Estrogens are hormones of femininity. What is their role in a woman’s body?

What is the hormone estrogen? The definition states that estrogens are a group of female hormones that are also found in small quantities in male bodies. There are many varieties of these hormones in the body, the main ones being estradiol, estriol and estrone.

What do the predominant three types of these hormones affect in women?

• Estradiol is the most active. It is administered by injection to women with severe hormonal deficiency. Estradiol is the basis of most combined oral contraceptives.
• Estrone - stimulates the development of the uterus and the growth of the mucous membrane in its cavity, as well as the formation of secondary sexual characteristics.
• Estriol - formed from the first two types. If its amount in the urine of a pregnant woman is increased, this indicates that the placenta is working well and the fetus is viable.

In women, in the first half of the menstrual cycle, these hormones are formed in the follicle, and in the second half - in the corpus luteum. Female estrogens are produced in smaller quantities by the adrenal glands. After menopause, their production occurs in the adrenal cortex. In men, these hormones are produced mainly in the testicles.

Estrogen production increases significantly during pregnancy. During this period, they are produced in the placenta.

Why are estrogens needed?

If the female body contains enough estrogen, the “symptoms” that first catch the eye are a beautiful figure with a thin waist and rounded hips, as well as velvety skin.

Estrogens in women are steroid hormones: they affect the growth and development of the genital organs, preparing the woman for motherhood. Under their influence, the following changes occur in the body:

• secondary sexual characteristics are formed (hair appears in the armpits and pubic area, the characteristic shape of the pelvis is formed, and the mammary glands enlarge);
• an acidic environment is created in the vagina (for the period from puberty to menopause);
• the size of the uterus increases;
• fat cells are distributed (on the chest, hips, buttocks, knees), which gives the figure a more feminine outline.

If the female body contains this hormone in sufficient quantities, symptoms appear in regular periods.

Recommendations for losing weight

If you are overweight due to estrogen imbalance, you should lose no more than 2-3 kg per month. This pace is favorable for hormonal recovery. Every month, estrogen, released from adipose tissue, will enter the blood in the required quantity and transform the figure, prevent the appearance of stretch marks and other negative consequences of losing weight.

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Increased hormone levels

Among women

Some of the most important hormones in a woman’s body are estrogen and progesterone. Both are produced in the ovaries. These hormones are released at different phases of the menstrual cycle.

On the first day of menstruation, the pituitary gland releases follicle-stimulating hormone (FSH). Under its influence, the follicle begins to develop on the ovary and estrogens are released. As soon as their level rises to a certain point, they block the release of FSH. This occurs approximately on the 12th–15th day of the cycle.

At this time, the pituitary gland begins to secrete another hormone - luteinizing hormone (LH). When its level rises, ovulation occurs - the follicle bursts and an egg ready for fertilization emerges. After ovulation, estrogen levels decrease and progesterone begins to be produced in the ovaries.

Schematically, the production of hormones during the menstrual cycle can be represented as follows:

follicle-stimulating hormone (pituitary gland) → estrogens (ovaries) → luteinizing hormone (pituitary gland) → progesterone (ovaries)

Oral contraceptives operate on this principle: they regulate the amount of female hormones in the body. At the same time, they reduce the level of FSH to such an amount that luteinizing hormone does not begin to be produced. No luteinizing hormone - no ovulation.

In men

Normally, in men, the amount of estradiol should fluctuate between 50–130 pmol/l. Increased hormone levels in men may indicate a tumor in the testicles.

What it is?

Phytoestrogens are substances of plant origin that resemble estrogens in their chemical structure. The largest amounts are found in soybeans, red clover, flax seeds, alfalfa, red grapes, and hops. They were discovered by scientists at the beginning of the last century, and gained popularity at the end of it.

Scientists have noticed that women living in Southeast Asia endure menopause much easier than European and American women and are less likely to suffer from osteoporosis, breast cancer and cardiovascular diseases. And in the diet of Asian women, soy, which is extremely rich in estrogen-like substances, occupies a significant place. True, at the moment the conclusions from these studies are called into question, because the difference in the incidence rate of women from different countries can be caused by many other reasons.

Soy, which is extremely rich in estrogen-like substances, occupies a significant place in the diet of Asian women, but at the moment the conclusions from these studies are called into question.

Lack of estrogen

Lack of female hormones in childhood is the reason for slow development:

• mammary glands;
• female genital organs;
• skeleton.

If adolescents have a lack of estrogen after puberty, the following symptoms may occur:

• reduction of the mammary glands (after the breasts have grown, they begin to shrink);
• absence of menstruation;
• reduction in the size of the uterus.

