deficiency in sport (RED-S) is a situation of low energy availability (LEA) that can be unintentional or intentional as a result of a mismatch between energy intake and energy requirement. The two sources of energy demand arise from exercise training load and maintenance of fundamental physiological function across multiple body systems [2]. In female athletes/dancers with RED-S the most obvious clinical sign is amenorrhoea as a result of FHA. In all cases of RED-S the management strategy is directed to address the underlying issue of LEA [3].

In female athletes/dancer with FHA due to RED-S, there is the possibility of pharmacological intervention based on the RED-S Clinical Assessment Tool [4]. In other words evidence from DXA of Z-score of lumbar spine < -1 and/or stress fracture. What are the most effect hormonal interventions in such cases?

What’s in a name? It is every woman’s right to choose the form of contraception she wishes to use. Hormonal contraception provides a convenient method. The combined oral contraceptive pill (OCP) contains oestrogen and progesterone to prevent ovulation. The OCP produces regular withdrawal bleeds in response to these external hormones. Progesterone-only contraception can be taken orally, via implant or delivered by an intrauterine coil and typically does not produce withdrawal bleeds. As with any medication there are potential side effects, which have to be weighed up against the benefits. Regarding the effect of hormonal contraception on bone in young menstruating women, there is evidence that such medication can impair bone health [5].

The OCP produces regular withdrawal bleeds. These are NOT menstrual periods; ovulation is prevented. Rather the OCP causes withdrawal bleeds driven by external non-physiological hormones, as opposed to internally physiologically produced hormones. This is a reason why the OCP is not recommended in FHA, as this medication will mask what is happening with internal hormones [6]. In other words the barometer of healthy hormones has been removed when taking the OCP.

Furthermore, studies show that the OCP can impact other hormone systems that play a role in bone health. The OCP is taken orally thereby producing first pass effects in the liver. These effects include induction of liver enzymes and increased production of binding proteins for hormones. Binding proteins reduce the freely available active form of hormones such insulin like growth factor 1 (IGF-1). This effect is particularly marked in those OCP with non-physiological ethinyl oestradiol. In the case of RED-S there is already a low level of active IFG-1, due to the general suppression of the hypothalamic-pituitary axis.

Therefore in addition to masking FHA, the OCP can also further decrease IGF-1 and thus compound the negative effect on bone. This has been shown to be the case in the clinical setting where the OCP was found to have no bone protective effect on bone mineral density (BMD) in women with FHA. Rather hormone replacement therapy (HRT) consisting of transdermal physiological oestrogen with cyclic micro-ionised progesterone was found to have a positive effect on BMD [7 , 8]

Therefore, if hormonal treatment is to be used in RED-S, HRT (transdermal oestradiol and cyclic micro-ionised progesterone) is best clinical practice. This decision requires careful discussion with the athlete/dancer clarifying that HRT should only be a short-term measure to protect bone health whilst the underlying issue of LEA is being resolved. Behavioural measures relating to training load, nutrition and recovery are essential to restore global hormonal function.

OCP V HRT

• What? Both provide oestrogen and progesterone, but in different forms: non-physiological v physiological

Why? Purpose of the OCP is to suppress production of endogenous female hormones and prevent ovulation. Purpose of HRT is to replace the physiological amount and form of oestrogen and progesterone

How? The OCP decreases levels of active, unbound IGF-1. Not bone protective in FHA of RED-S. HRT shown to improve BMD in FHA of RED-S

What to do? Hormonal contraception is a choice for women. In some medical conditions where there is adequate/excess oestrogen such as endometriosis or PCOS, hormonal contraception is effective in clinical management. However in the case of FHA, in particular when occurring as a consequence of LEA in RED-S there is evidence that the OCP is not bone protective and masks the clinical sign of menstruation.

The priority in managing RED-S is to address LEA. If bone protection is required, whilst addressing LEA, HRT (transdermal oestrogen and cyclic progesterone) is best clinical practice.

