Long-term low energy availability leads to adaptive changes throughout the body resulting in the clinical outcomes of REDs
Earlier this week the updated consensus statement from the International Olympic Committee (IOC) on relative energy deficiency in sport (REDs) 2023 was published in the British Journal of Sport Medicine (BJSM)[1]. What are the key points from the range of papers presented in this issue dedicated to REDs?
What’s in a name change?
Making “s” lower case is helpful as relative energy deficiency is not limited to those involved in sport. You can still be at risk of REDs even if you would not consider yourself an athlete; rather “just” someone that does regular exercise. Furthermore, most genres of dance are not sport, yet dancers are another group who can be at risk.
Time scale of low energy availability
The type of adaptive responses to low energy availability is dependent on the temporal component of this energy deficient. Energy availability is the amount of energy “available” once demand from exercise has been accounted for. If this available energy is not sufficient to maintain all the “housekeeping” physiological processes, then the body will respond by going into “eco” mode and down regulating body systems[2]. A small, short-term energy deficit may not be problematic. We have all been in situations where eating patterns don’t go according to plan. For example, a particularly busy time at work, disruption to travel plans, or lack of food availability.
However, sustained, cumulative energy deficit can lead to progressive adaptation shown in the figure.
These adaptive changes across many body systems have adverse outcomes on both health and performance. This is REDs. The clinical syndrome of health and performance consequences of long-term low energy availability. This is what happened in our study of male cyclists referenced in the BJSM publication. We quantified the negative effects of low energy availability on hormone networks, bone health and performance in male cyclists[3]. Those cyclists in low energy availability lost bone mass commensurate with an astronaut in space for 6 months and underperformed in races[4]. This negative impact of low energy availability on performance was underlined in our other studies of male athletes, referenced in the IOC papers [5,6]. Ultimately these are particularly important findings for athletes and their coaches, where performance is the priority.
Menstrual cycles
This concept of a gradated adaptive response to the combined effects of training load, nutrition and recovery can be applied when considering the spectrum of reproductive axis responses in female athletes and dancers, ranging from eumenorrhoea, subclinical ovulatory disturbances to functional hypothalamic amenorrhoea[7] shown in figure of Subclinical Ovulatory Disturbance. Functional hypothalamic amenorrhoea (FHA) is potentially just the tip of the iceberg when it comes to adaptive change to low energy availability. Report of menstruation and even signs of ovulation, may belie suboptimal production of progesterone. As progesterone increases metabolic rate, low production could be considered an early response to low energy availability. This hypothesis is currently being tested in a study of dancers, funded by the British Association of Sport and exercise Medicine.
Carbohydrate availability
Although we talk about low energy availability, the updated IOC consensus statement highlights that carbohydrate availability is the key. This is based on evidence that carbohydrate is the main substrate for exercise above a certain intensity. Furthermore, the hormones of the reproductive axis are particularly sensitive to carbohydrate availability. The IOC statement highlights studies, where despite isocaloric diets, those low in carbohydrate resulted in hormone disruption and poorer athletic performance outlined in the statement.
Health is essential for performance
Another important theme is that optimal health is a prerequisite for performance. This includes both physical and mental aspects of health. Many of the psychological characteristics of athletes and dancers can predispose individuals to developing REDs. For example, although dedication, perfectionism and motivation are laudable qualities, these can spill over into behaviours around training and nutrition. This can be associated with exercise dependence and disordered eating patterns.
If an individual is anxious about body shape, weight and food, this can have a negative health outcome. For example, in our study of dancers[8], quoted as a reference in the updated IOC statement, we found that there were significant relationships between anxiety about controlling weight and eating and missing training, and physical outcomes of low BMI and physiological health in terms of lack of regular menstrual cycles. Regular menstrual cycles in women are a barometer of internal healthy hormones. Similarly in another referenced study, we found that cognitive restraint in male athletes had an adverse effect on hormone profiles[9]. How you think impacts hormone health. This interaction is shown by the reversible arrow between psychological factors as both a driver and result of REDs shown in the updated REDs health conceptual model.
Weighty matter
Weight is a measurement of gravity, not athletic potential. Being a certain weight or body composition does not guarantee athletic success. This fact was emphasised by the lead author of the special edition on REDs on the BJSM podcast. Realistically most types of exercise will involve overcoming gravity, nevertheless, there comes a tipping point where being too light weight and/or having too low body fat means being unhealthy and compromising both physical and mental performance. Furthermore, we are all individuals so our personal optimal weight and body composition will be personal to each of us. Not the generic “lighter is faster”.
Identification
Ultimately low energy availability is a concept and not measured outside of research settings. Rather, making a diagnosis of REDs is a diagnosis of exclusion. In other words, other potential medical conditions must be excluded. This can be achieved through a process of identifying those at risk with energy availability questionnaires, followed by assessing clinical symptoms and signs: such as growth trajectories in young athletes and menstrual status in female athletes and dancers. Readily available and reliable investigations such as blood tests and DXA scans are outlined. These clinical findings have been presented as primary, severe indicators (hypothalamic reproductive disruption in men and women), primary indicators, secondary indicators and other supportive factors.
When considering hormone tests is really important to emphasise that even if a result is not out of range, where the result lies in the range is crucial. Together with considering hormones as networks providing a pattern that is informative. For example, in correctly identifying subclinical down regulation of the thyroid or reproductive axis[2].
Risk stratification
Each of indicators described in the consensus statement carries a score, so that an individual can be risk stratified. The REDsCAT2 has a finer grained zone compromising of green, yellow, orange and red, replacing the 3 zoned traffic light system.
Clinical management
Ultimately as the underlying aetiology of REDs is low energy availability, then the aim of supporting an individual experiencing REDs is to restore sufficient energy availability through a combination of nutrition and possibility reducing demand from intense training. As this will involve behaviour change, this can be challenging and a multidisciplinary team approach is advised. Highlighted for female athletes experiencing functional hypothalamic amenorrhoea (FHA) and associated poor bone health, that the combined oral contraceptive pill is not advised. Rather for bone protection in the short-term HRT (transdermal oestradiol and cyclic micronised progesterone) is recommended in line with updated NICE guidelines in UK[10].