If a woman of childbearing age is estrogen deficient, the most common symptoms include:

• sudden change in mood;
• “coldness” in bed;
• irregular monthly cycles;
• pain in the lower abdomen during menstruation;
• insomnia;
• decreased performance;
• memory impairment;
• skin problems.

With a lack of hormones, inflammation and stretch marks may appear on the skin, and elasticity may decrease. As you can see, problems due to hormonal imbalance are mainly “female”: these hormones help us to be more feminine and beautiful.

What happens when there is too little estrogen in a woman's body?

Somatic ailments are associated with the influence of estrogens on estrogen-dependent tissues. The lack of hormones dramatically changes their functioning.

• Low estrogen levels affect the circulatory system. When its concentration decreases, unfavorable changes in the lipid profile occur. The simultaneous occurrence of changes in the vascular walls and the promotion of the formation of atherosclerotic plaques increases the risk of developing coronary heart disease in postmenopausal women.
• A decrease in estradiol concentration also negatively affects bone health. Estrogen deficiency is associated with decreased bone density and bone loss.
• A decrease in the content of collagen and hyaluronic acid in the skin leads to its aging and decreased elasticity. Estrogen deficiency is also responsible for this process.
• Estrogen-dependent tissues include tissues of the genitourinary system. The condition of the connective tissue of the genital area and the supporting apparatus of the reproductive organ depends on the concentration of estrogen. When they are absent, the connective tissue and support system of the uterus weakens. This leads to a tendency to static disorders of the reproductive organ, hernias and urinary incontinence.
• The effect of estrogen deficiency on the condition of the mucous membrane of the genital tract is undeniable. In postmenopausal women, there is a predisposition to atrophic changes (atrophic vaginitis, vaginal atrophy) and dryness of the vaginal mucosa. A decrease in estrogen concentration causes a decrease in the amount of glycogen in the cells of the vaginal mucosa.

This affects the pH of the genital tract and the emergence of a tendency to bacterial infections. The effect of estrogens during atrophic changes in the skin of the vulva cannot be denied. Lack of estrogen can affect the occurrence of retrograde skin lesions.

How to increase estrogen?

If you notice the above signs of hormone deficiency, consult your doctor. Depending on the test results, he selects an individual way to increase hormones.

Doctors often prescribe tocopherol (vitamin E) to patients. It is also possible to take hormonal medications (oral contraceptives). Each tablet of combined oral contraceptives contains estrogen and progesterone (in different ratios).

You can also increase hormone levels in women with the help of food. They contain phytoestrogens - these are non-steroidal plant hormones, the structure of which is similar to human hormones. They contain:

• soybeans and soy products (milk, cheese, butter, flour, yogurt);
• other types of legumes (beans, peas, beans);
• products of animal origin (meat, fish oil, dairy products);
• some vegetables and fruits (carrots, red grapes, eggplants, tomatoes, pumpkin, cauliflower and Brussels sprouts);
• coffee.

If there is a lack of these hormones in the body, try to eat a dosed amount of these foods. Excessive portions can cause excess hormones.

Low estrogen levels - treatment

Therapeutic options for menopausal symptoms are based on hormone replacement therapy (HRT). There are specific indications and contraindications for the use of estrogens.

In each clinical case, the advantages and disadvantages of using HRT should be considered individually. There are different ways to administer estrogen - tablets, patches, gels, implants and creams. They can be administered intravenously, vaginally or orally.

To get rid of vaginal dryness, you can use special lubricants or vaginal moisturizing beads with hyaluronic acid. They reduce burning and discomfort. This is a good way to relieve pain during intercourse.

Any treatment should be prescribed by a gynecologist after receiving test results.

Excess estrogen

With an increased amount of these hormones in the body, the following side effects may occur:

• nausea, vomiting;
• headache and dizziness;
• insomnia;
• irritability;
• soreness of the mammary glands;
• swelling, including bloating;
• high blood pressure;
• irregular periods;
• cold extremities (arms, legs);
• weight gain;
• fatigue;
• acne;
• hair loss;
• blood clot formation;
• tumors (uterus, breast, endometrium).

Both excess and deficiency of these hormones immediately manifest themselves externally and internally. In Russia, a lack of female hormones is rare, but an excess of them is very common. This is why Russian women are often diagnosed with breast cancer, mastopathy, and severe premenstrual syndrome.

