Tag: female athlete triad

Sports Endocrinology

25 March 2017

SportsEndocrinologyWordCloud

The Endocrine system comprises various glands distributed throughout the body that secrete hormones to circulate in the blood stream. These chemical messengers, have effects on a vast range of tissue types, organs and therefore regulate metabolic and physiological processes occurring in systems throughout the body.

The various hormones produced by the Endocrine system do not work in isolation; they have interactive network effects. The magnitude of influence of a hormone is largely determined by its circulating concentration. This in turn is regulated by feedback loops. For example, too much circulating hormone will have negative feedback effect causing the control-releasing system to down regulate, which will in turn bring the level of the circulating hormone back into range. Ovulation in the menstrual cycle is a rare example of a process induced by positive hormonal feedback.

In the control system of hormone release, there are interactions with other inputs in addition to the circulating concentration of the hormone. The hypothalamus (gland in the brain) is a key gateway in the neuro-endocrine system, coordinating inputs from many sources to regulate output of the pituitary gland, which produces the major stimulating hormones to act on the Endocrine glands throughout the body.

growthhormone

The Endocrine system displays complex dynamics. There are temporal variations in secretion of hormones both in the long term during an individual’s lifetime and on shorter timescales, as seen in the diurnal variation of some hormones such as cortisol, displaying a circadian rhythm of secretion. The most fascinating and complex control system is found in the hypothalamic-pituitary-ovarian axis. Variation in both frequency and amplitude of gonadotrophin releasing factor (GnRH) secretion from the hypothalamus dictates initiation of menarche and the subsequent distinct pattern of cyclical patterns of the sex steroids, oestrogen and progesterone.

So what have the Endocrine system and hormone production got to do with athletes and sport performance?

  1. Exercise training stimulates release of certain hormones that support favourable adaptive changes. For example, exercise is a major stimulus of growth hormone, whose action positively affects body composition in terms of lean mass, bone density and reduction of visceral fat.
  2. Disruption of hormones secreted from the Endocrine system can impair sport performance and have potential long term adverse health risks for athletes. This picture is seen in the female athlete triad (disordered eating, amenorrhoea and low bone mineral density) and relative energy deficiency in sport (RED-S) with multi-system effects. In this situation there is a mismatch between dietary energy intake (including diet quality) and energy expenditure through training. The net result is a shift to an energy saving mode in the Endocrine system, which impedes both improvement in sport performance and health. RED-S should certainly be considered among the potential causes of sport underperformance, suboptimal health and recurrent injury,  with appropriate medical support being provided.
  3. Caution! Athletic hypothalamic amenorrhoea, as seen in female athletes (in female athlete triad and RED-S) is a diagnosis of exclusion. Other causes of secondary amenorrhoea (cessation of periods >6 months) should be excluded such as pregnancy, polycystic ovary syndrome (PCOS), prolactinoma, ovarian failure and primary thyroid dysfunction.
  4. Unfortunately the beneficial effects of some hormones on sport performance are misused in the case of doping with growth hormone, erythropoeitin (EPO) and anabolic steroids. Excess administered exogenous hormones not only disrupt the normal control feedback loops, but have very serious health risks, which are seen in disease states of excess endogenous hormone secretion.

So the Endocrine system and the circulating hormones are key players not only in supporting health, but in determining sport performance in athletes.

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

Sport Performance and RED-S, insights from recent Annual Sport and Exercise Medicine and Innovations in Sport and Exercise Nutrition Conferences Dr N. Keay, British Journal of Sports Medicine 17/3/17

Teaching module on RED-S for British Association of Sport and Exercise Medicine as CPD for Sports Physicians

Optimal Health: Including Female Athletes! Part 1 – Bones Dr N. Keay, British Journal of Sport Medicine 26/3/17

Optimal Health: Including Male Athletes! Part 2 – REDs 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 13/4/17

Optimal health: for all athletes! Part 4 Mechanisms Dr N. Keay, British Association of Sport and Exercise Medicine 13/4/17

Enhancing sport performance: part 1 Dr N. Keay, British Association of Sport and Exercise Medicine

Enhancing sports performance: part 3

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

Sleep for health and sports performance Dr N. Keay, British Journal of Sport Medicine

Balance of recovery and adaptation for sports performance Dr N. Keay, British Association of Sport and Exercise Medicine

Clusters of athletes Dr N. Keay, British Association of Sport and Exercise Medicine

Inflammation: why and how much? Dr N. Keay, British Association of Sport and Exercise Medicine

Fatigue, Sport Performance and Hormones…Dr N. Keay, British Journal of Sport Medicine

Keay N, Logobardi S, Ehrnborg C, Cittadini A, Rosen T, Healy ML, Dall R, Bassett E, Pentecost C, Powrie J, Boroujerdi M, Jorgensen JOL, Sacca L. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sport: a double blind, placebo controlled study. Journal of Endocrinology and Metabolism. 85 (4) 1505-1512. 2000.

Wallace J, Cuneo R, Keay N, Sonksen P. Responses of markers of bone and collagen turover to exercise, growth hormone (GH) administration and GH withdrawal in trained adult males. Journal of Endocrinology and Metabolism 2000. 85 (1): 124-33.

Keay N. The effects of growth hormone misuse/abuse. Use and abuse of hormonal agents: Sport 1999. Vol 7, no 3, 11-12.

Wallace J, Cuneo R, Baxter R, Orskov H, Keay N, Sonksen P. Responses of the growth hormone (GH) and insulin-like factor axis to exercise,GH administration and GH withdrawal in trained adult males: a potential test for GH abuse in sport. Journal of Endocrinology and Metabolism 1999. 84 (10): 3591-601.

