Burnout in young girls
Dr. John Kamsteeg
There is a big difference between the occurrence of burnout in men and women. These burnout symptoms are associated with the occurrence of specific autoimmune diseases. Generally in the population, Bechterev’s disease, Hashimoto’s thyroiditis, systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis are two to ten times more common in women than in men. The autoimmune diseases that are more common in women usually occur during sexual maturity. It is remarkable that not all autoimmune diseases are equally well represented in burnout and certainly not in HPU. Since HPU is also much more common in women and there are large differences in symptoms between women and men, this must have something to do with the difference between men and women. If so, it means not only that there is a difference in the incidence of autoimmune diseases in men and women, but that there should perhaps also be a difference in treatment.
Hier you can read the original in the German language: OM_&_Ernährung_Sonderheft 14_2019,14-20 or below you can read the translation.
The underlying mechanisms regarding the differences in the occurrence of burnout and the possibilities of a specific treatment of women with burnout and autoimmune diseases are discussed. There are a number of factors that can explain a difference between men and women:
The pro-inflammatory effect of estrogens and the anti-inflammatory effect of progesterone and testosterone[1,2].
Many authors describe the influence of sex hormones on the immune system and the stress regulation system. It appears that estrogens mainly have a pro-inflammatory effect, while testosterone and dihydrotestosterone are more likely to have anti-inflammatory effects . Testosterone seems to shift from Th2 to Th1, while estrogens have a stimulating effect on the Th2 system. Most people with HPU have a Th1 dominance.
|Th1 dominance in HPU||Th2 dominance in HPU|
|Sjögren Syndrome||Inflammatoire Bowel Disease|
|Lichen planus||Ulcerative colitis|
|Reumatoid artritis||Multiple Chemical Sensitivities|
|Chronic viral infections||Food supplement intolerances|
It seems that in any case men, but also women suffering from autoimmune diseases or stress or having burnout, have free and total testosterone plasma levels that are significantly lower than in healthy control groups [3,4]. This is not the case in women who do top-level sport; in them the testosterone level increases and the oestrogen level decreases; in men the oestrogen increases and the testosterone decreases.
Programmed sex hormone sensitivity at the beginning of life.
Another factor is the change in regulation due to early exposure to steroids . By the age of eighteen, lymphocytes have both estrogenic and androgenic receptors. After the eighteenth year, all androgenic receptors in lymphocytes disappear and are only sensitive to estrogen. The programming of estrogen sensitivity can therefore influence the development of stress processing and the development of autoimmune diseases after the age of eighteen. This increased sensitivity to estrogen occurs early in life during pregnancy when the unborn child is exposed to obesogens and organotin compounds (organotins). Women who have taken the pill also have children who are sensitised to oestrogens.
Produktion of larger amounts of prolactin in women.
The production of larger amounts of prolactin in women is also a possible factor in the occurrence of stress, burnout and autoimmune diseases in women. If you want to measure prolactin, you need to be careful; it has a circadian rhythm; it is high late at night and low during the day. Prolactin has a pro-inflammatory effect at high concentrations. Hyperprolactinaemia has been associated with the occurrence of several autoimmune diseases. The exact mechanism of action is unclear, but measures that reduce the amount of prolactin appear to improve autoimmune diseases [7,8]. Estrogens stimulate the production of prolactin in women. But the difference in stress response between men and women also leads to increased prolactin production in women. When a stress reaction occurs in men, this means primarily an increased activation of the right orbitofrontal lobe in the brain and a reduced third activation of the left orbitofrontal lobe. In women, however, the stress reaction has a completely different effect. In women, a stress reaction does not significantly alter the frontal lobes, but leads to a limbic, dopaminergic, oxytocin, angiotensin and prolactin-containing reaction. Women therefore produce more prolactin than men, not only because of the higher production of estrogens, but especially because of the higher production of prolactin during the stress reaction. Prolactin increases the adhesion of leukocytes to the tissue. Oxidative stress causes prolactin to be proteolytically degraded to a factor that is, among other things, strongly pro-inflammatory .
Young girls who participate in top-level sport have without exception an elevated prolactin level in their blood. These elevated levels are accompanied by a more pronounced development of the breasts, which is an undesirable situation. This increase in prolactin is accompanied by a sharp rise in testosterone and oestrogen. This often prevents menstruation, which is a welcome side effect. In young men who do top-class sport, the prolactin increases much less, but here the testosterone level drops and the oestrogen level rises. We expect female athletes to be more or less male, given their appearance, but the fact that male athletes are more feminine is often not recognised or is quite wrongly attributed to the use of stimulants.
