HOTFLUSHES/HOT FLASHES/NIGHT SWEATS

Are you finding yourself experiencing them? These symptoms can lead to significant discomfort and restless nights for many women. They typically begin around the time of Peri-Menopause and Menopause, when hormone levels become erratic. Approximately 50% of women face these symptoms to varying extents, and they can persist for several years. Menopause is also linked to a heightened risk of estrogen-related cancers, such as breast and endometrial cancers. These symptoms can manifest during puberty, pregnancy, and even just days before menstruation, coinciding with hormonal fluctuations as progesterone and estrogen levels decline. When the balance between these hormones becomes disrupted, particularly with excess estrogen in relation to progesterone, these symptoms tend to arise. With age, the capacity of adipose tissue to produce estrogen increases significantly, but there isn’t a corresponding rise in progesterone production. This suggests that the underlying causes of hot flushes, as well as breast and endometrial cancers, may be more closely related to drops in progesterone rather than rises in estrogen. The fact that hot flushes begin during peri-menopause when estrogen levels are still elevated provides a potential clue for alleviating these symptoms.

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

The normal oral body temperature for adult men and women ranges from 33.2 to 38.2°C (92 to 101°F), with an average typical value around 37.0°C (98.6°F).

In women, temperature variations occur between the follicular and luteal phases. The follicular phase sees temperatures ranging from 36.45-36.7°C (97.6-98.1°F). In the subsequent 12-14 day luteal phase, temperatures rise by 0.15-0.45°C (0.2-0.9°F), attributed to the elevated metabolic rate brought on by a swift increase in progesterone levels. Following several days of menstruation, temperatures return to follicular levels.

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During a hot flash, it is believed that a sudden trigger activates a response in a specific body part or organism, disrupting the temperature regulation centre within the hypothalamus and leading to a loss of control. This insight suggests a potential remedy for hot flashes. Additionally, blood pressure (BP), sleep, and Anxiety are now influenced.

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 warm beverage, such as coffee or wine, can also exacerbate the situation, likely due to their potential to disrupt blood glucose levels.

The skin serves as the body's primary barrier against increasing internal temperatures, which is why flushing and sweating occur when it becomes overheated. However, our understanding of the physiology behind hot flushes remains incomplete, hindering the quest for an effective cure.

Despite being classified as a result of estrogen deficiency, hot flushes are absent in pre-pubertal girls, women with Turner syndrome who are not undergoing estrogen treatment, and older menopausal women. These individuals typically have minimal to no estrogen levels! Furthermore, young women with ovarian dysgenesis, characterized by extremely low estrogen, do not experience hot flushes unless they are first administered estrogen.

Evidence indicates that the mechanism underlying hot flushes is considerably more complex than merely a decrease in estrogen, implicating the involvement of the neuroendocrine system.

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 is situated in the brain and regulates various essential functions, including blood pressure, body temperature, hunger, thirst, and water balance, as well as playing a role in sleep and emotional activities. It serves as a connection between the nervous and endocrine systems by releasing neurotransmitters, neuromodulators, and neurohormones.
One straightforward neurohormone is TRH, which plays a crucial role in regulating temperature by maintaining energy homeostasis. TRH promotes wakefulness and suppresses appetite. Additionally, it is present in pancreatic islets and the gastrointestinal tract, where it enhances motility, particularly in women suffering from irritable bowel syndrome. Released in response to stress, TRH works to sustain the body’s equilibrium.

Thyrotropin-releasing hormone (TRH) prompts the pituitary gland to produce Prolactin Elevated levels of TRH can inhibit dopamine, subsequently leading to an increase in prolactin. Additionally, high estrogen levels contribute to heightened prolactin levels as well. An excess of prolactin, in turn, suppresses dopamine levels. While prolactin is primarily known as the hormone responsible for lactogenesis, it also functions as an inflammatory agent. A decrease in dopamine can result in feelings of anxiety and depression. Furthermore, it triggers the release of noradrenaline from the frontal cortex and stimulates the pituitary to secrete thyroid-stimulating hormone (TSH). TSH, in turn, encourages the thyroid to release thyroxine and triiodothyronine, hormones that regulate the body's metabolic rate, heat production, neuromuscular function, and heart rate.

Nonetheless, it seems that nitric oxide (NO) production might regulate the activity of the hypothalamus-pituitary-thyroid axis. NO serves as an intercellular signal that modulates vascular tone (and consequently blood pressure), insulin secretion, airway tone, and peristalsis. When NO is inhibited, the production of TSH declines, leading to reduced levels of thyroxine and triiodothyronine, which subsequently lowers the metabolic rate and temperature. The brain detects this change and stimulates the release of TRH, which then increases metabolic rate and temperature. If this response occurs too rapidly, it could cause the body to overheat.

Noradrenaline is linked to the activation of the hypothalamic-pituitary-thyroid axis and plays a role in the biosynthesis and secretion of TRH. Progesterone promotes the production of nitric oxide (NO) while concurrently inhibiting noradrenaline. A decline in progesterone levels would hinder the release of NO, resulting in an increase in noradrenaline.

