“Sleep is the chief nourisher in life’s great feast”

Macbeth, Shakespeare

At the start of every year there is always a lot of talk about refraining from certain activities like drinking alcohol, advice about eating a particular way, or recommendations to do certain types/amount of exercise. Trends in these lifestyle choices may come and go, but there is one behaviour that remains constant to achieve optimal health. Sleep.

In my book “Hormones, Health and Human Potential: A guide to understanding your hormones to optimise your health and performance” I discuss how our lifestyle choices and behaviours around sleep, exercise and nutrition influence hormone networks and consequently our health.

Illustration from “Hormones, Health and Human Potential”

Sleep for hormone health

Why is sleep such an essential component for health? Although being asleep is a physical state of inactivity, it is when many hormone networks are at their most active. For example, one of the main stimuli for growth hormone (GH) release is sleep. Despite its name, GH is not just about growth in children. All adults continue to produce GH and this is an important anabolic (tissue building) hormone. GH maintains a healthy body composition: favouring muscle over fat deposition. GH also plays a role in bone health.

Sleep for fitness

Another stimulus for GH release is exercise. However, you don’t get fitter in real time while you exercise. You get fitter when you are asleep. After stopping exercise and during sleep these two combined stimuli for GH release drive the positive adaptations to exercise. Sleep enables you to become citius, altius, fortius. 

Sleep for sex steroid hormone networks

Sleep is also essential for other hormone networks, such as those of the reproductive axis, in both men and women. Studies show that men who have reduced sleep tend to have lower levels of testosterone and poorer bone health. Essentially if you do not have sufficient quality and quantity of sleep this has a negative effect on many aspects of both physical and mental health.

Sleep for metabolic health

Hormones that control appetite and satiety are linked with the sleep/wake cycle. People who have disrupted sleep patterns are more likely to struggle with blood glucose and weight control.

Timing of sleep

The timing of sleep is also important. Hormone networks run on a variety of internal biological clocks, known as biochronometers. The trick is to try and synchronise the timing of your behaviours with these internal biochronometers. If you have an “scheduling conflict” between external and internal clocks, this leads to a situation of circadian misalignment. Circadian misalignment can lead to many adverse consequences on mental and physical health, including metabolic and cardiovascular health. This negative combination can lead to metabolic syndrome which increases the risk of type 2 diabetes mellitus, cardiovascular disease and high blood pressure.

Consequences of disrupted sleep patterns

Shift workers, for example junior doctors, are at risk of developing circadian misalignment. Disrupted sleep patterns, clashing with internal hormone timing becomes a vicious circle. Poor sleep interferes with the diurnal variation of cortisol, which peaks as an awakening response. Disruption of this cortisol awakening response can disrupt subsequent night sleeping.

A degree of circadian entrainment is possible. In other words, our hormone clocks can adapt to slight changes in sleeping patterns. For example, getting up early for exercise training. It is also possible to reset internal biological clocks, as we do after a long-haul flight. This is because in our brain we have a biological light sensor which has direct communication with the manager of the hormone orchestra, conveniently situated in very close proximity in the brain. The timing of daily hormone release can be reset to correspond with local night and day timing. This contrasts to the situation of doing shift work, where you are continuously in conflict with night/day timing and internal hormone clocks.

Top tips for sleep to optimise hormone health

So, if there is one behaviour that you are going to improve this year, it should be sleep.  

Sleep hygiene is the term used to cover strategies to ensure a good night’s sleep. One of the tops tips is to try and go to bed at a regular time, before midnight. A recent study shows that is these hours before midnight that are particularly valuable for hormone health. In fact, it is useful to set an alarm for going to bed.

Another strategy to help sleep is finding a bedtime “wind down” routine that suits you. For example, reading or listening to music. Looking at mobile electronic devices is not one of these. The reason being that the light emitted from these devices prevents the production of the sleep hormone melatonin.

When it comes to hormone health, sleep is indeed the chief nourisher. Sleep and other lifestyle choices to harness hormones for optimal health, through life, are explored in detail in “Hormones, Health and Human Potential: A guide to understanding your hormones to optimise your health and performance”.

Next steps

“Hormones, Health and Human Potential: A guide to understanding your hormones to optimise your health and performance” is available in paperback and Kindle (illustrations in colour) from Amazon and direct from Sequoia books (ship overseas)

Hormone Health advisory appointments are available

Presentations and workshops

Excess is a Fatal Thing. Nothing Succeeds like Moderation

Oscar Wilde quipped that “Moderation is a fatal thing. Nothing succeeds like excess.” However, when it comes to enjoying a healthy lifespan, nothing succeeds like moderation.

Harnessing Hormones through Lifestyle Choices for Health

Personalising Health through Lifestyle

Hippocrates advocated that giving each individual just the right amount of exercise and nourishment, not too little and not too much, is the safest way the health. Although Hippocrates is often known as the father of medicine, more accurately he could be described as the father of health. Health being not just the absence of disease, rather the positive combination of physical, mental and social health.