The risk of low energy availability and REDs in dancers will be dicsuused at the forthcoming British Association of Sports and Exercise Medicine annual conference 6/10/23. https://health4performance.basem.co.uk/
3 Keay N, Francis G, Hind K 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 Exerc Med 2018;4:e000424. doi:10.1136/bmjsem-2018-000424
4 Keay N, Francis G, Entwistle I et al Clinical evaluation of education relating to nutrition and skeletal loading in competitive male road cyclists at risk of relative energy deficiency in sports (RED-S): 6-month randomised controlled trial BMJ Open Sport & Exercise Medicine 2019;5:e000523. doi: 10.1136/bmjsem-2019-000523
5 Jurov I, Keay N, Spudić D et al Inducing low energy availability in trained endurance male athletes results in poorer explosive power. Eur J Appl Physiol 2022;122:503–13. doi:10.1007/s00421-021-04857-4
6 Jurov I, Keay N, Rauter S Reducing energy availability in male endurance athletes: a randomized trial with a three-step energy reduction. Journal of the International Society of Sports Nutrition 2022;19:179–95. doi:10.1080/15502783.2022.2065111
7 Keay N. Interactions of the female hormone network, exercise training and nature of adaptation. ResearchGate. June 2023 DOI: 10.13140/RG.2.2.28787.71204
8 Keay N, Overseas A, Francis G Indicators and correlates of low energy availability in male and female dancers. BMJ Open Sport ExercMed 2020;6:e000906. doi:10.1136/bmjsem-2020-000906
9 Jurov I, Keay N, Hadžić V et al Relationship between energy availability, energy conservation and cognitive restraint with performance measures in male endurance athletes. J Int Soc Sports Nutr 2021;18:24. doi:10.1186/s12970-021-00419-3
Hormone responses to exercise drive adaptive changes which impact health and performance. The nature of these adaptive changes will depend not only on the exercise training load. There will be individual variation in the nature of the endocrine response.
Given that female hormone networks are one of the most complex of all the endocrine systems, special consideration needs to be given to the exercising female population. Female hormones vary over the menstrual cycle and also change considerably over a woman’s lifespan. So, it is important to consider the detail of endocrine adaptations to exercise in the context of the temporal dimension: both the short term and long term. Furthermore, there will be individual differences in terms of gynaecological age, hormone levels, timings and biological response.
In addition to the effect of exercise training on hormone networks, these endocrine responses will be modulated by other lifestyle factors including the amount and timing of nutrition and recovery. To gain the most effective hormone response to exercise it is important to have an optimal combination of exercise, nutrition and recovery, appropriate for an individual. Any imbalances or mistiming in these external behavioural inputs can potentially lead to suboptimal and even negative hormone adaptations for health and performance.
This narrative opinion piece on exercise endocrinology focuses on the interactive effects of female hormones and exercise over lifespan.
Introduction
Hormones act by determining gene expression. Through this mechanism of action, hormones support homeostasis and are key determinants of all aspects of health. In addition, hormones interact with behaviours, including lifestyle choices around exercise, nutrition and sleep. In this way, hormone networks drive adaptations to exercise. We exercise in the hope and expectation that this will improve our health and fitness, which occurs through the action of hormones in the short term and long term over the lifespan[1].
“If we could give every individual the right amount of nourishment
and exercise, not too little and not too much, we would have found the
safest way to health.”
Hippocrates
Of all the hormone networks, the female hormones of the menstrual cycle are surely the most complex with intricate control mechanisms, including both positive and negative feedback loops. Furthermore, each woman will have individual hormone variations in terms of timing, concentration and biological response to these hormones. This why a personalised approach for each female exerciser is important to support the most beneficial endocrine adaptations to exercise.
Fluctuations in menstrual cycle hormones change over a woman’s lifespan, adding an extra layer of complexity in striving to optimise the interaction between exercise and internal hormones. Furthermore, exercise as a behaviour and lifestyle choice cannot be considered in isolation. Nutrition and sleep are other factors that interact with hormone networks. This triad of exercise, nutrition and sleep act in combination to determine endocrine adaptive responses[1].
This narrative opinion piece will explore the interactions of female hormone networks and exercise over a woman’s lifespan.
Female hormones and exercise interactions over the lifespan
Childhood
During childhood the hypothalamic-pituitary ovarian (HPO) axis is quiescent. This party explains why the energy systems required for anaerobic, intense exercise have not yet developed. For this reason, aerobic type exercise is advised during childhood to match the hormone milieu. Encouraging children to train like adults can lead to mental and physical “burnout”[2]. As girls have an earlier growth spurt than boys, girls are often faster in the 10-12 age group. Although moving into puberty and beyond, the higher levels of testosterone in men account for ergometric differences in exercise performance[3].
Adolescence
The HPO axis comes to life during puberty. The average age of menarche is around 12 years of age, although this may be a bit later in exercising young women. Nevertheless, failure of periods to start by age 15 years, primary amenorrhoea, necessitates medical investigation[4]. If no medical cause is found, a high exercise training load often combined with low energy intake, can be the aetiology of an adaptive down regulation of the HPO axis. This is a health concern as primary amenorrhoea will attenuate the accrual of peak bone mass (PBM), rendering young aspiring athletes at higher risk of bone stress injury with increasing training load when moving from junior to senior ranks[5]. From a study of retired, premenopausal dancers there is evidence that this adaptive down regulation of the reproductive axis can have a long term detrimental effect on bone health[6].
The reproductive years
Regular menstruation acts as barometer of internal hormone health. Menstrual cycle tracking can also help individual women to identify stages in the cycle when certain types of training might lead to the most positive athletic performance adaptations. For example, it has been suggested as beneficial to adaptation to perform strength training during the later follicular phase where oestradiol predominates and more endurance training during the luteal phase of the cycle where progesterone is the dominant ovarian hormone[7]. Nevertheless, the practical challenge is correctly identifying the timing of phases of the cycle associated with these hormone profiles. Although evidence indicates that the main source of temporal variability occurs during the follicular phase[8], even taking this into account there will be individual variation in terms of levels of hormones and biological response to these. Most likely these variations between women account for the finding of a null effect of the menstrual cycle on exercise performance from a large meta-analysis study[9] suggesting that statistical significance is not necessarily synonymous with clinical significance. This means a personalised approach is needed when matching up training and female hormones to gain the maximal positive adaptations for the individual female exerciser.
Functional hypothalamic amenorrhoea
Functional hypothalamic amenorrhoea (FHA) is a lack of periods for 3 months or more where there is no underlying physiological or medical cause. The aetiology of FHA is down regulation at the hypothalamic level due to an imbalance of behaviours around exercise, nutrition, recovery and/or psychological factors. Female exercisers may experience FHA as an adaptive response to low energy availability.
