Hormone Knowledge is Power

Hormones are the directors of health, enabling us to reach our personal full potential. To unlock the power of hormones and harness our hormone networks, we need to be empowered with understanding. This was the motivation for my book “Hormones, health and Human Potential: A guide to understanding your hormones to optimise your health and performance

I was one of the panel discussing hormone power at Bloomfest last week. I started by suggesting that if you are ever labelled as being “hormonal”, take this as a compliment. After all, Horme is the goddess of action and energy. We discussed how to navigate the lifetime female hormone odyssey

Female Hormone Choreography

Hormone networks are complex. Out of all the networks, those of the female hormones is the most intricate. A beautiful interactive dance of hormones occurs every menstrual cycle, following characteristic choreography. However, this hormone dance will be personal to each woman, with subtleties in timing, hormone levels and crucially individual biological response. This is why knowledge is power when it comes to female hormones. Tuning into your personal variation of hormones in terms of how you feel, takes away the mystery. This empowers you to be proactive and work with your hormones, not against them. Periods are the barometer of internal hormone health and a free monthly medical check. I mentioned the potential flash points of the menstrual cycle in terms of menstruation and the luteal phase (occurring after ovulation, in the 2 weeks or so before menstruation) and practical strategies to put in place. This area is discussed in detail in Act 1, Scene 5XX “Of Mice and Men….and Women”.

Hormonal Contraception

Hormonal contraception is often an area of confusion. It is every woman’s choice regarding her personal choice of contraception. However, in order to make an informed choice about the most suitable form, it is really important to clarify the different types available. Non hormonal options, barrier methods include condoms and the copper coil. Hormonal contraception can be divided into combined (synthetic oestradiol and progesterone) and synthetic progesterone-only options. Incidentally a hormonal contraception was trialled men, but they didn’t not like the side effects. As I explain in my book, it is really important that women (and their doctors) know that combined hormonal contraception (eg combined oral contraceptive pill) and certain types of synthetic progesterone-only options, suppress the internal production of female hormones across the board. This is why these medications are very effective contraception. This suppression of internal female hormones can be very useful for women with endometriosis and polycystic ovary syndrome (PCOS) which are conditions effectively fuelled by female hormones. However, this suppression of female hormones is absolutely not suitable for women whose periods have stopped. After writing to NICE, I am pleased to report the guidelines are now updated to advise against giving hormonal contraception to women who are not experiencing periods.

Hormone Injury

Unbalanced external lifestyle choices, rather than harnessing hormones, can cause female “hormone injury”. In my book Act 1, Scene 10 “In the Red” goes into the detail of how an imbalance in behaviours around exercise and nutrition can derail female hormone choreography. I outline practical advice of how to recover from this type of “hormone injury” and what to do to restore and reboot hormone networks and return to full health.

Graduation to Menopause and beyond

Variation in female hormone choreography occurs over the longer time scale of a woman’s lifespan. Menopause is a hot topic. Although it is great to see this being discussed, I suggest we need a more positive narrative. I prefer to talk about the graduation to menopause, rather than a decline. This stage in a woman’s life is something I cover in depth in my book in Act 2 looking through the “The Seven Ages of Man and Woman”. In some cultures, being older and wiser is revered. Menopause is something that all women will experience during their life. A point in time when the ovaries retire in their production of hormones and release of eggs.

The graduation to menopause can be the most challenging. During the perimenopause the ovaries work on an unpredictable, part time basis. The female hormone choreography works smoothly in some cycles. Other cycles there will be a mistiming and confused choreography, causing some of the typical indicators of menopause. These include changes in cycle length and nature, temperature regulation issues, labile mood and brain fog being some of the most frequent. We discussed that probably the most helpful approach for women in the workplace is to facilitate discussions, sharing experiences and putting in place practical things that are helpful for the individual: for example, having a desk fan nearby, sitting near a window. From the medical support point of view, providing the facts and practical aspects of taking HRT is something that I am very pleased to be able to provide.

The quote from the Vice President of the Royal College of Obstetrics and Gynaecologists: “Treat women as individuals, not statistics” is something that resonates when it comes to discussing how to unlock and harness the power of female hormones, throughout each woman’s personal female hormone odyssey.

Reference

Hormones, Health and Human Potential: A guide to understanding your hormones to optimise your health and performance”

Hormones, Health and Human Potential

“Hormones, Health and Human Potential” explains how hormones play a crucial role in determining health. Hormone networks provide the feedback mechanism by which our lifestyle and behaviours enable us to reach our personal potential.

Introduction


Over 2,000 years ago Hippocrates advocated that the “safest way to health” was through “the right amount of nourishment and exercise” for “every individual”. As it turns out Hippocrates was way ahead of his time in articulating the principles of personalised and preventative medicine.

Hormones as the missing link to health


Although Hippocrates understood that lifestyle and behaviours are key to health, he did not know why. We now know that hormones are the key players in this vital role. Hormones are instigators in bringing our DNA to life by determining gene expression. Hormones direct the production of proteins, in the optimal amounts and at the right time. Hormones work as networks to maintain mental and physical health.

Lifestyle factors influencing health through hormones networks


Complex internal negative feedback loops between hormones and the biological variables that they regulate, enable homeostasis for good physiological function. Challenges to homeostasis, due to our interactions with the environment are detected by the hypothalamus, which manages hormone network response. In this way there is another layer of feedback loops between lifestyle behaviours and hormones.

Well-balance lifestyle behaviours, in terms of quantity and timing, support healthy hormone network function, leading us to the “safest way to health”. Conversely, circadian misalignment, where lifestyle choices conflict between internal biochronometers, can lead to hormone dysregulation found in conditions such as metabolic syndrome.

Harnessing hormones as preventative and supportive medicine


A good balance of lifestyle factors can harness hormones as a form of supportive and preventative medicine. This is particularly relevant for type 2 diabetes mellitus and metabolic syndrome. For women, where there are physiological changes in hormones, such as occurs at menopause, attendant symptoms and impacts on long term health can be mitigated by lifestyle as part of the management of menopause. For example, exercise has been shown to have a beneficial effect on temperature regulation, metabolism, body composition, bone health and reducing the risk of breast cancer.

