“Of Mice and Men….”

“We need to treat individual women, not statistics” was the concluding sentence of an insightful BMJ Editorial 2019 [1]

However, as Caroline Criado Perez points out in her recent, science prizing-winning book, Invisible Women, in many instances there are no scientific or medical statistics on women[2].

Mouse
“Where are the females?”

The efficacy of drugs is predominately initially tested in vivo on male cells. So at inception, potentially many medications, which might have been effective in females are discarded at the earliest stage of research, because no effects are observed in male cells. The trend of the default male organism in research follows through into animal experimentation on male mice. Although animal models may not be entirely predictive of effects in humans, certainly the effects in female humans will be even less certain. Does it matter that research is conducted predominately on male tissue, male organisms and men? Thalidomide, specifically one of the optimal isomers, is a drug that had devastating teratogenic effects when taken by women. Indeed, a wide range of potential sex differences in the effects and metabolism of drugs has been reported. Furthermore the action of drugs, including adverse effects, can vary according the phases of the menstrual cycle, due to variations in circulating sex steroids. For example, certain drugs are likely cause arrhythmia in the follicular phase of the menstrual cycle[3]. Yet the effect of many drugs in females is not well understood, as research had not included females, let alone women in different phases of the menstrual cycle.

Why is research focused on males? There is an argument that the menstrual cycle in females is “too complicated” or including women in a study at difference phases of the menstrual cycle “will interfere with results”. Menstrual cycles have been around since women evolved, so this is not a phenomenon that is going to go away anytime soon. Therefore, welcoming the complexity of the intricate choreography of hormones during the menstrual cycle and during the lifetime of a women, is a more constructive approach. Certainly a more acceptable scientific approach is where the objective is to elucidate similarities and differences between men, rather than excluding the female half of the population and assuming no differences in physiology and metabolism exist. Furthermore there are differences between individual women. Individual women will be impacted by fluctuations of hormones during the menstrual cycle in different ways, depending on varying tissue sensitivities to steroids between individuals.

This concept is especially important in sports science where the vast majority of studies are conducted in males. As I outlined in my presentation recently at Barça Innovation Hub, before discussing external factors (training load, nutrition, recovery), researched in males, for female athletes is is vital to take into account internal bio-chronometers[4]. Circadian misalignment leads to suboptimal health and performance[5]. For female athletes, the most important cyclical variation of hormones during the menstrual cycle. Furthermore, these periodic changes in hormones have individual effects. Only when these are recognised can external factors be integrated with internal periodicity. In other words by taking account of individual internal variations, this makes it possible to provide personalised advice. Tracking menstrual cycles provides an important training metric as menstrual cycles are a barometer of healthy hormones[6]. As it becomes easier to track personal health and performance data on a daily basis, both researchers and individual women can gain a better understanding of how female physiology varies over the menstrual cycle. Optimising health and performance for the individual female athlete, makes for a stronger team.

What about in the clinical medical setting? I recently attended an excellent update on acute medicine for medical doctors. An eminent cardiologist presented a series of case studies, including a woman who started experiencing symptoms in the morning, which both she and doctors thought were due to indigestion. Eventually when this “indigestion” had not settled by later afternoon, she attended A&E. She had suffered an extensive myocardial infarction (heart attack). The cardiologist explained that even though she went to a hospital with an on-site primary percutaneous coronary intervention facility, unfortunately due to the long delay in presenting to hospital, the heart muscle had died. The opportunity had been missed to take her into the catheterisation laboratory to restore blood flow and function to the cardiac muscle. He outlined how this delay in diagnosis would have a big impact on her future quality of life and life span. Unfortunately this is not an isolated case. Women are far more likely to be misdiagnosed as not having acute coronary syndrome, when in fact they are indeed suffering a “heart attack”. Why is this? The “typical” presentation of myocardial infarction of central crushing chest pain with radiation to left neck and arm, disseminated to the public and medical students, is in fact only typical for men. Women present with “atypical” symptoms, in other words atypical for men[7]

Even where female specific statistics do exist, the emphasis should be on considering the individual woman in clinical context. The recent BMJ editorial on HRT emphasised providing women with high quality, unbiased information on which women can weigh up their personal risk/benefit outcomes from HRT. As, each woman can experience changes in hormones differently, including those occurring at the menopause; so the emphasis should be on an individual woman’s quality of life rather than epidemiological statistics[1].

There are important differences between mice, men and women.