References

[1] Joy, E., De Souza, M. J., Nattiv, A., Misra, M., Williams, N. I., Mallinson, R. J., … Borgen, J. S. (2014). 2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad. Current Sports Medicine Reports, 13(4), 219–232. https://doi.org/10.1249/JSR.0000000000000077

[2] Mountjoy, M., Sundgot-Borgen, J., Burke, L., Carter, S., Constantini, N., Lebrun, C., … Ljungqvist, A. (2014). The IOC consensus statement: Beyond the Female Athlete Triad-Relative Energy Deficiency in Sport (RED-S). British Journal of Sports Medicine48(7), 491–497. https://doi.org/10.1136/bjsports-2014-093502

[3] Mountjoy, M., Sundgot-Borgen, J. K., Burke, L. M., Ackerman, K. E., Blauwet, C., Constantini, N., … Budgett, R. (2018). IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update. British Journal of Sports Medicine, 52(11), 687–697. https://doi.org/10.1136/bjsports-2018-099193

[4] Mountjoy, M., Sundgot-Borgen, J., Burke, L., Carter, S., Constantini, N., Lebrun, C., … Ackerman, K. (2015, April 1). Relative energy deficiency in sport (RED-S) clinical assessment tool (CAT). British Journal of Sports Medicine. BMJ Publishing Group. https://doi.org/10.1136/bjsports-2015-094873

[5] Beksinska M, Smit J, Hormonal contraception and bone mineral density. Expert Review of Obstetrics & Gynecology, 2011 vol: 6 (3) pp: 305-319

[6] Gordon, C. M., Ackerman, K. E., Berga, S. L., Kaplan, J. R., Mastorakos, G., Misra, M., … Warren, M. P. (2017). Functional hypothalamic amenorrhea: An endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism102(5), 1413–1439. https://doi.org/10.1210/jc.2017-00131

[7] Ackerman, K. E., Singhal, V., Baskaran, C., Slattery, M., Campoverde Reyes, K. J., Toth, A., … Misra, M. (2018). Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: A randomised clinical trial. British Journal of Sports Medicine. BMJ Publishing Group. https://doi.org/10.1136/bjsports-2018-099723

[8] Singhal, V., Ackerman, K. E., Bose, A., Torre Flores, L. P., Lee, H., & Misra, M. (2018). Impact of Route of Estrogen Administration on Bone Turnover Markers in Oligoamenorrheic Athletes and its Mediators. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/jc.2018-02143

 

 

Surprisingly low levels of Vitamin D in Cyclists

There is growing evidence that for athletes, being replete in vitamin D is important for many key areas of health and performance. For bone health, muscle strength and to support immune function.

Slide1

At the recent International Association of Dance Medicine conference, in addition to presenting on Dance Endocrinology I also took part in a “duel” on vitamin D to argue the case for vitamin D supplementation, in dance/athletic populations. In fact Vitamin D is a type of steroid hormone. An article in BJSM discussed the synergistic action of steroid hormones, in particular vitamin D and the sex steroids. In dancers who train in studios inside, away from the sun then there is evidence that levels of vitamin D can become low, particularly during winter months. Supplementing with vitamin D in these elite female dancers reduced injuries and significantly improved muscle strength and jump height.

What about athletes that train outside? What about male athletes? You might think that competitive road cyclists would benefit from plenty of time spent outside and that vitamin D levels would be close to athlete recommended level of 90 nmol/L. However, in our recent study of 50 competitive male road cyclists, the majority had low athlete levels of vitamin D. Even some cyclists who reported taking supplementation for this vitamin were found to have low levels, reflecting variations and uncertainties in what dose to take. Conversely some riders taking supplementation had levels that were well above recommended athlete levels. More is not necessarily better in this situation and very high levels can lead to toxicity.

Bone health in road cyclists can be compromised due to 2 factors. In the first instance, being a non weight bearing sport means lack of mechanical osteogenic (bone stimulating) skeletal loading. In addition, road cycling is a gravitational sport where being light weight confers a performance advantage in terms of power to weight ratio. This can lead to restrictive nutrition practices and low energy availability (LEA) in athletes/dancers. LEA is a situation where dietary energy intake is insufficient to support both training demands and the energy requirement to keep healthy.  So LEA has adverse effects on both health and athletic performance described in the clinical model RED-S (relative energy availability in sport). This includes a negative impact on bone health. DXA is regarded as “gold standard” quantification of impact of LEA and RED-S on bone health. In our study a specially designed SEAQ-I (sports specific questionnaire and clinical interview) was found to be the most effective indicator of poor bone health found with DXA. 28% of the cyclists were identified as having LEA with correspondingly low bone mineral density for their age.