Athlete performance mediated by hormones


Hormones mediate the positive adaptive changes due to exercise training. Understanding these mechanisms can benefit both athletes and patients .

Imbalances in behaviours causing hormone dysregulation


Too little exercise and excess nutrition can lead to hormone dysregulation, seen in metabolic syndrome and type 2 diabetes mellitus. On the other hand, too much of a “good thing” can also cause health and performance issues in exercisers. Relative energy deficiency in sport (RED-S) can occur in exercisers of all ages and levels, where there is either an unintentional or intentional mismatch between energy intake and energy demand. Consequent low energy availability causes hormone network disruption, which in the long-term results in adverse effects on both health and performance .

Conclusions


• Hormone network function plays an important role in mental and physical health
• Hormones are influenced by our lifestyle behaviours of exercise, nutrition and sleep
• The benefits of lifestyle behaviours are derived from the positive adaptive changes driven by hormones
• Imbalances in lifestyle behaviours can cause hormone disruption leading to adverse effects on health and exercise performance

References

Keay N. Health Hormones and Human Potential. Sequoia books. 2022

McCarthy O, Pitt J, Keay N et al Passing on the exercise baton: What can endocrine patients learn from elite athletes? Clinical Endocrinology 2022 96;(6):781-792

Keay N, Francis G Infographic. Energy availability: concept, control and consequences in relative energy deficiency in sport (RED-S) British Journal of Sports Medicine 2019;53:1310-1311.

New book

Hormones, Health and Human Potential

A guide to understanding your hormones to optimise your health and performance

Welcome to the world of hormones!

My book is now available to pre-order with 20% discount when you add “Nicky” at checkout. Publication date 28/10/22

Full details here

Hormones Health and Human Potential

Think Menopause

“Think Menopause” is at the core of the NHS England and Improvement (NHSEI) initiative to encourage healthcare professionals to consider perimenopause and menopause in all women over 40 years of age, who present with symptoms that could be explained by declining ovarian hormone production as the underlying cause.

Personalisation, personalisation, personalisation…
Last week at the British Menopause Society (BMS) conference there were a wealth of eminent speakers. All shared clinical and research experience and a passion for advancing healthcare provision for women in this age cohort. I was honoured that my abstract was selected for oral presentation in front of the large audience assembled for this conference. My presentation was on the novel approach of modelling female hormones over the menstrual cycle using artificial intelligence techniques, in order to personalise female hormone health. In fact, personalisation of care for women was one of the key messages of this conference.

Although individual women are different, all women share the need for personalised healthcare with tailored individual treatment plans. This approach is particularly relevant when it comes to perimenopause.

Think Perimenopause: the time of uncertainty
At the BMS conference, perimenopause was described as a time in a woman’s life where there is an information gap and uncertainty. Perimenopause is the transition from having regular periods, with associated characteristic fluctuations of female hormones over the menstrual cycle, to the situation of menopause. Menopause is defined as not having periods for 1 year. So, menopause is a retrospective diagnosis. The challenging thing about perimenopause for both women and healthcare professionals is that the typical symptoms of perimenopause are very diverse and could be due to a range of causes and co-morbidities. For example, the onset of irregular periods is one of the key clinical indicators of perimenopause. However, decreasing ovarian responsiveness and reduced hormone production is just one potential cause. With an increasing number of women taking regular exercise and becoming masters athletes, there is the possibility of low energy availability causing hypothalamic down regulation of ovarian hormone production. Conversely, an imbalance of behaviours featuring lack of exercise can lead to energy surplus which can impact hormone networks and regularity of periods. Women are also more likely than men to develop autoimmune conditions, such as that affecting thyroid hormone production, which can impact periods.

This diversity of symptoms, which could be attributable to a multitude of conditions, is why there is uncertainty about whether perimenopause is the underlying cause, particularly in women between 40 and 45 years of age. For this reason, the BMS and National Institute of Clinical Excellence (NICE) guidelines advise that blood testing is useful in distinguishing between potential causes in this age bracket. During my abstract presentation, I argued that this is where modelling female hormones in this age cohort could be particularly helpful as an “anomaly” detector. Essentially identifying in which direction and to what extent the hormone fluctuations of an individual woman deviate away from those hormone patterns found in women with fully functioning hormone networks. As with any clinical measurement, monitoring over time provides the most detailed insights. Furthermore, this approach removes the uncertainty of the perimenopause journey for women and healthcare professionals. Extending the clinical application of modelling a woman’s hormones over her lifespan would help personalise female hormone health and assist women navigate her individual hormone odyssey.

Personalising Menopause: Hormone Replacement Therapy (HRT)
Another area of personalisation of female hormone health that was discussed in depth at the BMS conference was the provision of choice and options when it comes to quality of life and maintaining health during the menopause years. After addressing lifestyle factors, hormone replacement therapy (HRT) improves both quality of life and reduces the risk of health issues in the long term such as cardiovascular disease (CVD) and osteoporosis. CVD is the main cause of death in menopausal women. Titrating the type and dose of HRT for the individual women is very important. Body identical HRT offers many advantages. This is HRT comprised of oestradiol and progesterone which are the identical molecular structure to those hormones that the ovaries produce. This is not to be confused with “bioidentical” HRT which are not advised by BMS as these forms of HRT are neither licensed nor regulated. Personalisation of HRT dose can be achieved with body identical HRT which is both licensed and regulated.

In terms of the route of the oestradiol component of HRT, transdermal options such as via patch or gel offer the advantage over oral forms by not increasing the risk of venous thrombo-embolic events. Furthermore, the transdermal route of oestradiol has a beneficial effect on metabolic health, in particular a favourable lipid profile and reactivity of arterial walls. Gel oestradiol provides the opportunity for small adjustments in dose.