References

[1] Rymer J, Brian, K, Regan L. HRT and breast cancer risk. BMJ Editorial 2019. dx.doi. org/10.1136/bmj.l5928

[2] Caroline Criado Perez. Royal Society Book Prize. Invisible Women. Publisher Chatto & Windus 2019

[3] Soldin O, Chung S, Mattison D. Sex Differences in Drug Disposition. Journal of Biomedicine and Biotechnology 2011, Article ID 187103 doi:10.1155/2011/187103

[4] N. Keay “Dietary periodisation for female football players” Barca Innovation Hub conference, Camp Nou, Barcelona, 9 October 2019

[5] N.Keay, Internal Biological Clocks and Sport Performance BJSM 2017

[6] N.Keay, What’s so good about Menstrual Cycles? BJSM 2019

[7] Khamis R, Ammari T, Mikhail G. Gender differences in coronary heart disease. Education in Heart. Acute coronary syndromes. BMJ Heart http://dx.doi.org/10.1136/heartjnl-2014-306463

 

 

 

RED-S Research: Bones and Ballet

BJSM Blog 26/8/2019

Dr Nicky Keay

BJSMThere are many areas of RED-S (relative energy deficiency in sport) that are currently being researched. Whilst there is animated discussion about scientific evidence for energy availability thresholds in men and women, in the clinical setting what are the most effective ways to identify and support these athletes and dancers at risk of the health and performance consequences of RED-S?

Bone stress injuries, including stress fractures and other complications of suboptimal bone heath such as compression fractures are some of the most clinically significant sequalae of low energy availability described in the RED-S (relative energy deficiency in sport) clinical model[i]. Suboptimal bone health with associated recurrent stress fractures can be career ending for athletes and dancers.

Therefore early identification of those with suboptimal bone health is crucial. In terms of identifying athletes/dancers at risk of developing bone health consequences due to RED-S, a sport specific questionnaire in male cyclists has been demonstrated to be effective[ii]. The purpose of identifying those at risk of suboptimal bone health is in order to put in place interventions, to prevent progression, and in some cases, improve bone health. Evidence for positive outcomes of these behavioural interventions are reported in male cyclists[iii].

Currently bone mineral density (BMD) is measured using DXA (dual X ray absorptiometry), which although low in dose, nevertheless involves ionising radiation. This limits the frequency of measurement, although bone is metabolically active and often one of first systems to change in response to low energy availability[iv]. The new technology of R.E.M.S. (Radiofrequency Echographic Multi Spectrometry) involves totally safe ultrasound. Furthermore this technology provides information on bone microarchitecture. Currently assessment of bone microarchitecture is only possible with pQCT (peripheral quantitative computerised tomography), which is not only involves a high radiation dose, furthermore is limited to assessment of peripheral skeletal sites. Although BMD is undoubtedly an important factor in determining bone health, nevertheless bone strength and structure also plays an important part.

Therefore the main objective of a forthcoming study[v] is to establish the effectiveness of identifying those at risk of suboptimal bone health with this new specialised ultrasound based technology and correlate with questionnaire and blood markers in both athletic and non athletic populations.

Ballet and other Dance forms

RED-S is more prevalent in sports where being of low body weight confers a performance or aesthetic advantage. Although dance is not a sport, nevertheless this type of activity requires low body weight from both a performance and aesthetic point of view for both male and female dancers. Dance training often starts at a young age[vi] and as with early sport specialisation, there is an increased risk of developing low energy availability during this time of high-energy demand for growth and development[vii]. So much so, that this situation can have a negative impact on accumulation of peak bone mass and adverse potential long-term effects[viii].

Although there is a validated questionnaire LEAF-Q[ix] for assessing low energy availability in female athletes, this excludes half the population and is not sport specific. A questionnaire-based study amongst female athletes was found to be effective at identifying and quantifying the clinical consequences of low energy availability[x]. Our recent study of competitive male road cyclists found that a sport specific energy availability questionnaire combined with interview (SEAQ-I)[xi] was the measured factor most effective in indicating low BMD of the lumbar spine. BMD of the lumbar spine is a quantifiable measure of chronic low energy availability. Other objective measures of low energy availability include indicators of endocrine function. In women menstrual function and in men testosterone, which in turn are clinked to the clinical outcome of impaired bone health and stress fracture in runners[xii]

To date there is a dearth of sport specific questionnaires to assess low energy availability and none that are dance specific. Dance involves both male and female and is certainly a type of activity where individuals are at risk of low energy availability and the clinical consequences of RED-S. Therefore the aim of the current dance study is to use a dance specific energy availability questionnaire (DEAQ)[xiii] to asses awareness, risk factors and consequences of low energy availability and RED-S.