Energy availability is the energy available from food intake, once the energetic demands of exercise have been subtracted. The value is expressed in Kcal/Kg of lean body mass, where sufficient energy availability is roughly equivalent to resting metabolic rate. Low energy availability arises as a result of an imbalance between energy intake and energy demand from exercise training, leaving insufficient energy to maintain health and performance[10]. Chronic low energy availability causes adaptive down regulation of many endocrine axes, including the HPO axis. This leads to the syndrome of relative energy deficiency in sport (RED-S)[11]. In female exercisers, FHA is a clinical symptom of RED-S. FHA is a diagnosis of exclusion and so can be considered an adaptive response to exercise training where low energy availability prevails. From an evolutionary point of view, FHA is an energy conserving mechanism, which allows prioritisation of movement as an escape strategy from danger. However, the global adaptive down regulation of the endocrine system in RED-S has adverse effects on health and athletic performance in the long-term[12]
Although RED-S and overtraining syndrome (OTS) are often described as separate entities, in reality there is no hard dividing line[13]. External factors act in combination to influence hormone networks. Furthermore, the psychological element of how an individual interpretates events, impacts hormone function. In a study of dancers significant correlations were found between psychological factors and the relationship with physical characteristics and the physiological outcome of menstrual status[14]. Non-exercise related stressors were found to cause adaptive, functional neuroendocrine downregulation of the reproductive axis in military recruits participating in arduous training[15]. These findings demonstrate that psychological factors impact endocrine system function, in particular the female reproductive axis. This is why cognitive behavioural therapy (CBT) can help in restoration of full HPO axis function. Psychological factors need to be factored in when considering adaptive responses of the endocrine network to exercise in women.
Subclinical ovulatory disturbances as a spectrum of adaptive endocrine responses
FHA is a very obvious clinical indication of endocrine dysregulation. However, in subclinical ovulatory disturbances, regular periods may belie a down regulatory adaptive response[16]. Subclinical ovulatory disturbances encompass a spectrum of adaptive changes in the HPO axis in response to an imbalance of external inputs around exercise, nutrition and recovery. This is illustrated in Figure 1 Spectrum of adaptive response to exercise of the female hormone network.
The evolutionary purpose of the menstrual cycle is ovulation for reproduction. However, the action of the ovarian hormones associated with the menstrual cycle go far beyond reproduction. Oestradiol is well recognised as vital for many areas of health encompassing the musculoskeletal, cardiovascular, neurological and gastrointestinal systems. Less well recognised is the importance of progesterone, particularly for bone and cardiovascular health[17]. This is why it is crucial to consider the detail of any adaptive changes of the HPO axis to the combinations of exercise training, nutrition and recovery. Furthermore, tracking menstrual cycles alone may not be sufficient as a training metric to assess adaptation to exercise training.
Assessing the details of the menstrual cycle hormone profile would provide insights into the nature and degree of endocrine adaptation of the HPO axis. Although saliva and urine provide convenient mediums from which to measure hormones, these are limited to analysis of steroid hormones in the case of saliva and in urine metabolites for some of the female hormones. The gold standard way of assessing the “full house” of menstrual cycle hormones: follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol and progesterone is from a blood sample. Measuring both pituitary and ovarian hormones is important in order to distinguish between hypothalamic and ovarian causes of suspected subclinical ovulatory disturbances. When combined with an exercise specific screening questionnaire and clinical interaction, this approach was found to be effective and well received from female athletes in a longitudinal study of dancers in a professional dance company[18] and in professional female football players[19].
Assessment of menstrual hormone health, using the non-invasive method of Quantitative Basal Temperature (QBT) has been extensively researched and validated[20]. This is based on the principle that progesterone, produced during the luteal phase increases metabolic rate and has a thermogenic effect. However, low levels of progesterone, as found in subclinical ovulatory disturbances, will not be sufficient to produce a sustained increase in body temperature. Low progesterone will prevent an increase in metabolic rate and consequent increased energy intake requirement. Therefore, low progesterone production during the luteal phase, can be considered as an adaptive response to stressors; whether thee stressors arise from high training load, low energy availability or other psychological factors[16].
Further ongoing research will help identify subtle adaptive changes to exercise in the female endocrine system. A validated clinical tool, drawing on a number of inputs, will support the early detection, and monitoring of recovery from, down regulatory adaptive responses of the HPO axis. An example of passing the baton between increasing understanding of the interactions between exercise and the endocrine system[21].
Management of hypothalamic-pituitary-ovarian axis down regulation
Where any degree of adaptive functional endocrine down regulation is detected, the priority is to rebalance the factors of training load, nutrition and recovery to restore full HPO axis function to support optimal health and performance. Psychological support may also be needed to facilitate behavioural change, especially in the case of intentional low energy availability. Depending on the status of bone health in FHA, pharmacological bone protection may be indicated. Although exercise has a positive osteogenic effect on bone, this is negated in the presence of down regulated adaptive endocrine response. The International Olympic Committee (IOC) consensus statement advises treatment with transdermal hormone replacement therapy (HRT) in female exercisers with FHA and 2 or more stress fractures, or a Z score of less than -1 of the lumbar spine[22]. The lumbar spine being trabecular bone is especially sensitive to suboptimal endocrine and nutritional status. The combined oral contraceptive pill (COCP) is not suitable for bone protection as this reinforces down regulation of the HPO axis[23]. Nevertheless, HRT for bone protection is a temporising measure while support is being provided to modify behaviours to ensure health and beneficial endocrine adaptations to exercise.
Intracrinology as a hormone adaptation to exercise?
A novel form of exercise induced hormone adaptation could be attributable to intracrinology. This is the process whereby there is cell specific production of androgens from the precursor DHEA. Androgens produced in this way have a site-specific effect[24]. In answer to the question of whether athletes are born or made, it could be that this intracrine adaptive response could go some way to explaining why higher levels of DHEA, anabolic body composition and performance measures were found on Olympic athletes compared to sedentary controls[25].
Hormonal contraception
It is every woman’s personal choice whether to take hormonal contraception, or not. There are some medical conditions where suppression of ovulation with hormonal contraception can be a helpful management strategy. For example, in the situation of conditions “fuelled” by fluctuation in female hormones such as endometriosis and polycystic ovary syndrome (PCOS). On the other hand, there are situations where hormonal contraception is not appropriate, such as in FHA as outlined above. The jury is still out as to whether hormonal contraception has an effect on endocrine adaptations to exercise and subsequent athlete performance. As with anything to do with female hormones, this is very variable according to the individual. Furthermore, there are such a vast range of hormonal contraceptive preparations, that it is virtually impossible to make generalisations about the impact of hormonal contraception on endocrine adaptation to exercise.
