Dr Nicky Keay, Sports/Dance Endocrinologist
How do you feel on Monday morning, when the alarm wakes you at 7am with a day of work ahead after the weekend? A bit tired, slightly lethargic, sluggish, maybe a little bit down, perhaps a few regrets about somewhat too much alcohol/food over weekend, frustrated that the exercise training schedule didn’t go according to plan?
There are many causes of fatigue and sport underperformance: Endocrine, immunological, infective, metabolic, haematological, nutritional, digestive, neoplastic….. The adrenal gland in the Endocrine system in particular has come in for some bad press recently.
Undoubtedly the adrenal glands have a case to answer. Situated above the kidneys these Endocrine glands produce glucocorticoids, mineralocorticoids, androgens from the adrenal cortex and from the adrenal medulla adrenaline. Glucocorticoids (e.g. cortisol) have a metabolic function to maintain energy homeostasis and an immune function to suppress inflammation. Mineralocorticoids (e.g. aldosterone) maintain electrolyte and water balance. As mineralocorticoids and glucocorticoids are similar biological steroid molecules, there is some degree of overlap in their actions.
Addison’s disease and Cushing’s disease are serious medical conditions, corresponding respectively to under or over production by the adrenal glands of steroid hormones. Someone presenting in Addisonian crisis is a medical emergency requiring resuscitation with intravenous hydrocortisone and fluids. Conversely those with Cushing’s can present with hypertension and elevated blood glucose. Yet, apart from in the extremes of these disease states, cortisol metrics do not correlate with clinical symptoms. This is one reason why it is unwise and potentially dangerous to stimulate cortisol production based on clinical symptoms. Inappropriate exogenous steroid intake can suppress normal endogenous production and reduce the ability to respond normally to “stress” situations, such as infection. This is why the prescription of steroids, for example to reduce inflammation in autoimmune disease, is always given in a course of reducing dose and a steroid alert card has to be carried. Athletes should also be aware that exogenous steroid intake is a doping offence.
However, what is the “normal” concentration for cortisol? Well, for a start, it depends what time of day a sample is taken, as cortisol is produced in a circadian rhythm, with highest values in the morning on waking and lowest levels about 2/3am. Nor is this temporal periodicity of production the only variable, there are considerations such as tissue responsiveness and metabolism (break down) of the hormone. On top of these variables there are other inputs to the feedback control mechanism, which can in turn influence these variables. In other words, focusing on the steroid hormone production of the adrenal gland in isolation, could overlook underlying hypothamalmic-pituitary-adrenal (H-P-A) axis dysfunction and indeed wider issues.
Much maligned thyroid
That is not end of the possible causes of fatigue and sport underperformance: the H-P-A axis is just one of many interrelated, interacting Endocrine systems. There are many neuroendocrine inputs to the hypothalamus, the gate keeper of the control of the Endocrine system. Furthermore there are network interaction effects between the various Endocrine control feedback loops. For example cortisol towards the top end of “normal” range can impede the conversion at the tissue level of thyroxine (T4) to the more active triiodothyronine (T3) by enzymes which require selenium to function. Rather T4 can be converted to reverse T3 which is biologically inactive, but blocks the receptors for T3 and thus impair its action. This in turn can interfere with the feedback loop controlling thyroid function (hypothalamic-pituitary-thyroid axis). The physiological ratio of T4 to T3 is 14:1, which is why supplementation with desiccated thyroid is not advisable with ratio of 4:1. There are other processes which can crucially interfere with this peripheral conversion of T4 to T3, such as inflammation and gut dysbiosis, which can occur as result of strenuous exercise training. So what might appear to be a primary thyroid dysfunction can have an apparently unrelated underlying cause. Indeed amongst highly trained athletes thyroid function can show an unusual pattern, with both thyroid stimulating hormone (TSH) and T4 at low end of the “normal “range, thought to be due to resetting of the hypothalamic-pituitary control signalling system. This highlights that the “normal” range for many hormones comprises subsets of the population and in the case of TSH, the “normal” range is not age adjusted, despite TSH increasing with age. As described by Dr Boelaert at recent conferences, there is certainly no medical justification for reports of some athletes in the USA being given thyroxine with TSH>2 (when the normal range is 0.5-5mU/l). Although thyroxine is not on the banned list for athletes, it could have potentially serious implications for health due to its impact on the Endocrine system as a whole.
Symptoms of fatigue are common to many clinical conditions, not just dysfunction in an Endocrine control axis in isolation, nor even the network interactive effects of the Endocrine system in isolation. For example, the impact of nutrition relative to training load produces a spectrum of clinical pictures and Endocrine disturbances seen in Relative Energy Deficiency in Sport (RED-S) in terms of health and sport performance.
Underlying mechanisms of Endocrine dysfunction
There may be predisposing factors in developing any clinical syndrome, the usual suspects being inflammation: whether infective, dysbioses, autoimmune; nutritional status linked with endocrine status; training load with inadequate periodised recovery to name a few….