Prolactin is produced in both the pituitary gland and the body. Prolactin is produced, among other things, by the activation of histamine receptors. The binding of antihistamines to H1 receptors such as cimetidine also ensures the additional release of prolactin.
Prolactin inhibits the release of GnRH and reduces LH (luteinizing hormone) and FSH (follicle stimulating hormone). Prolactin lowers hepcidin, which causes the iron level in the blood to rise, but the ferritin level to fall. In addition, prolactin with parathormone stimulates serotonin production and leads to bone loss.
Prolactin and celiac disease
Celiac disease is a gluten-sensitive autoimmune enteropathy in which both adaptive immunity and innate immunity are involved . Serum prolactin levels were positively correlated with disease activity, the degree of mucous membrane atrophy and the serum concentration of anti-endomysial antibodies. Recently, a longitudinal study showed that prolactin decreased six months after a gluten-free diet. The evidence that prolactin decreases simultaneously with the decrease in antibodies against transglutaminases suggests a direct relationship with gluten-free diet and hormone levels .
Indeed, women have improved immunoreactivity: they have a better ability to present antigens and mitogenic reactions, increased antibody production, higher immunoglobulin (Ig) levels and the ability to reject antigens more quickly . The immune and neuroendocrine systems are closely linked and participate in dynamic two-way communication. Prolactin has a recognised immunostimulatory effect, in particular it inhibits the negative selection of autoreactive B-lymphocytes and promotes autoimmunity. Therefore, hyperprolactinemia is associated with several autoimmune diseases. Prolactin stimulates the production of immunoglobulin. It also stimulates the development of antigen-presenting cells, class II histocompatibility complexes and stimulation molecules (CD86, CD80 and CD46) .
Prolactin and thyroid autoimmune diseases
Autoimmune thyroid diseases consist mainly of two diseases, Graves’ disease and Hashimoto’s thyroiditis . Hyperprolactinemia was found in 20% of patients with autoimmune thyroid disease and was twice as common in patients with hypothyroidism. About 90% of inflammatory thyroid patients with Hashimoto showed significantly higher prolactin levels associated with reduced cortisol titers . The role of dopamine agonists in the treatment of autoimmune thyroid diseases is not yet known.
Hyperprolactinaemia due to D2-receptor blocking antipsychotics
D2-receptor blocking antipsychotics cause hyperprolactinemia in 60% of children and adolescents and in 40% of men and 60% of women. A long-standing hyperprolactinemia in adults leads to reduced bone density and a doubled risk of hip and thigh fractures. In addition, women with hyperprolactinemia have a 16% increased risk of developing breast cancer.
Activation of the HPA axis by estrogens that produce more cortisol[15,16].
The increase in cortisol production is often attributed to the stress response, but it is precisely the continuous stress response that causes less and less cortisol to be produced and this production is initially maintained by sacrificing DHEA and pregnenolone (Pregnenolone Steal Syndrome). DHEA inhibits cortisol production, so sacrificing DHEA for cortisol production is the beginning of a major problem.
A fourth factor is therefore the activation of the HPA axis (hypothalamic-pituitary-adrenal cortex axis), which produces more cortisol. Normally, this increase is regulated by increased production of cortisol binding globulin (CBG) and DHEA. However, if the HPA axis remains (over)active for a longer period of time, there is a prolonged (over)production of cortisol, which causes a change in sensitivity to cortisol and thus reduces the immunoregulatory effect. This can lead to a further shift from Th1 to Th2.
There is also a correlation between the production of estrogens and the activity of the HPA axis. Thus, increased cortisol levels may be associated with periods of infertility . Conversely, estrogens can influence the function of the HPA axis. There is evidence that estrogens contribute via estrogen receptors to the activation of CRH in the CRH neurons [18,19]. In this way they may have a stimulating effect on the HPA axis [20,21]. It should be noted that neurotransmitters such as dopamine and serotonin may play a modulating or even decisive role in this . Estrogens can also reduce the number of glucocorticoid receptors in the hypothalamus and pituitary gland and interrupt the inhibitory effect of cortisol on HPA axis activity . Research by Lindholm & Schultz-Moller  gives an indication of the activating effect of estrogens on the HPA axis activity. They compared pregnant women and women who had been given estrogens with a control group of patients. They found elevated basal cortisol levels in the pregnant women and the experimental group. Elevated cortisol levels were also found in men who were administered oestrogens and who were subsequently exposed to a stressor . Ultimately, therefore, fluctuations in oestrogen levels lead to changes and possibly also to disturbances in the activity of the HPA axis. This can lead to an increased susceptibility to burnout symptoms.