References

[i] Mountjoy M, Sundgot-Borgen J, Burke L et al. IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update British Journal of Sports Medicine 2018; 52(11): 687-697 DOI: 10.1136/bjsports-2018-099193

[ii] 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 and Exercise Medicine 2018; 4(1) DOI: 10.1136/bmjsem-2018-000424

[iii] 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 and Exercise Medicine 2019; 5(1) DOI: 10.1136/bmjsem-2019-000523

[iv] Professor Louise Burke presenting at annual ISENC conference Newcastle 2018

[v] Assessment of Echographic Technology in Measuring Bone Health in the Clinical Setting

[vi] N. Keay. Dancing through adolescence British Journal of Sports Medicine 1998 DOI: 10.1136/bjsm.32.3.196

[vii] N. Keay. The modifiable factors affecting bone mineral accumulation in girls: The paradoxical effect of exercise on bone Nutrition Bulletin 2000 DOI: 10.1046/j.1467-3010.2000.00051.x

[viii] N. Keay, G.Blake, I. Fogleman.  Bone mineral density in professional female dancers British Journal of Sports Medicine 1997; 31(2): 143-147

DOI: 10.1136/bjsm.31.2.143

[ix] Melin A, Tornberg Å, Skouby S et al. The LEAF questionnaire: A screening tool for the identification of female athletes at risk for the female athlete triad British Journal of Sports Medicine 2014: 48 (7)

[x] K. Ackerman, B. Holtzman et al. Low energy availability surrogates correlate with health and performance consequences of Relative Energy Deficiency in Sport British Journal of Sports Medicine 2018; 53(10) 628-633

DOI: 10.1136/bjsports-2017-098958

[xi] N. Keay, G. Francis, K. Hind. 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 2018 4(1) DOI: 10.1136/bmjsem-2018-000424

x Heikura 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 Metabolism 2018; 28(4): 403-411 DOI: 10.1123/ijsnem.2017-0313

[xiii] DEAQ Dance Energy Availability Questionnaire on line with ethical approval from Durham University

Energy Availability: Concept, Control and Consequences in relative energy deficiency in sport (RED-S)

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].

Slide1

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].

Slide1

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 and Royal National Orthopaedic Hospital, London

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

Relative Energy Deficiency in Sport (RED-S) and Dance

Relative energy deficiency in sport (RED-S)[1] is a clinical syndrome encompassing adverse health and performance (figure 1) consequences of low energy availability (LEA)[2] in male[3] and female exercisers of all ages and all levels from recreational to elite.

Slide1
Figure1 

LEA is a situation where energy intake is insufficient to cover the combined energy demands of training and baseline physiological processes to maintain health. LEA can arise unintentionally or intentionally (figure 2). Unintentional LEA results from increased training load, which is not matched by an increased energy intake. Intentional LEA is more likely to arise in sports where low body weight confers a performance or aesthetic advantage, for example, gravitational sports including cycling, ski-jumping, climbing; weight-category sports including boxing and judged artistic sports including gymnastics, aquatic disciplines. RED-S is also a risk in dancers of all genres, but in particular ballet[4]. Intentional LEA can be due to spectrum of disordered eating to eating disorders. The body responds to LEA by downregulating fundamental physiological processes. This ‘energy saving mode’ is of particular clinical significance in the endocrine network system (figure 3).

Slide1
Figure 2

For women, LEA can manifest itself as menstrual disruption, in men this corresponds to low testosterone. The net effects of dysfunctional endocrine feedback loops are adverse effects on health and dampened response to training stimuli. For example, endocrine dysfunction manifests as suboptimal bone health with increased risk of bone stress injuries. Increased duration of LEA accrues cumulative effects on endocrine networks and hence health and performance (figure 2). Although the exerciser may initially improve athletic performance with short-term LEA, long-term LEA will lead to deterioration in health and performance.

Slide1
Figure 3

Therefore, early identification of those at risk of LEA is essential in preventing the clinical consequences of RED-S. This is the purpose of the BASEM website Health4Performance[5] to raise awareness of RED-S among athletes/dancers, coaches, parents, friends and healthcare professionals to encourage a multidisciplinary team approach to identifying and supporting those at risk of RED-S.

Authors:

Dr Nicola Keay, Department of Sport and Exercise Sciences, Durham University, UK.