From population based norms to personalised medicine: Health, Fitness, Sports Performance British Journal of Sport Medicine 2017
Sports Endocrinology – what does it have to do with performance? British Journal of Sport Medicine 2017
Advanced Medicine Conference, Royal College of Physicians, London 13-16 February 2017, Endocrine session: Dr Kristien Boelaert, Dr Helen Simpson, Professor Rebecca Reynolds
Subclinical hypothydroidism in athletes. Lecture by Dr Kristeien Boelaert, British Association of Sport and Exercise Medicine Spring Conference 2014. The Fatigued Athlete
Sport Performance and RED-S, insights from recent Annual Sport and Exercise Medicine and Innovations in Sport and Exercise Nutrition Conferences British Journal of Sport Medicine 2017
Sleep for health and sports performance British Journal of Sport Medicine 2017
Clusters of athletes BASEM
Enhancing Sport Performance: Part 1 British Association of Sport and Exercise Medicine 2017
Balance of recovery and adaptation for sports performance British Association of Sport and Exercise Medicine
Annual Sport and Exercise Medicine Conference, London 8/3/17 Gut Dysbiosis, Dr Ese Stacey
Adrenal fatigue does not exist: a systematic review BMC Endocrine Disorders. 2016; 16(1): 48.
A Controversy Continues: Combination Treatment for Hypothyroidism Endocrine News, Endocrine Society April 2017
How does low energy availability causes the health and perforamnce consequences of RED-S?
Optimal Health: Especially Young Athletes! Part 3 – Consequences of Relative Energy Deficiency in Sports
Optimal health: especially young athletes! Part 3 Consequences of Relative Energy Deficiency in sports BASEM
Dr Nicky Keay, Sports/Dance Endocrinologist
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 .
Optimal Health: including female athletes! Part 1 Bones British Journal of Sport Medicine
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.
If you are a male athlete, or work with male athletes, and think that Relative Energy Deficiency in sport (RED-S) is just a problem for females, think again.
By Dr Nicky Keay, Sports/Dance Endocrinologist
It is hard to dispute that women are underrepresented in medical research and certainly there are not many studies that include female athletes. Does this matter? After all whatever your gender, the same physiological and metabolic processes occur. However, the Endocrine system is where there are distinct differences in sex steroid production, which in turn have different responses in multiple target cells.
Although studies on changes in exercise performance in response to various dietary interventions and training regimes are often very interesting and well described, I am left feeling slightly uneasy when the subjects are all males. The cause for my concern is that the female hypothalamus-pituitary-ovarian axis is a particularly sensitive system with complex feedback loops and interacting networks.
Menstrual disturbance is not unusual amongst women in sport/dance where low body weight is an advantage. When a ballet dancer performs pointe work, putting full body weight through the big toe is hard enough, without extra load! Some women might consider it a convenience to be spared the hassle of menstruation. At age 24, I was perfectly fine never having had a period (primary amenorrhoea), or so I thought, being no more tired than other hospital medical colleagues working full time, studying for postgraduate medical exams and also involved in exercise training.
While working as a SHO at Northwick Park Hospital, I volunteered to be included in a study at the British Olympic Medical Association. The study was of female lightweight rowers and ballet dancers to look at VO2 max, percentage body fat and bone mineral density (BMD). I had been doing Ballet intensively (and obsessively) from a very young age, together with restricted fat and carbohydrate intake. Sounds a familiar scenario? Although I looked perfectly healthy (and I did not fit into a clinical condition requiring treatment), worked and danced well, my bone density was worryingly low. So if you are a female doing weight-bearing exercise or resistance training which loads the skeleton, these activities promoting osteogenesis will be negated if you are not ovulating and producing adequate oestrogens. The female athlete triad composed of disordered eating, amenorrhoea and low BMD was originally described by Drinkwater in 1984. However, once pathological states causing amenorrhoea have been excluded, in medical terms the female athlete triad did not necessarily constitute a disease state requiring intervention, rather subset of the “normal population”.
How significant is having low BMD compared to the age-matched population during your 20s? Could this even be viewed as a reversible adaptation to training, reflected in site specific differences in BMD according to sport? After all, when female athletes retire with decreased training “stress” and more “relaxed” diet, menses often resume and therefore does BMD also improve? This was the question I sought to answer in my study on 57 premenopausal retired professional dancers. Even with return of menses, if these athletes had experienced previous amenorrhoea of more than 6 month duration, then bone loss was irrecoverable. Current low BMD was also correlated to lowest body weight (independent of amenorrhoea) during dance career and later age of menarche. There did not appear to be any protective effect of being on the oral contraceptive pill. Constructing a model of BMD using multiple regression 33.6% of total variation in z (age matched) score for BMD at lumbar spine was accounted for by duration of amenorrhea, age at menarche and lowest body weight during dance career. So “athletic” hypothalamic amenorrhea rather than being a reversible, adaptive response has long term, irreversible effects on BMD.
Apart from bone metabolism, what other systems are impacted by mismatch of energy intake and expenditure in overtly healthy athletes? Are the endocrine and metabolic systems in male athletes also affected by subtle imbalances in training energy expenditure and dietary intake? What about young athletes? In my next blog I will explore the rationale behind the original female athlete triad now being described as part of Relative Energy Deficiency in sports (RED-S). The implications for current health and sports performance, as well as long term health in both adult men and women and young athletes.
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Keay N. Bone mineral density in professional female dancers. IOC World Congress on Sports Sciences. October 1997.
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Keay N, A study of Dancers, Periods and Osteoporosis, Dance Gazette, Issue 3, 1996, 47
Fit to Dance? Report of National inquiry into dancers’ health
Fit but fragile. National Osteoporosis Society
Your body your risk. Dance UK