If you experience the symptoms described, contact your doctor immediately. Adjust your hormonal levels before the situation gets worse.

hormone, estrogen, hormones

Possible consequences and complications

If estrogens are secreted in insufficient quantities, there is no therapy, and pathological conditions develop:

• obesity;
• bone destruction;
• thrombosis;
• infertility;
• mastopathy;
• breast tumors;
• metabolic disorders;
• thyroid pathology;
• mental and nervous disorders;
• ovarian cysts;
• menstrual cycle disorders.

With excess estrogen, weight also increases, skin condition worsens, breast sensitivity increases, and blood pressure rises. Sleep, gastrointestinal function, and psycho-emotional background suffer.

The main task of estrogen is to provide a woman with the opportunity to become pregnant and bear a fetus. It is also thanks to this hormone that girls develop a typically female figure, thinner and more elastic skin than men, and no hair in the chest and abdomen. With an excess or deficiency of all fractions of estrogen, hormonal levels are disrupted, which is fraught with health complications and difficulties in conceiving and bearing a fetus.

Cruciferous vegetables and garlic

First of all, these are all types of cabbage known to us. They have been studied for a long time and carefully; phytoestrogens, in significant quantities, have been found in each representative of this family ().

Broccoli and cauliflower are rich in one of the representatives of lignans – secoisolariciresinol. And cabbage and Brussels sprouts contain coumestrols, which also have estrogenic activity (31).

We should also talk about garlic. An ambiguous plant due to its smell. However, its benefits to the body are beyond doubt.

Most studies on the effects of garlic on estrogen-deficient individuals have been conducted on animals. Thus, in female rats with removed ovaries, while feeding with garlic oil, an improvement in the condition of bone tissue was noted (18, 19, 20).

For postmenopausal women, the results of taking garlic have been mixed. The activity of inflammation, an inducer of osteoporosis, decreased, but the hormonal levels did not statistically change ().

6. Cereals

Cereals and cereal products contain significant amounts of phytoestrogens, in particular lignans. As expected, the leader in this indicator is bread with soy and flax additives (26).

Doctors also paid attention to bran, which actually turned out to be rich in lignans. However, in a number of studies, the use of bran in food led, on the contrary, to a decrease in estrogen levels. A more pronounced drop occurred with daily intake of 10 and 20 g of bran, and 5 g did not have a noticeable effect on the concentration of sex hormones (27). This effect is associated with the fact that fiber, which bran is also rich in, binds phytoestrogens and does not allow them to realize themselves.

Folk remedies

The use of folk recipes can both increase estrogen in a woman and lower it. Herbal decoctions and infusions of medicinal plants show high effectiveness in therapy for a lack of estrogen in the female body. The use of proven methods quickly normalizes hormonal levels.

Nettle

This plant protects the reproductive system from the appearance of inflammatory processes, and also normalizes the menstrual cycle. When combined with lemon juice, nettle stimulates estrogen production. As a result, the negative symptoms of menopause appear in a milder form.

Medicine recipe:

1. Nettle leaves are crushed.
2. The plant is placed in a pan of water.
3. Add lemon juice and zest, grated on a fine grater.
4. The products are cooked for 20 minutes. under the lid.
5. The broth is filtered.
6. Take internally as tea.

The use of nettle decoction may have contraindications. It is recommended to consult a doctor before using a prescription.

Raspberries

Raspberry leaves saturate the body with vitamin E. They balance hormones and strengthen the immune system.

How to increase estrogen in a woman with raspberries:

• The raspberry decoction is poured with boiling water and left for 1 hour. During this time, the product infuses well.
• Add a little mint. It will make the nervous system strong and tone the body.
• The resulting decoction should be drunk at least 2 times a day. Tea can be completely replaced with it.
• Gynecologists recommend drinking raspberry infusion in courses, starting from the 15th day of the cycle until the start of menstruation.

Red clover

The plant is enriched with coumestrol and isoflavonoids from the isoflavone group. Red clover has shown good results in the fight against negative signs of the postmenopausal period. It is one of the medicinal herbs.

There are no data on studies of its effect on human health with constant and long-term use. There has also been little testing done on the effectiveness of the herb as a hormone replacement therapy.

Hibiscus

This tea variety has high estrogenic activity. The chemical elements included in its composition work like natural female hormones. It is contraindicated in the early stages of pregnancy, while taking oral contraception and undergoing replacement therapy. Hibiscus tones the walls of the uterus, which threatens miscarriage.

Red brush

Red brush contains phytoestrogens. The medicinal plant is a good substitute for synthetic drugs that are prescribed to normalize the ratio of progesterone and estrogen levels. Regular use of herbal decoction improves sleep and relieves aggression and irritability.