In ancient Greek times it was not known why moderation, of nutrition and exercise surely lead to health. As I describe in “Hormones, Health and Human Potential” it is the interactions of these behaviours with our hormone networks that maintain internal harmony known as homeostasis. Homeostasis is equilibrium of the internal environment to support all physiological processes for health. Hormone networks can adapt and withstand a certain degree of external excess in the form of too much or too little nutrition or exercise. However there comes a critical point, personal for each individual, where continued excess of unbalanced behaviours will tip over into adverse effects on health. Incidentally in this situation it is not hormones that become unbalanced, rather unbalanced behaviours have forced hormone networks into extensive adaptive changes.

Rebalancing Lifestyle Choices

There are certainly ever emerging challenges for attaining just the right amount and timing of each lifestyle choice around nutrition and exercise. Everyone likes a “quick fix”: apart from your hormones and your health. This is why New Year’s resolutions around extreme dieting or exercise at either end of the spectrum don’t lead to long term benefits. Another problem is that it is difficult to override in-build “safety” mechanisms, so it is challenging psychologically to stick to original intentions. Your body and millions of years of evolution knows best. This can leave you deflated and demotivated. You can’t stick to your plan and this plan does not bring the success you expected. What are the ways to set you on the surest path for optimal heath?  

Lifestyle choices for 2023

Exercise

There are two very important factors in your choice of exercise. Firstly, that this is something you personally enjoy. Studies show that those who chose exercise that they enjoy are more likely to keep exercising and make healthy food choices. My personal favourite is taking a ballet class with my excellent teacher and friends of many years. Dance also covers the second important point about exercise choice in that it should involve different types of fitness. I see many people just focusing on a cardiovascular type of exercise, neglecting strength, flexibility and neuromuscular skills. However, if ballet is not your thing, then choose your exercise types wisely for enjoyment and to cover all bases of fitness.

Nutrition

Nutrition is very similar to exercise in that food choices should cover all the nutritional requirements for the individual and not neglect the enjoyment element of eating. Trying to adhere rigidly to any type of diet that does not encompass these elements will not end well for health in the long run. I see a lot of exercisers who end up in unintentional or intentional low energy availability with associated adaptative down regulation of hormones, which can be challenging to rectify. At the other end of the spectrum, for those who maybe have favoured energy intake over energy expenditure, the type of weight reduction diets that purport to give rapid weight loss, can often be counterproductive in the long term. If it sounds too good to be true, it probably is.   

Sleep

“Sleep is the chief nourisher in life’s great feast”. Although Shakespeare did not realise at the time of writing “Macbeth”, sleep certainly is the chief nourisher when it comes to hormones. Many hormone biological clocks, biochronometers, are set according to our sleep patterns with recent research showing that lack of sleep adversely impacts hormone health for men and women. So aiming for good sleep patterns is something relatively straight forward and actionable to support health.

Stress management

We often have our own personal responses to “stress”. This could be responding through an excess of behaviour at either end of spectrum: eating and/or exercising too little or too much. Especially when combined with disrupted sleep patterns, this creates the perfect storm for challenging hormone health. This vicious circle can become a repeating pattern of response to “stress”. I put “stress” in inverted commas intentionally, because “stress” is our personal interpretation of external stressors. We each have our own interpretation of events and our personal response.

For this reason, “stress” management strategies are a personal choice. Identifying your personal triggers for deviating away from balanced behaviours is an important starting point. Then noting what tends to be your typical response is to these triggers. Can you explore more helpful ways to deal with your personal triggers? Is this listening to music, reading, mediation, meeting with friends or as Hippocrates advised going for a walk? I often see people (including myself) who have tendency to over exercise when confronted with stress provoking situations. So, in this case, going for more walks wouldn’t be the best option. Make sure your strategies are personal to you.

Moderation for Optimal Health 2023

The top tip for optimal health in 2023 and beyond is to aim for moderation and balance across the key lifestyle choices of exercise, nutrition and sleep. Combined with your personal stress management strategies to avoid too much or too little of any of these behaviours, this is the surest way to health as Hippocrates advised. If you do need to modify or fine tune your choices, making small changes that you can sustain over the whole year and beyond will bring success in health.

Next steps

“Hormones, Health and Human Potential: A guide to understanding your hormones to optimise your health and performance” is available in paperback and Kindle (illustrations in colour) from Amazon and direct from Sequoia books (ship overseas)

Hormone Health advisory appointments are available

Presentations and workshops

Subclinical Ovulatory Disturbances

Adaptation of menstrual cycle hormones

In my book “Hormones, Health and Human Potential”, I really enjoyed writing the chapter 5XX “Of Mice and men….and Women!” Celebrating Horme the goddess of effort, energy and action. However, there are some instances where even this formidable goddess is challenged and adaptations are required[1].

Challenges to menstrual cycle hormones

Menstrual cycle hormone choreography is as beautiful as it is complex. Generally, this repeating motif follows the score faithfully during a woman’s reproductive years. However, when external stressors become too great, then menstrual hormone fluctuations respond and adapt.

