A pathological state of hormonal balance in the female body, in which there is an excessive production of male sex hormones - androgens, is called hyperandrogenism. The disease is associated with impaired work endocrine system... The syndrome of hyperandrogenism is noted in about 5-7% of women, about 20% of them cannot become pregnant or bear a child.

Normally, androgens are produced by the genitals in an amount that ensures the growth of hair on the pubis and armpits, the formation of the clitoris, timely puberty and sexual desire. Androgens are responsible for the normal functioning of the liver and kidneys.

The active production of androgens occurs during adolescence, during the formation of secondary sexual characteristics. In adulthood, androgens are needed to strengthen bone tissue. However, excessive production of these hormones leads to pathological changes that significantly impair a woman's quality of life. The most deplorable results include and. In these cases, treatment is needed that will help normalize hormonal levels.

Varieties and causes of the syndrome

The maturation process of androgens occurs in the ovaries and adrenal glands. The normal amount of the hormone produced and its correct ratio with estrogen provides the hormonal balance necessary for the full functioning of the body.

Depending on the origin of the pathology, several of its forms are distinguished:

• Hyperandrogenism ovarian genesis- occurs with polycystic ovary syndrome. The reason is a malfunction of the hypothalamus-pituitary gland system. The disorder is hereditary.
• Hyperandrogenism of the adrenal genesis is caused by a malfunction of the adrenal cortex. The disease is congenital and can also be caused by tumors (Itsenko-Cushing's disease). In this case, the first menstruation begins late, with scanty discharge, and over time may even stop altogether. Other characteristic signs- an abundance of acne in the back and chest, underdevelopment of the mammary glands, the formation of a male figure, an increase in the clitoris.

A number of patients are diagnosed with hyperandrogenism of mixed genesis. In this case, the functioning of the ovaries and adrenal glands is simultaneously disrupted in the body. This pathology is caused by hypothalamic and neuroendocrine disorders. Disruptions in hormonal balance are aggravated by autonomic neurotic disorders. In some cases, mild hyperandrogenism is diagnosed, in which the androgen indicators are normal, and does not detect the presence of tumors in the internal organs.

The mixed form prevents pregnancy and makes it impossible to successfully carry a child.

Given the degree of excess acceptable level androgens, isolate the absolute and relative form of adrenogenital syndrome. In the first case, the concentration of male hormones exceeds allowable norms... Relative hyperandrogenism is diagnosed with acceptable levels of male hormones. At the same time, an increased sensitivity of the organs and glands of a woman to their effects is noted.

Summing up, the following main causes of this syndrome can be distinguished:

• improper production of a special enzyme that synthesizes androgens, resulting in their excessive accumulation in the body;
• the presence of adrenal tumors;
• diseases and malfunctions of the ovaries, provoking excessive production of androgens;
• pathology of the thyroid gland (hypothyroidism), pituitary tumors;
• long-term use of steroids during professional strength sports;
• childhood obesity;
• genetic predisposition.

In case of disorders of the ovaries, an increase in the adrenal cortex, hypersensitivity of skin cells to the effects of testosterone, tumors of the genital and thyroid glands development of pathology is possible in childhood.

Congenital hyperandrogenism sometimes does not allow us to accurately establish the sex of the child born. A girl may have large labia, an enlarged clitoris to the size of a penis. The appearance of the internal genital organs is normal.

One of the varieties of adrenogenital syndrome is the salt-wasting form. The disease is hereditary and is usually detected in the first months of a child's life. As a result of unsatisfactory work of the adrenal glands, girls develop vomiting, diarrhea, and convulsions.

At an older age, hyperandrogenism causes excessive hair growth throughout the body, a delay in the formation of the mammary glands and the appearance of the first menstruation.

Clinical manifestations

Symptoms can range from mild (excess body hair growth) to severe (secondary male sex characteristics).

Clinical manifestations of hyperandrogenism in women in the form of acne and male-pattern hairiness

The main manifestations of pathological disorders are:

• acne - occurs when the skin is oily, which leads to blockage and inflammation of the sebaceous glands;
• seborrhea of ​​the scalp;
• hirsutism - the appearance of strong hair growth in places atypical for women (face, chest, abdomen, buttocks);
• thinning and loss of hair on the head, the appearance of bald patches;
• increased muscle growth, the formation of masculine muscles;
• coarsening of the timbre of the voice;
• , paucity of discharge, sometimes complete cessation of menstruation;
• increased sex drive.

The occurring disruptions in the hormonal balance cause the development of diabetes mellitus, the appearance of excess weight, and lipid metabolism disorders. Women become very susceptible to different infectious diseases... They often develop depression, chronic fatigue, increased irritability and general weakness.

One of the most severe consequences of hyperandrogenism is virilization or viril syndrome. This is the name of the developmental pathology female body, in which he acquires pronounced male characteristics. Virilization is a rare abnormality; it is diagnosed in only one patient out of 100 who have excessive body hair growth.

A woman forms a male figure with increased muscle growth, menstruation stops completely, and the size of the clitoris increases significantly. Very often, similar symptoms develop in women who uncontrollably take steroids to increase endurance and physical strength when playing sports.

Establishing diagnosis

Diagnostics of the pathological condition includes an external and gynecological examination of the patient, an analysis of her complaints about the general state of health. Pay attention to the duration of the menstrual cycle, the localization of excess hair growth, body mass index, appearance genitals.

What tests need to be done to determine the level of androgens?

Doctors (gynecologist, endocrinologist, geneticist) prescribe the following studies:

• determination of the level of testosterone, follicular hormone, prolactin, estradiol in the blood and cortisol in the urine;
• tests with dexemethasone to determine the cause of the development of the syndrome;
• Ultrasound of the ovaries and adrenal glands;
• CT scan of the pituitary gland;
• studies of glucose, insulin, cholesterol levels.

An ultrasound of the pelvic organs will determine the possible presence. Analyzes are necessary to establish the type of disease.

Materials for research are taken in the morning, before meals. Since the hormonal background is unstable, three samples are taken at intervals of at least half an hour for accurate diagnosis. It is advisable to take tests in the second half of the menstrual cycle, closer to the expected start of menstruation.

Principles of therapy

Treatment of hyperandrogenism should be comprehensive and, first of all, aimed at eliminating problems and diseases that act as provoking factors. The list of such diseases includes pathologies of the thyroid gland, polycystic ovary syndrome, adrenogenital syndrome.

The choice of treatment methods depends on the form of pathology and the goal pursued by therapy (combating hirsutism, restoring reproductive function, maintaining pregnancy in case of a threat of miscarriage).

The main therapeutic measures include:

• drug therapy;
• surgical intervention;
• the use of traditional medicine;
• normalization of nutrition and physical activity.

Conservative therapy

It is used to reduce the amount of male hormones produced and to block the processes that contribute to their excessive activity. The presence of tumors in the genitals, causing ovarian hyperandrogenism, is eliminated with the help of surgical intervention.

If a woman does not plan pregnancy in the near future, but suffers from acne and an excessive amount of hair on the body, to get rid of these symptoms, they are prescribed with an antiandrogenic effect (for example, Diana 35).

Such drugs not only eliminate unpleasant outward signs, but also contribute to the normalization of the menstrual cycle. For a cosmetic effect, anti-inflammatory ointments are prescribed, which reduce the production of sebum.

If there are contraindications to the use of contraceptives, Spironolactone is used for treatment. It is prescribed for severe premenstrual syndrome and polycystic ovaries. It successfully treats acne and excess hair growth.

An analog drug is Veroshpiron. Its main active ingredient also is spironolactone. Reception of Veroshpiron is highly undesirable without the agreement of the doctor with the duration of use and the required dosage.

If hypereandrogenism is caused by the absence of an enzyme that converts androgens into glucocorticoids, agents are shown that normalize this process. The drug Metypred is very effective. Forms of its release - tablets and powders for injection. The remedy is contraindicated in the presence of infectious and viral diseases, tuberculosis, heart failure. The duration of the course of treatment and the dosage are determined by the doctor.

Drugs used to treat hyperandrogenism

One of the successful methods conservative treatment is a low-calorie diet. It is necessary to get rid of excess weight, which often complicates the course of the disease and brings the woman additional psychological discomfort.

The total number of calories consumed daily should not exceed 2000. In this case, with sufficient physical activity, the amount of calories consumed will be lower than consumed, which will lead to a gradual weight loss.

The diet shown for hyperandrogenism provides for the elimination of fatty, salty and spicy foods, as well as alcohol, sauces and fatty gravies from the diet.

Compliance with the principles proper nutrition supported by regular exercise. Running, aerobics, swimming, active games in the fresh air are useful.

The fight against hirsutism is carried out using various cosmetic procedures: removal with wax, depilation, removal of unwanted hair with a laser.

The use of traditional medicine

Treatment with folk remedies is quite applicable in the complex of drug therapy, but it is not a complete substitute for traditional methods.