What about the effect of vitamin D levels on bone health? In those cyclists assessed as having adequate EA from SEAQ-I, then vitamin D was an important factor in bone health. However, in those 28% cyclists assessed as having LEA, vitamin D did not feature as as such an important factor. Essentially having adequate EA is the top priority for health and performance. The other observation is that many of those cyclists in LEA, although not consuming adequate calories, nevertheless were taking plenty of supplements in the belief that this would reduce any negative effects of restrictive nutrition. This strategy does not work. The reason being that LEA causes dysfunction not just of one hormone in isolation, rather interactive hormone networks become disrupted. Hormones are crucial for supporting bone health, particularly IGF-1, testosterone and vitamin D in males. Furthermore there is evidence to show that there is a synergistic interaction between testosterone and vitamin D in men. In out study those riders with chronic LEA were found to have significantly lower testosterone than the other cyclists. So even if male athletes with LEA have adequate levels of vitamin D, then low levels of other hormones, such as testosterone, will have net negative effect on bone health.

VitD Histogram

So male cyclists are at risk of poor bone health for the following reasons:

  • Cycling is a non-weight bearing sport,
  • Vitamin D can be below athlete recommended levels, even if EA adequate
  • Long term LEA causes clinical consequences of RED-S including disruption of hormones necessary for maintaining bone health

Does this matter? An early warning sign in runners of LEA is stress fracture. In cyclists the first evidence of an issue with bone health could be vertebral fracture from a bike crash, as this is area of skeleton most adversely effected by LEA and most serious in terms of fracture site requiring longest time off bike. Moreover our study found that in some cyclists with chronic, long term LEA cycling performance in terms of 60 minute functional threshold power (FTP) was below that anticipated from training load.

To perform at your full athletic potential you need adequate EA and vitamin D.

References

Low energy availability assessed by a sport-specific questionnaire and clinical interview indicative of bone health, endocrine profile and cycling performance in competitive male cyclists BMJ Open Sport and Exercise Medicine. Keay, Francis, Hind 2018

How do you identify male cyclist at risk of RED-S? BJSM, Dr N Keay 2018

Fuelling for Cycling Performance Science4Performance 2018

Synergistic interactions of steroid hormones BJSM, Dr N Keay 2018

Raising Awareness of RED-S in Male and Female Athletes and Dancers BJSM, Dr N Keay 2018

2018 UPDATE: Relative Energy Deficiency in Sport (RED-S) BJSM, Dr N Keay 2018

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

 

What is Dance Medicine?

Traditionally dance medicine has been somewhat the poor relation of sports medicine. Why is this the case? There is no doubt that dancers, of whatever genre, require the physical and psychological attributes of athletes. However, dance involves an additional artistic component where ultimately performance on stage is judged not according to a score card as in aesthetic sports, rather on the ability of the dancers to forge an emotional connection with the audience.

As with athletes, injuries are always an important topic for dancers: how to recognise the aetiology of injuries and thus develop prevention strategies. Dance UK have published two reports on national enquiries into the health of dancers. Dance UK has now evolved into the organisation One Dance which includes the National Institute of Dance Medicine and Science (NIDMS). One Dance provides delivery of the Healthier Dancer Programme (HDP) whose talks regularly engage 1500+ dancers and dance professionals per year and which will be a part of the One Dance UK conference at the end of November, an overarching event for the entire dance sector. One Dance holds a list of healthcare professionals with experience and expertise in dance. One Dance is an especially an important resource for independent dancers who will not have access to the provision for those working in larger dance companies.

However, beyond injury management, there are important aspects of the health of dancers which need to be considered, highlighted in an information booklet “Your body, Your risk” from Dance UK. The female athlete triad is well established as a clinical spectrum comprising of disordered eating, menstrual dysfunction and impaired bone health. Indeed impaired bone mineral density many persist even after retirement in female dancers. The recent evolution of the female athlete triad into relative energy deficiency in sports (RED-S) provides an important clinical model. RED-S includes male athletes/dancers, involves multiple body systems and crucially, evidence of detrimental effects on athletic performance is being researched and described. In other words RED-S is not restricted to female dancers/athletes with bone stress injuries.

BalletDials
Integrated periodisation of training, nutrition and recovery support perforamnce

The fundamental cause of RED-S is low energy availability where nutritional intake is insufficient to cover energy requirements for training and resting metabolic rate. In this situation the body goes into energy saving mode, which includes shut down of many hypothalamic-pituitary axes and hence endocrine network dysfunction. As hormones are crucial to backing up adaptations to exercise training, dysfunction will therefore have an effect not just on health, but on athletic performance. In dance, neuromuscular skills and proprioception are key for performance. Hence, of concern is that these skills are adversely impacted in functional hypothalamic amenorrhoea, which together with impaired bone health from RED-S, greatly increases injury risk.