A single stressor, for example financial concerns or a life event can impact hormones and disrupt menstrual cycles on a short time scale of a handful of cycles. However, a combination of stressors can have a synergistic effect on disrupting female hormone networks. Additive stressors over a long-time scale are known as an allostatic load. A high allostatic load causes a more extensive adaptation of female hormones[2]. For example, a high level of stress from intense exercise training together with metabolic stress from insufficient food intake can result in total suppression of menstrual cycle hormone fluctuation and cessation of periods (amenorrhoea) found in relative energy deficiency in sport (RED-S).

Unbalanced behaviours

Although “hormone imbalance” is a popular phrase, this has no medical meaning. This misleading phrase does a massive disservice to Horme and to millions of years of evolution in fine-tuning the most intricate hormone network. It is not the hormone network that has become “unbalanced”, rather it is our unbalanced behaviours and/or management of external stressors that have caused hormones to adapt and change appropriately. On a positive note, understanding hormones empowers us to nurture and harness our hormones through our lifestyle choices.  

Spectrum of female hormone adaptation

There is a graded response of female hormones to external stressors, depending on the number and the time scale of these. A cumulative combination of stressors results in a high allostatic load which causes amenorrhoea. Physiological causes of amenorrhoea must be excluded: pregnancy and menopause; as should medical causes such as prolactinoma and polycystic ovary syndrome (PCOS).

The type of amenorrhoea occurring as an adaptive response to a high allostatic load is functional hypothalamic amenorrhoea (FHA). This means that the neuroendocrine gatekeeper in the brain, the hypothalamus, has taken the executive decision to suspend female hormone fluctuations, in order to conserve resources to deal with the stressful situation. From an evolutionary point of view this is not the time for the high demand state of pregnancy. The good news is that being an adaptive functional response, FHA is reversible if the underlying cause is addressed.

Tip of the iceberg

Amenorrhoea is a very obvious clinical sign. Similarly, oligomenorrhoea (less than 9 periods per calendar year). However, these menstrual disruptions are just the tip of the iceberg. Less obvious are the subclinical ovulatory disturbances (rather unflatteringly referred to as SODs). This is where a women may experience a menstrual period, but the full repertoire of female hormone fluctuation has not occurred. Specifically, progesterone has not increased to levels that would be expected in the luteal phase of the cycle (second half of the cycle). If ovulation has occurred, then the remnant of the egg follicle in the ovary forms the corpus luteum which secretes progesterone. Progesterone increases resting metabolic rate and energy demand. So, keeping progesterone low is a good adaptive response to high allostatic load by keeping energy demand low.

If subclinical ovulatory disturbances are an adaptive physiological response, does this matter for a woman’s health? The answer is yes. Oestradiol (the most active form of oestrogen) often takes the limelight when it comes to positive effects on bone, soft tissue, cardiovascular, and neurological health. However, evidence is emerging that progesterone plays an equally important supporting role in these areas of health. For this reason, it is important to identify these elusive disturbances in menstrual hormone choreography.

How to detect subclinical ovulatory disturbances

As I discuss in my book in the chapter “Hormone Supermodels”, applying artificial intelligence (AI) techniques to modelling menstrual cycle hormones can help in identifying subtleties in hormone disruption. This is a fast-moving field and even since publishing on this topic, further advances are being made as more data is emerging and employment of different mathematical techniques, with reduction in the number of samples required. Personalisation of female hormone health is on the move. Nevertheless, the cornerstone of any medical AI focused on hormones is the medical doctor with expertise in hormones, putting the results in clinical context for the individual. Explaining and advising with practicality and empathy is vital.

This personalised medical approach is crucial when, by definition, subclinical ovulatory disturbances will require guidance on changing behaviours to reverse adaptive hormone changes. When I work with athletes and dancers experiencing hormone disruption due to imbalances in exercise and nutrition, I find it helpful in referring to recovery from a hormone injury as comparable to recovering from a physical injury. Furthermore, there can be a psychological dimension to subclinical ovulatory disturbances. How we interpret external events and think impact our hormones. For example, cognitive dietary restraint (just thinking you should eat less/be thinner) can cause subclinical ovulatory disturbances.

Nurturing Horme

Menstrual cycle hormone choreography is the most intricate and beautiful of all the hormone networks. There is a spectrum of hormone adaptation according to the degree of “stress” put on the system. The visible tip of the iceburg is menstrual disruption such as amenorrhoea and oligomenorrhoea. Less obvious, beneath the surface are subclinical ovulatory disturbances. Subclinical ovulatory disturbances are adaptive hormone responses to unbalanced behaviours and/or interpretation of external events. These subtleties of subclinical ovulatory disturbances can be challenging to identify. However, it is important to do so and provide appropriate medical support to restore these hormones for long term health.


[1] Keay N. Hormones, Health and Human Potential 2022 Sequoia books

[2] Prior J. Adaptive, reversible, hypothalamic reproductive suppression: More than functional hypothalamic amenorrhea Front. Endocrinol 2022 Sec. Reproduction
https://doi.org/10.3389/fendo.2022.893889

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/