Graduation to menopause
The graduation to menopause marks an important point in a woman’s life when her ovaries stop producing eggs and ovarian hormones. In the face of the changing backdrop of female hormones, the nature of lifestyle factors, including exercise will need to be reconsidered in order to benefit from adaptative changes. Exercise remains the cornerstone and has been shown to help alleviate menopausal symptoms, in particular thermoregulatory issues[26]. Furthermore exercise, with a focus on strength training supports metabolic health[27], body composition[28] and bone strength[29], resisting the consequences of reduced production of sex steroid hormones. HRT can improve quality of life and reduce all-cause mortality, and for many women helps in maintaining their exercise levels[30]. In terms of preparations of HRT, transdermal oestradiol has the optimal profile for metabolic health and body identical oestradiol and micronised progesterone is available in licensed, regulated forms[31]. Testosterone can be given for hypoactive sexual desire disorder (HSDD). Although the aim is to restore testosterone to previous physiological levels, external testosterone cannot be taken by athletes competing in sporting events under world anti-doping authority (WADA) jurisdiction.
Conclusions
The interaction of female hormone function and exercise varies between individuals, resulting in a range of possible adaptive changes, both in the short and long term. As menstrual cycle hormones change over the lifespan, so does the response to exercise. Furthermore, exercise training should not be considered in isolation, rather in combination with other modifiable external factors such as nutrition and recovery. Psychological factors also play a part in determining responses of the female reproductive endocrine axis. It is important to characterise the nature of these endocrine adaptations, as not all will be favourable to health and performance. Therefore, a personalised approach is required when considering the interaction of exercise and female hormones.
[2] Bergeron MF, Mountjoy M, Armstrong N et al. International Olympic Committee consensus statement on youth athletic development. British Journal of Sports Medicine. 2015; 49: 843–851
[3] Hirschberg A. Female hyperandrogenism and elite sport, Endocrine Connections 2020, 9(4), R81-R92.
[4] Gordon CM, Ackerman KE, Berga SL, Kaplan JR, Mastorakos G, Misra M, et al. Functional hypothalamic amenorrhea: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2017 102(5):1413–39. doi: 10.1210/jc.2017-00131
[5] Ackerman K, Cano S, De Nardo M et al. Fractures in relation to menstrual status and bone parameters in young athletes. Med Sci Sports Exerc. 2015; 47 (8): 1577–1586. https://doi.org /10 .1249 /MSS .0000000000000574
[6] Keay N, Fogelman I, Blake G Bone mineral density in professional female dancers. British Journal of Sports Medicine 1997;31:143-147.
[7] Oosthuyse, T., Strauss, J.A. & Hackney, A.C. Understanding the female athlete: molecular mechanisms underpinning menstrual phase differences in exercise metabolism. Eur J Appl Physiol 2022. https://doi.org/10.1007/s00421-022-05090-3
[8] Fehring RJ, Schneider M, Raviele K. Variability in the phases of the menstrual cycle. J Obstet Gynecol Neonatal Nurs. 2006 ;35(3):376-84. doi: 10.1111/j.1552-6909.2006.00051.x. PMID: 16700687.
[9] McNulty KL, Elliott-Sale KJ, Dolan E et al. The effects of menstrual cycle phase on exercise performance in eumenorrheic women: a systematic review and meta-analysis. Sports Med. 2020; 50: 1813–1827.
[10] Keay N, Francis G Infographic. Energy availability: concept, control and consequences in relative energy deficiency in sport (RED-S) British Journal of Sports Medicine 2019;53:1310-1311.
[11] Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, et al. The IOC consensus statement: beyond the female athlete triad–relative energy deficiency in sport (RED-S). Br J Sports Med (2014) 48(7):491–7. doi: 10.1136/bjsports-2014-093502
[12] Keay N, Rankin A Infographic. Relative energy deficiency in sport: an infographic guide British Journal of Sports Medicine 2019;53:1307-1309.
[13] Stellingwerff T, Heikura IA, Meeusen R et al. Overtraining Syndrome (OTS) and Relative Energy Deficiency in Sport (RED-S): Shared Pathways, Symptoms and Complexities. Sports Med 2021 51, 2251–2280. https://doi.org/10.1007/s40279-021-01491-0
[14] Keay N, Overseas A, Francis G Indicators and correlates of low energy availability in male and female dancers BMJ Open Sport & Exercise Medicine 2020;6:e000906. doi: 10.1136/bmjsem-2020-000906
[15] Gifford R, O’Leary T, Wardle S etc al. Reproductive and metabolic adaptation to multistressor training in women Endocrinology and Metabolism 2021; 321; 2 https://doi.org/10.1152/ajpendo.00019.2021
[16] Prior, J. C. Adaptive, reversible, hypothalamic reproductive suppression: More than functional hypothalamic amenorrhea. Frontiers in Endocrinology. 2022 Frontiers Media S.A. https://doi.org/10.3389/fendo.2022.893889
[17] Exercise and the Hypothalamus: Ovulatory Adaptations. Prior J. Endocrinology of Physical Activity and Sport 2020. Hackney A., Constantini N. (eds) Contemporary Endocrinology. Humana, Cham. https://doi.org/10.1007/978-3-030-33376-8_8
[18] Keay N, Lanfear M, Francis G. Clinical application of monitoring indicators of female dancer health, including application of artificial intelligence in female hormone networks. Internal Journal of Sports Medicine and Rehabilitation, 2022; 5:24. DOI: 10.28933/ijsmr-2022-04-2205
[19] Keay N, Craghill E, Francis G Female Football Specific Energy Availability Questionnaire and Menstrual Cycle Hormone Monitoring. Sports Injr Med 2022; 6: 177. DOI: 10.29011/2576-9596.100177
[20] Bedford J, Prior J, Hitchcock C et al Detecting evidence of luteal activity by least-squares quantitative basal temperature analysis against urinary progesterone metabolites and the effect of wake-time variability European Journal of Obstetrics & Gynecology and Reproductive Biology 146 (2009) 76–80
[21] McCarthy O, Pitt J, Keay N et al Passing on the exercise baton: What can endocrine patients learn from elite athletes? Clinical Endocrinology 2022: 96(6): 781-792 https://doi.org/10.1111/cen.14683
[22] Mountjoy M, Sundgot-Borgen JK, Burke LM, et al IOC consensus statement on relative energy deficiency : 2018 update British Journal of Sports Medicine 2018;52:687-697.
[24] Labrie F, Martel C, Bélanger A, Pelletier G. Androgens in women are essentially made from DHEA in each peripheral tissue according to intracrinology. J Steroid Biochem Mol Biol. 2017;168:9-18. doi: 10.1016/j.jsbmb.2016.12.007. Epub 2017 Jan 30. PMID: 28153489.
[25] Eklund E, Berglund B, Labrie F, Carlström K, Ekström L, Hirschberg AL Serum androgen profile and physical performance in women Olympic athletes Br J Sports Med 2017; 51(7):1301–1308
[26] Berin E, Hammar M, Lindblom H et al. Resistance training for hot flushes in postmenopausal women: A randomised controlled trial. Maturitas. 2019;126:55-60. doi: 10.1016/j.maturitas.2019.05.005. Epub 2019 May 14. PMID: 31239119.
