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I find it astonishing that despite the high prevalence of symptoms in menopausal women, in particular, hot flushing, there is remarkably little research on the mechanisms by which these symptoms occur. Of course, if one is to treat any illness the starting point is to work out the mechanisms which cause that clinical picture to arise. Having answered the question why, one can then look at how one can go about mitigating the problem.
What is the mechanism of the Hot Flush?
Perhaps the most distressing symptom of the menopause is the hot flush. This has often been described as “vasomotor instability” i.e. a problem with the autonomic nervous system. (The autonomic nervous system is responsible for those functions that occur automatically and over which we have little conscious control such as blood vessels dilating or constricting, heart rate, sweating, temperature control and so on.)
However, the autonomic nervous system is not the cause of flushing – it is simply the “messenger boy”. We cannot blame the autonomic nervous system for hot flushes – it is simply relaying a message from another department.
Rather than blaming the “messenger boy”, we must look for the “mechanism” (cause).
Cleopatra reacted angrily to the “messenger boy”, who told of Antony’s marriage to Octavia. She said to this unfortunate “messenger boy”:
Horrible villain! … I'll spurn thine eyes Like balls before me; I'll unhair thy head: Thou shalt be whipp'd with wire, and stew'd in brine, Smarting in lingering pickle. (Shakespeare, Baptised 26 April 1564, birth date unknown, died, 23 April 1616)
But then, later, Cleopatra begins to look for the “mechanism” (cause):
Report the feature of Octavia, her years, Her inclination, let him not leave out The colour of her hair: bring me word quickly (Shakespeare, Baptised 26 April 1564, birth date unknown, died, 23 April 1616)
We too should look for reports of Octavia!
And, we have some excellent clues (“reports”) as to the cause of hot flushes.
- Firstly, they only occur with the menopause when there are falling levels of oestrogen and progesterone in the body.
- Secondly, they can be banished instantly by taking oestrogen and progesterone supplements. (HRT)
I certainly do not advocate HRT as a treatment – oestrogens and progesterones are potentially dangerous hormones, doubling our risk of hormone sensitive cancers, increasing our risk of heart disease and thromboembolism, suppressing the immune system and inducing metabolic syndrome. They are not an answer to hot flushes, but their effectiveness in the treatment of hot flushes gives us very valuable insights into the mechanisms that cause such flushes.
Oestrogen and progesterone levels decline as the ovaries run out of eggs, age and fail. However, the pituitary gland does not realise this – indeed there is a huge biological imperative to procreate. According to Richard Dawkin’s selfish gene theory there is only one biological imperative i.e. to reproduce our genes in another generation. (Please see Amazon link to "The Selfish Gene" ) This imperative to procreate is more powerful than the survival of the individual. The business of procreation is extremely dangerous for the procreator – sex hormones induce a form of madness and make us do mad things. We call this lust and lust is responsible for the spread of a great many nasty killer diseases such as syphilis, hepatitis B and HIV!
This time we turn to Romeo, rather than Cleopatra, for an exposition of love:
Love is a smoke raised with the fume of sighs; …………a madness most discreet, (Shakespeare Baptised 26 April 1564, birth date unknown, died 23 April 1616)
So our primitive brains are geared to reproduction and as levels of oestrogen and progesterone fall, the brain works harder to kick it into life.
So I think there are three threads which explain the mechanism of flushes.
- Falling levels of oestrogen and progesterone – as above
- The fact that hormones from the pituitary gland do not leak out in a uniform way – they are released in pulses. Indeed many hormones are released in a pulsatile fashion – I suspect that this is because the body is more sensitive to changes in the environment rather than absolute levels, so that if there is a sudden rapid rise in hormone production then the target receptor cells are alerted to this and the ongoing response is maintained by subsequent higher levels of hormone in the blood. This makes perfect biological sense.
- Molecular mimicry - I suspect the mechanism of hot flushing has to do with this. Molecular mimicry occurs in many cases and is essentially as it sounds – one molecule mimics another because they are in some way similar, perhaps, physically similar. For example, auto-immunity may be switched on because the body makes antibodies against foods or microbes which then, through sheer chance, cross react with the body’s own molecules. This kind of molecular mimicry was put forward and studied by Dr Alan Ebringer (Autoimmunity in Rheumatic Diseases Is Induced by Microbial Infections via Crossreactivity or Molecular Mimicry. Rashid T Ebringer A A different form of molecular mimicry, as described below, may be at work here.