Keay N, Logobardi S, Ehrnborg C, Cittadini A, Rosen T, Healy ML, Dall R, Bassett E, Pentecost C, Powrie J, Boroujerdi M, Jorgensen JOL, Sacca L. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential usefulness as in the detection of GH abuse in sport: a double blind, placebo controlled study. Endocrine Society Conference 1999.

Wallace J, Cuneo R, Keay N. Bone markers and growth hormone abuse in athletes. Growth hormone and IGF Research, vol 8: 4: 348.

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.

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.

Keay N, Fogelman I, Blake G. Bone mineral density in professional female dancers. British Journal of Sports Medicine, vol 31 no2, 143-7, June 1997.

Keay N. Bone mineral density in professional female dancers. IOC World Congress on Sports Sciences. October 1997.

Keay N, Bone Mineral Density in Professional Female Dancers, Journal of Endocrinology, November 1996, volume 151, supplement p5.

Optimal health: for all athletes! Part 4 Mechanisms

17 January 2017

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

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

9 January 2017

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As discussed in my previous blog Optimal health: including female athletes! Part 1 Bones, the female athlete triad is well described since 1984. The triad comprises disordered eating, amenorrhoea and reduced bone mineral density (BMD). What was uncertain was whether this was a reversible training effect. My study of professional retired pre-menopausal female dancers demonstrated that such bone loss is irreversible, despite resumption of menses. Furthermore, low body weight, independent of amenorrhoea, causes BMD loss. A few female athletes in my subsequent longitudinal study of professional dancers in the English National Ballet company were “robust” and continued to menstruate, in spite of low body weight. However this could have involved anovulatory cycles and therefore low oestrogen. One parameter cannot be considered in isolation.

Furthermore, it has become apparent that the female athlete triad is just part of a much larger picture, known as Relative Energy Deficiency in sport (RED-S). The fundamental issue is that of energy deficiency caused by a mismatch of energy intake and energy expenditure from exercise training. Quality of diet, including micronutrients is also important.

If you are a male athlete, you may be thinking that this is all just a problem for female counterparts? No. Male athletes can also develop RED-S, especially in sports where low body weight confers a sport performance advantage, for example long-distance runners and road cyclists (especially climbers). In a fascinating lecture, Professor Jorum Sundgot-Borgen from the Department of Sport Medicine, at the Norwegian School of Sport and Exercise Science, described the occurrence in male ski jumpers.

This energy deficient state in RED-S in both female and male athletes produces a cascade, network effect on multiple systems: immune, cardiovascular, endocrine, metabolic and haematological effects. Clearly suboptimal functioning in these key areas has implications for current physical and psychological health of athletes and therefore their sport performance. The psychological element is of note as this may be both cause and effect of RED-S. After all in order to be a successful, especially in sport, a high level of motivation, bordering on obsession, is required. Although athletes with RED-S may not fall into a defined clinical disease state, they demonstrate a subclinical condition that impacts health. Performance implications include decreased training response with reduced endurance, muscle strength and glycogen storage, alongside an increased risk of injury, probably due to impaired adaptive response to training and a decrease in co-ordination and concentration. Psychological sequelae include depression and irritability.

Some features of RED-S may be lead to irreversible health issues in the future, as seen in the case of athletic hypothalamic amenorrhoea in female athletes with permanent loss of BMD. In both male and female athletes low energy density diet relative to energy expenditure with training results in low levels of insulin like growth factor 1 (IGF-1) and sex steroid hormones which impair not only sport performance but bone microarchitecture and mineralisation. Although hypothalamic suppression in females is manifest by lack of menstruation, there is no such obvious clinical sign in males, who may nevertheless also be experiencing suppression of the hypothalamic-pituitary-gonadal axis. It has been shown that oestradiol is the key sex steroid hormone in promoting bone mineralisation: for both male and female. In males testosterone is aromatised to oestradiol which in turn acts on bone. As the same mechanisms are involved in the aetiology and effects of RED-S, then the long term consequences will most likely be the same for both female and male athletes.

In my next blog I will explore the consequences of RED-S in young athletes and delve into the Endocrine mechanisms involved in the aetiology and multi-system outcomes for male and female athletes of all ages.

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

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

Keay N, Fogelman I, Blake G. Bone mineral density in professional female dancers. British Journal of Sports Medicine, vol 31 no2, 143-7, June 1997.

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

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.

Margo Mountjoy, IOC Medical Commission Games Group. Relative Energy Deficiency in Sport. Aspetar Sports Medicine Journal.

Optimal health: including female athletes! Part 1 Bones

6 January 2017

webmd_rm_photo_of_porous_bonesIt 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.

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

Keay N, Fogelman I, Blake G. Bone mineral density in professional female dancers. British Journal of Sports Medicine, vol 31 no2, 143-7, June 1997.

Keay N. Bone mineral density in professional female dancers. IOC World Congress on Sports Sciences. October 1997.

Keay N, Bone Mineral Density in Professional Female Dancers, Journal of Endocrinology, November 1996, volume 151, supplement p5.

Keay N, Bone Mineral Density in Female Dancers, abstract Clinical Science, Volume 91, no1, July 1996, 20p.

Keay N, Dancers, Periods and Osteoporosis, Dancing Times, September 1995, 1187-1189

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

From population based norms to personalised medicine: Health, Fitness, Sports Performance British Journal of Sport Medicine 22/2/17

Optimal Health: Including Male Athletes! Part 2 – REDs Dr N. Keay, British Association Sport and Exercise Medicine

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

Optimal health: for all athletes! Part 4 Mechanisms Dr N. Keay, British Association Sport and Exercise Medicine