[27] Bermingham K, Linenberg I, Hall W et al. Menopause is associated with postprandial metabolism, metabolic health and lifestyle: the ZOE PREDICT study. Preprint Lancet. Available at SSRN: https://ssrn .com /abstract 4051462; http://dx .doi .org /10 .2139 /ssrn4051462
[28] Mandrup C, Roland C, Egelund Jon et al. Effects of high-intensity exercise training on adipose tissue mass, glucose uptake and protein content in pre- and post-menopausal women. Frontiers in Sports and Active Living. 2020; (2): 60. https://www .frontiersin .org /article /10 .3389 /fspor .2020 .00060 DOI 10.3389/fspor.2020.00060
[29] Watson S, Weeks B, Weis L et al. High-intensity resistance and impact training improves bone mineral density and physical function in postmenopausal women with osteopenia and osteoporosis: the LIFTMOR randomized controlled trial. JBMR. 2018; 33 (2): 211–220. https://doi .org /10 .1002 /jbmr .3284
[30] Rymer J, Brian K, Regan L. HRT and breast cancer risk. Editorial BMJ. 2019; 367: l5928. https://doi .org /10 .1136 /bmj .l5928
[31] Management of Menopause. Sixth Edition. British Menopause Society 2017
Although relative energy deficiency in sport (RED-S) and overtraining syndrome (OTS) are often described as distinct entities, these can be considered as different facets of the same unbalanced behaviours. For an exerciser these behaviours consist of exercise training load, nutritional intake and recovery.
What is RED-S?
RED-S is a clinical syndrome describing adverse consequences in terms of health and performance due to sustained low energy availability (LEA). LEA is where there is a mismatch between energy intake and the combined energy demand from exercise and resting metabolic rate.
What is OTS?
OTS is a clinical syndrome describing adverse consequences in terms of health and performance when there is sustained non-functional overreaching (NFOR). NFOR is where there is an imbalance between training load relative to recovery.
It’s all about time scales
Thinking about RED-S and OTS in more detail, neither suddenly occur overnight. Rather it is the cumulative effect of energy deficit, or lack of recovery, that causes these syndromes over longer time scales of months.
Short time scales
Facets of LEA and NFOR
For example, the occasional day of suboptimal fuelling/high energy demand, with accompanying relative low energy availability, although not ideal, is nevertheless recoverable. This is shown by the warning masque of LEA of the rotating cube. On the opposite side is the warning masque of NFOR, where there have been some occasions of insufficient recovery over a short time scale of days. As with LEA, this is potentially a recoverable situation.
Longer time scales
Facets of RED-S and OTS
In practical terms, imagine you have been on a training camp or a dance intensive over a week or two. You may have unintentionally incurred a degree of LEA and NFOR, but if you take some time to rest and refuel afterwards, then you will be able to resume usual training fitter and stronger. On the other hand, if you continue to try and train at high intensity, in relative energy deficit you will progress after more weeks and months into the alert red masques of OTS and RED-S. In each case these outcomes are different facets of the same underlying imbalances in athlete/dancer behaviours around training load, nutrition and recovery.
Practical implications
When an athlete or dancer presents with symptoms that could include fatigue, poor sleep, menstrual disruption, recurrent injury (soft tissue or bone), digestive issues and other issues; it is very important to exclude medical conditions. Once this has been done and a diagnosis of exclusion made to confirm a functional issue, then deciding whether to use the terminology RED-S or OTS has a subtle nuance because in practice these syndromes are facets of the same underlying imbalance in athlete behaviours. In all cases the most important aspect is to outline a course of action for the athlete that includes training load, nutrition and recovery, in combination.
Athlete and dancer support
For example, athletes experiencing RED-S often ask if they can restore healthy hormone network function by simply eating more while maintaining a high training load. The simple answer is that this makes recovery less certain as a high training load, specifically high intensity, will most likely mean there is also a degree of NFOR. Therefore, adjustment in all athlete behaviours in synchrony is more effective for health and performance restoration. Similarly in an athlete experiencing OTS, in addition to reduction in training load, optimising nutritional intake will help.
Prevention is always better than cure
The prevention of adverse outcomes for the athlete or dancer is the other important practical implication of considering these clinical syndromes as facets of the same underlying issue. From the rotating cube of unbalanced athlete behaviours, LEA is the precursor to RED-S. Similarly, NFOR is the precursor to OTS. The progression in each case being determined by a longer time scale. Early identification of those at risk is essential to prevent this negative progression. Reversing the situation is a far easier task physiologically and psychological at an early stage of LEA and NFOR, rather than once in a “deeper hole” of RED-S or OTS.
Conclusions
RED-S and OTS being different facets of the same underlying issues of unbalanced athlete behaviours is a concept with practical implications.
References
Keay N. Hormones, Health and Human Potential. 2022 Sequoia books Act 1 Scene 9 “A Balancing Act” and Act 1 Scene 10 “In the Red”.
“Hormones, Health and Human Potential” explains how hormones play a crucial role in determining health. Hormone networks provide the feedback mechanism by which our lifestyle and behaviours enable us to reach our personal potential.
Introduction
Over 2,000 years ago Hippocrates advocated that the “safest way to health” was through “the right amount of nourishment and exercise” for “every individual”. As it turns out Hippocrates was way ahead of his time in articulating the principles of personalised and preventative medicine.
Hormones as the missing link to health
Although Hippocrates understood that lifestyle and behaviours are key to health, he did not know why. We now know that hormones are the key players in this vital role. Hormones are instigators in bringing our DNA to life by determining gene expression. Hormones direct the production of proteins, in the optimal amounts and at the right time. Hormones work as networks to maintain mental and physical health.
Lifestyle factors influencing health through hormones networks
Complex internal negative feedback loops between hormones and the biological variables that they regulate, enable homeostasis for good physiological function. Challenges to homeostasis, due to our interactions with the environment are detected by the hypothalamus, which manages hormone network response. In this way there is another layer of feedback loops between lifestyle behaviours and hormones.
Well-balance lifestyle behaviours, in terms of quantity and timing, support healthy hormone network function, leading us to the “safest way to health”. Conversely, circadian misalignment, where lifestyle choices conflict between internal biochronometers, can lead to hormone dysregulation found in conditions such as metabolic syndrome.
Harnessing hormones as preventative and supportive medicine
A good balance of lifestyle factors can harness hormones as a form of supportive and preventative medicine. This is particularly relevant for type 2 diabetes mellitus and metabolic syndrome. For women, where there are physiological changes in hormones, such as occurs at menopause, attendant symptoms and impacts on long term health can be mitigated by lifestyle as part of the management of menopause. For example, exercise has been shown to have a beneficial effect on temperature regulation, metabolism, body composition, bone health and reducing the risk of breast cancer.