Activation of estrogen receptors by organotins and obesogens.
Last, but not least, the activation of estrogen receptors is enhanced by the presence of organotins and obesogens. Organotins are harmful to the visceral organs and obesogens lead to obesity. Both substances are present in daily nutrition (as pesticide and herbicide residues), are used in plastics, are contained in hormone preparations in animal husbandry (e.g. for chickens and cows), are used as fungicides in paints and reduce textile abrasion. Organotins and obesogens are considered to be one of the main factors for endocrinological, neurological and immunological disorders. This is because they have a high affinity for estrogen receptors and a half-life at least ten times longer than that of natural sex hormones. This means that organotins and obesogens pathologically prolong the activation of estrogen receptors. This activates a large number of genes with pro-inflammatory and fat-producing effects. Due to the increased presence of estrogen receptors, women therefore have an increased risk of developing autoimmune diseases. The overactivity of the oestrogen receptor indicates, among other things, reduced insulin sensitivity, increased cholesterol levels and reduced production of vitamin D, which further promotes pro-inflammatory activation.
In recent neurotoxicological studies, there is growing interest in chemical pollutants with endocrine disrupting factors . Endocrine disrupting chemicals (EDCs) are compounds that are able to alter and modulate the normal function of the endocrine system, either by increasing or blocking the synthesis, release and action of a natural hormone or by acting like a xenohormone and mimicking the physiological effects of a specific endogenous hormone [7,3]. EDCs with neurological and behavioural effects include bisphenol A, phthalates, organometallic compounds such as methylmercury and organotins (OTs) [2,7,4]. OTs are organometallic compounds with one or more bonds between a carbon atom and a tin atom. They disturb the metabolism of gonadal and metabolic hormones [15,4] and show cytotoxic and genotoxic effects, are known to cross the blood-brain barrier and show neurotoxic effects leading to abnormalities of the nervous system [2,6,8,9]. Obesogens are certain substances that can impair the action of hormones. This is due to the hormones leptin, ghrelin, cortisol and insulin. Obesogens are not only associated with obesity, but also with birth defects, premature puberty in girls, breast cancer and other diseases. In boys it can lead to loss of sexual characteristics and loss of libido. When pregnant women are exposed to these chemicals, the unborn child is more likely to become fatter later.
Bisphenol-A, also known as BPA, is a synthetic substance that occurs in many product types. Think of baby bottles, drinking cups and food wrapped in plastic. It can also be found in cans and canned foods. Bisphenol has been used commercially for many decades. However, recent studies have shown that high concentrations can be harmful to people.
Exposure to BPA is associated with, among other things, obesity, insulin resistance, heart disease, diabetes, thyroid disease, cancer, genital malformations, neurological diseases. There is consensus that high levels of BPA can make people fatter and it can have other adverse health effects.
Weight increase due to phthalates
Phthalates are chemicals used to make plastics soft and flexible. You can find them in various products such as bread and food trays, toys, medicines, paints, shower curtains and beauty products. The disadvantage of phthalates is that they can be easily dissolved from the plastic. As a result, you absorb them through your food, drinks and even through the air you breathe. Just like BPA, phthalates are endocrine disrupters. This can lead to weight gain. They do so by affecting certain hormone receptors that are involved in your metabolism. Men in particular seem to be susceptible. Exposure to phthalates in the womb can cause genital malformations, low testosterone levels, etc., and not descending testicles.
Atrazine is one of the most widely used herbicides in the USA. Its use has been banned in Europe for more than 10 years. This is due to the pollution of ground water. Atrazine also interferes with hormones. Various studies have shown that exposure to atrazine correlates with congenital abnormalities in humans. In the USA, there is a correlation between the areas where this herbicide is widely used and people who are fatter (obesity). Research on rats shows that atrazine damages mitochondria, reduces the metabolic rate and increases weight.
Organotins are a specific type of artificial chemicals (organotin compounds) used for various industrial purposes. The European Union has banned a number of such compounds for consumer products.
Some compositions of these chemicals are used to lubricate the hulls of boats. This prevents all kinds of aquatic animals and organisms from growing on the hull. However, this is one of the reasons why many lakes and coastal waters are contaminated with these chemicals. A test-tube study showed that these chemicals led to rapid growth of fat cells. This leads to weight gain.