Melissa and rosehips

Rosehip protects the organs of a woman’s reproductive system from the development of various diseases, enriches the body with vitamins B and C. Melissa has a positive effect on menstrual irregularities, increasing blood circulation in the pelvis.

It also has a rejuvenating effect on the body and relieves stress.

To prepare the decoction, dried lemon balm leaves and rose hips are mixed in 1:1 proportions. I fill them with water so that it covers the plants. Bring the mixture to a boil and cook for 40 minutes. The resulting decoction should be taken warm instead of tea.

Herbs

Herbal decoctions and infusions, the use of which replaces regular tea, help a woman survive the difficult period of menopause. They calm, soften hot flashes, relieve drowsiness and insomnia. After a course of treatment, heart rate and blood pressure return to normal, metabolism improves.

Plants containing estrogen:

• sage;
• mint;
• hop;
• Melissa;
• ginseng;
• chamomile;
• arnica;
• valerian;
• linden flowers;
• oregano;
• liquorice root;
• hawthorn;
• calendula;
• St. John's wort.

Flaxseed oil and psyllium seeds

Flax oil helps soften the course of menopause and normalize the menstrual cycle. It relieves headaches, mood swings, and insomnia. Plantain seeds are used in the treatment of infertility. They have a positive effect on a woman’s genitals and hormonal levels.

Plantain seeds are poured with linseed oil and left to brew for 24 hours. You need to take the medicine on an empty stomach, 3 times a day, 1 tsp. You should not expect a strong effect from the product. The effect will be much weaker than when using synthetic drugs.

Hop cones and mint

Hop cones quite quickly raise the concentration of estrogen in a woman’s blood. They help shape your figure and relieve fatigue.

How to increase estrogen in a woman with a decoction of hops and mint:

1. The hops are poured with hot water.
2. Place on fire and bring to a boil.
3. Add mint leaves.
4. The mixture is boiled for 40 minutes.

The medicine is taken warm 3 times a day, half a glass.

Signs of Hormone Imbalance

The coordinated work of all hormones is an intricately woven system, which can be disrupted by stress, heredity, illness, smoking, weight gain or loss, and taking certain medications.

The most common symptoms of low estrogen levels are:

• Infrequent periods or their cessation;
• hot flashes or night sweats;
• Sleep problems;
• Vaginal dryness;
• Mood swings;
• Low libido;
• Dry skin.

Typically, low estrogen levels occur after menopause, the period when periods stop and eggs mature, which usually occurs after age 45. Because this condition is associated with an increased risk of heart disease and osteoporosis, women are advised to discuss starting hormone replacement therapy with their gynecologist.

There is no proven way to delay the onset of menopause. Quitting smoking, a balanced diet, physical activity, and stress management will help you feel better and reduce the risk of diseases, the treatment of which can lead to the development of menopause before age 45.

In addition to menopause, hunger and a low body mass index can lead to low estrogen levels. For this reason, women lost their periods during World War II.

Symptoms of high estrogen levels:

• Weight gain;
• Problems with menstruation;
• Low libido;
• Fatigue;
• Feelings of anxiety and depression.

High levels of estrogen may occur after menopause in women with a high body mass index, as it will then be produced by fat tissue. This increases the risk of developing malignant breast tumors.

How to reduce your risk of breast cancer

Obesity in girls accelerates the onset of puberty and menstruation, while being underweight can, on the contrary, delay them.

In women of any age, elevated estrogen levels can lead to thickening of the endometrium and associated diseases such as endometriosis and endometrial cancer.

During pregnancy, estrogen levels may also be high, but this is nothing to worry about. This is normal and levels will return to normal after delivery.

Estrogen imbalance can be confused with other diseases and conditions. Therefore, if you have symptoms, it is recommended to consult a specialist. He will help you find out what is causing the problems and prescribe the necessary treatment.

ESTROGEN METABOLISM IN WOMEN

(general concepts and clinical practice)

PART I

In recent years, the incidence of endometriosis, fibrocystic mastopathy, uterine fibroids, etc. has increased significantly. The reasons for the development of these diseases lie in the high level of estrogen, which is not only their basis, but can also significantly accelerate the aging process, reduce the quality and shorten the life expectancy of a woman. In order to understand what causes the appearance of these diseases, it is necessary to consider how the process of metabolism of female sex hormones occurs in a woman’s body. As is known, female sex hormones are synthesized in the ovaries and adipose tissue and enter the systemic bloodstream. In the systemic circulation, most estrogens are bound to sex hormone transport protein (SHBG). Only a small part of estrogens is in a free state. Only the free form of the hormone has biological activity. Bound hormones are the body’s “operational” reserve and, if the need for them increases, they are mobilized from the bound state, turning into a free form.