Athlete performance mediated by hormones
Hormones mediate the positive adaptive changes due to exercise training. Understanding these mechanisms can benefit both athletes and patients .
Imbalances in behaviours causing hormone dysregulation
Too little exercise and excess nutrition can lead to hormone dysregulation, seen in metabolic syndrome and type 2 diabetes mellitus. On the other hand, too much of a “good thing” can also cause health and performance issues in exercisers. Relative energy deficiency in sport (RED-S) can occur in exercisers of all ages and levels, where there is either an unintentional or intentional mismatch between energy intake and energy demand. Consequent low energy availability causes hormone network disruption, which in the long-term results in adverse effects on both health and performance .
Conclusions
• Hormone network function plays an important role in mental and physical health • Hormones are influenced by our lifestyle behaviours of exercise, nutrition and sleep • The benefits of lifestyle behaviours are derived from the positive adaptive changes driven by hormones • Imbalances in lifestyle behaviours can cause hormone disruption leading to adverse effects on health and exercise performance
McCarthy O, Pitt J, Keay N et al Passing on the exercise baton: What can endocrine patients learn from elite athletes? Clinical Endocrinology 2022 96;(6):781-792
Keay N, Francis G Infographic. Energy availability: concept, control and consequences in relative energy deficiency in sport (RED-S) British Journal of Sports Medicine 2019;53:1310-1311.
Relative energy deficiency in sport (RED-S) is an issue of increasing concern in sports and exercise medicine. RED-S impact exercisers of all levels and ages, particularly where low body weight confers a performance or aesthetic advantage. Key to mitigating adverse health and performance consequences of RED-S is supporting athletes and dancers to change behaviours. These infographics aim to assist clinicians in communicating the concepts to exercisers and in implementing effective management of athletes in their care[1].
Figure 1 illustrates the concept of energy availability (EA) in RED-S. Preferentially energy derived from dietary intake covers the demands of training and the remaining energy, EA, is, quantified in Kcal/Kg of fat free mass[2]. In Figure 1, the central bar illustrates adequate EA in an athlete where energy intake is sufficient to cover the demands of training and fundamental life processes to maintain health. Conversely, low energy availability (LEA) is a situation of insufficient EA to cover basic physiological demands. LEA leads to the adverse consequences of RED-S[3]. LEA can arise unintentionally or intentionally, due to a mismatch between energy intake and energy requirement. In Figure 1 the bar on the left shows LEA resulting from reduced energy intake with maintained training load. On the right, LEA is a consequence of increased training load with maintained energy intake.
Figure 2 illustrates that EA is under the control of an athlete[4]. The three behaviours relating to training, nutrition and recovery determine EA. Integrated periodisation of these behaviours results in optimal health and performance. Conversely, an imbalance in these behaviours results in suboptimal functionally. LEA in the case of high training loads relative to nutritional intake. Thus, this figure reinforces the important point in the IOC statements on RED-S that psychological factors which determine these behaviours are key in both the development, continuation and management of RED-S[2,3].
Figure 2 also shows the temporal, synergistic effect of these behaviours to ensure a fully functioning endocrine system. Hormones are key for health and to drive positive adaptations to exercise, to improve athletic performance. Thus hormones can be informative in tracking the response of an individual to these three input variables. Furthermore, endocrine markers relate to the RED-S clinical outcome of stress fracture in athletes, being more reliable as objective, quantifiable indicators of EA than numerical calculation of EA from direct assessment[5].
Authors
Nicola Keay1, Gavin Francis2
1 Department of Sport and Exercise Sciences, Durham University
2 Science4Perforamnce, London
Br J Sports Med 2019;0:1–2. doi:10.1136/bjsports-2019-100611
References
1 http://health4performance.co.uk (accessed 21/01/2019) Health4Performance Educational BASEM website raising awareness of RED-S Working group on RED-S British Association of Sport and Exercise Medicine 2018
2 Mountjoy M, Sundgot-Borgen J, Burke L et al. IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update Br J Sports Med2018;52(11):687-697
3 Mountjoy M, Sundgot-Borgen J, Burke L et al. The IOC consensus statement: beyond the Female Athlete Triad–Relative Energy Deficiency in Sport (RED-S). Br J Sports Med2014;48(7):491-7
4 Burke L, Lundy B, Fahrenholtz L et al, & Melin. Pitfalls of conducting and interpreting estimates of energy availability in free-living athletes. International Journal of Sport Nutrition and Exercise Metabolism2018; 28(4):350–363. https://doi.org/10.1123/ijsnem.2018-0142
5 2Heikura I, Uusitalo A, Stellingwerff T et al. Low energy availability is difficult to assess but outcomes have large impact on bone injury rates in elite distance athletes. International Journal of Sport Nutrition and Exercise Metabolism2018; 28(4):403–411. https://doi.org/10.1123/ijsnem.2017-0313
Although improvements are being made in raising awareness and in effective medical management of relative energy deficiency in sport (RED-S)[1, 2] what about once an athlete/dancer is “medically cleared” to return to sport/dance? What advice/support is there for athletes/dancers and their coaches/teachers? After discussions with coaches, here are some suggestions on how to achieve return to sport/dance after RED-S.
To recap, RED-S is a situation of low energy availability (LEA), which can lead to adverse health and performance consequences[3,4]. LEA can be a result of intentional energy restriction, which covers a spectrum of issues with eating from disordered eating to full blown clinical eating disorder. Ironically the original intention of these eating issues may have been to improve athletic performance, yet sustained LEA will ultimately lead to stagnation and deterioration in performance as found in male athletes[5].
The desire to return to full fitness can be a powerful incentive to address LEA. Nevertheless return to sport/dance needs to be carefully structured in collaboration with coaches to prevent injury and avoiding regression to the LEA state.
Structured return to training and nutrition
Initially focus should be on body weight strength and conditioning (S&C). Inevitably in RED-S adaptive responses to training stimuli will be dampened due to shut down of hormones networks into an energy saving mode. Once adequate EA has been established, hormone networks will be able to respond. Restoring muscle tone and working on proprioception forms a good basis to build from to mitigate injury risk. Impaired neuromuscular skills have been reported in female athletes in LEA[6], together with adverse effects of LEA on bone health increases injury risk.
The other reason for gradual return to training is that a routine of fuelling around training (before, during, after) needs to be established. In particular recovery nutrition within 30 minutes window to enable hormonal responses to training. Note that having this recovery nutrition does not mean reducing intake at the next meal!