So the progression of events is as follows: The pituitary gland kicks the ovaries by secreting luteinising hormone and follicle stimulating hormone. It produces these hormones in large amounts and indeed levels in the body in the post-menopausal woman are 100 fold higher than those in a woman seeing a regular period. These hormones are released in a pulsed way and that means they can flood into the blood stream in levels perhaps thousands of times higher than in the pre-menopausal woman. By the mechanism of molecular mimicry, these pituitary hormones mimic other hormones such as bradykinin which is known to cause flushing. I suggest bradykinin because it is inhibited by clonidine and this is used to prevent flushing.
Sometimes Nature gets things a little wrong and because post-menopausal women are on the “evolutionary scrap heap” when it comes to the business of reproduction, Nature does not mind if it makes things uncomfortable for these women, even if by mistake. A summary of this mechanism by which post-menopausal women experience hot flushes is shown directly below.
Summary of a biologically plausible mechanism for hot flushes
1--Oestrogen and progesterone levels decline => =>
2--Brain reacts by secreting luteinising hormone (LH) and follicle stimulating hormone (FSH) from the pituitary gland to wake the ovaries up => =>
3--Because LH and FSH mimic hormones such as bradykinin, which are known to cause hot flushing, then the hot flushes inevitably follow.
So what this means is that treatment of the menopausal hot flush needs to be aimed at stopping, or at least keeping to a minimum, production of follicle stimulating hormone and luteinising hormone in the pituitary. One can also use herbal preparations which have mild oestrogen and progesterone like effects known as phytoestrogens but the emphasis should be on dealing with the levels of FSH and LH. Or one can block the effects of bradykinin with clonidine.
Stop, or reduce, the pituitary pouring out high levels of LH and FSH
Throughout evolutionary history, survival has been a battle of resources – resources of raw materials and resources of energy. The business of reproduction requires large amounts of raw materials and large amounts of energy and the brain will not permit a woman to be fertile unless these are available. So, for example infertility, by which I mean lack of egg maturation from the ovaries, results in the following cases:
- Women who restrict calorie intake, for example in cases of anorexia nervosa, will deplete their resources so much that the brain will stop producing FSH and LH and their periods will stop.
- Athletes who train to a high level so that they become a running machine with no resources of fat again often lose their periods – a mechanism of this is again lack of FSH and LH from the brain.
- Breast feeding – the brain perceives that all the resources of the body are going into nourishing the baby, which of course is a vital part of the selfish gene propagation, and will switch off FSH and LH so that the mother’s resources are not diverted into a second child.
- Pregnancy – women do not want to produce more eggs to be fertilised when one is already growing in their womb! Indeed this is how HRT works - it puts one into a hormonal state which mimics pregnancy - and all the dangers associated with such! Please see CFS and Pregnancy
Indeed, throughout evolution it could be argued that seeing a regular period is an abnormal state of affairs – women should either have been too young to see a period, too under-nourished, pregnant or breast feeding. Since most died before menopausal age, the problem of molecular mimicry as described above, rarely arose, if at all.
The reason, therefore that the brain, in a post-menopausal woman, kicks out high levels of FSH and LH to wake up the ovaries is because the primitive brain perceives that modern-day women have the necessary reserves to have a baby – it simply does not realise that the ovary has run out of eggs. So women suffering from hot flushes could greatly reduce the FSH / LH kick from the brain by adopting some of the above mechanisms. I am not advocating anorexia nor marathon running but it is clear from working with patients that there are some nutritional and other interventions which are very helpful and which at least reduce the severity of flushing.
These fall into three categories, as discussed in more detail below:
- prevent flushes in the first place
- mitigate flushes by keeping cool and
- mitigate a flush that is “in progress”.