Popular recipes:

1. The herbs of sweet clover, sage, meadowsweet and knotweed are mixed in equal proportions, 200 ml of water are poured, kept in a water bath for 20 minutes and filtered. To the resulting broth add 1.5 ml of rhodiola rosea tincture. Take a decoction of a third of a glass several times a day before meals.
2. 2 tablespoons of chopped string, 1 spoon of yarrow and motherwort are poured with boiling water, insisted for about an hour, filtered. Take half a glass on an empty stomach in the morning and at bedtime.
3. A few tablespoons of dry nettle leaves are poured with a glass of water, insisted in a sealed container, filtered. Take a tablespoon several times a day.
4. Rosehips, black currants are poured with boiling water, insisted for about an hour. Then add some honey. The resulting cocktail is drunk several times a day after meals.

Among the most common folk remedies in the fight against diseases of the gynecological sphere - boron uterus. It is shared with others remedies in the form of a decoction or tincture.

1. Pour 100 g of boron uterus with 500 ml of vodka and leave for 2 weeks. Take the tincture 0.5 teaspoon three times a day.
2. Pour 2 tablespoons of borax uterus with a glass of boiling water, leave for about an hour. Drink in small portions throughout the day.
3. Mix 100 g of green peeled nuts and boron uterus with 800 g of sugar, add the same amount of vodka. Place the bottle with the mixture in a dark place for 14 days. After straining, take a teaspoon half an hour before eating.

Mint is used to reduce the amount of androgens produced. On its basis, tinctures and teas are prepared. Milk thistle can be added to the mint for added potency. Regular intake of green tea normalizes female hormonal balance.

How to treat a problem with medicinal herbs and to combine this method with other types of treatment, the attending physician will always tell you. Self-medication is unacceptable!

Hyperandrogenism and infertility

The excess of androgens produced often becomes an obstacle to the desired pregnancy.

How to get pregnant with drug therapy and how realistic is it?

In this case, infertility treatment is aimed at using drugs that stimulate the release of an egg from the ovaries. An example of such medicinal product maybe Clomiphene.

One of the most effective drugs used to stimulate ovulation and normalize the menstrual cycle is Duphaston. After the onset of pregnancy, the drug is continued to prevent miscarriage and normalize the development of pregnancy.

If stimulation is ineffective, doctors advise resorting to surgical treatment. Modern medicine widely uses the method. During this procedure, the ovaries are excised to help the mature egg "exit". The likelihood of getting pregnant after laparoscopy is the higher, the less time passes from the day of the operation. The maximum ability to conceive is noted in the first three months.

But even after successful conception, the presence of hyperandrogenism can prevent the successful bearing of a child. Excess male hormones often lead to fetal egg cannot stay in the uterus. The likelihood of miscarriage remains high.

Dangerous weeks of pregnancy with hyperandrogenism are the period before the 12th week and after the 19th. In the first case, hormones are produced by the placenta, and after the 19th week, they can be produced by the fetus itself.

To maintain pregnancy, the patient is prescribed Dexamethasone (metipred). It helps to reduce androgen levels. The dosage of the drug is selected exclusively by the doctor!

Many expectant mothers are very afraid of the side effects of the drug and fear that it may harm an unborn baby. Many years of experience in application of this drug proves its safety, both for the development of the unborn child, and for the course of the birth itself.

In most cases, to avoid the risk of miscarriage, doctors advise that you first complete the full course of treatment, and only then plan a pregnancy. If a woman fails to conceive a child, it is possible to carry it out.

Prophylaxis

There are no specific measures for the prevention of hyperandrogenism, since this syndrome develops at the hormonal level.

General preventive measures include:

• rational nutrition, including fiber-rich foods in the menu, weight control;
• quitting smoking and alcohol abuse;
• regular visits to the gynecologist;
• taking medications and contraceptives only after a doctor's recommendation;
• timely treatment of pathologies of the thyroid gland, diseases of the liver and adrenal glands.

Hyperandrogenism is not only about skin, hair and menstrual problems. This is a common disease of the body that prevents a woman from leading a quality lifestyle and often deprives her of the joys of motherhood. Modern methods diagnostics and treatment allow to identify pathology in time and successfully eliminate its manifestations.

For citation: A.A. Pishchulin, E.A. Karpova Ovarian hyperandrogenism and metabolic syndrome // BC. 2001. No. 2. P. 93

Endocrinological science Center RAMS, Moscow

WITH indromo of ovarian hyperandrogenism of non-tumor genesis or hyperandrogenic dysfunction of the ovaries, formerly called Stein-Leventhal syndrome, now, according to the WHO classification, is better known in the world literature as polycystic ovary syndrome (SLEEP).

The clinical picture of PCOS is manifested by a chronic anovulatory state of the ovaries or severe hypofunction of the corpus luteum, which leads to a bilateral increase in the size of the ovaries with thickening and sclerosis of the tunica albuginea. These changes are manifested by a violation of menstrual function - opsomenorrhea, amenorrhea, but the development of metrorrhagia is not excluded. Folliculogenesis disorders lead to the development of anovulatory primary or secondary infertility.

One of the main diagnostic criteria for PCOS is hyperandrogenism. - an increase in the level of androgenic steroids in the blood (such as testosterone, androstenedione), which leads to the development of hirsutism and other androgen-dependent dermopathies.

Obesity or overweight is often associated with PCOS. Determination of body mass index (BMI) reveals the degree of obesity. Measurement of indicators of the volume of the waist (OT) and hips (OB) and their ratio indicates the type of obesity (the prognostically unfavorable is the abdominal type of obesity, in which OT / OB> 0.85).

In addition to the main symptoms of the disease, the clinical picture is largely determined by general metabolic disorders, such as dyslipidemia, impaired carbohydrate metabolism, an increased risk of developing hyperplastic and tumor processes from the genitals. Dyslipidemia is an increase in triglycerides, cholesterol, low-density lipoproteins, very low-density lipoproteins and a decrease in high-density lipoproteins. These disorders lead to the risk of early development of atherosclerotic vascular changes, hypertension and ischemic disease hearts.

Disorders of carbohydrate metabolism consist in the development of the insulin resistance-hyperinsulinemia complex, which has recently become the main direction in the study of the pathogenetic links in the development of PCOS.

In the 60s, the pathogenesis of PCOS was associated with a primary enzymatic defect of ovarian 19-hydroxylase and / or 3b-dehydrogenase, combining these disorders into the concept of primary polycystic ovary. However, in the works of subsequent years, it was shown that the aromatase activity of granulosa cells is a FSH-dependent function.

Identified in PCOS elevated level luteinizing hormone (LH), the absence of its ovulatory peak, normal or reduced levels of follicle-stimulating hormone (FSH) with an impaired LH / FSH ratio (2.5-3) suggested a primary violation of gonadotropic regulation of steroidogenesis in ovarian tissue with the development of secondary polycystic ovary disease.

Until the mid-1980s, it was believed (SSC Yen theory) that the trigger mechanism in the pathogenesis of PCOS is excessive synthesis of androgens by the adrenal glands during adrenarche as a result of altered sensitivity of the adrenal glands to ACTH or excessive stimulation of the retinal adrenal cortex by a non-ACTH-like factor or under the influence of b -endorphins, neurotransmitters, such as dopamine. Upon reaching critical mass body (especially when its norm is exceeded), the peripheral conversion of androgens to estrogens increases, primarily in the liver and adipose tissue. An increase in the level of estrogens, primarily estrone, leads to hypersensitization of gonadotrophs in relation to luliberin (GnRH). At the same time, under the influence of estrone, the production of GnRH by the hypothalamus increases, the amplitude and frequency of its secretion impulses increase, as a result of which the production of LH by the adenohypophysis increases, the LH / FSH ratio is disturbed, and a relative deficiency of FSH occurs. Strengthening the effect of LH on the ovaries contributes to an increase in the production of androgens by thecal cells and their hyperplasia. Relatively low level FSH leads to a decrease in the activity of FSH-dependent aromatase, and granulosa cells lose the ability to aromatase androgens to estrogens. Hyperandrogenism interferes with the normal growth of follicles and contributes to the formation of their cystic atresia. The lack of growth and maturation of follicles further inhibits the secretion of FSH. The increased pool of androgens in peripheral tissues is converted to estrone. A vicious circle closes.

Thus, the result of a violation of the central and peripheral mechanisms of regulation of steroidogenesis is the development of functional ovarian hyperandrogenism in patients with PCOS.

The pathogenesis of PCOS by S.S.C. Yen is shown in diagram 1:

Scheme 1.

In the early 80s, a number of authors proposed a new theory of the pathogenesis of polycystic ovary syndrome, different from the theory of S.S.C. Yen. PCOS has been found to be associated with hyperinsulinemia and is characterized by both reproductive and metabolic dysfunction.

The existence of a relationship between hyperinsulinemia and hyperandrogenism was pointed out as early as 1921 by Achard and Thieris. They described hyperandrogenism in an obese woman with type 2 diabetes and called the condition "diabetes in bearded women."