Some scientists believe that these chemicals act as hormonal disrupters and can make people fatter. In this way, it contributes to the obesity epidemic by increasing the number of fat cells. There is also evidence that unborn children who are exposed to these chemicals can increase the number of fat cells. This can lead to fatter babies.
Perfluorooctanoic acid (PFOA)
Perfluorooctanoic acid or PFOA is a synthetic compound used for a variety of applications. Think of the non-stick coating of pans and it is also found in microwave popcorn. It is remarkable that this substance is found in the blood of 98% of all people. PFOA is associated with various diseases such as low birth weight, chronic kidney disease, elevated insulin levels, thyroid disease and weight gain during midlife crisis.
HPU, vitamin D receptor, Borrelia infections and prolactin production
In HPU, Borrelia infections after a tick bite often have a different course and the clinical picture ends with a post-lymphma. The possible cause can be a decrease in the zinc content in the tissue and a disturbance of the vitamin D metabolism. Borrelia burgdorferi acts on the vitamin D receptor. The VDR (vitamin D receptor) has to ensure that vitamin D from the blood reaches the cells. Borrelia burgdorferi reduce the function of the vitamin D receptor (in monocytes) by half . This leaves more than 1.25 vitamin D in the bloodstream. The Epstein Barr virus also infects the VDR in the same way. Vitamin D, like hormones, has a feedback cycle. This means that when the levels in the blood become too high, a process begins to normalise the levels.
The VDR plays an important role in the body and is found in almost all body tissues and has numerous functions. The VDR would play a role in the production of insulin, prolactin, muscle function, immune and stress response, melanin synthesis and differentiation of skin and blood cells. As the Borrelia directly influence the function of the VDR, many body processes are disturbed in their function. Many, if not all tissues contain an intracellular receptor for 1,25-dihydroxyvitamin D3. (6) When 1,25-dihydroxyvitamin D is introduced into the cell and has formed a complex together with the receptor, a combination with a complex containing vitamin A is formed. This combination binds to a vitamin D response element on the genes involved, whereupon the gene can be expressed. About 3% of our genes contain a vitamin D response element, which means that the synthesis of many proteins in our body depends on the vitamin D status. Research in recent decades has provided increasing evidence of a role of vitamin D in immunological defence, autoimmune processes, muscle function, cell differentiation and inhibition of tumour cell proliferation. The question now is whether the additional intake of vitamin D helps if the cause of the deficiency is a reduced effect of vitamin D receptors. In this case, there is no vitamin D deficiency, as the activated vitamin D is deposited in the tissue up to the copper calcitriol.
The vitamin content in the bloodstream increases, which triggers the feedback cycle. Blood values then show a vitamin D deficiency, as often occurs in chronic infectious diseases. In this way, vitamin A and vitamin D are kept in balance in the body. And an excess of vitamin D without sufficient vitamin A reduces the amount of vitamin K in the body. A lack of vitamin K can lead to arteriosclerosis, problems with blood clotting, kidney stones, osteoporosis and the like.
Treatment in the practice
The mechanisms described above not only show why women are more sensitive to stress, but also provide us with tools for treatment. In addition to the use of Resoleomics* , there are interventions that influence the factors mentioned above. It is important to regulate sex hormones, desensitise oestrogen receptors and rid them of obesogens and organotins. Curcumin regulates both the HPG axis (Hypothalamic-Pituitary-Gonadal Axis) and the HPA axis and regulates both sex hormones, prolactin and cortisol. Panax ginseng and ginkgo biloba are another way to regulate the HPA axis. The further regulation of prolactin can be achieved with dopamine. Taking Mucuna pruriens can make a good contribution to this. Soy extracts and red clover desensitize the estrogen receptors and increase the production of SHBG in the liver. To force organotins and obesogens out of the oestrogen receptors, it is important to use natural ligands with a higher affinity to the oestrogen receptors than the organotins and obesogens. Instead of the organotins and obesogens they occupy the estrogen receptors, but only for a short physiological period .
These natural ligands are: phyto-oestrogens from soy products, other isoflavones from e.g. red clover, lucerne, curcumin, peas and other legumes. Organotins and obesogens are broken down by glutathione-dependent detoxification organisms, which are activated by sulphur-containing amino acids, proteins and selenium, among others. Cysteine, methionine and glutathione can be used to stimulate these detoxification mechanisms. It is also important to reduce the absorption of organotins and obesogens, e.g. by eating organic food and avoiding plastic packaging and preservatives for food and beverages.
* Resoleomics is a science that deals with the physiology of a pathological process such as an inflammatory process, whereby specific gene activating substances transform this pathological process into a healing or solving process.
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