Regarding the progesterone component of HRT, this is essential for all women who have not had a hysterectomy for endometrial protection. Preventing unopposed oestradiol making the endometrial lining very thick. Micronised progesterone is body identical and taken as a soft capsule. “Bioidentical” progesterone cream is not advised by the BMS as there is uncertainty about how well this is absorbed, jeopardising effective endometrial protection. Licensed, regulated body identical micronised progesterone has the advantage over other non-body identical forms of external progesterone in having the lowest androgenic effect and reduced side effect profile. Furthermore, it is the progesterone component of HRT that confers the low, but potential risk of breast cancer. Once again micronised progesterone has the advantage over other contenders with the lowest breast cancer risk. From a practical point of view, micronised progesterone has a mild hypnotic effect which is why it is advised to take in the evening. The advantage of helping sleep is a welcome benefit during menopause when sleep disruption can be problematic.

In conclusion, attending the BMS conference was inspiring. The key messages being to think about the possibility of perimenopause and menopause and to ensure personalisation of female health care to individual women.

Further discussion about the crucial role of hormones in health and practical ways to harness your hormones will be explored in my book on this topic, to be published 28/10/22
Hormones, Health and Human Potential: A guide to understanding your hormones to optimise your health and performance

References

British Menopause Society. Annual Conference 30 June- 1 July 2022. Menopause Care: Maintaining the Momentum https://thebms.org.uk/meeting/bms-31st-annual-scientific-conference/

Hamoda H, Moger S. Looking at HRT in Perspective. Helping women make informed choices. Editorial BMJ June 2022 BMJ 2022;377:o1425 http://dx.doi.org/10.1136/bmj.o1425

Perimenopause, perhaps?

We are all familiar with the binary result recorded doing a lateral flow test for COVID-19. You return a result which is negative or positive for COVID-19 antigen. The same principle applies for a pregnancy test where the early pregnancy hormone (beta human chorionic gonadotrophin) excreted in the urine will return either a positive or negative result.   

These are examples of clinical tests where a binary result is sufficient. This approach is not suitable where quantification is required. For example, blood glucose monitoring provides a value for blood glucose concentration which is crucial in determining the dose of insulin required. The other challenge is where the clinical situation you are trying to assess may have a variable course. For example, perimenopause.   

Perimenopause is the transition from having fully functioning female hormone networks, to menopause where the ovaries stop responding to hormone signals from the conductor of the hormone orchestra, the pituitary gland. This results in cessation of ovulation, drastic reduction of ovarian hormone production of oestradiol and progesterone and no further menstrual periods. The challenge for women is that this transition is not an on/off switch. Some menstrual cycles the ovaries may be working perfectly well, the female hormone network functioning beautifully with the hormones rising and falling in a biologically timed, co-ordinated manner. On the other hand, there may be some cycles where the ovaries are somewhat recalcitrant in their response to the control pituitary hormones, in particular follicle stimulating hormone (FSH). This is why consistently raised FSH over the cycle and over subsequent cycles can be a supportive piece of evidence for perimenopause. However, as outlined by the British Menopause Society, FSH is just one part of the picture when it comes to perimenopause.

The British Menopause Society are not in favour of performing an over-the-counter urine test for FSH as an indicator of transition to menopause[1]. In the first instance, this test returns a binary result of either high or low FSH. Although it is correct that high FSH in the cycle when not expected, can indicate reduced ovarian responsiveness, this is based on a quantified value from a blood test at a known time in the cycle. A one-off test showing a non-quantified “high” FSH level might simply reflect the rise before ovulation occurs, rather than a reduced ovarian response. As the timing of hormone release becomes more variable during perimenopause, this makes even quantified single time point FSH tests challenging to interpret. The urine test for FSH does not provide either quantification, or detail of timing.

The other major problem highlighted by the British Menopause Society is that any clinical test must be put in the clinical context of the individual. Perimenopause is characterised by change in the nature and regularity of menstrual periods and other symptoms. This is why interpretation of all clinical tests is performed by medical doctors who have received extensive clinical training. This can include specialised training from the British Menopause Society.

Ultimately, however accurate and specific a particular clinical test, the true value lies in the medical interpretation in the clinical context of the individual. This is especially important in the case of perimenopause where every woman has to be treated as an individual and a personalised approach to hormone health is vital[2]. This personalised approach to female hormone health has recently been developed employing artificial intelligence techniques used in other fields of medicine. This allows consideration of personal variation in cycle length, wellbeing metrics and laboratory analysed blood test results. From these personal inputs, combined with medical, mathematical and technological expertise, characterisation of the variation of the “full house” of female hormones over the cycle for an individual woman can be characterised. These personalised hormone curves can be compared to the variation of menstrual cycle hormones in women of reproductive age, known to be ovulating, with similar hormone timing[3]. An expert report system provides in depth medical explanation and advice[4].

When it comes to female hormones, as stated by the Vice President of the Royal College of Obstetrics and Gynaecology, it is crucial to “treat women as individuals, not statistics”[5]. Although the transition to menopause is normal physiology, every woman will follow a different path and experience this is in a different way. Providing personalised information and advice will empower women to make informed decisions for their quality of life and long-term health.

“Hormones, Health and Human Potential” is the title of the book I have written, which will be published in Autumn 2022 and will explore further the connections between hormones, health and lifestyle across the lifespan.

References


[1] BMS statement on over-the-counter menopause tests British Menopause Society10 June 2022

[2] Hamoda H, Mukherjee A, Morris E et al. Optimising the menopause transition: Joint position statement by the British Menopause Society, Royal College of Obstetricians and Gynaecologists and Society for Endocrinology on best practice recommendations for the care of women experiencing the menopause. Post Reproductive Health 2022, Vol. 0(0) 1–2 DOI: 10.1177/20533691221104882

[3] Keay N. Female Hormones https://nickykeayfitness.com/female-hormones/

[4] Keay N. Delivering Personalised Female Hormone Health through an Expert Report System https://nickykeayfitness.com/2021/08/22/delivering-personalised-female-hormone-health-through-an-expert-report-system/

[5] Rymer J, Brian K, Regan L. HRT and breast cancer risk British Medical Journal 2019; 367 doi: https://doi.org/10.1136/bmj.l5928 

Female Hormone Health part 2

Why have my periods stopped?