The free fraction of estrogens, due to its lipophilicity, can easily penetrate into the cell nucleus. It is in the nucleus that the receptors for estrogen and progesterone are localized. By binding to its nuclear receptor, the hormone forms a hormone-receptor complex, which initiates the activation or inhibition of certain genes, which in turn causes an acceleration or weakening of the synthesis of proteins encoded by these genes. A change in the concentration of certain proteins inside a cell causes a change in the function of that cell.

After exposure to the cell, the estrogen molecule is destroyed and excreted from the body. But steroid hormones are lipophilic compounds, the molecules of which are excreted from the body only after they are converted into a water-soluble form. To do this, the body has an arsenal of enzymes. They are also used for detoxification of xenobiotics (xenobiotics are foreign organisms, compounds that enter the body from the external environment).

1 PATHWAYS OF ESTROGEN METABOLISM

A. Stages of hormone transformation

The process of hormone transformation takes place in 2 stages.

1). At the first stage, estrogens, under the influence of enzymes of the cytochrome P450 group, undergo transformation with the formation of intermediate products (2-hydroxy-, 16-hydroxy-, 4-hydroxyestrogens (Scheme 1).

A. The most preferred for premenopausal women are 2-hydroxyestrogens. They are formed as a result of the effect of cytochrome P450 1A2 on estradiol or estrone. These metabolites have a weak estrogenic effect (approximately 48% of the activity of estradiol) and therefore do not have a proliferative effect on cells.

When estrogens are exposed to cytochrome P450 3A4, 16-hydroxyestrone or 16-hydroxyestradiol (estriol) is formed. Unlike 2-hydroxyestrogens, 16-hydroxyestrone is more active than estrone. Its activity is 8 times higher than that of estradiol. The high rate of formation of this metabolite in a woman’s body causes a state of hyperestrogenemia, despite the normal concentration of estradiol in the blood. A decrease in the ratio of 2-hydroxyestrone to 16-hydroxyestrone, that is, the dominance of 16-hydroxyestrone over 2-hydroxyestrogens, is evidence of a high risk of developing uterine and breast cancer [1].

B. But there is another way of converting estrogens. If cytochrome P450 1B1 acts on estrogens, the result is the formation of 4-hydroxyestrogens and, despite their relatively low activity (approximately 79 EC of the activity of estradiol), they can damage the DNA of the cell and cause its cancerous degeneration. It is these metabolites that are responsible for benign and malignant neoplasms of the uterus, mammary gland and ovaries. This is confirmed by studies of breast biopsies performed outside the affected area in women with breast cancer. Thus, it was found that the concentration of 4-hydroxyestrogens in such patients is 3 times higher than the concentration of this metabolite in breast tissue in the control group. The authors of the works suggest that 4-hydroxyestrogens initiate processes of cancerous transformation of breast tissue and may be precursors to the development of cancer [2, 3].

2). After passing through the first stage of transformation, 2-hydroxy- and 4-hydroxy-metabolites of female sex hormones can be converted either into semiquinones, compounds that have a genotoxic effect, or, through methylation, into 2- and 4-methoxyestrogens, compounds that are absolutely harmless to body.

B. Factors that determine the pathway of estrogen metabolism

The pathway of estrogen metabolism depends on the following factors.

1. If a large number of free radicals are formed in a woman’s body (as a result of smoking, excessive exercise, exposure to toxic compounds, etc.). She accumulates aggressive semiquinones. From semiquinones, 2.3- and 3.4-quinones are formed. Quinones are highly reactive molecules that can covalently bind to DNA and thus disrupt its structure.

2. If a woman does not have oxidative stress and has a sufficiently high level of protective reactions, for example, methylation, then harmless methoxyestrogens are formed.

Methylation is a biochemical reaction as a result of which a methyl group (-CH3) is added to a substrate (for example, estrogens) using the enzyme catechol-O-methyl-transferase. The universal donor of methyl groups in the body is s-adenosine methionine, formed as a result of the interaction of the amino acid methionine with the ATP molecule (adenosine triphosphate). After s-adenosylmethionine donates a methyl group to any substrate, it is converted into s-adenosylhomocysteine, and subsequently into homocysteine ​​(Scheme 2). Homocysteine ​​can later be converted back to methionine by the enzyme methionine synthetase. But for such a transformation the following cofactors are necessary: ​​vitamins B2, B12 and folic acid.