Low energy availability can arise in dance and sport where low body weight confers an aesthetic and/or performance advantage. There is no doubt that being light body weight facilitates pointe work in female dancers and ease of elevation in male dancers. Thus, low energy availability can occur intentionally in an effort to achieve and maintain low body weight. Low energy availability can also be unintentional as a result of increased expenditure from training, rehearsal and performance demands and the practicality of fuelling. This situation is of particular concern for young dancers in training, as this represents a high energy demand state, not just for full time training, additionally in terms of energy demands for growth and development, including attainment of peak bone mass.

Despite the significance of RED-S in terms of negative consequences on health and performance, as outlined by the IOC in the recent consensus update, further work is required in terms of raising awareness, identification and prevention. Fortunately these issues are being addressed with the development of an online educational resource on RED-S for athletes/dancers, their coaches/teachers/parents and healthcare professionals which is backed by British Association of Sport and Exercise Medicine (BASEM) and with input from One Dance and NIDMS. In terms of research to facilitate the proliferation of evidence base in dance medicine, One Dance lists calls for research, whilst NHS NIDMS clinics provide access to clinical dance medicine. The importance of the application of this growing field of dance medicine and science for the health and performance of dancers was recently outlined in an article “Raising the barre: how science is saving ballet dancers“.

On the international stage, the International Association for Dance Medicine & Science (IADMS) strives to promote an international network of communication between dance and medicine. To this end, IADMS will hold its 28th Annual Conference in Helsinki, Finland from October 25-28, 2018. In addition to extensive discussion of dance injuries, there will be presentations on “Sleep and Performance” and “Dance Endocrinology”.

So maybe Dance Medicine and Science is not so much the poor relation of Sports Medicine, rather showing the way in terms of integrating input between dancers, teachers and healthcare professionals to optimise the health of dancers and so enable dancers to perform their full potential.

References

Presentations

Fit to Dance? Report of National inquiry into dancers’ health.

Fit to Dance 2 Dance UK

One Dance

Your body your risk. Dance UK

Fit but fragile. National Osteoporosis Society

Bone mineral density in professional female dancers N. Keay, BJSM

2018 UPDATE: Relative Energy Deficiency in Sport (RED-S) Dr N Keay BJSM 2018

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

Dancing through Adolescence Dr N Keay BJSM

Healthy Hormones Dr N Keay BASEM 2018

Dancers, Periods and Osteoporosis, Keay N, Dancers, Periods and Osteoporosis, Dancing Times, September 1995, 1187-1189

A study of Dancers, Periods and Osteoporosis, Keay N, Dance Gazette, Issue 3, 1996, 47

Raising the barre: how science is saving ballet dancers The Guardian 2018

International Association for Dance Medicine and Science Medicine & Science in Sports and Exercise

 

 

Male Cyclists: Bones, Body composition, Nutrition, Performance

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There has been much recent coverage regarding female runners suffering with health and performance issues due to relative energy deficiency in sports (RED-S). What about male athletes? A recent article about male cyclists who explained how they developed RED-S, did not receive as sympathetic a response as articles concerning female athletes. Yet multiple Endocrine network disruption in RED-S, associated with suboptimal health and performance, is equally applicable to male and female athletes.

Although competitive road cycling is excellent for cardiovascular (CV) fitness, why are male cyclists at particular risk of impaired bone health and RED-S? Cycling is a non-weight bearing type of exercise, as is swimming, so does not provide much osteogenic (bone building) stimulus. The additional element in road cycling is that, in the short term, low body weight, with associated low body fat, confers a performance advantage. However this can lead to restrictive nutrition and RED-S, that have adverse effects on health and performance, over the longer term.

A recent study looking at bone acquisition in adolescent males found that bone mass, microarchitecture and makers of bone formation were more favourable in footballers compared with cyclists and swimmers. Swimmers had the lowest Vitamin D, presumably as this is generally an indoor sport (unless you live in Australia where outdoor 50m pools abound). Another study found reduction in femoral neck bone mineral accumulation in adolescent male cyclists compared against increases over the same time frame seen in controls.