Periods

Periods, also known as menstruation, are bleeds that occur roughly every lunar month when the lining of the uterus (endometrial lining) is shed. Periods are a result of the fluctuation of menstrual cycle hormones. Oestradiol builds up the endometrial lining and progesterone maintains this. If fertilisation of the egg and implantation of the embryo does not occur, progesterone levels will drop and the endometrial lining will shed. So, periods are a barometer of healthy internal hormone networks. All women of reproductive age, not taking hormonal contraception, and regardless of the amount of exercise undertaken, should experience periods[1].

Eumenorrhea is the name used where a woman is experiencing regular periods, occurring every 22 to 35 days. Polymenorrhoea is where periods occur less that 22 days apart. Oligomenorrhoea is where a woman has less than 9 periods per calendar year. Amenorrhoea is a situation of lack of periods. This can be primary amenorrhoea, where periods have not established by 16 years of age. Or secondary amenorrhoea, where periods have stopped for 6 months or more, in a previously regularly menstruating woman. As regular periods are a sign of healthy internal hormones, women who are not eumenorrheic need to seek answers.

Amenorrhoea is a clinical sign

Amenorrhoea is a clinical sign, not a diagnosis. It is really important to identify the underlying cause of amenorrhoea. Depending on the aetiology of amenorrhoea, oestrogen levels will not necessarily be low. So as a starting point it is essential to establish the cause of amenorrhoea to direct appropriate management.

The figure shows the pathway to follow to identify the cause of amenorrhoea.

Physiological amenorrhoea with high oestradiol In any woman presenting with amenorrhoea, pregnancy, a physiological cause of amenorrhoea, must be excluded. A pregnancy test measures beta human chorionic gonadotrophin (beta hCG) which is secreted by the embryo.

After excluding pregnancy, the cause of amenorrhoea is identified based on follicle stimulating (FSH) and luteinising hormone (LH) levels in keeping with world health organisation (WHO) criteria. Investigations to identify the underlying cause of amenorrhoea are outlined in the updated National Institute for Health and Care Excellence (NICE) in the Clinical Knowledge Summaries (CKS)[2], and summarised in the figure.


Ovarian causes of amenorrhoea Raised FSH and LH in the presence of low oestrogen suggests primary ovarian insufficiency (POI) in women who are under 40 years of age. The British Menopause Society advise that HRT is more beneficial in improving bone health and cardiovascular markers compared to the combined oral contraceptive pill (COCP) containing ethynyl oestradiol. HRT, unlike the COCP, offers the possibility to deliver body identical oestradiol and progesterone and this optimal form of HRT is available in licensed, regulated forms on the NHS. Barrier methods of contraception are advisable if pregnancy is not sought [3].

Where FSH and LH are not unduly raised and oestrogen is in range, or raised; in the presence of elevated testosterone, this is suggestive of polycystic ovary syndrome (PCOS). Supplementary tests such as dehydroepiandrosterone (DHEA) and 17-hydroxy progesterone

may be considered to exclude congenital adrenal hyperplasia (CAH). In the presence of amenorrhoea, an ultrasound is advisable to check endometrial lining thickness. If this is thickened a “progesterone challenge test” may be considered to induce shedding of the endometrial lining

Hypothalamic-pituitary causes of amenorrhoea Where FSH and LH are low range, together with low range oestradiol, prolactin should be scrutinised to exclude prolactinoma as the cause of hypothalamic amenorrhoea (HA).

Before settling on a diagnosis of functional hypothalamic amenorrhoea (FHA), other endocrine causes of amenorrhea should be considered, such as thyroid disorders. FHA is a diagnosis of exclusion [4].

Functional Hypothalamic Amenorrhea (FHA)

FHA is where amenorrhoea is due to down regulation of the hypothalamic control of menstrual periods. FHA can be a presenting symptom of relative energy deficiency in sport (RED-S) [5]. The good news is that being functional, FHA is a reversible situation. That is not to say that this is an easy situation to reverse. Changes in behaviours around exercise, nutrition and recovery will be needed [6].

The updated NICE guidelines for the management of bone health in the situation of amenorrhoea with low oestrogen advise hormone replacement therapy (HRT) rather than the combined oral contraceptive pill (COCP) [2]. This update is particularly relevant for female exercisers, athlete and dancers presenting with FHA where the underlying cause is RED-S. Pharmaceutical bone protection with transdermal HRT is in keeping with Endocrine Society guidelines [7] and the International Olympic Committee (IOC) consensus statements on RED-S. The British Association of Sports and Exercise Medicine has further information on the website https://health4performance.basem.co.uk/healthcare-professionals/

Conclusions

Amenorrhoea is a symptom, not a diagnosis. It is crucial to identify the underlying cause for amenorrhea in any woman presenting with absent periods. Female hormones are not just about reproduction. These hormones support many aspects of physical and mental health. Oestrogen is the protagonist when it comes to mediating the multisystem beneficial effects on the musculoskeletal, cardiovascular and neurological systems. So, where amenorrhoea is accompanied by low levels of oestrogen it is essential to address the underlying cause and consider providing temporising oestrogen replacement in line with updated NICE guidelines, discussed in previous blog https://nickykeayfitness.com/2022/05/04/female-hormone-health/


References


1 Keay N. What’s so good about Menstrual Cycles? British Journal of Sports Medicine 2019 https://blogs.bmj.com/bjsm/2019/02/08/whats-so-good-about-menstrual-cycles/

2 National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summaries (CKS) Managing risk of osteoporosis (primary and secondary amenorrhoea) 2022 https://cks.nice.org.uk/topics/amenorrhoea/management/secondary-amenorrhoea/#managing-osteoporosis-risk

3 British Menopause Society https://thebms.org.uk/publications/consensus-statements/premature-ovarian-insufficiency/

 4 McCarthy O, Pitt J, Keay N et al Passing on the exercise baton: what can endocrine patients learn from elite athletes? Clinical Endocrinology 2022 https://onlinelibrary.wiley.com/doi/10.1111/cen.14683

5 Mountjoy M, Sundgot-Borgen JK, Burke LM, et al IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update British Journal of Sports Medicine 2018;52:687-697.