Prevent flushes in the first place
- I suspect it is persistent levels of high blood sugar that make the brain think that there is an abundance of food and, therefore, the necessary raw materials for pro-creation. So, to avoid these persistent levels of high blood sugar, eat a Stone Age low carb diet in order to maintain a normal or low normal BMI. Please see Stone Age Diet. This should include windows of time of fasting – and indeed many women observe that if they breakfast like an Emperor, lunch like a King and supper like a Pauper, then this greatly reduces disturbed sleep from hot flushes at night. The smaller the evening meal and the further away from bedtime, the less the severity of nocturnal flushing. Alcohol seriously dysregulates blood sugar levels and should be taken very judiciously! The fermenting gut ferments carbohydrates to produce various alcohols and other substances all of which have the potential to disrupt blood sugar levels. Please see Fermentation in the gut and CFS. I suspect insulin is a player here – high insulin is a characteristic of metabolic syndrome and flags up to the brain that the body is in fat laying down mode, storing energy and ready for reproduction!
- Take exercise – exercise is of proven benefit in mitigating hot flushes and the mechanism of this is likely to be that it reverses metabolic syndrome and irons out blood sugar levels. It achieves this by squeezing dry the metabolic glycogen sponges in the liver and muscle as glucose is mobilised from glycogen. This means these sponges are “dry” and so available to mop up sugar following a meal, and so insulin does not spike and trigger metabolic syndrome. Please see Does physical exercise influence the frequency of postmenopausal hot flushes? Hammar M, Berg G, Lindgren R. and Exercise keeps hot flushes at bay in menopausal women
- Take a modest dose of pregnenolone, say 25-50 mg daily. As the ovaries shut down, most sex hormone production comes from the adrenal glands. As we age that output also falls and may be a cause or an effect of the ageing process. The point here is that we could function very much better for taking a modest dose of adrenal hormones to mimic more youthful levels.
- Use herbal preparations which have mild oestrogen and progesterone like effects known as phytoestrogens. Please see Wikipedia article on phytoestrogens for more detail.
- Take clonidine (a prescription drug) 0.05mgs (50mcgms) at night. This is a modest dose. Clonidine is used in doses up to 600mcgms daily for hypertension.
Mitigate the flushes by keeping cool
- Wear clothes that keep the body warm, but with bare arms and/or bare legs so that heat can be quickly lost if necessary.
- Try to sleep at night with minimal coverings. Choose a mattress which is not too well insulated. Position the bed directly under an open window where there is a cool down draught of air.
Interventions to mitigate an established flush
The quicker you can lose heat, the shorter will be the flush. Suggestions include:
- Drink ice cold water from the fridge (perhaps have a small fridge next to the bed, or have a bottle of frozen ice that slowly defrosts through the night but is ice cold to drink). Just as a hot drink is one of the fastest ways of warming up, an ice cold drink reduces body temperatures very quickly. (Be mindful that if you have heart disease, ice cold water can slow the heart and possibly trigger a dysrhythmia)
- Use a fan.
- Consider using a mild hypnotic such as valerian, melatonin or nytol because that helps to get you back off to sleep more quickly. Combine this with a sleep dream – the idea here is to take the brain out of “thinking about reality” mode. Please see Sleep is vital for good health – especially in CFS
The above mechanism I describe may not be the (100%) correct one, but it is at least biologically plausible, has a reasonable evidence base in the medical literature and squares with the observed clinical facts. Throughout medicine it is clinical observation that always precedes the science and I know from clinical experience, with many women, that the above techniques are indeed helpful. Moreover, these techniques are positively beneficial to overall health and so represent good things in and of themselves.
So let us carry on with those and let the science catch up and wait for more reports on Octavia!
- Fermentation in the gut and CFS
- Stone Age Diet
- Sleep is vital for good health – especially in CFS
- CFS and Pregnancy
- Menopause - problems and how to tackle them
- Autoimmunity in Rheumatic Diseases Is Induced by Microbial Infections via Crossreactivity or Molecular Mimicry. Rashid T Ebringer A
- Amazon link to "The Selfish Gene"
- Does physical exercise influence the frequency of postmenopausal hot flushes? Hammar M, Berg G, Lindgren R.
- Exercise keeps hot flushes at bay in menopausal women
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