Later, D. Bargen found that women with PCOS and hyperandrogenism had basal and glucose-stimulated hyperinsulinemia compared with a control group of women of the same weight, which suggested the presence of insulin resistance. There was a direct relationship between insulin and androgen levels, and it was suggested that hyperinsulinemia may be the cause of hyperandrogenism.

In 1988 G. Reaven first suggested that IR and compensatory hyperinsulinemia (GI) play a major role in the development of metabolic disorders syndrome. He named him "Syndrome X" ... Currently, the most commonly used term is "metabolic syndrome" or "insulin resistance syndrome".

Hypotheses of the pathogenesis of hyperinsulinemia and hyperandrogenism

The mechanism of occurrence of hyperandrogenism and hyperinsulinemia is not fully understood. Theoretically, three variants of interaction are possible: hyperandrogenism (GA) causes GI; GI leads to GA: there is some third factor responsible for both phenomena.

1. The assumption that GA causes GI is based on the following facts. In women who take oral contraceptives containing progestins with “androgenic properties,” impaired glucose tolerance is found. Long-term prescription of testosterone to transsexuals is accompanied by the occurrence of IR. It has been shown that androgens affect the composition of muscle tissue, increasing the number of muscle fibers of the second type, which are less sensitive to insulin compared to fibers of the first type.

2. Most of the factors suggest that GI leads to GA. It has been shown that IR persists in patients who underwent subtotal or total ovarian removal, as well as in women who have been using GnRH agonists for a long time, when there was a pronounced suppression of androgen levels. The administration of diazoxide, a drug that suppresses the secretion of insulin by the pancreas, caused a decrease in testosterone (T) levels and an increase in sex steroid binding globulin (SSSH) levels in patients with PCOS, obesity and hyperinsulinemia. Intravenous insulin in women with PCOS led to an increase in circulating levels of androstenedione and T. Interventions aimed at increasing insulin sensitivity (weight loss, fasting, and a low-calorie diet) were accompanied by a decrease in androgen levels. There is evidence that insulin can directly suppress the production of CCH by the liver, and under conditions of hyperinsulinemia, this effect is enhanced. At the same time, it is believed that insulin, and not sex hormones, is the main regulator of CCCC synthesis. A decrease in the level of SHBG leads to an increase in the concentration of free and, therefore, biologically active T (normally 98% of T is in a bound state).

The hypothesis linking HA with hyperinsulinemia does not answer the question of how the ovary retains insulin sensitivity when the body is insulin-resistant. Several possible explanations have been proposed. Since insulin has many functions, a selective defect in some of them can be assumed. Insulin sensitivity may be organ specific. But it is more likely that insulin acts on the ovary not only through insulin receptors, but also through receptors for insulin-like growth factors (IGF).

Insulin receptors and IGF-1 receptors have been identified in human ovaries (in the stromal tissue of the ovaries of healthy women, women with PCOS, in follicular tissue and granulosa cells). Insulin can bind to IGF-1 receptors, although with a lower affinity than its own receptors. However, with GI, as well as in a situation where insulin receptors are blocked or deficient, insulin can be expected to bind to IGF-1 receptors to a greater extent.

Possibly, the mechanisms of insulin / IGF-1 stimulation of steroidogenesis in the ovary can be divided into nonspecific and specific. Nonspecific are the classic effects of insulin on glucose, amino acid metabolism and DNA synthesis. As a result, the viability of the cell increases and, consequently, the synthesis of hormones is enhanced. Specific mechanisms include direct action insulin / IGF-1 on steroidogenic enzymes, synergism between insulin and LH / FSH, and effects on the number of LH receptors.

Insulin / IGF-1, acting synergistically with FSH, stimulates aromatase activity in granulosa cell culture and thereby increases estradiol synthesis. In addition, they lead to an increase in the concentration of LH receptors, enhancing the LH-dependent synthesis of androstenedione by theca and stromal cells.

The increasing concentration of androgens in the ovary under the action of insulin / IGF-1 causes follicular atresia, which leads to the gradual elimination of estrogen- and progesterone-producing granulosa cells, followed by hyperplasia of thecal cells and luteinization of the interstitial tissue of the ovary, which are the site of androgen production. This explains the fact that stimulation of ovarian steroidogenesis by insulin manifests itself mainly in the form of hyperandrogenism.

It has been suggested that insulin / IGF-1 can stimulate both the LH-dependent activity of cytochrome P450c17a in the ovaries and the ACTH-dependent activity of P450c17a in the adrenal glands. This, apparently, explains the frequent combination of ovarian and adrenal forms of hyperandrogenism in patients with PCOS.

There is also a possible relationship with the S.S.C. Yen on the involvement of adrenal steroidogenesis in PCOS pathogenesis (Scheme 2).

Scheme 2. Action of insulin in polycystic ovary syndrome

V. Insler (1993), conducting a study of the levels of insulin, IGF-1, growth hormone and their correlation with the levels of gonadotropins and androgens in women with PCOS, proposed two models for the development of this syndrome. In obese patients, GI induces excess production of androgens via IGF-1 receptors, which, acting in synergy with LH, cause an increase in the activity of cytochrome P450c17a, the main controlling enzyme in androgen synthesis. In patients with normal body weight, a relative increase in the concentration of growth hormone stimulates the excessive production of IGF-1. From this point on, synergism with LH leads to androgen overproduction by the same mechanism as in obese patients. An increase in the level of androgens causes a change in the function of the hypothalamic centers, leading to a violation of the secretion of gonadotropins and changes typical for PCOS (Scheme 3).

Scheme 3. Pathogenesis of polycystic ovary syndrome

3. However, there are a number of well-known IR conditions that are not associated with GA, such as simple obesity and type 2 diabetes. To explain why not all obese patients with GI develop hyperandrogenism and PCOS, put forward a hypothesis about the existence of a genetic predisposition to the stimulating effect of insulin on the synthesis of androgens in the ovary ... Apparently, there is a gene or group of genes that make the ovaries of a woman with PCOS more sensitive to insulin stimulation of androgen production.

The molecular mechanisms leading to the development of insulin resistance are not fully understood. However, recent advances in molecular biology have made it possible to determine the structure of the gene encoding the insulin receptor in women with ovarian hyperandrogenism.

Moller and Flier studied the amino acid sequence in the structure of DNA chains in patients with ovarian hyperandrogenism. They found a substitution of tryptophan for serosin at codon 1200. The researchers suggested that such a change disrupts the activation of the tyrosine kinase system in the insulin receptor. Low activity of insulin receptors leads to the development of IR and compensatory GI.

Yoshimasa et al. described another variant of a point mutation in a patient with hyperandrogenism, insulin resistance and acanthosis nigricans. They found the substitution of serine for arginine in the tetrameric structure of the insulin receptor. This mutation in the active locus made it impossible to connect the a- and b-subunits, as a result of which a functionally active receptor was not synthesized. The above studies are only the first attempts to identify the specific genetic etiology of ovarian stromal tekomatosis.

Later, Dunaif A. notes that in polycystic ovary syndrome, IR can be caused by impaired autophosphorylation of b-subunits of the insulin receptor (IR), the cytoplasmic part of which has tyrosine kinase activity. At the same time, insulin-independent phosphorylation of serine residues (PCOS-ser) increases with suppression of tyrosine kinase activity (a secondary signal transmitter that determines the sensitivity of insulin to receptors of the same name). This defect is characteristic only for PCOS-dependent IR; in other insulin-resistant conditions (obesity, NIDDM), these changes are not detected.

It cannot be ruled out that some serine phosphorylating factor exists in PCOS-ser. Thus, for example, a serine / threonine phosphatase inhibitor is isolated, which, apparently, interferes with the phosphorylation of IR in PCOS-ser. This compound is similar to the recently isolated membrane glycoprotein PC-1 (an inhibitor of insulin receptor tyrosine kinase), but the latter does not increase the non-insulin-dependent phosphorylation of serine IR.

Tumor necrosis factor-a (TNF-a) has similar properties: phosphorylation of serine residues IRS-1 (one of the secondary transmitters of the IR signal) under the influence of TNF-a entails suppression of the tyrosine kinase activity of IR.

Moller et al. found that phosphorylation of human serine P450c17, a key enzyme that regulates the biosynthesis of adrenal and ovarian androgens, increases 17,20-lyase activity. The modulation of the enzymatic activity of steroidogenesis by serine phosphorylation has been described for 17b-hydroxysteroid dehydrogenase. If we assume that the same factor (enzyme) phosphorylates insulin receptor serine, causing IR, and P450c17 serine, causing hyperandrogenism, then the relationship between PCOS and IR can be explained. In experiments in vitro, it was shown that protein kinase A (serine / threonine kinase) catalyzes the phosphorylation of serine of insulin receptors (Scheme 4).

Scheme 4. Gene of insulin resistance in PCOS

Role of leptin in PCOS

Recently, a number of studies have been carried out on biological role leptin, the results of which are encouraging. As a protein hormone, leptin influences feeding behavior and has a permissive effect on the initiation of puberty in animals. The role of this hormone in the regulation of metabolism and reproductive function in humans, unfortunately, has not been completely elucidated. For this reason, the data on the level of leptin in ovarian hyperandrogenism in combination with insulin resistance and the concept of its role in the development of these changes are very contradictory.