6 Keay N. Returning to Sport/Dance restoring Energy Availability in RED-S? British Journal of Sports Medicine 2019 https://blogs.bmj.com/bjsm/2019/03/26/returning-to-sport-dance-restoring-energy-availability-in-red-s/

7 Gordon C, Ackerman K, Berga S et al, Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, 2017, 102 (5): 1413–1439, https://doi.org/10.1210/jc.2017-00131


Female Hormone Health part 1

NICE guideline update 2022

What’s new for female hormone health?

At the start of the year, the National Institute for Health and Care Excellence (NICE) in the Clinical Knowledge Summaries (CKS) updated the guidelines for the management of bone health in the situation of amenorrhoea (lack of periods) with low oestrogen. Hormone replacement therapy (HRT) is advised, rather than the combined oral contraceptive pill (COCP)[[1]]. This update is particularly relevant for female exercisers, athlete and dancers presenting with functional hypothalamic amenorrhoea (FHA) where the underlying cause is relative energy deficiency in sport (RED-S)[[2]]. Pharmaceutical bone protection with transdermal HRT is in keeping with Endocrine Society guidelines[[3]] and the International Olympic Committee (IOC) consensus statements on RED-S[2].  

Importance of female hormone health

Why is this update so important? Female hormones are not just about reproduction. These hormones support many aspects of physical and mental health. Oestrogen is the protagonist when it comes to mediating the multisystem beneficial effects on the musculoskeletal, cardiovascular and neurological systems[[4]]. So, where amenorrhoea is accompanied by low levels of oestrogen it is essential to address the underlying cause and consider providing temporising oestrogen replacement. The COCP does neither.

Combined oral contraceptive pill: the good, bad and the ugly

It is every woman’s personal choice what form of contraception she chooses. The COCP is an effective hormonal contraception which is also often used to manage medical conditions where supressing female hormones can help alleviate symptoms. For example, in PCOS, the COCP lowers testosterone and in endometriosis where fluctuation of female hormones over the menstrual cycle can trigger symptoms, supressing these hormones with the COCP can reduce pain.

On the other hand, suppression of female hormone production is not always advisable. The mechanism of action of COCP is the suppression of the hypothalamic-pituitary axis. This can be seen on blood testing where low levels of follicle stimulating hormone (FSH), luteinising hormone (LH) oestradiol and progesterone are found. This is also precisely the pattern seen in FHA. In other words, the COCP acts as a masking agent of internal hormone function, reinforcing and maintaining the hormone suppression pattern of FHA. This is shown in the figure of suppressed of endogenous female hormones due to hypothalamic suppression found in FHA and from hormonal contraception use (COCP and also certain progestone contraception preparations).

The COCP induces a withdrawal bleed which may give a psychological boost to the athlete with FHA and her prescribing doctor. However, this is not a menstrual period, as it is not the result of internal hormone function. Although exogenous non-body identical oestrogen, ethynyl oestradiol, found in most forms of COCP may “fool” the hypothalamus-pituitary and the endometrium, this is not the case either for the specific assay for endogenous 17β-oestradiol, nor for bone. In FHA, the COCP does not have any bone protective effect compared to HRT which does have a beneficial effect on bone health[[5]]. This is also the case for women with amenorrhoea due to POI (primary ovarian insufficiency) where the British Menopause Society advise that HRT is more beneficial in improving bone health and cardiovascular markers compared to the COCP containing ethynyl oestradiol[[6]].

HRT to the rescue

In terms of the type of HRT, the most favourable is transdermal oestradiol (patch or gel) with cyclical body identical micronised progesterone. The transdermal route of 17β-oestradiol avoids the first pass effect of being metabolised in the liver. Furthermore, the purpose of HRT is replacement to physiological levels, rather than suppression of internal production with the COCP. However, women should be advised that HRT is not a contraceptive and so non-hormonal, barrier methods should be used if contraception is required[3].

Female hormone health in RED-S

It is also important to discuss with the athlete experiencing FHA due to RED-S, that HRT is a temporising step to protect bone health. It is essential to strive to retore energy availability and endocrine function for long term health and athletic performance. FHA is reversible with appropriate behavioural changes around nutrition and training load. This will often require medical, dietetic and psychological support, with contributions from coach and physiotherapist where indicated[[7]].

Amenorrhoea is a clinical sign

Another important point is that amenorrhoea is a clinical sign, not a diagnosis. Amenorrhoea is a situation of lack of periods. This can be primary amenorrhoea, where periods have not established by 16 years of age. Or secondary amenorrhoea, where periods have stopped for 6 months or more, in a previously regularly menstruating woman. Depending on the cause of amenorrhoea, oestrogen levels will not necessarily be low. So as a starting point it is essential to establish the cause of amenorrhoea to direct appropriate management. We will discuss in next blog https://nickykeayfitness.com/2022/05/15/female-hormone-health-2/

Conclusions

Female hormone disruption due to RED-S, can produce adverse effects on health and performance. Therefore, early identification of those individuals at risk is an important prevention strategy[[8]]. New approaches including application of artificial intelligence techniques to model female hormones are being explored[[9]]. For a female athlete presenting with amenorrhoea, directed investigation is required to confirm FHA. The priority is to provide the athlete with support to change behaviours to restore hormone health. For bone protection during this restorative process, updated NICE guidelines advise treatment with HRT.

References


[1] National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summaries (CKS) Managing risk of osteoporosis (primary and secondary amenorrhoea) 2022 https://cks.nice.org.uk/topics/amenorrhoea/management/secondary-amenorrhoea/#managing-osteoporosis-risk

[2] Mountjoy M, Sundgot-Borgen JK, Burke LM, et al IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update British Journal of Sports Medicine 2018;52:687-697.

[3] Gordon C, Ackerman K, Berga S et al, Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, 2017, 102 (5): 1413–1439, https://doi.org/10.1210/jc.2017-00131

[4] Keay N. What’s so good about Menstrual Cycles? British Journal of Sports Medicine 2019 https://blogs.bmj.com/bjsm/2019/02/08/whats-so-good-about-menstrual-cycles/

[5] Ackerman KE, Singhal V, Baskaran C, et al Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial British Journal of Sports Medicine 2019;53:229-236.