After conversion to methoxyestrogens, female sex hormones bind to sulfates or glucuronic acid in the liver and are excreted from the body through bile. Disruption of these processes can significantly interfere with the conversion of estrogens and increase the risk of diseases of the female reproductive system. Thus, according to the literature, a decrease in sulfotransferase activity in endometrial tissue increases the risk of malignant neoplasms. Sulfotransferase is an enzyme that transfers inorganic sulfates to compounds to be detoxified, particularly estrogens. Conversely, with an increase in the activity of sulfatase, an enzyme that splits sulfates from detoxified estrogens, there is a significant increase in the risk of endometrial carcinoma formation, which is associated with an increase in the tissue concentration of free estrogens [4]. Other researchers have shown that the process of glucuronidation in breast tissue plays a key role in carcinogenesis in this organ [5].

So, after estrogens are bound to sulfates or glucuronic acid, they are secreted by the liver into the bile ducts, enter the intestines with bile and are then excreted from the body. It is obvious that diseases of the gastrointestinal tract significantly affect the metabolism of female sex hormones. In our practice, we have never observed women with impaired estrogen metabolism and healthy intestines.

2 ESTROGEN METABOLISM AND THE CONDITION OF THE GASTROINTESTINAL TRACT

Once in the intestines, hormones modified in the liver must be excreted from the body. However, not all women experience this process normally. If a woman has dysbiosis and/or does not consume enough fiber, the intestinal flora produces the enzyme beta-glucuronidase, which cleaves glucuronic acid from detoxified estrogens. Estrogens, left without glucuronic acid, acquire the ability to re-enter the body through the intestinal wall and, thus, increase the total amount of estrogens in the body.

Consumed fiber also has a positive effect on estrogen metabolism: it has the ability to sorb estrogens on its surface and prevent their reabsorption from the intestinal lumen. This fact is confirmed by studies showing that women following a vegetarian diet have higher hormone excretion and therefore lower levels of estrogen in the systemic circulation [6].

3 FACTORS INTERFERING ESTROGEN METABOLISM

Due to the fact that the exchange of female sex hormones is a delicate, complex and very vulnerable process, there are a large number of factors that, despite their apparent harmlessness, can cause quite serious disturbances in the exchange of female sex hormones.

In general, estrogen metabolism is disrupted by a combination of unfavorable environmental factors and genetic predisposition to them.

Among the genetic factors that lead to high susceptibility to impaired estrogen metabolism, one can highlight polymorphisms of genes encoding enzymes of the first and second phases of detoxification (CYP 1A1, CYP 1B1, CYP 3A4, COMT, MTHFR, GST, etc.).

Among the unfavorable environmental factors, the following can be noted:

1. Smoking leads to a decrease in the activity of cytochrome P-450 1A2, which is responsible for the conversion of estrogens into 2-hydroxyestrogens, the most friendly metabolites for a woman’s body during the premenopausal period. In addition, smoking provokes oxidative stress, which promotes the conversion of 2-hydroxy- and 4-hydroxyestrogens into 2- and 4-semiquinones and quinones, which have a carcinogenic effect on the tissue of the uterus, breast and ovaries.

2. Taking hormonal contraceptives or female sex hormones for therapeutic purposes.

Unfortunately, most hormonal drugs on our market are synthetic in nature, and synthetic hormones are converted in the body into compounds with a potential carcinogenic effect. In addition, these hormones limit the detoxification capabilities of the body and therefore, when accumulated, can lead to the development of diseases of the female reproductive system and increase the risk of breast cancer [7].

3. Insecticides (insect repellents) are toxic compounds that can enter the body with food or inhalation when used in everyday life. Once in the body, they block the activity of the cytochrome P-450 1A2 enzyme, which, as mentioned earlier, converts estrogens into 2-hydroxyestrogens. If this pathway is blocked, estrogens begin to follow the path of conversion into 16-hydroxy- and 4-hydroxyestrogens. The accumulation of such metabolites in tissues leads to the development of precancerous diseases of the uterus and breast [8].

4. Hormones in food.

Unfortunately, agricultural enterprises are increasingly using hormones to increase meat production, which, accumulating in the animals’ bodies, end up on our table with meat products. So in the USA in the 70s, 16 tons of hormones were used annually for meat production. Entering a woman’s body, they are absorbed from the gastrointestinal tract and competitively interact with hormonal receptors of the uterus, mammary gland, and ovaries.