Recently, a number of studies have been conducted on the biological role of leptin, the results of which are encouraging. As a protein hormone, leptin influences feeding behavior and has a permissive effect on the initiation of puberty in animals. The role of this hormone in the regulation of metabolism and reproductive function in humans, unfortunately, has not been completely elucidated. For this reason, the data on the level of leptin in ovarian hyperandrogenism in combination with insulin resistance and the concept of its role in the development of these changes are very contradictory.

Thus, according to a study by Brzechffa et al. (1996), a significant proportion of women in the PCOS population have higher leptin levels than expected given their BMI, free testosterone, and insulin sensitivity. On the other hand, recent work in this area has not shown significant differences in leptin levels in the study groups with PCOS and in the control groups. In addition, it was found that the basal insulin level, the content of gonadotropins and sex steroids do not affect the leptin content. However, Zachow and Magffin (1997), taking into account the data on the presence of mRNA of leptin receptors in ovarian tissue, demonstrated a direct effect of this hormone on steroidogenesis of rat granulosa cells in vitro. At the same time, a dose-dependent suppressive effect of leptin on IGF-1 was shown, potentiated by an increase in FSH-stimulated synthesis of E 2 by granulosa cells. These data support the hypothesis that elevated leptin levels in obese individuals may counteract dominant follicle maturation and ovulation. Very interesting are the data of Spicer and Franciso (1997), indicating that leptin in increasing concentrations (10-300 ng / ml) inhibits insulin-dependent production of E 2 and progesterone in granulosa cell culture. This effect is due to the presence of specific binding sites for leptin. By analogy with this, it can be assumed that a high level of leptin can reduce the sensitivity of other target tissues to the action of endogenous insulin, leading to the development of IR in obesity.

Diagnosis

Diagnostics of the syndrome of ovarian hyperandrogenism with typical clinical picture is not difficult. First of all, this is a violation of menstrual function of the type of oligo-, opso- or amenorrhea, anovulation and the resulting primary or secondary infertility, hirsutism, acne, 40% of patients are obese varying degrees severity. A gynecological examination reveals a bilateral increase in the size of the ovaries, often against the background of a hypoplastic uterus.

Hormonal research methods play an important role in the diagnosis of PCOS. , aimed at identifying hyperandrogenism, its source and determining the level of gonadotropic hormones: LH and FSH. Patients with PCOS often have a predominance of LH levels over FSH, their ratio is impaired and increased (more than 2.5-3). The prolactin level is normal, although some increase is observed in 30% of patients.

The level of urinary excretion of total 17-KS in PCOS varies widely and is not very informative. Determination of 17-KS fractions (DHA, 11-oxidized ketosteroids, androsterone, etiocholanolone) also does not provide identification of the localization of the source of hyperandrogenism. Confirmation of the ovarian source of hyperandrogenism is an increase in the level of androstenedione (A) and testosterone (T) in the blood and an increase in the A / T ratio. The adrenal genesis of hyperandrogenism is confirmed by an increase in the level of dehydroepiandrosterone (DHA) and its sulfate (DHA-S) and 17-hydroxyprogesterone (17-OH-R) in the blood. To clarify the localization of the source of hyperandrogenism, various functional tests have been proposed, the most common of which are the test with dexamethasone, synacthen-depot.

Taking into account the discovery of new pathogenetic links in the development of PCOS, to assess the state of carbohydrate metabolism, it is necessary to conduct a standard glucose-tolerance test (75 ml of glucose per os) with the determination of glucose and immunoreactive insulin (IRI) levels. The evidence in favor of insulin resistance is also BMI over 25 and OT / OB over 0.85, as well as dyslipidemia.

Treatment

At the heart of modern approach To pathogenetic treatment Sleep lies the principle of restoring impaired ovarian function , that is, the elimination of anovulation, which in turn leads to a decrease in hyperandrogenism and restoration of folliculogenesis. However, the study of the features of the etiopathogenesis of ovarian hyperandrogenism leads to the conclusion that the choice of methods of adequate treatment for PCOS is not an easy task.

Combined oral contraceptives - the most commonly used group of drugs for PCOS. The mechanism of action is to suppress elevated LH, normalize the LH / FSH ratio, and increase the liver synthesis of CCH. After cancellation, a "rebound effect" is achieved, which consists in normalizing the hypothalamic-pituitary function, reducing androgen overproduction by ovarian tissue, normalizing folliculogenesis and restoring ovulation.

Treatment is carried out according to the standard scheme: 1 tablet per day from 5 to 25 days of the cycle for 3-6 months. If necessary, the courses are repeated. However, it is known that long-term use of estrogen-progestational contraceptives can lead to hyperinsulinemia, thereby aggravating the main pathogenetic link in PCOS.

Some contraceptives contain progestogenic components, derivatives of 19-norsteroids (norethisterone, levonorgestrel), which have varying degrees of androgenic effects, and therefore the appointment of drugs containing these components is limited in patients with hirsutism. It is more advisable to use oral contraceptives with a gestagen without androgenic action for symptoms of hyperandrogenism.

Perhaps the use of gestagenic drugs, devoid of androgenic properties in the form of monotherapy, especially with endometrial hyperplasia. Dydrogesterone is prescribed 1 tablet (10 mg) 2 times a day from 14-16 to 25 days of a cycle lasting from 3 to 6 courses.

Most effective remedy ovulation stimulation in PCOS is an antiestrogenic drug clomiphene citrate ... The main effects of antiestrogens are a decrease in pituitary hypersensitization to the action of GnRH, a decrease in LH production, induction of ovulatory LH release, and ovulation stimulation. The drug is prescribed at 50 mg, 100 mg per day from 5 to 9 days of the cycle until ovulation is achieved according to functional diagnostics tests, but not more than 3 courses in a row. Recently, there have been publications on the effect of clomiphene citrate on the insulin-insulin-like growth factor system. They indicated that by the 5th day of stimulation of ovulation with clomiphene (150 mg / day), a progressive decrease (by a maximum of 30%) in the level of IGF-1 was determined. However, in a number of other similar studies, a significant decrease in basal insulin levels in response to the introduction of clomiphene was not found.

The advent of drugs with antiandrogenic properties has significantly expanded the therapeutic options for PCOS. The most widely used drug is Diane-35, which contains 35 mg of ethinylestradiol and 2 mg of cyproterone acetate. In addition to the action characteristic of oral contraceptives, the drug blocks the action of androgens at the level of target cells, in particular, hair follicles... The latter leads to a decrease in hirsutism. The drug is used according to the standard scheme, as an oral contraceptive in courses of 6 or more cycles. However, it should be noted the presence of a negative effect of these drugs on lipid and carbohydrate metabolism, manifested in an increase in cholesterol, low-density lipoprotein levels, as well as in an increase in hyperinsulinemia, which requires constant dynamic monitoring of these parameters in patients with PCOS. Spironolactone, which is widely used in the treatment of androgen-dependent dermopathies, also has antiandrogenic properties.

One of the main directions in modern therapy ovarian hyperandrogenism is the search and use of drugs and agents aimed at eliminating insulin resistance and compensatory hyperinsulinemia.

First of all, these are measures that ensure a decrease in excess body weight: a low-calorie diet (in the range of 1500-2200 kcal / day) with restriction of fats and easily digestible carbohydrates, limiting salt intake to 3-5 g per day, moderate physical activity, normalization of the work regime and rest. It is possible to use drugs that reduce BMI, for example, orlistat, which selectively inhibits gastrointestinal lipases (“fat blocker”), or sibutramine, which blocks the reuptake of norepinephrine and serotonin in the synapses of the hypothalamic saturation center. The increased energy expenditure (thermogenesis) is also due to a synergistic interaction between the enhanced function of norepinephrine and serotonin in the central nervous system... This is reflected in the selective activation of the central sympathetic impact on brown adipose tissue due to indirect activation of β 3 -adrenergic receptors.

The next step is the use of drugs that improve the impaired sensitivity of tissues to the action of insulin. In the literature, there is evidence of a decrease in hyperandrogenism and restoration of menstrual and ovulatory function when prescribing drugs of a number of biguanides (metformin / Siofor® /, “Berlin-Chemi”). They potentiate the action of insulin at the receptor and post-receptor levels and significantly improve the sensitivity of tissues to this hormone. Some studies have shown a significant decrease in fasting insulin levels and 2 hours after a load of 75 g glucose in women with PCOS who used metformin. This decrease was correlated with a decrease in androgen levels. It should also be noted that the use of biguanides, which normalize carbohydrate disorders, often leads to a decrease in BMI in obese patients and has a positive effect on lipid metabolism.

The world literature reports the results of the use of drugs belonging to the class of thiazolidinediones. Studies have shown that during treatment troglitazone (200-400 mg / day) improves insulin sensitivity in women with PCOS, and decreases the level of androgens. However, the revealed cytotoxic, hepatotoxic effect of this group of drugs limits the possibility of their widespread use. The search is underway for new drugs that selectively affect insulin sensitivity.