[6] British Menopause Society https://thebms.org.uk/publications/consensus-statements/premature-ovarian-insufficiency/

[7] Keay N. Returning to Sport/Dance restoring Energy Availability in RED-S? British Journal of Sports Medicine 2019 https://blogs.bmj.com/bjsm/2019/03/26/returning-to-sport-dance-restoring-energy-availability-in-red-s/

[8] British Association of Sport and Exercise Medicine educational website on RED-S www.health4performance.co.uk

[9] Keay N. Hormone Intelligence for Female Dancers, Athletes and Exercisers British Journal of Sports Medicine 2019 https://blogs.bmj.com/bjsm/2021/06/28/hormone-intelligence-for-female-dancers-athletes-and-exercisers/

Dancing to your Full Potential?

Online Courses for Dancers, Teachers and Parents

Endorsed by British Association of Sport and Exercise Medicine

TRAINING AS A HIGH-PERFORMING FEMALE DANCER – TEAM

TRAINING AS A HIGH-PERFORMING FEMALE DANCER

Dance is a performance art form that is both athletically and mentally demanding. The success of young female dancers depends on their ability to manage these demands as their bodies develop. Dance-specific online courses for performers, teachers and parents can help young female dancers prepare for a rewarding future.

As a medical doctor, who is passionate about dance, I have created these courses to provide young female dancers with the latest professional-level training and medical performance strategies. The aim is for every dancer to achieve her personal best in a healthy and sustainable fashion.

Why do dancers need these courses?

These photographs show how the demands of dance have changed over two generations. On the left is my grandmother in her early 20s, during the 1920s. To the right is her granddaughter at about the same age in the 1980s. My grandmother is wearing a loose-fitting ballet costume and has a soft, romantic posture. Although she is en pointe, she has two feet on the ground. In contrast, 60 years later, I am wearing a tighter fitting, shorter tutu and I am balancing on one leg, en pointe, in a more athletic pose. This not to say that one style of dance is better than another or that I am a better dancer than my grandmother at the same age. Looking over my grandmother’s ballet books, the ballet steps have remained the same. I can understand and dance the enchainment (collection of steps) that she wrote down back in the 1920s. What has changed is how these steps are performed. Dancers now need to be more athletic, requiring greater physical demands. These physical demands require more intense training, balanced by attention to nutritional intake.

Similar changes have occurred in sport. Athletes take on heavier training loads, becoming “citius, altius, fortius”. The downside is that increased training, especially in younger age groups, has seen the emergence and recognition of relative energy deficiency on sport (RED-S)[1]. The female athlete triad was described in 1980s, where female athletes with insufficient energy intake to match training demands fell into a state of low energy availability, resulting in negative effects on menstrual function and bone health. In 2014, the International Olympic Committee published a consensus statement on RED-S. This broadened the spectrum beyond the female athlete triad, pointing out that the adverse consequences of low energy availability were not limited to female athletes, periods and bones. Low energy availability has negative consequences across a range aspect of mental and physical health. RED-S can affect men and women, across all levels of activity. Crucially, RED-S, unlike the female athlete triad, highlights the negative effects on performance.

How is this relevant to dancers?

Although the IOC mentions aesthetic sports in its description of RED-S, there is, nevertheless, a distinction between sport and dance at the organisational and cultural level. Evidence of relative energy deficiency in dance comes from a study we conducted in dancers worldwide[2]. Younger dancers are particularly susceptible, because the energy demand of dance training comes in addition to the concurrent high energy demands of growth and development. Puberty and adolescence can be challenging times of physical and psychological change. The demands of dance training can create a difficult balance of biopsychosocial factors[3].

Dancing provides joy and supports mental and physical health. These courses provide knowledge and understanding to help navigate this tricky period in a young dancer’s life, in order to reap to the wealth of benefits offered by dance.

What’s covered in the online dancer courses?

These courses are endorsed by the British Association of Sport and Exercise Medicine[4]. They provide dancers, teachers and parents with the latest professional-level training and medical performance strategies on how young female dancers can reach their full potential in dance.

The starting point is to explore the meaning of health and the fundamental physiology relevant to young female dancers. Discussion moves on to how to support optimal health for dance through nutrition, recovery and type of training, providing dancers with practical, actionable strategies. Top tips highlight what to watch out for to indicate that things are going well, as well as early warning signs that things might be out of balance. The online course also has a quiz and links to further resources. You can select a course for a group of dancers, teachers or parents or you can opt for an individual dancer course format. Online courses

References


[1] Keay N. 2018 UPDATE: Relative Energy Deficiency in Sport (RED-S) British Journal of Sports Medicine. https://blogs.bmj.com/bjsm/2018/05/30/2018-update-relative-energy-deficiency-in-sport-red-s/

[2] Keay N, Overseas A, Francis G Indicators and correlates of low energy availability in male and female dancers BMJ Open Sport & Exercise Medicine 2020;6:e000906. doi: 10.1136/bmjsem-2020-000906

[3] Keay N. Energy Availability in Dancers – and lessons for all sports British Journal of Sports Medicine. https://blogs.bmj.com/bjsm/2020/12/30/energy-availability-in-dancers/

[4] British Association of Sport and Exercise Medicine www.health4performance.co.uk

Delivering personalised female hormone health through an expert report system

I am passionate about helping women improve their wellbeing and quality of life through a better understanding of their personal female hormones. But every woman is different and it takes time for me to interpret and explain her results. It has been extremely exciting to work towards a solution that enables many more women to access my medical knowledge in a personalised female hormone health report

Read more about delivering personalised Female Hormone Health

For the past 30 years I have been working with many women who come asking questions about their female hormone health. These some of the questions often asked:

  • Am I entering the perimenopause? Should I consider HRT?
  • Am I making the best lifestyle choices for my personal hormone health?
  • How can I better understand the interaction between my hormones and my sports performance?

Women are absolutely right to be asking these important questions. The answers can help optimise physical and mental health. Women also know that lifestyle behaviour choices influence their health. The key message is that hormones are the mediators between our behaviours and our health.

Out of all the hormone networks, the female menstrual cycle is the most complex. Furthermore, the timings and levels of female hormone fluctuations are highly individual to each woman. There is also individual variation in the way that each personal female hormone network pattern interacts with behaviours and impacts wellbeing.

