Are you experiencing them? They can cause some woman terrible discomfort and sleepless nights. They start at around Peri-Menopause and Menopause when hormone levels start to go crazy. About 50% of woman experience these in various degrees of discomfort and can last for a number of years. Menopause is also associated with an increase in estrogen related cancers, breast and endometrial They can also occur during puberty and while pregnant and even a few days before menstruation, again at a time when hormones are going crazy as progesterone and estrogen levels drop. When the ratio between the two hormones become skewed as in excess estrogen in the ratio to progesterone, do these occur. The capacity of adipose cells to produce estrogen increase greatly with age, but there is no corresponding increase in progesterone production. Surely the reasons behind hot flushes, breast and endometrial cancers would be the drop in progesterone and NOT estrogen? Taking into account that hot flushes begin around peri-menopause when estrogen levels are still high, indicates a clue to cure hot flushes.

Let's examine this further.

Normal Flushing

Causes:

  • physical exercise
  • hot temperatures
  • spicy food
  • alcohol
  • embarrassment
  • anger
  • fever
  • heat exhaustion
  • heat stroke
  • allergic reactions
  • inflammatory conditions

Adult men and women's normal oral body temperatures range from between 33.2-38.2C (92-101F). Typical average range is 37.0C (98.6F).

In women it varies between the follicular and luteal phase. During the follicular phase it can range from 36.45-36.7C (97.6-98.1F). During the 12-14 day luteal phase, temperatures increase by 0.15-09.45C (0.2-0.9F). This is due to the increased metabolic rate caused by rapidly rising levels of progesterone. After a few days of bleeding temperatures drops down to follicular levels.

During a hot flush it is thought that something sudden causes a response in a body part or organism affecting the temperature control centre within the hypothalamus and causes it to go out of control. This gives a pointer to a possible cure for hot flashes. Blood pressure (BP), sleep and Anxiety are now affected. 

Sudden causes are:

  • drop in hormones
  • rapid drop in blood glucose level
  • stress
  • carcinoid syndrome
  • chronic lymphocytic leukemia
  • systemic mast cell disease
  • tamoxifen
  • pheochromocytoma
  • medullary carcinomia of the thyroid
  • pancreatic islet-cell tumours
  • renal cell carcinoma
  • hyperthyroidism
  • neurological flushing
  • somatostatinoma

A hot drink, coffee or wine can aggravate things too, possibly because these disturb blood glucose.

The skin is the body's main defence against rising internal temperature, hence the flushing and/or sweating that occurs when it overheats. But as yet there is an incomplete understanding of the physiology of hot flushes which limits the search for a cure.

Although regarded as a estrogen deficiency, hot flushes do not occur in pre-pubertal girls, women with Turner's syndrome, unless taking estrogen and older menopausal women. They all have little to no estrogen! Young women with ovarian dysgenesis, and therefore very low levels of estrogen, never have hot flushes unless first given estrogen.

There is evidence suggesting that the mechanism behind hot flushes is far more complicated than a decline in estrogen, and that the neuroendocrine system is involved.

These includes:

  • corticotropin-releasing hormone (CRH)
  • thyrotropin-releasing hormone (TRH)
  • calcitonin gene-related peptide (CGRP)
  • adrenaline (epeniphrine American)
  • noradrenaline (norepeniphrine American)
  • serotonin
  • endorphins
  • estrogen
  • testosterone
  • progesterone

The above all play a role.

The hypothalamus lies within the brain, it controls blood pressure, body temperature, hunger, thirst, water balance, and is involved in sleep and emotional activity. It links the nervous system to the endocrine system by secreting neurotransmitters, neuromodulators and neurohormones.
One simple neurohormone is TRH. It's involved in the control of temperature, as it controls energy homeostasis. TRH causes wakefulness and loss of appetite. It's also found in pancreatic islets and the gastrointestinal tract, where it increases motility, notably in women with irritable bowel syndrome. It's released when stressed in an effort to keep the body in homeostasis.

TRH stimulates the pituitary to secrete Prolactin. Excess levels of TRH inhibit dopamine, which also causes prolactin to increase. Excess estrogen causes prolactin to rise too. Excess prolactin inhibits dopamine. Although prolactin is the hormone of lactogenesis, it's also an inflammatory hormone. A drop in dopamine can lead to anxiety and depression. It also stimulates the release of noradrenaline from the frontal cortex, and the pituitary to release thyroid-stimulating hormone (TSH). TSH stimulates the thyroid to secrete thyroxine and triiodothyronine which control the body's metabolic rate, heat generation, neuromuscular function and heart rate.

