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

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Unfortunately I continue to see athletes, both male and female, whose health and athletic performance is hampered due to Relative Energy Deficiency in Sports (RED-S). There have been some high profile athletes who have been very open about how RED-S has affected them, alerting younger athletes to potential pitfalls.

Does this issue warrant highlighting? Yes! The athletes I see and those that speak out are only just the tip of the iceberg. In a study of exercising females, half were found to have subtle menstrual hormone disruption such as luteal phase deficit or anovulation. A third were amenorrhoeic, with no periods at all. All women of reproductive age, whether an athlete or not, should have regular periods, otherwise there are potential serious health and performance sequaelae. However studies in both the USA and Australia have revealed that the majority of young exercising women are not aware of the link between menstrual disruption and deleterious, potentially irreversible effects on bone health.

The impact of non-integrated periodisation of training, nutrition and recovery has evolved since the early description of the female athlete triad. The constellation of amenorrhoea, disordered eating and osteoporosis is now considered to be a clinical spectrum. In turn the female athlete triad is part of a much broader picture of RED-S, which includes adverse multi-system effects beyond bone health and is also seen in male athletes.

Although an athlete may appear healthy, what are the underlying Endocrine disruptions occurring in RED-S that ultimately will impede both optimal health and performance to full potential? In general, female exercisers are more susceptible to internal and external perturbations as the female Endocrine system is more finely balanced than in males. Nevertheless, in a study of male athletes, in the short time period after completing a training session, bone turnover was adversely affected, with an increase in markers of resorption relative to formation, if an athlete did not refuel rapidly with protein and carbohydrate. In the now classic research by Loucks, 5 days of manipulated energy restricted availability, via dietary intake and exercise output, caused disruption in LH pulsatility in previously eumenorrhoeic women. From this research and subsequent studies, not only is the reproductive axis disrupted with reduced energy availability, in addition hypothalamus-pituitary-thyroid (decreased T3) and adrenal axes (increased cortisol) and decreased IGF1 due to relative GH resistance are all disrupted. These interactive hormonal dysfunctions occur even before reduction in sex steroids. A recent study demonstrated that beyond the average energy availability over a 24 hour time window, within day energy deficits in terms of duration and magnitude are associated with a greater degree of disruption of Endocrine and metabolic markers, in particular decreased oestradiol and increased cortisol. So consistency of nutrition, not only during a training season but from day to day is vital.

Although energy availability is the crucial factor in the pathophysiology of RED-S, measuring this is not practical for all athletes in terms of accuracy and cost. Clinical menstrual status in female athletes and basic Endocrine markers are proposed as being more reliable and accessible. The Endocrine system is very sensitive to internal and external perturbations, as described above, and presages performance consequences of RED-S, such as injury. An important starting point is for all female athletes is to ask themselves: are my periods regular? This is also a vital question that coaches and parents need to consider for athletes in their care. If the answer is no, then this needs to be assessed, ideally by those with experience in Sports Endocrinology.

Why are these clinical and biochemical markers of Endocrine dysfunction important for athletes? Essentially there are significant health and performance implications for athletes. As outlined in the stories of female athletes, by the time career limiting stress fractures become obvious, typically in early twenties, the Endocrine system has been in disarray for a significant time. Long term, irreversible poor bone health and adverse body composition have been established.

In my opinion, emphasis should be placed on the positive outcome of integrating periodised training, nutrition and recovery to support a functional Endocrine system and therefore optimal health and ability to reach full athletic potential. For example for female athletes, competing in sports where low body mass confers a performance advantage, such as ballet, gymnastics and road cycling, finely tuned neuromuscular skills are essential to reach maximal potential and minimise injury risk. Yet these are the athletes most at risk of developing RED-S, with consequential adverse effects on menstrual cycles, endogenous oestrogen secretion and neuromuscular function.

Rather than reading headlines about the concerning health issues amongst athletes, more guidance for athletes and those working with them, on the warning signs and how to combat RED-S are needed so that athletes can reach their full potential and the headlines become about athlete achievements.