What about adult male road cyclists? When runners and cyclists were matched for age and body weight, there were no significant differences in hormone or nutrition status, yet cyclists were 7 times more likely to have osteopenia of the lumbar spine than runners. Similar results were found in another study where competitive male road cyclists were found to have reduced lumbar spine bone mineral density (BMD) for age, despite normal levels of testosterone and insulin-like growth factor 1 (IGF1), although intriguingly an inverse correlation with lumbar spine BMD and IGF1 was found. It appears that the biomechanical stress patterns on the spine in cycling are not oesteogenic in nature, which contrasts with rowing where, although also seated, the biomechanical load exerted through the spine does provide an osteogenic effect.

In addition to the non-load bearing nature of cycling on the skeleton, restrictive nutrition can contribute to suboptimal bone health. Reducing energy availability by restricting energy intake whilst increasing training load can be a strategy, especially during pre-season training to reduce body weight and body fat. Essentially, cycling up a steep incline demands less power through the pedals if your body weight is low. Nevertheless, reducing energy availability runs the risk of developing RED-S, associated Endocrine dysfunction and suboptimal bone health, on top of the non-beneficial mechanical osteogenic effect of cycling. On a practical note, with long training rides in the saddle it can be physically and practically difficult to fuel optimally. Recent research in female athletes shows that within day energy deficits magnify hormonal disruption. Could this be a factor in male cyclists where consistent fuelling is either actively avoided and/or practically difficult?

The psychological element of disordered eating has been described amongst elite male cyclists. Male cyclists, in particular, collect many metrics associated with training and racing which could be a manifestation of a drive to perfectionism. Determination and attention to detail are laudable qualities for athletes, but there is a fine line when the balance swings to behaviours and attitudes that can be detrimental to health and performance. Even starting off with good intentions can lead to problems as seen with the growing emergence of orthorexia: “clean eating”, which, ironically, becomes detrimental to health and performance with exclusion of food groups such as carbohydrates.

Exclusively practising a non weight bearing sport such as cycling although great for CV fitness, is not so good for bone health. Does this matter? Potentially injury is more likely in bike spills, which occur both in training and competition even for the most experienced bike handler. Combined with the drive for low body weight in competitive road cycling, health and performance issues can be compounded with RED-S. What are the solutions for the cyclist to support favourable body composition and bone health, which ultimately also optimises performance? A further planned study, following a current pilot study of competitive road cyclists, aims to investigate the potential beneficial effects of strength and conditioning to load the skeleton combined with a review of nutrition. See details of next study to see if you wish to participate.

For more discussion on the Endocrine aspects of Sports and Exercise Science and Medicine, BASEM Spring conference 22 March 

References

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

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

Too healthy to ride? How clean living could slow you down Cycling Weekly 2017

Body Composition for Health and Sports Performance

Longitudinal Adaptations of Bone Mass, Geometry, and Metabolism in Adolescent Male Athletes: The PRO-BONE Study JBMR 2017

Bone Related Health Status in Adolescent Cyclists Plos 2011

Participation in road cycling vs running is associated with lower bone mineral density in men Metabolism 2008

Evaluation of the Bone Status in High-Level Cyclists Journal of Clinical Densitometry 2012

Effect of exercise training programme on bone mineral density in novice college rowers BJSM 1995

Energy Intake and Energy Expenditure of Elite Cyclists During Preseason Training Int J Sports Med 2005
Kings and Queens of the Mountains Science4Performance 2017

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

Perfectionism and Risk for Disordered Eating among Young French Male Cyclists of High Performance Perceptual and Motor Skills 2004

Kings and Queens of the Mountains Science4Performance 2017

Addiction to Exercise – what distinguishes a healthy level of commitment from exercise addiction? BJSM 2017

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

 

 

 

 

 

Endocrine system: balance and interplay in response to exercise training

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

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

F=MA

Local responses in exercising tissues

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

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

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

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

Gut microbiota

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

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

Metabolic adaptations

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

Hierarchy of control

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

Conclusion

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

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

References

Keay N, Logobardi S, Ehrnborg C, Cittadini A, Rosen T, Healy ML, Dall R, Bassett E, Pentecost C, Powrie J, Boroujerdi M, Jorgensen JOL, Sacca L. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sport: a double blind, placebo controlled study. Journal of Endocrinology and Metabolism. 85 (4) 1505-1512. 2000.

Sport Endocrinology presentations

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

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

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

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

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

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

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

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

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

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

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

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

Metabolic Flexibility in Health and Disease Cell Metabolism

Hormones and Sports Performance

PPARδ Promotes Running Endurance by Preserving Glucose Cell Metabolism