5. Obesity contributes to the accumulation of female sex hormones in the body.

The reason for this is that fat fiber contains large amounts of the aromatase enzyme - CYP19, which converts male sex hormones produced in the adrenal glands into estrogens.

6. Phthalates are toxic compounds that are found in all plastic products and polymer household products (cellophane, food packaging film, plastic bags, air fresheners, polishes, paints, varnishes, etc.). Phthalates are able to interact with estrogen receptors and activate them, thus masking the effect of estrogens themselves.

7. Diseases of the gastrointestinal tract.

8. Stress.

9. Nutrient deficiency also disrupts estrogen metabolism.

This is due to the fact that many vitamins and minerals are cofactors of enzymes that take part in the transformation of female sex hormones in the body. Without cofactors, enzymatic systems malfunction, which in turn leads to the accumulation of estrogens. Thus, low levels of beta-carotene (provitamin A), folic acid, lycopene, and selenium increase the risk of developing cervical dysplasia [9-11].

10. Sedentary lifestyle.

It turns out that physical activity stimulates 2-hydroxylation and detoxification of estrogens.

4 CLINICAL AND PATHOGENESIS OF ESTROGEN METABOLISM DISORDERS

What happens in a woman’s body if the previously mentioned factors still disrupt estrogen metabolism? In the initial stages there is nothing to worry about. The body has enormous compensatory capabilities, with the help of which it tries to restore violations. Moreover, during this period the woman has no complaints and during the examination the gynecologist does not find any pathology. Only special laboratory tests can detect violations at this stage. This stage of compensation can be quite long and its duration depends on the capabilities of the woman’s body. The body's capabilities, in turn, are determined by genetic predisposition, the supply of vitamins, minerals, fatty acids, antioxidants, as well as the quality of nutrition, physical activity, the presence or absence of concomitant diseases, etc. But if unfavorable environmental factors affect a woman’s body for a long time, then sooner or later the body will begin to malfunction, and the first complaints may appear: painful and heavy menstruation, chest pain associated with menstruation, the appearance of lumps in the mammary gland, sudden weight fluctuations , mood swings. However, these symptoms are nonspecific. Excessive amounts of estrogen stimulate the proliferation (division) of epithelial and stromal cells of the uterus and mammary gland. And this, in turn, can lead to the development of endometriosis, fibrocystic mastopathy, uterine fibroids and endometrial polyps. The state of hyperestrogenemia also contributes to the introduction of human papillomavirus infection into the cervix and the development of dysplasia. This is primarily due to the fact that estrogens have an anti-apoptotic effect on cervical epithelial cells, and this effect is not associated with their mitogenic effect [12]. In addition, estrogens stimulate the expression of the HPV16 Eb oncogene, which in turn binds to the tumor suppression gene p53 and helps to weaken its expression using the ubiquitin-protease system [13]. Another negative effect of estrogens on the development of dysplasia is that, on the one hand, they stimulate the expression of two viral genes Eb and E7, which cause oncogenic activity, and on the other hand, they inhibit immunological resolution during initial damage to the mucous membrane of the cervix by the papilloma virus human (HPV) by reducing the expression of major histocompatibility complex class I and II antigens [14].

5 DIAGNOSIS OF HYPERESTROGENEMIA

Diagnosis of hyperestrogenemia, on the one hand, is simple, on the other hand, it does not always accurately identify impaired metabolism of female sex hormones. First, it is necessary to conduct the following hormonal studies in the follicular and luteal phases of the menstrual cycle: determine the levels of estradiol, estrone, estriol, progesterone, testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin in the blood serum. If in one of these studies the levels of estradiol and estrone are higher than normal values, we can talk about excess estrogen levels. However, in the best case, studies are carried out twice during the entire menstrual cycle and, thus, the real situation the rest of the time is unknown. To solve this problem, it is necessary to study hormone levels throughout the cycle.

Modern non-invasive methods of hormonal research make it possible to determine hormone levels from saliva samples. This research method makes it possible to accurately determine the concentration of free estradiol and progesterone throughout the menstrual cycle.

In addition, additional information about hormonal status can be obtained by measuring fibrinogen and sex hormone binding protein levels. An increase in the concentration of these proteins in the blood indicates a high level of estradiol in the body, since the latter is a stimulator of the production of these proteins in the liver. However, in some cases, the clinically manifested state of hyperestrogenemia is not confirmed by biochemical parameters, which remain within normal values. You can understand the situation only by studying the metabolism of estrogen.

