Fatigue, Sport Performance and Hormones…

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?sleep

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.

Adrenal woes

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.

Endocrine system interactions

SportsEndocrinologyWordCloud

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….

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

References

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

Relative Energy Deficiency in Sport CPD module British Association of Sport and Exercise Medicine 2017

Sleep for health and sports performance British Journal of Sport Medicine 2017

Inflammation: why and how much? British Association of Sport and Exercise Medicine 2017

Clusters of athletes British Association of Sport and Exercise Medicine 2017

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 2017

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

Optimal health: for all athletes! Part 4 Mechanisms

As described in previous blogs, the female athlete triad (disordered eating, amenorrhoea, low bone mineral density) is part of Relative Energy Deficiency in sports (RED-S). RED-S has multi-system effects and can affect both female and male athletes together with young athletes. The fundamental issue is a mismatch of energy availability and energy expenditure through exercise training. As described in previous blogs this situation leads to a range of adverse effects on both health and sports performance. I have tried to unravel the mechanisms involved. Please note the diagram below is simplified view: I have only included selected major neuroendocrine control systems.

REDs

Low energy availability is an example of a metabolic stressor. Other sources of stress in an athlete will be training load and possibly inadequate sleep. These physiological and psychological stressors input into the neuroendocrine system via the hypothalamus. Low plasma glucose concentrations stimulates release of glucagon and suppression of the antagonist hormone insulin from the pancreas. This causes mobilisation of glycogen stores and fat deposits. Feedback of this metabolic situation to the hypothalamus, in the short term is via low blood glucose and insulin levels and in longer term via low levels of leptin from reduced fat reserves.

A critical body weight and threshold body fat percentage was proposed as a requirement for menarche and subsequent regular menstruation by Rose Frisch in 1984. To explain the mechanism behind this observation, a peptide hormone leptin is secreted by adipose tissue which acts on the hypothalamus. Leptin is one of the hormones responsible for enabling the episodic, pulsatile release of gonadotrophin releasing hormone (GnRH) which is key in the onset of puberty, menarche in girls and subsequent menstrual cycles. In my 3 year longitudinal study of 87 pre and post-pubertal girls, those in the Ballet stream had lowest body fat and leptin levels associated with delayed menarche and low bone mineral density (BMD) compared to musical theatre and control girls. Other elements of body composition also play a part as athletes tend to have higher lean mass to fat mass ratio than non-active population and energy intake of 45 KCal/Kg lean mass is thought to be required for regular menstruation.

Suppression of GnRH pulsatility, results in low secretion rates of pituitary trophic factors LH and FSH which are responsible for regulation of sex steroid production by the gonads. In the case of females this manifests as menstrual disruption with associated anovulation resulting in low levels of oestradiol. In males this suppression of the hypothamlamic-pituitary-gonadal axis results in low testosterone production. In males testosterone is aromatised to oestradiol which acts on bone to stimulate bone mineralisation. Low energy availability is an independent factor of impaired bone health due to decreased insulin like growth factor 1 (IGF-1) concentrations. Low body weight was found to be an independent predictor of BMD in my study of 57 retired pre-menopausal professional dancers. Hence low BMD is seen in both male and female athletes with RED-S. Low age matched BMD in athletes is of concern as this increases risk of stress fracture.  In long term suboptimal BMD is irrecoverable even if normal function of hypothamlamic-pituitary-gonadal function is restored, as demonstrated in my study of retired professional dancers. In young athletes RED-S could result in suboptimal peak bone mass (PBM) and associated impaired bone microstructure. Not an ideal situation if RED-S continues into adulthood.

Another consequence of metabolic, physiological and psychological stressor input to the hypothalamus is suppression of the secretion of thyroid hormones, including the tissue conversion of T4 to the more active T3. Athletes may display a variation of “non-thyroidal illness/sick euthyroid” where both TSH and T4 and T3 are in low normal range. Thyroid hormone receptors are expressed in virtually all tissues which explains the extensive effects of suboptimal levels of T4 and T3 in RED-S including on physiology and metabolism.

In contrast, a neuroendocrine control axis that is activated in RED-S is the hypothalamic-pituitary-adrenal axis. In this axis, stressors increase the amplitude of the pulsatile secretion of CRH, which in turn increases the release of ACTH and consequently cortisol secretion from the adrenal cortex. Elevated cortisol suppresses immunity and increases risk of infection. Long term cortisol elevation also impairs the other hormone axes: growth hormone, thyroid and reproductive. In other words the stress response in RED-S amplifies the suppression of key hormones both directly and indirectly via endocrine network interactions.

The original female athlete triad is part of RED-S which can involve male and female athletes of all ages. There are a range of interacting endocrine systems responsible for the multi-system effects seen in RED-S. These effects can impact on current and future health and sports performance.

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

References

Teaching module on RED-S for BASEM as CPD for Sports Physicians

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

Optimal health: especially young athletes! Part 3 Consequences of Relative Energy Deficiency in sports Dr N. Keay, British Association of Sport and Exercise Medicine

Keay N, Fogelman I, Blake G. Effects of dance training on development,endocrine status and bone mineral density in young girls. Current Research in Osteoporosis and bone mineral measurement 103, June 1998.

Jenkins P, Taylor L, Keay N. Decreased serum leptin levels in females dancers are affected by menstrual status. Annual Meeting of the Endocrine Society. June 1998.

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

Keay N, Effects of dance training on development, endocrine status and bone mineral density in young girls, Journal of Endocrinology, November 1997, vol 155, OC15.

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.

Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, Meyer N, Sherman R, Steffen K, Budgett R, Ljungqvist A. The IOC consensus statement: beyond the Female Athlete Triad-Relative Energy Deficiency in Sport (RED-S).Br J Sports Med. 2014 Apr;48(7):491-7.

“Subclinical hypothydroidism in athletes”. Lecture by Dr Kristeien Boelaert at BASEM Spring Conference 2014 on the Fatigued Athlete

From population based norms to personalised medicine: Health, Fitness, Sports Performance Dr N. Keay, British Journal of Sport Medicine