Despite the significant arsenal of various agents used to treat ovarian hyperandrogenism, the therapy of this pathology should be comprehensive and consistent, taking into account the leading pathogenetic link at this stage of treatment.

Treatment of women with PCOS should be aimed not only at correcting the identified symptoms of this disease, but also at preventing possible future complications. It is very important to suppress excess secretion of androgens and induce the stability of monthly menstrual bleeding, which is happily achieved with the use of drugs with antiandrogenic properties (Diane-35).

In case of ineffectiveness of conservative therapy after a year, the question of surgical treatment can be raised - laparoscopy with wedge resection of the ovaries or their laser vaporization ... The effectiveness of surgical treatment is high (up to 90-95% of ovulation recovery), and preliminary pathogenetic therapy increases the stability of the achieved result.

Literature:
1. Ovsyannikova T.V., Demidova I.Yu., Glazkova O.I. Reproduction problems, 1998; 6: 5-8.

2. Ginzburg MM, Kozupitsa G.S. Endocrinology Problems, 1997; 6: 40-2.

3. Starkova N.T. Clinical endocrinology. Guide for Physicians, 1991; 399.

4. Givens J.R., Wiedeme E. B-endorphine and B-lipotropin levels in hirsute women: correlation with body weight. J Clin Endocr Metabol. 1980; 50: 975-81.

5. Aleem F.A., McIntosh T. Elevated plasma levels of f-endorph in a group of women with polycystic ovarian desease. Fertil and Steril. 1984; 42: 686-9.

6. Dedov I.I., Suntsov Yu.I., Kudryakova S.V. Endocrinology problems. 1998; 6: 45-8.

7. Francis S., Greenspan, Forshman P.H. Basic and clinical endocrinology. 1987.

8. Akmaev I.K. Endocrinology problems. 1990; 12-8.

9. Barbieri R.L., Hornstein M.D. Hyperinsulinemia and ovarian hyperandrogenism: cause and effect. Endocrinol Metab Clin North Am. 1988; 17: 685-97.

10. Barbieri R.L., Macris A., Ryan K.J. Insulin stimulates androgen accumulation in incubation of human ovarian stroma and theca. Obstet Gynecol. 1984; 64: 73-80.

11. Barbieri R.L., Ryan K.J. Hyperandrogenism, insulin resistence, acantosis nigricans: a common endocrinopathy with unique pathophysiologic features. Am J Obstet Gynecol. 1983; 147: 90-103.

12. Barbieri R.L., Smith S., Ryan K.J. The role of Hyperinsulinemia in the pathogenesis of ovarian Hyperandrogenism. Fertil and Steril. 1988; 50: 197-210.

13. Stuart C.A., Prince M.J., Peters E.J. Obstet Gynecol. 1987; 69: 921-3.

14. Yen S.S.C. Chronic anovuletion causet by peripheral endocrine disorders. In: Yen S.S.C., Jaffe R.B. Reproductive endocrinology: physiology, pathophysiology, and clinical managment. Philadelphia: Saunders W.B. 1986; 462-87.

15. Moller D.E., Flier J.S. Detection of an alteration in the insulin-reseptor gene in a patient with insulin resistance, acantosis nigricans and polycystic ovarian syndrome. N Engl J Med. 1988; 319: 1526-32.

16. Burgen G.A., Givens J.R. Insulin resistance and hyperandrogenism: clinical syndromes and possible mechanisms. Hemisphera Pablishing CO, Washington, DC. 1988; 293-317.

17. Speroff L., Glass R. H. Clinical gynecologic. Endocrinology and Infertiliti 5th ed. 1994.

18. Yoshimasa Y., Seino S., et al. Insulin resistance diabetes due to a point mutacion that privents insulin proreceptor processing./ Science. 1988; 240: 784-9.

19. Dunaif A. Endocrin. Rev. 18 (6): 1997; 12: 774-800.

Ethinylestradiol + Cyproterone Acetate

Diane-35 (trade name)

(Shering AG)

found just such a very detailed article. many words, but I hope who will help

R. A. MANUSHAROVA, MD, DSc, Professor, E. I. CHERKEZOVA, medical sciences, department of endocrinology and diabetology with a course of endocrine surgery GOU DPO RMA PO, Moscow

"Hyperandrogenism", or " hyperandrogenemia", - this term denotes an increased level of male sex hormones () in the blood of women. The syndrome of hyperandrogenism implies the appearance in women under the influence of androgens of signs characteristic of men: growth of hair on the face and body according to the male pattern; the appearance of acne on the skin; hair loss on head (alopecia); decreased voice timbre (baryphony); change in physique (masculinus - "male" phenotype) with the expansion of the shoulder girdle and narrowing of the hips The most frequent and earliest manifestation of hyperandrogenism is hirsutism - excess hair growth in women in androgen-dependent areas, male pattern hair growth Hair growth in hirsutism is noted on the abdomen along the midline, face, chest, inner thighs, lower back, in the intergluteal fold.

Women with hyperandrogenism are at increased risk for complications of childbirth. The most common of them are untimely rupture of amniotic fluid and weakness of labor.

It is necessary to distinguish between hirsutism and hypertrichosis - excess hair growth in any part of the body, including those where hair growth does not depend on androgens.
Hypertrichosis can be either congenital (inherited autosomal dominantly), or acquired as a result of anorexia nervosa, porphyria, and also occur with the use of certain drugs: phenotoin, cyclosporine, diazoxide, anabolic steroids, etc.

There are three stages of hair growth: the growth stage (anagen), the transitional stage (catagen), and the resting stage (telogen). During the last stage, the hair falls out.

Androgens affect hair growth depending on hair type and location. So, on early stages sexual development under the influence of a small amount of androgens begins hair growth in the axillary and pubic regions. With more androgens, hair appears on the chest, abdomen and face, and with very high levels, hair growth on the head is suppressed and bald patches appear over the forehead. Moreover, androgens do not affect the growth of vellus hair, eyelashes and eyebrows.

The severity of hirsutism is often determined arbitrarily and is assessed as mild, moderate, and severe. One of the objective methods for assessing the severity of hirsutism is the Ferrimann and Gallway scale (1961). On this scale, the growth of androgen-dependent hair is assessed in 9 areas of the body in points from 0 to 4. If the score is more than 8, hirsutism is diagnosed.

With functional hyperandrogenism (polycystic ovary syndrome (PCOS), ovarian thecamatosis, etc.), hirsutism develops gradually, accompanied by the appearance of acne, an increase in body weight and irregular periods... The sudden appearance of hirsutism with signs of rapidly developing virilization may indicate androgen-producing tumors of the ovaries or adrenal glands.

Hyperandrogenism- an increase in the level of male sex hormones in the blood of women, leads to menstrual irregularities, excessive hair growth, virilization, infertility.

With hyperandrogenism, tissue sensitivity to insulin is often impaired. The level of insulin in the blood rises in this condition and the risk of developing diabetes mellitus increases.

The increase in the number of male sex hormones may be associated with the pathology of other endocrine organs, such as the thyroid gland or pituitary gland. With neuroendocrine syndrome (dysfunction of the hypothalamus and pituitary gland), the disease is accompanied by a significant increase in body weight.

The main androgens include testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and its sulfate, androstenedione, d5 - androstenediol, d4 - androstenedione.

Testosterone is synthesized from cholesterol entering the human body with animal products or synthesized in the liver, and is delivered to the outer mitochondrial membrane. Transport of cholesterol to the inner mitochondrial membrane is a gonadotropin-dependent process. On the inner mitochondrial membrane, cholesterol is converted into pregnenalone (the reaction is carried out by cytochrome P450). In the smooth endoplasmic reticulum, following two pathways for the synthesis of sex hormones: d5 (mainly in the adrenal glands) and d4 (mainly in the ovaries), subsequent reactions take place. Free and albumin-bound testosterone is biologically available.

In women, testosterone is produced in the ovaries and adrenal glands. In the blood, 2% of testosterone circulates in a free state, 54% is associated with albumin, and 44% with SHBGs (globulin-binding sex steroids). The SHBG level is increased by estrogens, and the androgens are lowered, therefore the SHBG level in men is 2 times lower than in women.

A decrease in the level of SHBG in blood plasma is observed when:

• obesity;
• excessive formation of androgens;
• corticosteroid treatment;
• hypothyroidism;
• acromegaly.

An increase in the level of SHBG occurs when:

• estrogen treatment;
• pregnancy;
• hyperthyroidism;
• cirrhosis of the liver.

Testosterone, associated with SHBG, performs part of the functions on the cell membrane, but cannot penetrate inside. Free testosterone can be converted into 5a-DHT or by connecting to a receptor and penetrate into target cells. Biologically available is the sum of the fractions of free and albumin-bound testosterone.