The study of estrogen metabolism is carried out from the 19th to the 25th day of the menstrual cycle. If the patient has a high level of 16-hydroxyestrone and (or) the ratio of 2-hydroxyestrogens to 16-hydroxyestrogens is less than normal (0.40), then this will indicate hyperestrogenemia.

In addition to studying the concentrations of hormones and their metabolites, it is also necessary to evaluate a number of biochemical processes in the body that take part in the detoxification of estrogens and, in particular, methylation processes. A generally accepted marker of methylation processes in the body is homocysteine, the level of which increases in cases of disturbances [15].

At the final stage of detoxification, estrogens undergo sulfation and glucuronidation. Therefore, an accurate analysis of these processes allows us to trace the final stage of the transformation of female sex hormones. They can be objectively assessed using a test proposed in the GSDL laboratory (Great Smokies Diagnostic Laboratory, USA) - (www.anti-aging.kiev.ua, www.gsdl.com.) A routine biochemical blood test allows indirect assessment of glucuronidation processes. An increase in the level of indirect bilirubin, with normal concentrations of transaminases and direct bilirubin-glucuronide, allows us to identify a violation of glucuronidation processes in the body: indirect bilirubin, a breakdown product of hemoglobin, is detoxified, like estrogens, through glucuronidation. The addition of glucuronic acid to bilirubin converts it from indirect to direct.

6 CONCLUSIONS

Estrogen metabolism is a very delicate, complex and vulnerable process that can be disrupted by many unfavorable environmental factors. In order to restore the balance of female sex hormones, it is necessary to accurately understand which link or links of this metabolic chain are disturbed. And only understanding this will make it possible to purposefully and effectively restore the disturbed balance and save a woman from diseases that can significantly worsen the quality and reduce her life expectancy.

The treatment of these dysfunctions will be discussed in the second part of the article.

BIBLIOGRAPHY

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2. Rogan EG; Badawi AF; Devanesan PD; Meza JL; Edney JA; West WW; Higginbotham SM; Cavalieri EL. Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer. Carcinogenesis (England), Apr 2003;24(4):697-702.
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Causes of hormone reduction

Normally, estrogen levels fluctuate throughout life and only decrease towards menopause. In other cases, low levels of the hormone indicate to the woman that there is a problem in the body.

The following factors can lead to pathological phenomena:

• Excessive physical activity.
• Physical inactivity.
• Use of drugs, tobacco and alcohol.
• Unbalanced diet.
• Iron deficiency.
• Strict diet.
• Sudden weight loss or gain.
• Incorrectly selected hormonal drugs for contraception.
• Long-term use of antidepressants and nootropics.
• Bad heredity.
• Inconsistent sex life.
• Tumors of a malignant nature.
• Chemotherapy of the reproductive system.
• Removal of the appendages, ovaries or uterus.
• Constant depression, moral tension and depressed state.

Before prescribing a course of treatment, the gynecologist conducts a complete examination of the woman. For therapy to be effective, all causes of the problem must be excluded.

Sesame seeds

A fairly common spice used in Asian dishes. By analogy with flax seeds, they are rich in lignans and other beneficial substances.

One placebo-controlled study included 50 women after menopause. The respondents were divided into two groups. Then the first group was given 50 g of crushed sesame seeds every day for 5 weeks, and the second group was given rice in a similar amount. The results showed that sesame lignan is transformed into enterolactone, a compound with estrogenic activity (17).

In addition, women who added sesame seeds to their food had improved blood lipid metabolism and decreased cholesterol levels (17).

What functions does estrogen perform?

Researchers note that estrogen is involved in the functioning of almost all tissues in the human body.

In teenage girls, estrogen is involved in puberty. He is responsible for:

• Enlargement of the mammary glands;
• Growth of pubic hair and armpits;
• Beginning of menstruation;
• Regulation of the menstrual cycle.

In adult women, estrogen is responsible not only for the menstrual cycle, but also for the health of the heart, blood vessels and bones, brain function and mood, as well as the condition of the skin. It regulates the levels of bad and good cholesterol, the formation of blood clots, and the condition of the walls of blood vessels.

Possible consequences of hormone deficiency

With estrogen deficiency, there is a lack of fluid in the body. Against the background of moisture loss, salts are deposited at an accelerated pace. As a result, the skin ceases to be written and elastic, dryness and flaking appear. The epidermis becomes thinner. Wrinkles, blackheads and acne actively form on the face.

The figure deteriorates, problem areas become covered with cellulite. Dehydration makes the mucous membranes of the mouth, eyes and vagina dry. In this case, a lack of hormones often leads to involuntary urination. It also affects the bones. They become brittle and porous.