However, it appears that the production of nitric oxide (NO) may control the activity of the hypothalamus-pituitary-thyroid axis. NO is the intercellular signal that controls vascular tone (hence blood pressure), insulin secretion, airway tone, and peristalsis. Inhibition of NO decreases production of TSH, which reduces thyroxine and triiodothyronine and therefore the metabolic rate and temperature. The brain sensing this stimulates the secretion of TRH which would in turn increase metabolic rate and temperature. If this was too sudden, the body would overheat.

Noradrenaline is also associated with activation of the hypothalamic-pituitary-thyroid axis. It's also involved in the protein biosynthesis and secretion of TRH.  Progesterone stimulates the production of NO and suppresses noradrenaline. A drop in progesterone production would inhibit the release of NO and cause noradrenaline to rise.

Another neurohormone secreted by the hypothalamus is CRH. It's released in response to stress, whether physical or emotional, external or internal. CRH in turn stimulates the pituitary to release corticotropin, also called adrenocorticotropic hormone (ACTH). This in turn stimulates the adrenals to secrete cortisol, and together with the sympathetic nervous system and certain precursor chemicals, adrenaline and noradrenaline, the three stress hormones. CRH also suppresses appetite, increases anxiety and improves memory and selective attention. It increases throughout pregnancy being produced by the foetus and placenta. It's thought that this increase ultimately starts labour. It's found in the gut, where it can initiate inflammation. It is inhibited by progesterone, but excess CRH suppresses progesterone. An excess is also associated with depression, anxiety, sleep disturbances and anorexia. It can worsen, or possibly play a role in inflamed conditions such as arthritis, psoriasis, ulcerative colitis and Crohn's disease. Progesterone levels rise sharply in pregnancy, suppressing CRH. But eventually the rising level of CRH from the foetus and placenta suppress progesterone, and labour starts.

Increased levels of Calcitonin gene-related peptide (CGRP) are found in postmenopausal women compared with premenopausal women. Adipose cells are important for the production of CGRP, with increased levels seen in the abdominal subcutaneous fat in postmenopausal women. Adipose cells are also the main site of estrogen production in these women. Estrogen stimulates adipose cells to divide and multiply, so a vicious cycle starts. Elevated CGRP levels are found particularly during hot flushes. They are also found in pregnancy which suggests that estrogen and progesterone may influence their secretion.

Men also experience hot flushes. These can be caused by low testosterone, particularly in older men going through andropause. But it's more likely to occur in those on anti-androgen therapy for prostate or testicular cancer, or after removal of the testes. A few studies have found CGRP is involved in hot flushes in men who had castration or androgen deprivation therapy due to prostate cancer. One study found ovarian hormones and testosterone inhibited CGRP.

Flushes can last from 0.5 to 60 minutes, but generally 3 to 6 minutes, with the average being 3.3 minutes

If a substance causes adrenaline and noradrenaline to rise, it provokes a hot flush. The converse is true, if a substance causes a reduction, it ameliorates a hot flush. Major triggers of adrenaline and noradrenaline release are:

  • physical threat
  • excitement
  • noise
  • bright lights
  • a drop in blood glucose
  • high ambient temperature

Adrenaline and noradrenaline are part of the fight-flight response. They increase vascular tone such as:

  • constricts blood vessels
  • cause the heart to beat faster
  • trigger the release of glucose from glycogen (stored glucose)
  • increase oxygen to the brain

This has the effect of increasing heat within the body.

Serotonin levels in post menopausal women can drop by 50%. There are 13 sub-types of serotonin receptors, but will only mention 5-HT 1A and 5-HT 2A.  5-HT 2A causes neuronal excitation and is implicated in hot flushes. It also causes behavioural effects, platelet aggregation and anxiety. If 5-HT 2A receptors increase, it's thought to cause a change in body temperature. This causes the autonomic system to switch on to try to cool the body down. It does this via 5-HT 1A which dilates blood vessels in the skin. This increases heat dissipation from the body out into the environment, causing sweating and a decrease in body temperature. It also causes a decrease in blood pressure, heart rate and anxiety.

Progesterone is a potent vasodilator, it's also thermogenic, which would increase skin temperature, particularly if a transdermal application was used. It's also an anxiolytic and so reduces anxiety.

It is currently thought that reduced estrogen levels cause 5-HT 2A to increase. But it's not listed amongst the antagonists which decrease 5-HT 2A. Antagonists of 5-HT 2A, such as some SSRI antidepressants, reduce hot flushes. Whereas activation by an agnonist upsets the thermoregluatory system and causes a hot flush. The psychedelic drugs like LSD, psilocin and mescaline, act as agonists on the receptor.

Nighttime prevalence (NTP) of hot flushes could be due to the drop in serotonin due to it's conversion to melatonin. There is a slight improvement with the use of SSRI's, but the side effects are in some cases, the same symptoms that are experienced with hot flushes.