Dehydroepiandrosterone (DHEA) is produced in the testes, ovaries and adrenal glands. It was first isolated in 1931 and is a weak androgen. Once converted to testosterone in peripheral tissues, it has an effect on the cardiovascular and immune systems.
Androstenedione, a testosterone precursor, is produced in the testes, ovaries, and adrenal glands. The conversion of androstenedione to testosterone is a reversible process.

Androgens act at the cellular level through high-affinity nuclear receptors. The enzyme aromatase converts androgens into estrogens.
Free testosterone enters the target cell and binds to the androgen receptor on the X chromosome DNA. Testosterone or DHT, depending on the activity of 5a-reductase in the target cell, interact with the androgen receptor and change its configuration, as a result of which there is a change in receptor dimers transmitted to the cell nucleus and interacting with the target DNA.

Dehydrotestosterone has a high affinity for androgen receptors, then testosterone, and a low affinity for adrenal androgens (DHEA, androstenedione).
The effects of testosterone include: differentiation of male sex characteristics; the appearance of secondary sexual characteristics; the growth of male genital organs; pubic hair; hair growth in the armpits and on the face; growth spurt during puberty; closure of the epiphyses; the growth of "Adam's Apple"; thickening of the vocal cords; increase in muscle mass, thickening of the skin; the functioning of the sebaceous glands. Testosterone also affects libido and potency, increases aggression.

With hyperandrogenism, it is noted:

• male-pattern hair growth on the face and body;
• the appearance of acne on the skin;
• hair loss on the head (alopecia);
• lowering the timbre of the voice (barithony);
• change in physique (masculinization) with the expansion of the shoulder girdle and narrowing of the hips.

Hyperandrogenism develops with the following diseases of the hypothalamic-pituitary system:

• neuroendocrine metabolic syndrome with obesity and gonadotropic
  dysfunction;
• corticotropinoma (Itsenko-Cushing's disease);
• somatotropinoma (acromegaly);
• functional hyperprolactimemia and against the background of prolactinoma;
• gonadotropinomas, hormone-inactive pituitary adenoma, syndrome of "empty" sella turcica;
• anorexia nervosa;
• obesity and type 2 diabetes mellitus;
• insulin resistance syndromes (including type A acanthosis nigricans (mutation of the insulin receptor gene) and leprehaunism);
• secondary hypothyroidism.

Ovarian and adrenal forms of hyperandrogenism are distinguished, each of which has tumor and non-tumor forms. PCOS, stromal hyperplasia and ovarian tecamatosis are evidenced by non-tumor or functional hyperandrogenism of ovarian origin, congenital dysfunction of the adrenal cortex (ADCN) - functional hyperandrogenism of adrenal genesis. The tumor form of hyperandrogenism causes androgen-producing tumors of the ovaries or adrenal glands. With corticosteroma, severe hyperandrogenism is observed.

Treatment of the nonclassical form of congenital adrenal cortex dysfunction should begin with suppression of elevated ACTH (corticotropin) levels. For this purpose, dexamethasone is used. In equivalent doses, it has a more pronounced effect compared to other glucocorticoids and retains fluid to a lesser extent. When treating with dexamethasone, it is necessary to control the concentration of cortisol. Control is carried out in the morning.

In patients with UDKN, after taking adequate doses of dexamethasone, the menstrual cycle, as a rule, is restored, and in the majority it becomes ovulatory.

In the absence of ovulation while taking glucocorticoid drugs with a nonclassical form of VDKN or in case of insufficiency of the luteal phase of the menstrual cycle, clomiphene citrate (clostilbegit (Egis, Hungary); clomid (Hoechst Marion RousseI, Germany) is prescribed according to the generally accepted scheme from 5 to 9 or from 3 to 7 days of the menstrual cycle Due to the similarity with the estrogen receptors in the target cells in the ovaries, pituitary and hypothalamus, the drug clomiphene citrate has two opposite effects: weak estrogenic and pronounced antiestrogenic. adrenal glands, ovulation should be stimulated while taking glucocorticoids.

Women often ovulate and become pregnant on the background of combined therapy. Discontinuation of glucocorticoid treatment after pregnancy can lead to spontaneous miscarriage or cessation of the development of a fertilized egg, so therapy should be continued.

Gonadotropic drugs LH and FSH can be used to stimulate ovulation in the usual way, but always while taking glucocorticoids.

If, against the background of therapy with clostilbegit on the days of the expected ovulation (13-14 days of the cycle), the phase of the corpus luteum persists, then drugs containing gonadotropins (LH and FSH) are administered: prophasi, pregnyl, pergonal, etc. in large doses (5000-10,000 UNITS). It should be remembered that when using these drugs, ovarian hyperstimulation syndrome (OHSS) may develop.

Patients with UDKN over the age of 30 with ineffective treatment of infertility for more than 3 years and the presence of an ultrasound picture of polycystic ovaries is shown surgery- Carrying out wedge resection by laparoscopic access, demedulation or electrocautery of the ovaries. In this case, treatment with glucocorticoids continues.
Low- and micro-dose combined oral contraceptives (COCs) with antiandrogenic action are used to treat patients with VDKN and severe hirsutism. The most effective among them are: Diane-35, Janine, Yarina, etc. These drugs contain estrogens and gestagens. Under the influence of estrogens, the production of globulin binding sex steroids (SHBG) in the liver is enhanced, which is accompanied by an increase in the binding of androgens. As a result, the content of free androgens decreases, which reduces the manifestations of hirsutism. The antigonadotropic effect of these drugs suppresses the formation of gonadotropins in the anterior lobe of the pituitary gland, and the gonadotropic function of the pituitary gland in VDKN is depressed high level androgens circulating in the blood. Consequently, the action of COCs can lead to an even greater decrease in the concentration of gonadotropins and aggravate menstrual irregularities. In this regard, the use of COCs for VDKN should not be long-term.

Treatment of androgen-producing ovarian tumors. In order to identify metastases, the pelvis and omentum are examined. Chemotherapy is performed when distant metastases are detected. In the absence of signs of malignant growth and dissemination in such patients of reproductive age, unilateral adnexectomy is performed, and in postmenopausal women, extirpation of the uterus with appendages is performed. After the operation, it is necessary to monitor patients dynamically, control the level of hormones, ultrasound of the pelvic organs. In the absence of metastases and dissemination, after removal of the ovarian tumor in patients of reproductive age, complete recovery occurs: the symptoms of virilization disappear, the menstrual cycle and fertility are restored. The ten-year survival rate depends on the histological characteristics and size of the tumor and is 60-90%.

For hormone-active adrenal tumors, surgical intervention is indicated, since there is no conservative treatment. A contraindication is only a pronounced dissemination of the process. With decompensation of cardio-vascular system, purulent complications, the operation is postponed. In this case, according to indications, cardiac, antihypertensive, sedatives are prescribed; patients with diabetes mellitus before the operation are transferred to therapy with simple insulin in fractional doses.

The surgical approach depends on the size and location of the tumor. Recently, surgical treatment of the adrenal glands has been performed by the laparoscopic method. The course of the postoperative period depends on the degree and type of hormonal activity of the tumor and caused by it metabolic disorders... Therefore, patients need to prescribe specific hormonal therapy.

Treatment of idiopathic hirsutism. For the treatment of idiopathic hirsutism, antiandrogens are used - modern microdose drugs containing estrogens and gestagens. The greatest antiandrogenic activity among these drugs is possessed by Diane-35 in combination with androkur, as well as Zhanin, Belara, Yarina.

In addition to combined oral contraceptives, androgen antagonists are prescribed:

• spironolactone, which inhibits 5a-reductase at the cellular level and reduces the rate of conversion of testosterone to dehydrotestosterone;
• cyproterone acetate - a progestin that blocks androgen receptors at the cellular level;
• cimetidine is an antagonist of histamine receptors that block the action of androgens at the cellular level;
• desogestrel, ketoconazole, metrodin - increasing the level of SHBG, binding testosterone and making it biologically inactive;
• flutamide - a non-steroidal antiandrogen that binds to androgen receptors, to a lesser extent suppressing testosterone synthesis;
• finasteride - having an antiandrogenic effect by inhibiting the activity of 5a-reductase and does not affect androgen receptors;
• ketocanazole - suppressive steroidogenesis;
• medroxyprogesterone - suppressing the secretion of gonadoliberin and gonadotropins, reducing the secretion of testosterone and estrogen;
• analogs of gonadotropin-releasing hormone (GnRH) - acting on functional state ovaries, suppressing the secretion of estrogens, androgens;
• glucocorticoids.

In the absence of an effect from the use of combined oral contraceptives, the appointment of flutamide reduces hair growth, reduces the level of androstenedione, dihydrotestosterone, LH and FSH. COCs and flutamide may cause the following side effects: dry skin, hot flashes, increased appetite, headache, dizziness, engorgement of the mammary glands, decreased sex drive, etc.

The use of ketoconazole is accompanied by a significant decrease in the level of androstenedione, total and free testosterone in serum. A decrease in androgen levels leads to a weakening or elimination of hair growth.