Dr Alan Rankin Department of Sports Medicine, Sport Ireland Institute, Dublin, Ireland

Br J Sports Med 2019;0:1–3. doi:10.1136/bjsports-2018-100354

References
1 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 Med 2014;48:491–7.
2 Mountjoy M, Sundgot-Borgen JK, Burke LM, et al. IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update. Br J Sports Med 2018;52:687–97.
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.
4 Keay N. Raising Awareness of RED-S in Male and Female Athletes and Dancers. Br J Sport Med blog 2018. https://blogs.bmj.com/bjsm/2018/10/30/raisingawareness-of-red-s-in-male-and-female-athletes-anddancers/ (accessed 19 Jan 2019).

5 Health4Performance. Educational BASEM website raising awareness of RED-S Working group on RED-S. BMJ Open Sport Exerc Med 2018. http:// health4performance.co.uk (accessed 19 Jan 2019).

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. To cite Keay N, Rankin A. Br J Sports Med Epub ahead of print: [please include Day Month Year]. doi:10.1136/ bjsports-2018-100354

Returning to Sport/Dance restoring Energy Availability in RED-S?

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.

LifeSeasonDayTo 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.

References

1 BASEM Educational website www.health4perforamnce.co.uk

BJSM blog: Update on RED-S N Keay 2018

3, 4 IOC consensus statements on RED-S BJSM 2014 and update 2018

5 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. N Keay, G Francis, K Hind. BMJ Open in Sport and Exercise Medicine 2018

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

7 What’s so good about Menstrual Cycles? N Keay BJSM blog 2019

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.

Screen Shot 2019-01-30 at 12.09.28

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

 

Low Energy Availability in Climbers

Listen into a great discussion I had with Dr Nigel Callender an ex competitive climber and climbing coach about the “elephant in the room” in competitive climbing.

Discussion of Low Energy Availability and RED-S

As a gravitational sport, being a light-weight climber confers a performance advantage. However, being alert to low energy availability and the clinical consequences of RED-S on health and performance is important for climbers. With climbing being included the next Olympics, then hopefully this will raise awareness of being alert to athletes at risk of low energy availability and RED-S.

IMG_0175

Insights from Dr Nigel Callender, sports scientist turned medical doctor (anaesthetics/critical care trainee) an active researcher, largely into the exercise physiology aspects of climbing and ex-competitor, having represented Ireland at international level and been British bouldering champion before shoulder injuries ended that. Sport climbing is included in the 2020 Tokyo summer games in its three competitive disciplines; bouldering, lead climbing and speed climbing. Each sub-discipline has a slightly different athlete profile and physiological demands, but all are obviously under the heading of gravity dependent sports. Current participation figures put yearly indoor climbing participation at around the one million mark in the UK and it is said to be one of the fastest growing sports worldwide. The sport is being recognised as a great way to improve overall health and fitness, with recent papers citing it as a useful rehab activity for many physical and mental health conditions and also as a health promotion tool.

Although climbing has been a formal competitive sport in some sense since the late 80’s, it still lacks much in the way of formal training and medical guidelines. Being a gravity dependent sport, strength to weight ratio is important, however Dr Callender and his colleagues are seeing a high incidence of restrictive eating patterns at all levels of the sport and a lack of awareness around the performance impairments and health risks associated with a significant or prolonged negative energy balance in some athletes.

The Outdoor Athlete Podcast is a bit of a winter project that came about to establish a gold-standard resource, driven by credible experts in their relevant fields, as an attempt to provide high-quality and evidence-based information amongst the confusing advice that is now the internet. It’s free and always will be and it was inspired by the BJSM Podcasts though broadly aiming at ‘Outdoor Athletes’ e.g. Climbers, Fell/Trail runners, Mountain bikers and anyone happy to listen.

For more information on climbing in the UK, including competition climbing see http://www.thebmc.co.uk

Raising Awareness of RED-S in Male and Female Athletes and Dancers

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.

EnergyBalance

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.

Slide1

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.

References

Heath4Performance BASEM Educational Resource

Video introduction to Health4Performance website

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

What is Dance Medicine? BJSM 2018

Identification and management of RED-S Podcast 2018

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 Keay, Francis, Hind. BJM Open Sport and Exercise Medicine 2018

How to Identify Male Cyclists at Risk of RED-S? 2018

Pitfalls of Conducting and Interpreting Estimates of Energy Availability in Free-Living Athletes IJSNM 2018

Low Energy Availability Is Difficult to Assess but Outcomes Have Large Impact on Bone Injury Rates in Elite Distance Athletes IJSNM 2017

The LEAF questionnaire: a screening tool for the identification of female athletes at risk for the female athlete triad BJSM 2013

IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update BJSM 2018