The gold standard for measuring the four key female hormones (Oestradiol, Progesterone, Follicle Stimulating Hormone and Luteinising Hormone) is to perform a blood test. This can be done at home using a simple capillary finger prick kit.

What is my approach to answer these questions about hormone health for an individual woman?

I start by asking about some background details, including age, menstrual history, lifestyle and wellbeing. Next, we look over the blood hormone results and I explain what these numbers mean. When I look at a set of hormone results, I scan for patterns and biological meaning. This is bit like translating a complex piece of prose written in a foreign language, but it is a language in which I am entirely fluent and conversant with all the grammar and subtle nuances, because it is the language of hormones.

After explaining the hormone patterns, we discuss how these personal patterns tie into wellbeing and what is the best course of action to optimise hormone health through lifestyle behaviours and sometimes medication, where clinically indicated. After our discussion, I write a summary letter that includes a suggested evidence-based personal action plan.

If there were a way I could make the process of delivering a personalised hormone health report more efficient, I would be able to support more women with hormone health questions. This is where artificial intelligence techniques can help.

Personalisation of health through the clinical application of artificial intelligence techniques is revolutionising health care

The Chief Medical Officer of England outlines how access to personalised medicine can be extended through the application of artificial intelligence techniques, such as machine learning[1]. This revolution in healthcare is underway. Every month I attend webinars for medical doctors run by the world leading research group based at Cambridge University to discuss the latest developments in this exciting field of clinical medical artificial intelligence[2].

Artificial intelligence (AI) [3] is somewhat of a misnomer. The “intelligence” does not come from a sterile computer; human programmers collaborate with experts to write the software. By encoding the language of hormones, the computer is able to recognise patterns and then draw upon my medical knowledge to interpret the results in a personalised report, at lightning speed.

For me, this is “intelligence augmentation”: IA rather AI.

You might wonder how a sophisticated computerised system can increase personalisation of healthcare? Even the most experienced individual doctor does not have the time or expertise to mathematically interrogate all clinical and research data in their particular field of medicine. By working closely with mathematicians, doctors can augment their clinical expertise to identify the best management and treatment for an individual. The other big advantage of mathematically modelling medical data is that it is possible to perform extensively testing, by generating lots of “virtual” patients with their medical data to feed into the system.

How can an expert report system deliver a personal female hormone health report?

An expert report system produces a personal hormone health report that is exactly what I write for a woman I see in clinic. The only difference is that this is produced in a fraction of the time it would take me to “download” my medical assessment through typing up a clinic letter[4].

The starting point to delivering a personalised female hormone health report was to work closely with a mathematician with expertise in statistics and computer science AI techniques. To help me in my interpretation of menstrual cycle hormone results, I needed graphs to show the variation of an individual’s hormone network over a menstrual cycle. This makes it easier to pick out hormone patterns and compare to a “reference” group of women matched for cycle length, who are known to be ovulating.

The process of making an expert report library

The next step was to work on an expert report system in order to access a vast library of clinic letters currently stored in my brain. This library covers all possibilities of hormone network results for women over a range of ages and activity level. The mathematical model generated an enormous range of possible graphs from “virtual” hormone blood tests from women of different ages and exercise levels. I sat for hours, days and months to harness my 30 years medical experience into how I would explain and advise a “real” woman sitting in front of me with those particular personal characteristics and results. In other words, I downloaded my medical brain.

All these medical summaries with evidence-based advice were definitely not generated by “artificial” intelligence. Rather the expert report system acts as a very efficient librarian. Presented with the request for a particular book and a specific page in the chapter, the expert librarian retrieves the exact page written by me, the author of all the books in this hormone library.

Hormonal digital fingerprint

In practical terms, a woman can now create a personalised digital fingerprint of her menstrual cycle hormone network from just two finger prick capillary blood samples taken during a cycle. Together with her personalised hormone health report, she can empower herself with insights into her hormone health in order to make informed decisions to optimise physical and mental health.

As pointed out at every webinar I attend on the medical application of AI for health, AI can never replace medical doctors.

Furthermore, as with any medical measurement, the true value lies in monitoring trends over time. This monitoring process directs further informed decisions about next steps for lifestyle modification, or discussion about medication where clinically indicated.

Answering the questions about personal female hormone health

This new approach in assessing female hormone networks for individual women is proving a valuable clinical tool[5]. This enables me to answer the questions that women are asking and move away from generic advice to personalised evidence-based advice. Having these personal hormone health insights empowers women to make informed, personal decisions that will help each individual attain her personal best quality of life.

Read more about delivering personalised Female Hormone Health

References


[1]Machine learning for individualised medicine” Mihaela van der Schaar, Annual Report of the Chief Medical Officer. 2018, Chapter 10. Health 2040 – Better Health Within Reach. Accessed 2021

[2] Van der Schaar M. Revolutionising Healthcare webinars for clinicians, Cambridge University 2021

[3] Artificial Intelligence AI council. UK Government 2021

[4] Keay, N. Fingerprinting Hormones St John’s College, Cambridge University 2021

[5] Keay N. Hormone Intelligence for Female Dancers, Athletes and Exercisers. British Journal of Sports Medicine 2021

When will I reach the menopause?

What does new research into the genetics of the age of menopause reveal? How does this translate to female health in practical terms?

Biological Clock

Every woman will reach menopause around middle age. This is when ovarian responsiveness declines to the extent that ovarian hormone production is no longer sufficient for ovulation to occur.

Ovarian function

The natural age of menopause is on average 51, with a range from 45 to 55 years. About 1% of women experience primary premature ovarian insufficiency (POI), which means reduced ovarian function before the age of 40. For a tiny minority, of 0.1%, this occurs under the age of 30. POI may lead to early menopause, occurring between 40 and 45, or premature menopause occurring before 40 years of age. It is important to identify POI promptly, as a drop in ovarian hormones increases the risk of cardiovascular disease, osteoporosis and decline in cognitive function. So, replacing ovarian hormones through hormone replacement therapy (HRT) is important for long term health, especially for those women with POI[1].  Fertility may also be compromised, although the British Menopause Society stresses that, it is only when menopause is reached, that ovarian function completely stops.