Medroxyprogesterone acts on the level of globulin that binds sex hormones, reducing the content of the latter. When using the drug, 95% of patients note a decrease in hirsutism. When using the drug, the following may be observed side effects: amenorrhea, headache, edema, weight gain, depression, changes in the biochemical parameters of liver function.

The use of GnRH analogs causes reversible medical castration, which is accompanied by a weakening of hirsutism. However, their use for more than 6 months leads to the development of postmenopausal symptoms (hot flashes, fever, vaginal dryness, dyspareunia, osteoporosis). The development of the above symptoms prevents the appointment of estrogens or COCs simultaneously with GnRH analogues.

With an increased level of dehydroepiandrosterone or 17 OH-progesterone in the blood, glucocorticoids are prescribed. Of these, dexamethasone is most effective. While taking the drug in patients, hirsutism decreases and other symptoms of hyperandrogenism disappear. When dexametozone is prescribed to patients, it is possible to suppress the pituitary-adrenal system, therefore it is necessary to control the level of cortisol in the blood.

Treatment for polycystic ovary syndrome

In the treatment of PCOS, it is necessary to restore the ovulatory menstrual cycle and fertility, to eliminate the manifestations of androgen-dependent dermopathy; normalize body weight and correct metabolic disorders; prevent late complications of PCOS.
Insulin resistance (IR) and obesity potentiating it is the most important pathogenetic link of anovulation in PCOS.

If you are obese (BMI> 25 kg / m2), PCOS treatment should be started with weight loss. Drugs that reduce body weight are prescribed against the background of a low-calorie diet containing no more than 25-30% fat, 55-60% slowly digestible carbohydrates, 15% protein from the total calorie intake. Limit salt intake. Diet therapy must be combined with increased physical activity.

Overweight in PCOS causes hyperinsulinemia (GI) and decreased sensitivity of peripheral tissues to insulin (IR). However, a number of studies have shown that with PCOS, insulin sensitivity is reduced in patients not only with increased, but also with normal or decreased BMI. Thus, PCOS is an independent factor that reduces tissue sensitivity to insulin. Obesity, observed in 50-70% of patients with PCOS, has an independent negative effect, potentiating IR.

To remove IR, biguanides are prescribed. Metformin is used in Russia (Siofor, Verlin Chemie, Germany). The use of this drug for PCOS lowers blood glucose levels, suppresses gluconeogenesis in the liver and increases the sensitivity of peripheral tissues to insulin. As a result of the use of metformin, body weight decreases, the menstrual cycle normalizes, the level of testosterone in the blood decreases, but ovulation and pregnancy are not always observed.

Stimulating ovulation is the second step in PCOS treatment. But when obesity and PCOS are combined, stimulating ovulation is considered a medical error. After normalization of body weight, clomiphene is prescribed to stimulate ovulation. If stimulation is ineffective after 6 months of treatment, the patient can be considered clomiphene-resistant. It is observed in 20-30% of patients with PCOS. In this case, FSH drugs are prescribed: menogon - human menopausal gonadotropin or synthesized recombinant FSH. GnRH analogues are prescribed for patients with PCOS and high LH levels. Under the influence of these drugs, the pituitary gland is desensitized, increasing the frequency of ovulation after the administration of FSH drugs.

If there is no effect of conservative therapy, they resort to surgical stimulation of ovulation. The laparoscopic approach is performed by wedge resection or demedulation or cauterization of both ovaries. The use of the endoscopic method of intervention has significantly reduced the incidence of adhesive process compared to laparotomy.

Surgical treatment for PCOS is used in the following cases:

• when combined with PCOS with recurrent dysfunctional uterine bleeding and endometrial hyperplasia, regardless of the presence or absence of obesity;
• in women with normal body weight with a significant increase in plasma LH levels;
• in women over 35 years old, even with obesity. In this case, immediately after the operation, intensive therapy for obesity is carried out.

The following factors can lead to a decrease in the frequency of regulation of the menstrual cycle and the onset of pregnancy:

• the duration of anovulation and the woman's age over 30 years;
• large ovaries with a subcapsular arrangement of atretic follicles around the hyperplastic stroma;
• pronounced IR and GI regardless of body weight;
• violation of the menstrual cycle as amenorrhea.

Treatment of hirsutism in PCOS. For the treatment of hirsutism in PCOS, the same drugs are used as for the treatment of idiopathic hirsutism (see above).

Due to the fact that hirsutism is caused by hyperandrogenism, drugs are used for treatment that reduce the level of androgens, suppressing androgen receptors; reducing the formation of androgens; suppressive enzyme systems involved in the synthesis of androgens, in the production of (extragonadal) testosterone and its conversion to DHT.

Due to the fact that the treatment of hirsutism with medication is a long process, many women use different kinds epilation (electrical, laser, chemical, mechanical, photoepilation).

Treatment of PCOS complications

To prevent the development of metabolic disorders, it is necessary to reduce body weight. To prevent the development of endometrial hyperplasia, it is necessary to carry out an ultrasound control of the endometrium and, if necessary, treat with progesterone derivatives. In the presence of HE (endometrial thickness more than 12 mm), curettage of the uterine mucosa is prescribed under the control of hysteroscopy, and a histological examination is also performed.
In addition to restoring fertility, PCOS treatment must be carried out in order to correct metabolic disorders that are the background for the onset of type 2 diabetes mellitus, early atherosclerosis, hypertension, as well as a high risk of developing endometrial hyperplasia and adenocarcinoma.

Hyperandrogenism in women is increased content male sex hormones (testosterone). He is the predecessor. The transformation takes place under the influence of the aromatase enzyme. Testosterone is produced in the weaker sex in the adrenal glands, ovaries and adipose tissue. A breakdown at any of these levels can lead to different types hyperandrogenism in women.

The main types of hyperandrogenism in women

At the moment, depending on the causes of the origin of hyperandrogenism, there are two main forms. This is true and others. The true include ovarian and adrenal hyperandrogenism. By origin, they can be functional and neoplastic.

Functional true hyperandrogenism in women and their causes:

• Ovarian hyperandrogenism. It is associated with a deficiency of the enzyme aromatase, which ensures the conversion of testosterone into estrogens. As a rule, this is a congenital defect. Often there is mild ovarian hyperandrogenism - erased forms (testosterone levels may be normal, there may be no ultrasound signs of sclerocystic ovaries).
• Adrenal hyperandrogenism. Associated with a lack of an enzyme that converts testosterone precursors. Symptoms of adrenal hyperandrogenism: characterized by significant increased levels of testosterone and, as a manifestation of this, hirsutism;

Other forms include:

• Transport. Associated with a deficiency of sex hormone binding globulin (SHBG). This globulin binds and prevents it from entering the target organ cell. SHBG is produced in the liver, its levels depend on the work of the thyroid gland and the amount of estrogen.
• Metabolic hyperandrogenism. Associated with a violation of carbohydrate and fat metabolism... It is based on insulin resistance;
• Hyperandrogenism of mixed genesis. Combination different forms and the causes of hyperandrogenism syndrome in women;
• Iatrogenic. It occurs as a result of the action of various medications.

The main symptoms of hyperandrogenism

Target organs for the action of testosterone: ovaries, skin, sebaceous and sweat, as well as mammary glands, hair. The leading symptoms of hyperandrogenism in women are the following manifestations:

1. (maturation and release of the egg), which can provoke infertility and lead to hyperestrogenism. Long-term hyperestrogenism is a risk in hormone-dependent organs (uterus, ovaries);
2. Insulin resistance (tissue insensitivity to insulin, as a result of which the cell does not absorb glucose and remains "hungry"). Leads to the development of type 2 diabetes mellitus;
3. Hirsutism. Signs of hyperandrogenism in this case: hair growth in androgenic zones (on the beard, chest, anterior abdominal wall, arms, legs, back);
4. Skin manifestations (acne, seborrhea, androgen-dependent alopecia)
5. Sclerocystic ovaries: enlarged, with a dense tunica albuginea, but many maturing follicles located on the periphery. The necklace symptom is created.

The diagnosis of hyperandrogenism is based on at least two of the above symptoms.

Diagnosis of hyperandrogenism in women

Treatment of hyperandrogenism in women depends on the correct diagnosis of the cause and type of this syndrome. Diagnostics consists of the following stages:

• Complaints about increased hair growth in places atypical for women, the appearance of acne, infertility, menstrual irregularities, often obesity;
• Anamnesis: manifestations of hyperandrogenic syndromes coincide with the period of puberty and reproductive age;
• Inspection data: obesity, hirsutism, the above-described skin manifestations;
• Hormonal examination data: increased levels of free testosterone, adrenocorticotropic hormone, dehydroepistendinone, prolactin;
• Ultrasound data: sclerocystic ovaries, an increase in the volume of the ovaries or their tumors, adrenal tumors;
• Decrease in the level of globulin that binds sex hormones;
• Increased insulin levels and impaired glucose tolerance.