5-HTP reduced hot flushes non-significantly in one study, but generally tryptophan is more effective than 5-HTP. Another small study found tryptophan depletion did not increase hot flushes. Depleting tryptophan defeats the purpose, increasing it would be more effective.

Sumatriptan, a 5-HT1 receptor agonist, is structurally similar to serotonin, and is used to treat increased CGRP levels in migraine by inhibiting it's release. An interesting concept would be to study whether serotonin or it's precursor tryptophan, would inhibit CGRP and provide a possible cure for hot flashes.

A natural inhibitor of noradrenaline is nucleoside adenosine. Dopamine and serotonin also inhibit it. Progesterone is a mono amine oxidase inhibitor, therefore preventing the breakdown of serotonin and dopamine. It also increases the release of adenosine.

Allopregnanolone, a metabolite of progesterone, is a potent anxiolytic and anti-inflammatory, which also increases dopamine levels.

Adrenaline and angiostensin stimulate noradrenaline release. Vitamin D3 inhibits angiotensin, progesterone inhibits adrenaline and noradrenaline.

To recap in simple terms:

  • Hot flushes increase in severity and frequency during the last year or so of Peri-menopause. Progesterone is dropping precipitously during this period, as anovulatory cycles occur with greater frequency. But ovarian estrogen does not drop until the last viable egg has completed it's growth. Estrogen in the form of estrone, is still produced by adipose cells, these do not secrete progesterone to counter the estrogen.
  • An interesting point, but women with Turner's syndrome, or young women with ovarian dysgenesis, having very low levels of estrogen, or none at all, never have hot flushes unless first given estrogen. This makes one wonder if the reason is nothing more than excess estrogen causing hot flushes, and not a drop in estrogen as women are lead to believe. This is certainly supported by the fact that progesterone is dropping sharply during the last year or two of peri-menopause, but estrogen is not.
  • A sudden surge in adrenaline and noradrenaline can cause a hot flush. This surge can be provoked by blood glucose dropping too suddenly. This itself is often caused by eating or drinking something sweet.
  • Stress, if sudden, causes a surge in the two hormones, see Anxiety.
  • A drop in serotonin can cause a hot flush. This drop can occur because of stress, lack of the precursor amino acid tryptophan in the diet, or a reduced ability to convert tryptophan into serotonin. This latter could be due to a lack of the necessary co-factors vitamin B6 and folic acid which drop when stressed, as do all the B vitamins. Interestingly enough, Vitamin B3 can cause hot flushes if too much is taken.
  • Excess CRH and TRH could possibly be implicated, released in response to stress.
  • A high level of CGRP is found in menopausal women. An elevated level of CGRP is implicated in hot flushes, particularly during a hot flush. Men who've been castrated or are on anti-androgen therapy can have an increase in CGRP during a hot flush.
  • Although high levels of CGRP have been found in pregnancy, it seems likely the increase is due to excess estrogen and NOT progesterone. This is certainly the case in peri-menopause with dropping progesterone levels. Estrogen is an excitatory hormone, whereas progesterone is calming.
  • Progesterone is a potent anxiolytic, in part due to it's action on the GABA receptor sites. GABA is a calming neurotransmitter. And in part because it inhibits the release of adrenaline and noradrenaline from the adrenals. It's also a monoamine oxidase inhibitor, so increasing serotonin and dopamine levels slightly. Plus it inhibits the release of CRH. All of which points to progesterone being a potential cure for hot flashes.

The disturbed ratio of progesterone and estrogen is more than likely behind hot flushes in women. Probably in men too if they have been castrated or are on anti-androgen therapy. Testes bein a source of progesterone and testosterone.

Hot flushes and night sweats are associated with:

  • higher blood pressure
  • cardiovascular risk
  • higher factor Vllc (a clotting factor)
  • higher inflammatory markers, and are a marker for risk of adverse bone health

CGRP, CRF, prolactin and estrogen are inflammatory hormones, often found in excess in peri-menopause and menopause. Progesterone is an anti-inflammatory hormone, mainly due to it's metabolite allopregnanolone. It inhibits mast cell secretions, CGRP, CRF, prolactin and estrogen, all inflammatory. It also inhibits platelet aggregation, which leads to increased clotting, and stimulates osteoclasts involved in bone formation. Being a potent vasodilator, it can reduce blood pressure, plus it increases the production of NO, itself a potent vasodilator.

Menopause is associated with an increased prevalence of Insulin Resistance and metabolic syndrome (MetS), which are risk factors for cardiovascular disease. There is a higher frequency of symptoms such as hot flashes and sweating in women with MetS. Excess estrogen is one of the causes IR. So is a lack of vitamin D3.