What determines age of menopause?

As with the timing of many physiological processes, the natural age of menopause is thought to be determined by both genetic and environmental factors. A recent paper published in Nature[2] describes how clusters of genes can be used to provide a polygenetic score (PGS) which accounts for 10% of the variation in the age of natural menopause (as opposed to medically induced menopause). The impact of each genetic variant ranged from 3.5 weeks to 1.5 years. Whilst the PGS accounted for a very modest 10% variation in natural age of menopause, the top 1% of the PGS range corresponded to a 5-fold increase in POI compared with women with mid-range scores. The authors themselves urge caution in the clinical application of this multi genetic test approach for predicting natural age of menopause, even in those families with a family history of POI.

The PGS as an indicator of increased risk of POI, is not the novel finding of this paper. The authors state that this result is the same as that obtained through a current single gene test. The most interesting part of the research was how these genes influence the age of menopause. These specific genes code for the DNA repair system for the eggs in the ovary.

Incredibly all the eggs in the ovary are “prepared” while the female foetus is in the mother’s uterus during pregnancy. The double stranded DNA in each egg unwinds and is partially split, leaving it literally in suspended animation. These eggs have to wait another 15 to 50 years before being called upon to complete the halving of double stranded DNA. Ultimately an egg has one DNA strand when ovulated during the menstrual cycle, ready to be united with a matching single strand from a sperm. Some eggs never make the cut for ovulation.

As all the eggs were prepared in the ovaries of the female foetus, they all have the same “shelf life”. Over adult life, the shelf on which the eggs are resting metaphorically starts to tip. The DNA repair mechanisms try to keep the shelf level. However, inevitably the shelf tips over at menopause. This shelf life of eggs, contrasts with sperm in men, which are made continuously throughout adult life.

From an evolutionary perspective having a shelf life on eggs and reaching menopause is probably for the benefit of the mother and the potential baby. Although life expectancy has increased, the ageing process is something that none of us can avoid. Pregnancy, childbirth and raising a child are demanding, even more so beyond middle age. From the baby’s point of view, it is well documented that increasing maternal age increases the risk of genetic issues for the embryo. This is where genetic repair mechanisms outlined in the research paper become really important. As the DNA in the eggs in the foetal ovaries are in suspended animation, in a delicate state for the rest of the woman’s life, the DNA repair enzymes need to be on high alert to keep the eggs “fresh” and ready for ovulation.

In experiments on female mice, manipulating the two genes for DNA repair did prolong fertility and for one of these genes, also bolstered the ovarian response to hormone stimulation. However, the downside is that in the latter case this could also increase the risk of cancer. Furthermore, we do not know how manipulating maternal genetics would translate to the genetics of the offspring; nor how this genetic manipulation translates from mice to women.

Ideally it would be helpful to keep a watching brief on all factors contributing to egg health.

The missing link: female hormone networks

The authors state that their paper focused on genetics and did not consider the other key influencers of female health, fertility and definition of menopause: hormones[3]. If genetic factors account for 10% of the variation in the age of menopause, that leaves 90% unexplained. A significant proportion of the variation is likely to be due to environmental factors. Lifestyle and behavioural choices influence hormones and it is hormones that regulate gene expression in DNA.

This means that, whatever your genetic endowment, making good choices around lifestyle factors of nutrition, exercise and sleep, while avoiding negative choices like smoking, certainly helps hormone networks and therefore impacts gene expression.

Ideally a measure of dynamic hormone function would be more informative about transition to menopause. Such an approach is now possible, by combining medical and mathematical expertise through artificial intelligence techniques[4]. Quantifying ovarian responsiveness with a scoring system of female hormone network function gives a real time watching brief on female health[5]. Monitoring over time can track any decline suggesting transition to menopause.     

What can we conclude about age of menopause?

  • Menopause is a significant physical and psychological event in a woman’s life. Declining ovarian hormones pose challenges for long term health.
  • Average age of natural menopause is 51 (range 45-55 years). Early menopause occurs between 40 and 45 years of age and premature menopause under 40. Primary ovarian insufficiency (POI) is where the ovaries start to loose responsiveness before the age of 40.
  • The age of menopause is determined through a combination of genetic and environmental factors. A new research genetic test combining various genes can predict up to 10% of the variation in the natural age of menopause, leaving 90% determined by non-genetic factors. In 1% of the outlying genetic scores, this corresponded to an increased likelihood of premature ovarian insufficiency, the same as current single gene test.
  • The authors of the research urge cation that this multiple gene test is not a suitable clinical test for women, even for those with family history of POI. Nevertheless, this research sheds light on the DNA repair mechanisms that play a part in determining age of menopause.
  • This paper focused on genetics and did not discuss the hormone networks. Menopause is defined as no further menstruation when the ovaries stop producing hormones.

Practical take home points

  • You can obtain a free genetic test by asking your female family members about their age of menopause. This also opens up conversations about menopause.
  • Premature Ovarian Insufficiency does not definitively exclude the possibility of pregnancy
  • For all women, ovarian responsiveness and fertility decline after 40 years, at a variable rate.
  • Female hormone networks should be considered and can now be assessed as part of the personalised assessment of ovarian function, with medical explanation and evidence based advice. For further details
  • For medical doctors, membership of British Menopause Society provides a wealth of resources and specialist training opportunities

It is every woman’s personal choice when and if she wishes to become pregnant. Nevertheless, it is important for women to be aware of their personal female physiology. Genes are passed down through the generations, but the expression of those genes is determined hormone networks. Since lifestyle choices affect hormones, they determine to a large extent how your personal story unfolds.

References


[1] Management of the Menopause. Sixth Edition. British Menopause Society

[2] Ruth, K.S., Day, F.R., Hussain, J. et al. Genetic insights into biological mechanisms governing human ovarian ageing. Nature (2021). https://doi.org/10.1038/s41586-021-03779-7

[3] Genomic analysis identifies variants that can predict the timing of menopause. Nature 2021

[4] Keay N. Hormone Intelligence for Female Dancers, Athletes and Exercisers British Journal of Sports Medicine 2021

[5] Keay N Fingerprinting hormones St John’s College Cambridge 2021