Long endurance should be eased into after restoring muscle strength and control, in order to prevent injury. Additionally this type of training will necessitate a higher energy requirement. If adequate energy availability has only recently been restored, the balance is fragile and so too much training too soon can have negative effects. Especially if a fuelling strategy around training has not been established as described above.
High intensity/interval training should be the last type of training to be resumed as this places the highest stress and requires the highest energy demand on the athlete/dancer.
Injury, soft tissue and bone stress responses are more frequent in hormonal dysfunction of RED-S in both male and female athletes[7]. If an injury has been sustained during this period of LEA then particular emphasis needs to be on initial S&C. In the case of previous bone stress responses, multi-direction loading is key to build bone strength before resuming formal run training in athletes who are runners. Even if a bone injury has not occurred, bone turnover is one of the first systems to be adversely impacted by RED-S, so including this type of multidirectional bone loading in the initial structured return for all athletes/dancers would be beneficial.
Discuss with your coach a realistic, attainable goal if this will help. Maybe a low key race/event several months down the track
What to look out for
Don’t ignore injury niggles, illness or fatigue. Discuss with your coach and back off if necessary. This is a process, not a sprint.
Female athletes. You may well have experienced menstrual disruption during your time in LEA. This is a crucial training metric. Please use it! If your menstruation becomes irregular/stops this is your warning sign that your body is not ready to step up training[7]. Male coaches please reinforce this and be aware of this point. Remember Gwen Jorgensen posting her periods on Training Peaks as a training metric?
Flexibility in approach. Try not to put pressure on yourself to return to your previous PBs. It is important to have a plan, but you can be flexible. Everyone is different so this process of returning to sport/dance does not have a set, rigid timetable.
Enjoyment! Don’t forget the original reason that you started your sport/dance was for enjoyment! This is an opportunity to rediscover that joy, whether you return to competition or not.
“Recovery?” Does anyone fully “recover” from disordered eating/eating disorder? I don’t think so. To be a successful athlete, or indeed successful in life you need self-motivation, drive, determination. All admirable qualities, but sometimes these can get diverted to cause unhealthy eating/training patterns. So be aware that in times of stress it may be tempting to revert to old habits of under eating/over exercise to reassure yourself that you are in control.
Be prepared for questions: why have you been off training? Why are you not doing fully training schedule? Maybe you want to tell your team mates/friends. Maybe you don’t. That is your call.
So good luck with your return to sport/dance after RED-S, if that is what you want to do. Always discuss with you coach how to approach this.
5 Reduced Neuromuscular Performance in Amenorrheic Elite Endurance Athletes.
Tornberg Å Melin A Koivula F Johansson A Skouby S et. al.Medicine and science in sports and exercise 2017 vol: 49 (12) pp: 2478-2485
6 Low Energy Availability Is Difficult to Assess but Outcomes Have Large Impact on Bone Injury Rates in Elite Distance Athletes Heikura, Ida A. Uusitalo, Arja L.T. Stellingwerff, Trent et al International Journal of Sport Nutrition and Exercise Metabolism 2018, 28, 4, 403-411
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.
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 Medicine, 48(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 Metabolism, 102(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
Health4Performance is a recently developed BASEM open access educational resource
This is a world premier: a resource developed for and by athletes/dancers, coaches/teachers, parents/friends and healthcare professionals to raise awareness of Relative Energy Deficiency in Sport (RED-S)
What?
Optimal health is required to attain full athletic potential. Low energy availability (LEA) can compromise health and therefore impair athletic performance as described in the RED-S clinical model.
Dietary energy intake needs to be sufficient to cover the energy demands of both exercise training and fundamental physiological function required to maintain health. Once the energy demands for training have been covered, the energy left for baseline “housekeeping” physiological function is referred to as energy availability (EA). EA is expressed relative to fat free mass (FFM) in KCal/Kg FFM. The exact value of EA to maintain health will vary between genders and individuals, roughly equivalent to resting metabolic rate of the individual athlete/dancer. LEA for an athlete or dancer will result in the body going into “energy saving mode” which has knock on effects for many interrelated body systems, including readjustment to lower the resting metabolic rate in the longer term. So although loss in body weight may be an initial sign, body weight can be steady in chronic LEA due to physiological energy conservation adaptations. Homeostasis through internal biological feedback loops in action.
The most obvious clinical sign of this state of LEA in women is cessation of menstruation (amenorrhea). LEA as a cause of amenorrhoea is an example of functional hypothalamic amenorrhoea (FHA). In other words, amenorrhoea arising as a result of an imbalance in training load and nutrition, rather than an underlying medical condition per se, which should be excluded before arriving at a diagnosis of FHA. All women of reproductive age, however much exercise is being undertaken, should have regular menstrual cycles, which is indicative of healthy hormones. This explains why LEA was first described as the underlying aetiology of the female athlete triad, as women in LEA display an obvious clinical sign of menstrual disruption. The female athlete triad is a clinical spectrum describing varying degrees of menstrual dysfunction, disordered nutrition and bone mineral density. However it became apparent that the clinical outcomes of LEA are not limited to females, nor female reproductive function and bone health in female exercisers. Hence the evolution of the clinical model of RED-S to describe the consequences of LEA on a broader range of body systems and including male athletes.
A situation of LEA in athletes and dancers can arise unintentionally or intentionally. In the diagram below the central column shows that an athlete where energy intake is sufficient to cover the demands from training and to cover basic physiological function. However in the column on the left, although training load has remained constant, nutritional intake has been reduced. This reduction of energy intake could be an intentional strategy to reduce body weight or change body composition in weight sensitive sports and dance. On the other hand in the column on the right, training load and hence energy demand to cover this has increased, but has not been matched by an increase in dietary intake. In both these situations, whether unintentional or intentional, the net results is LEA, insufficient to maintain health. This situation of LEA will also ultimately impact on athletic performance as optimal health is necessary to realise full athletic potential.
Although LEA is the underlying aetiology of RED-S, there are many methodological and financial issues measuring LEA accurately in “free living athletes“. In any case, the physiological response varies between individuals and depends on the magnitude, duration and timing of LEA. Therefore it is more informative to measure the functional responses of an individual to LEA, rather than the value calculated for EA. As such, Endocrine markers provide objective and quantifiable measures of physiological responses to EA. These markers also reflect the temporal dimension of LEA; whether acute or chronic. In short, as hormones exert network effects, Endocrine markers reflect the response of multiple systems in an individual to LEA. So by measuring these key markers, alongside taking a sport specific medical history, provides the information to build a detailed picture of EA for the individual, with dimensions of time and magnitude of LEA. This information empowers the athlete/dancer to modify the 3 key factors under their control of training load, nutrition and recovery to optimise their health and athletic performance.