Another neurohormone produced by the hypothalamus is CRH, which is released in response to stress—be it physical, emotional, external, or internal. In turn, CRH prompts the pituitary gland to secrete corticotropin, known as adrenocorticotropic hormone (ACTH). This hormone then stimulates the adrenal glands to release cortisol, which, alongside the sympathetic nervous system and specific precursor chemicals like adrenaline and noradrenaline, constitutes the trio of stress hormones. Additionally, CRH suppresses appetite, heightens anxiety, and enhances memory and selective attention. Levels of CRH rise during pregnancy as it is produced by both the fetus and placenta, and this increase is believed to ultimately trigger labour. Furthermore, CRH is present in the gut, where it can trigger inflammation. While progesterone inhibits CRH, an excess of CRH can suppress progesterone levels. High CRH levels have also been linked to conditions such as depression, anxiety, sleep disturbances, and anorexia. Moreover, it may exacerbate or potentially contribute to inflammatory disorders such as arthritis, psoriasis, ulcerative colitis, and Crohn's disease. Although progesterone levels surge during pregnancy to suppress CRH, the rising CRH levels from the fetus and placenta eventually counteract this suppression, initiating labour.

Postmenopausal women exhibit higher levels of Calcitonin gene-related peptide (CGRP) compared to their premenopausal counterparts. Adipose cells play a crucial role in CGRP production, with significant increases observed in the abdominal subcutaneous fat of postmenopausal women. Additionally, these cells serve as the primary source of estrogen production in this group. Estrogen prompts adipose cells to proliferate, leading to a self-reinforcing cycle. Elevated CGRP levels are particularly evident during hot flushes and are also present during pregnancy, indicating that estrogen and progesterone may influence their secretion.

Men can also experience hot flushes, which may be attributed to low testosterone levels, especially in older men undergoing andropause. However, these symptoms are more frequently observed in individuals receiving anti-androgen therapy for prostate or testicular cancer, or following the removal of the testes. Several studies indicate that CGRP may play a role in hot flushes among men who have undergone castration or androgen deprivation therapy due to prostate cancer. One study identified that ovarian hormones and testosterone have a suppressive effect on 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 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.

Night-time 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/flashes. 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/flashes usually start on the onset of Peri-Menopause and increase in severity and frequency during the last year or so of Peri-menopause. Progesterone drops precipitously during this period, as anovulatory cycles occur more frequently. However ovarian estrogen does not drop until the last viable egg has completed its growth. Estrogen in the form of estrone, is still produced by adipose cells, these do not secrete progesterone to counter the estrogen.
  • An intriguing observation is that women with Turner’s syndrome, or young women experiencing ovarian dysgenesis who possess very low, or even nonexistent, levels of estrogen, do not experience hot flushes unless they are first administered estrogen. This raises the question of whether the cause of these flushes is merely excess estrogen rather than a decrease in estrogen, as commonly believed by women. This notion is further reinforced by the observation that progesterone levels decline significantly during the final year or two of peri-menopause, while estrogen levels do not exhibit the same sharp decline.
  • A sudden spike in adrenaline and noradrenaline can trigger a hot flush. This surge may be triggered by a rapid drop in blood glucose levels, which is often the result of consuming something sugary.
  • Stress, if sudden, causes a surge in the two hormones, see Anxiety.
  • A decrease in serotonin levels can trigger hot flushes. This reduction may arise from stress, insufficient dietary intake of the precursor amino acid tryptophan, or a diminished capacity to convert tryptophan into serotonin. The latter may result from a deficiency in essential co-factors such as vitamin B6 and folic acid, both of which decline under stress, along with all B vitamins. Interestingly, excessive consumption of Vitamin B3 may also lead to hot flushes or flashes.
  • Excess CRH and TRH could be implicated, released in response to stress.
  • Elevated levels of CGRP are observed in menopausal women and are associated with hot flushes, especially during these episodes. Additionally, men who have undergone castration or are undergoing anti-androgen therapy may experience a rise in CGRP during a hot flush as well.
  • While elevated levels of CGRP have been observed during pregnancy, it appears that this increase is primarily attributed to excess estrogen rather than progesterone. This is particularly evident in peri-menopause, where progesterone levels decline. Estrogen acts as an excitatory hormone, in contrast to the calming effects of progesterone.
  • Progesterone serves as a powerful anxiolytic, partly owing to its interaction with GABA receptor sites, where GABA acts as a soothing neurotransmitter. Additionally, it plays a role in reducing the secretion of adrenaline and noradrenaline from the adrenal glands. Furthermore, it functions as a monoamine oxidase inhibitor, leading to modest increases in serotonin and dopamine levels. It also curbs the release of CRH. Collectively, these factors suggest that progesterone may hold promise as a remedy 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 being 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, i.e. 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.

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 Society, GrassrootsHealth, Birmingham 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

References - cure for Hot Flushes

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