For more discussion on the Endocrine and Metabolic aspects of Sport and Exercise Medicine, all members of multi-disciplinary team working with athletes, including athletes and coaches are welcome to the BASEM Spring Conference



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

British middle-distance runner Bobby Clay is struggling with osteoporosis but wants her experience to act as a lesson for fellow young athletes Athletics Weekly 2017

In a special AW report, former English Schools champion Jen Walsh reveals the devastation that the female athlete triad can wreak Athletics Weekly 2017

Optimal Health: Especially Young Athletes! Part 3 – Consequences of Relative Energy Deficiency in Sports BASEM 2017

Prevalence High prevalence of subtle and severe menstrual disturbances in exercising women: confirmation using daily hormone measures. Human Repro 2010

Energy deficiency, menstrual disturbances, and low bone mass: what do exercising Australian women know about the female athlete triad? Int J Sport Nutr Exerc Metab. 2012

Female adolescent athletes’ awareness of the connection between menstrual status and bone health J Pediatr Adolesc Gynecol. 2011

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

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

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

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

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

Luteinizing hormone pulsatility is disrupted at a threshold of energy availability in regularly menstruating women JCEM 2003

Within-day energy deficiency and reproductive function in female endurance athletes Scandinavian Journal of Science and medicine in Sports 2017

Low Energy Availability is Difficult to Assess But Outcomes Have Large Impact on Bone Injury Rates in Elite Distance Athletes Sports Nutrition and Exercise Metabolism 2017

Body Composition for Health and Sports Performance

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

Conferences in Sport/Dance, Exercise Science and Medicine 2018

Conferences for the New Year:


If you are interested in any aspects of Sport/Dance, Exercise and Lifestyle Medicine here are some suggestions:

British Association of Sport and Exercise Medicine Spring Conference 22 March 2018 “Health, Hormones and Human Performance” Covering the Endocrine and Metabolic aspects of Sport, Dance, Exercise Science and Medicine. From the elite athlete to the reluctant exerciser. Aimed at all those members of the multidisciplinary team working with athletes/dancers, plus athletes/dancers and their coaches/teachers.

CPD points awarded from Faculty of Sports and Exercise Medicine FSEM

BASES British Association of Sport and Exercise Sciences CPD awarded

British Journal of Sports Medicine Quality International Education Approved

CPD points from Royal College of Physicians

CPD from REP-S


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Why? The balance and timing of exercise, nutrition and recovery is key to optimising health and all aspects of human performance. Intricate network interactions between the Endocrine system and metabolic signalling pathways drive these positive adaptations. However, non-integration of these lifestyle factors can disrupt signalling feedback pathways and predispose to maladaptation and potentially disease states.

What? Discussion, led by experienced clinicians and researchers will cover:

· Key role of Sports Endocrinology in health and performance

· Effects of exercise modalities on body composition and bone health

· Machine learning in interpreting biochemical & metabolomic patterns

· Endocrine & metabolic markers in assessing health & training status

· Gut metabolism in supporting health and performance

· Exercise as crucial lifestyle factor in pre-existing metabolic dysfunction

Who? This conference is relevant to all members of multidisciplinary teams supporting both reluctant exercisers and elite athletes. Medics, researchers, physiologists, physiotherapists, nutritionists, psychologists, coaches, athletes. All welcome.

Health, Hormones and Human Performance will be a conference of interest to all those involved with aspiring and elite athletes, including dancers (National Institute of Dance Medicine and Science NIDMS) and those supporting reluctant exercisers through Lifestyle Medicine.

Latest news from BASEM. Interview with BASEM Today Issue 41 – Winter 2017


Wales Exercise Medicine Symposium by Cardiff Sports & Exercise Medicine Society 27/1/18. This includes Dr Peter Brukner, founder of the Olympic Sports Medicine Park in Melbourne, and an afternoon session discussing the female athlete through the lifespan. CPD points applied for from the Royal College of Physicians, the Faculty of Sports and Exercise Medicine, REPs and the Royal College Of General Practitioners.



Women in Sport and Exercise Conference 2018  13-14 June Organised by The Women in Sport and Exercise Academic Network and attracting British Association of Sport and Exercise Sciences (BASES) CPD points.



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

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

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

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

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

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

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


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

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


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

Optimal health: including male athletes! Part 2 Relative Energy Deficiency in sports Dr N. Keay, British Journal of Sport Medicine 4/4/17

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

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

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

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

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

Bone health and fractures in children. National Osteoporosis Society

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

Relative Energy Deficiency in sport (REDs) Lecture by Professor Jorum Sundgot-Borgen, IOC working group on female athlete triad and IOC working group on body composition, health and performance. BAEM Spring Conference 2015.

Health and fitness in young people