Reducing stress will help to cure hot flashes. Something that most of us find extremely difficult to do as we live in a stressful world!  Keeping blood glucose stable by avoiding all sugars, any food or drink containing sugar, any sweet starchy foods which convert to sugar, ie grains, legumes or sweet fruits and vegetables that fall into this category. By reducing the stress response, which increases anxiety and inflammation, progesterone assists in regaining homeostasis.

It is vital too to keep the ratio of progesterone to estrogen high

In conclusion, It seems all the more likely that high levels of estrogen are responsible for hot flushes. As mentioned earlier, estrogen causes the temperature to drop, and it will stay down if excess estrogen is present.  The body sensing this sends out emergency messages to bring it up again. The end result being a hot flush.

Much the same overreaction occurs if blood glucose drops too sharply. The brain sends an emergency message to the adrenals to make adrenaline to bring it up again. But the end result is a pounding heart and possible panic attacks.

Hot flushes and night sweats are associated with higher blood pressure, cardiovascular risk, higher factor Vllc (a clotting factor), higher inflammatory markers, and are a marker for risk of adverse bone health. Excess estrogen is associated with all these.

Please read How to use Natpro Progesterone Cream and Estrogen Dominance.

 

Natural treatment/cure for Hot Flashes

  • progesterone
  • tryptophan/5-HTP
  • deep breathing
  • acupuncture
  • yoga
  • hypnosis
  • salvia officinalis

Usually women require 100-200mg per day Natpro Progesterone Cream, unless symptoms are severe. Hot flushes on the other hand, once started, will only respond to 400-500mg per day, sometimes more in the beginning. Once they clear, the amount can be reduced SLOWLY. Please read How to use Natpro Progesterone Cream.

Men generally need 10-100mg per day Natpro Progesterone Cream, but 100mg per day and over will be needed to stop hot flushes.

Consider taking tryptophan, the precursor amino acid to serotonin, and tyrosine, the precursor amino acid to dopamine. This will raise dopamine levels which will inhibit prolactin production. Please read the Anxiety page.

Vitamin D3 is essential for the normal functioning of all cells. It's also a potent anti-inflammatory and antioxidant, consider having a test done. For more information and vitamin D3, visit the Vitamin D Council, GrassrootsHealthBirmingham Hospital and Vitamin D3 Links.

Medical treatment

  • HRT
  • SSRI antidepressants
  • Clonidine an anti-hypertensive
  • Progestins
  • Gabapentin an anticonvulsant

Alternative treatments to HRT include the following.  They all have non-significant effects

  • Phyto-estrogens in particular the isoflavones from soy, which have an estrogenic effect
  • Herbs such as dong quai, agnus castus, red clover, black cohosh, all estrogenic
  • Vitamin E

Reference websites

Woman's Health Resource

Patient.co.uk

NHS

Thyrotropin - realising hormone (TRH)

Corticotropin - realsing hormone (CRH)

Adrenocorticotropic hormone (ACTH)

Adrenaline


References - cure for Hot Flushes

Treatment of menopausal hot flashes with 5-hydroxytryptophan

Evaluating the role of serotonin in hot flashes after breast cancer using acute tryptophan depletion

In vitro metabolic interactions between black cohosh (Cimicifuga racemosa) and tamoxifen via inhibition of cytochromes P450 2D6 and 3A4

Review of the efficacy of green tea, isoflavones and aloe vera supplements based on randomised controlled trials

A phase III, randomized, placebo-controlled, double-blind trial of flaxseed for the treatment of hot flashes: North Central Cancer Treatment Group N08C7

Hot Flashes Linked to Insulin Resistance

Acupuncture for Hot Flushes in Perimenopausal and Postmenopausal Women

Are vasomotor symptoms associated with alterations in hemostatic and inflammatory markers? Findings from the Study of Women's Health Across the Nation

Heart rate variability in menopausal hot flashes during sleep

The systemic inhibition of nitric oxide production rapidly regulates TRH mRNA concentration in the paraventricular nucleus of the hypothalamus and serum TSH concentration. Studies in control and cold-stressed rats

Association between menopausal symptoms and metabolic syndrome in postmenopausal women

Sexual Adjustment to Androgen Deprivation Therapy: Struggles and Strategies

Nonestrogenic Management of Hot Flashes

Information needs of men on androgen deprivation therapy

Effectiveness of compounded bioidentical hormone replacement therapy: an observational cohort study

Effects of menopausal status on circulating calcitonin gene-related peptide and adipokines: implications for insulin resistance and cardiovascular risks

Progesterone Prevents Estradiol-Induced Dendritic Spine Formation in Cultured Hippocampal Neurons

Progesterone alters GABA and glutamate responsiveness: a possible mechanism for its anxiolytic action

Nonestrogen Management of Menopausal Symptoms