Treatment of hyperandrogenism in women

Can hyperandrogenism be cured? True functional hyperandrogenism cannot be cured because it is associated with congenital enzyme defects. Treatment is carried out to eliminate certain symptoms of hyperandrogenism in women. After stopping treatment, symptoms of hyperandrogenism may recur.

Treatment of hyperandrogenism in women of ovarian origin consists in the use of steroid antiandrogenic drugs (Diana 35, Cyproterone, Levonorgestrel) and non-steroidal (Flutamine) types.

In the treatment of adrenal hyperandrogenism, Dexamethasone is used.

Treatment of hyperandrogenism associated with metabolic disorders consists in increased physical activity and reducing agents, for example, Metformin.

The syndrome of hyperandrogenism in women associated with an increase in the level of prolactin requires the appointment of prolactin-reducing drugs (Alactin, Bromcriptine).

Treatment of hyperandrogenism of tumor genesis consists in the prompt removal of these formations on the ovaries, adrenal glands, pituitary gland.

Hyperandrogenism in girls at an early age, as a rule, is associated with adrenal veritable syndrome of tumor genesis, requiring surgical treatment... Functional hyperandrogenism in children appears during puberty.

Hyperandrogenism during pregnancy

Infertility is not always the result of hyperandrogenism. However, it causes a disruption in the production of estrogen hormones and. In the syndrome of hyperandrogenism, this hormone is reduced. with this syndrome, the appointment of natural progesterone preparations is indicated, especially in the first trimester, when the placenta is "forming". Hyperandrogenism during pregnancy is a risk factor for miscarriage and prematurity, the development of metabolic syndrome in children.

Hyperandrogenism is a pathology in which the hormonal background of a woman undergoes significant changes. Too much of the hormone androgen, which is considered male, is produced. In a woman's body, this hormone performs many necessary functions, but its excessive amount leads to unpleasant consequences, the treatment of which is necessary.

Androgens are produced in women by adipocytes, adrenal glands and ovaries. These sex hormones directly affect the process of puberty in women, the appearance of hair in the genital area and armpits. Androgens regulate the functioning of the liver, kidneys, and also affect muscle growth and the reproductive system. They are necessary for mature women, since they synthesize estrogen, support on sufficient level libido and strengthen bone tissue.

What is hyperandrogenism?

Hyperandrogenism in women, its manifestations and the consequences of the photo

Hyperandrogenism is a pathological condition that most often leads women to amenorrhea (complete absence of menstruation) and infertility. Ovarian follicles in women are surrounded by cell layers, and an excess of androgens inhibits follicular growth, as a result, follicular atresia (follicular overgrowth) occurs. In addition, with an excessive amount of male hormones, fibrosis of the ovarian capsule develops, which in turn leads to polycystic disease (many cysts on the ovaries).

To master the mechanism of development of hyperandrogenism in women, you should remember:

• The hypothalamus is a central regulatory department in the brain of the head that controls metabolic processes in the human body; responsible for the functionality of the endocrine and gonads. It is the place of interaction of two important systems, such as the nervous and hormonal;
• The pituitary gland is the main endocrine gland found in the brain stem of the head. Responsible for the activity of the hormonal metabolism system under the guidance of the hypothalamus;
• Disturbances of central genesis are regulatory disorders in the brain, appear from the malfunctioning of the pituitary gland and hypothalamus;
• The adrenal glands are two small endocrine glands located above the kidneys. They consist of two layers - an internal cerebral and an external cortical;
• Test to determine the source of hyperandrogenism, using dexamethasone - through the introduction of this drug, the level of androgens in the blood of women is determined

Ovarian damage and how to deal with them

Ovarian hyperandrogenism is found in 4-5% of women of reproductive age. The variety of reasons does not make it possible to accurately determine the causality of its occurrence, however, the key link in the pathogenesis of the syndrome is highlighted - these are the main and secondary regulatory failures in the work of the hypothalamic-pituitary system. These disruptions cause excessive stimulation of LH production or lead to an increased ratio of gonadotropic hormones LH / FSH.

A relatively large or excessive amount of LH leads to hyperplasia of the connective tunica albuginea of ​​the ovaries, the outer and granulosa layers of the follicles. Because of this, the amount of ovarian androgens increases, signs of masculinization become visible. Insufficient production of FSH leads to the fact that the follicles do not mature, the woman begins to annovate, requiring treatment.

The reasons are strong stress and an excess of male hormones

Medical scientists suggest that ovarian hyperandrogenism occurs due to:

• relative or unconditional excess of LH, which has arisen due to the malfunctioning of the adenohypophysis or hypothalamus;
• excessive synthesis of male sex steroid hormones by the adrenal cortex during the prepubertal period;
• accumulation of excess fat in prepubertal age. Obesity is believed to be the dominant risk factor, as it is predominantly in fat that androgens are converted to estrogens;
• insulin resistance and hyperinsulinemia;
• due to the impaired genesis of steroids in the female ovaries. In some patients, there is an intense production of 17alpha-hydroxylase, an enzyme that converts 17-hydroxypregnenolone to DHEA and 17-hydroxyprogesterone to the steroid hormone androstenedione;
• primary hypothyroidism

Polycystic ovary disease in women may appear with nonclassical congenital adrenal hyperplasia.

Other causes of hyperandrogenism include androgen-secreting neoplasms on the ovaries (requiring surgical treatment), hyperthecosis and leydigoma.

Symptoms are excessive hair growth of the skin.

Symptoms of hyperandrogenism can be basic:

• active hair growth in a woman's extremities and other parts of the body (abdomen, mammary glands). Hair begins to grow on the cheeks - this type of hair growth is called hirsutism;
• bald patches on the head (alopecia);
• defects appear on the face, in the form of acne, acne, peeling and various inflammations (treatment by a beautician does not give results);
• osteoporosis develops, muscle atrophy is observed;

The syndrome of hyperandrogenism in women has secondary manifestations (depending on the stage and causes of the onset of the disease):

• increased blood glucose levels (type 2 diabetes);
• a sharp increase in excess weight (obesity that needs to be treated);
• the formation of the genital organs in women according to the intermediate type;
• the woman never menses or the cycle is separated by significant intervals;
• infertility or miscarriage of the fetus, if hyperandrogenism occurs during pregnancy (for the safe bearing of the fetus, the woman's body needs female hormones in a certain amount, and with hyperandrogenism they are practically not produced);
• arterial hypertension attacks

Women suffering from hyperandrogenism often catch colds, are prone to depressive conditions, fatigue. The patient's age is not important - you can get hyperandrogenism in absolutely any age period life, starting at birth itself.

Diagnostics consists in examining a doctor, identifying the causes of the disease

At the beginning of the examination of a woman, the doctor first of all tries to exclude diseases that are accompanying: liver diseases, sexual differentiation, Cushing's syndrome, androgen-secreting tumor formations on the adrenal glands.

Diagnosis of hyperandrogenism in women in a clinical laboratory:

1. Determination of the basic hormonal level. Find out what is the amount of prolactin, free and total testosterone, dehydroepiandrosterone sulfate, androstenedione and the level of FSH in the blood plasma. The material is taken in the morning on an empty stomach. Due to the constant change in the hormonal background, patients with hyperandrogenism are tested three times, with intervals between procedures for 30 minutes, then all three portions of blood are mixed. Dehydroepiandrosterone sulfate, in an amount of more than 800 μg%, indicates the presence of an androgen-secreting adrenal tumor;
2. The amount of ketosteroids-17 in urine is determined;
3. Take a marker to determine hCG (in the case when there are signs of hyperandrogenism, but the basic level of androgens remains normal).

Instrumental study: a patient with suspected hyperandrogenism is referred for MRI, CT, intravaginal ultrasound (to visualize tumor formations).

Treatment is performed various drugs depending on the shape and wishes of the woman

Depends on the personal desires of a woman with hyperandrogenism:

• if children are expected in the future, then treatment is carried out with clomiphene;
• if a woman does not plan to restore fertility, then she is prescribed hormone treatment (oral contraceptives). With a high LH content (after two months of taking the drugs), androstenedione and testosterone levels return to normal;
• if contraceptive drugs are contraindicated for a woman, then spironolankton is prescribed for her treatment. The course of treatment is six months.
• tumors on the ovaries are removed promptly

The adrenal form is congenital in 95%, its treatment must be accurate and of high quality

Adrenal hyperandrogenism is often congenital. Masculine symptoms appear early in this case. The first menstruation in women appears very late, and in the future they can either become very rare, or even stop altogether. With adrenal hyperandrogenism, all patients have profuse acne on the back and chest, local skin pigmentation.

In women, hypoplasia of the mammary glands is noted, the figure develops like a man's (the pelvis is narrow, the shoulders are wide). With adrenal hyperandrogenism, the woman's clitoris is somewhat hypertrophied, the uterus becomes smaller, but the ovaries remain of normal size.

Diagnosis and treatment of hyperandrogenism in women requires maximum accuracy. With hyperandrogenism of adrenal genesis, treatment with glucocorticoids is recommended. drugs, in order to maintain normal hormonal levels.