Why?
Who is at risk of developing RED-S? Any athlete involved in sports or dance where being light weight confers a performance or aesthetic advantage. This is not restricted to elite athletes and dancers. Indeed the aspiring amateur or exerciser could be more at risk, without the benefit of a support team present at professional level. Young athletes are at particular risk during an already high energy demand state of growth and development. Therefore early identification of athletes and dancers at risk of LEA is key to prevention of development of the health and performance consequences outlined in the RED-S clinical model. Although there is a questionnaire available for screening for female athletes at risk of LEA, more research is emerging for effective and practical methods which are sport specific and include male athletes.
How?
Early medical input is important as RED-S is diagnosis of exclusion. In other words medical conditions per se need to be ruled out before arriving at a diagnosis of RED-S. Prompt medical review is often dependent on other healthcare professionals, fellow athletes/dancers, coaches/teachers and parents/friends all being aware and therefore alert to RED-S. With this in mind, the Health4Performance website has areas for all of those potentially involved, with tailored comments on What to look out for? What to do? Ultimately a team approach and collaboration between all these groups is important. Not only in identification of those at risk of LEA, but in an integrated support network for the athlete/dancer to return to optimal health and performance.
Relative energy deficiency in sport (RED-S) is a clinical model that describes the potential adverse health and performance consequences of low energy availability (LEA) in male and female athletes. Identification of athletes at risk of LEA can potentially prevent these adverse clinical outcomes.
Athletes at risk of RED-S are those involved in sports where low body weight confers a performance or aesthetic advantage. In the case of competitive road cycling, being light weight results in favourable power to weight ratio to overcome gravity when cycling uphill. How can male cyclists at risk of LEA be effectively identified in a practical manner?
Energy availability (EA) is defined as the residual energy available from dietary intake, once energy expenditure from exercise training has been subtracted. This available energy is expressed as KCal/Kg fat free mass (FFM). A value of 45 KCal/Kg FFM is roughly equivalent to basal metabolic rate, in other words the energy required to sustain health. In order to quantify EA, accurate measurements of energy intake and expenditure, and FFM assessed from dual X ray absorptiometry (DXA), need to be undertaken. However this is not practical or feasible to undertake all these measurements outside the research setting. Furthermore, methodology for assessing energy intake and expenditure is laborious and fraught with inaccuracies and subjectivity in the case of diet diaries for “free living athletes“. Even if a value is calculated for EA, this is only valid for the time of measurement and does not give any insights into the temporal aspect of EA. Furthermore, an absolute EA threshold has not been established, below which clinical symptoms or performance effects of RED-S occur.
Self reported questionnaires have been shown to be surrogates of low EA in female athletes. However there are no such sport specific questionnaires, or any questionnaires for male athletes. Endocrine and metabolic markers have been proposed as quantitative surrogate measures of EA and shown to be linked to the RED-S clinical outcome of stress fractures in runners. In female athletes the clinical sign of regular menstruation demonstrates a functioning H-P ovarian axis, not suppressed by LEA. What about male athletes? Although hypothalamic suppression of the reproductive axis due to LEA can result in low testosterone, high training loads, in presence of adequate EA, can lead to the same negative effect on testosterone concentration.
Male cyclists present a further level of complexity in assessing EA status. In contrast to runners, stress fracture will not be an early clinical warning sign of impaired bone health resulting from low EA. Furthermore cyclists are already at risk of poor bone health due to the non weight bearing nature of the sport. Nevertheless, traumatic fracture from bike falls is the main type of injury in cycling, with vertebral fracture requiring the longest time off the bike. Chris Boardman, a serial Olympic medal winner in cycling, retired in his early 30s with osteoporosis. In other words, in road cycling, the combined effect of the lack of osteogenic stimulus and LEA can produce clinically significant adverse effects on bone health.
Using a decision tree approach, the factor most indicative of impaired age matched (Z score) lumbar spine BMD was sport specific clinical assessment of EA. This assessment took the form of a newly developed sports specific energy availability questionnaire and interview (SEAQ-I). Reinforcing the concept that the most important skill in clinical medical practice is taking a detailed history. Questionnaire alone can lead to athletes giving “correct” answers on nutrition and training load. Clinical interview gave details on the temporal aspects of EA in the context of cycle training schedule: whether riders where experiencing acute intermittent LEA, as with multiple weekly fasted rides, or chronic sustained LEA with prolonged periods of suppressed body weight. Additionally the SEAQ-I provided insights on attitudes to training and nutrition practices.
Cyclists identified as having LEA from SEAQ-I, had significantly lower lumbar spine BMD than those riders assessed as having adequate EA. Furthermore, the lowest lumbar spine BMD was found amongst LEA cyclists who had not practised any load bearing sport prior to focusing on cycling. This finding is of particular concern, as if cycling from adolescence is not integrated with weight bearing exercise and adequate nutrition when peak bone mass (PBM) is being accumulated, then this risks impaired bone health moving into adulthood.
Further extension of the decision tree analysis demonstrated that in those cyclists with adequate EA assessed from SEAQ-I, vitamin D concentration was the factor indicative of lumbar spine BMD. Vitamin D is emerging as an important consideration for athletes, for bone health, muscle strength and immune function. Furthermore synergistic interactions with other steroid hormones, such as testosterone could be significant.
What about the effects of EA on cycling performance? For athletes, athletic performance is the top priority. In competitive road cycling the “gold standard” performance measure is functional threshold power (FTP) Watts/Kg, produced over 60 minutes. In the current study, 60 minute FTP Watts/Kg had a significant relationship to training load. However cyclists in chronic LEA were under performing, in other words not able to produce the power anticipated for a given training load. These chronic LEA cyclists also had significantly lower testosterone concentration. Periodised carbohydrate intake for low intensity sessions is a strategy for increasing training stimulus. However if this acute intermittent LEA is superimposed on a background of chronic LEA, then this can be counter productive in producing beneficial training adaptations. Increasing training load improves performance, but this training is only effective if fuelling is tailored accordingly.
Male athletes can be at risk of developing the health and performance consequences of LEA as described in the RED-S clinical model. The recent study of competitive male road cyclists shows that a sport specific questionnaire, combined with clinical interview (SEAQ-I) is an effective and practical method of identifying athletes at risk of LEA. The temporal dimension of LEA was correlated to quantifiable health and performance consequences of RED-S.
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.
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.
To recap, RED-S is a situation of low energy availability (LEA), which can lead to adverse health and performance consequences[3,4]. LEA can be a result of intentional energy restriction, which covers a spectrum of issues with eating from disordered eating to full blown clinical eating disorder. Ironically the original intention of these eating issues may have been to improve athletic performance, yet 
Dr Nicky Keay 