Functional hyperandrogenism. Syndrome of hyperandrogenism

The most noticeable symptom of hyperandrogenism is hirsutism, but it must be remembered that it is not always due to hyperandrogenemia (for example, it can be constitutional). Conversely, an excess of androgens is not necessarily accompanied by severe hirsutism - as, for example, in Asian women with polycystic ovary syndrome.

Synthesis of androgens in women

Androgens are C19 steroids that are secreted from cholesterol in the reticular zone of the adrenal cortex, as well as in thecocytes and stroma of the ovaries. In addition, in these organs and in peripheral tissues, androgens can be converted into more active derivatives (for example, testosterone to dihydrotestosterone), into estrogens (under the action of aromatase) or inactivated by conjugation with glucuronic acid or sulfation and subsequently excreted from the body.

Androgens act both systemically (classic endocrine regulation) and locally (paracrine or autocrine regulation, for example, in skin hair follicles). They bind to intracellular androgen receptors located in the cytoplasm. Then the hormone-receptor complex moves to the nucleus, where, in the course of a complex interaction with other transcription factors and coactivator proteins, it regulates the transcription of target genes. In addition, androgens can also act indirectly, through metabolites (for example, through electrogens).

In plasma, androgens circulate in combination with a number of proteins, primarily with SHBG. Compared to the latter, albumin has a much higher binding capacity due to its higher concentration and greater total amount. However, the affinity of androgens for albumin is much lower, so the bulk of plasma testosterone circulates in combination with SHBG. In such a complex, androgens are less biologically available to target cells than in a complex with albumin. SHBG is produced by the liver. Estrogens, including those taken orally, stimulate the production of this protein, while androgens, and, most importantly, insulin, inhibit it. Therefore, women with hyperandrogenism and men have lower levels of SHBG. Androgens are metabolized in the liver and other peripheral tissues, and their metabolism is highly dependent on the level free hormones in plasma.

The production of androgens depends on age and the presence of obesity. With age, the level of adrenal androgens, especially dehydroepiandrosterone, its metabolite (dehydroepiandrosterone sulfate) and androstenedione, gradually decreases; this decline begins even before menopause. Age affects testosterone levels to a lesser extent; the ovaries continue to produce this hormone for quite a in large numbers and postmenopausal.

Symptoms and signs of hyperandrogenism

The clinical manifestations of hyperandrogenism are varied; they are caused by the action of androgens on the hair follicles and sebaceous glands(hirsutism, acne vulgaris, androgenetic alopecia) and on the hypothalamic-pituitary-ovarian system (ovulation and menstrual cycle disorders). In severe hyperandrogenism, other signs of virilization develop.

Clinical manifestations of hyperandrogenism

Hair follicles and sebaceous glands

• hirsutism
• Acne vulgaris A
• androgenetic alopecia

Hypothalamic-pituitary-ovarian system

• Ovulation disorders
• Oligomenorrhea
• Dysfunctional uterine bleeding
• Infertility caused by anovulation

Adipose tissue

• Obesity by male pattern

virilization

• Severe hirsutism
• Androgenetic alopecia
• Low voice
• Clitoral hypertrophy
• Obesity by male pattern
• Increase muscle mass
• Breast reduction

Effects on hair follicles and sebaceous glands

In androgen-dependent areas, instead of thin, colorless vellus hair, coarse, thick, pigmented terminal hairs begin to grow. The effect of androgens on peripheral tissues depends mainly on the activity of 17p-hydroxysteroide dehydrogenase (turns androstenedione into testosterone) and 5α-reductase and on the number of androgen receptors. Before puberty, mainly thin, short, colorless vellus hair (velus) grows on the body. During puberty, increased androgen levels cause some of these hairs to be replaced by coarser, longer, pigmented terminal hairs. It should be noted that the terminal hairs of the eyebrows, eyelashes, occipital and temporal parts of the head depend little on androgens.

Acne vulgaris

Androgens stimulate the production sebum and keratinization of the walls of the follicle, which contributes to the development of seborrhea, folliculitis and acne during puberty and with hyperandrogenism. In patients with acne vulgaris, plasma androgen levels and 5a-reductase activity, which converts testosterone to dihydrotestosterone, are elevated. Therefore, with the appointment of antiandrogens, COCs or glucocorticoids, improvement often occurs.

Androgenetic alopecia

An excess of androgens, which stimulates the growth of hair on the face and trunk, on the hair follicles of the scalp, on the contrary, acts in the opposite way: the hair follicles decrease in size, instead of terminal hair, hair similar to fluff begins to grow. Androgenetic alopecia occurs in both men and women. In women, it can proceed in two ways. With severe hyperandrogenism and virilization symptoms, hair loss is observed on the parietal part of the head, a change in the front edge of hair growth with the formation of bald patches. But more often baldness comes down to thinning hair, mainly in the parietal region. Approximately 40% of women with androgenetic alopecia find hyperandrogenism, but if we take into account cases of isolated alopecia without hirsutism, this figure will decrease to 20%.

Effect on ovarian function

Hyperandrogenism is often accompanied by ovulation disorders, either due to a violation of the secretion of gonadotropic hormones, or as a result of the direct action of androgens on the ovaries. Androgens affect the hypothalamic-pituitary system and the secretion of gonadotropic hormones in women indirectly (after being converted into estrogens) or directly. In the experiment, dihydrotestosterone disrupted the ability of progesterone to control the frequency of GnRH impulses, which led to an increase in LH secretion. In addition, an excess of androgens can inhibit the maturation of ovarian follicles, resulting in the appearance of multiple small cysts in the cortex (so-called polycystic ovaries). The clinical expression of ovarian dysfunction in hyperandrogenism is menstrual irregularities, which can be considered as a symptom of androgen excess even in the absence of anrogen-dependent skin lesions.

Effect on the adrenal glands

25-50% of women with hyperandrogenism have elevated levels of adrenal androgens (eg, dehydroepiandrosterone and its sulfate). However, increased adrenal steroidogenesis and increased levels of adrenal androgens may be due, at least in part, to extra-adrenal (eg, ovarian) androgens. Elevated levels of dehydroepiandrosterone sulfate in women with polycystic ovary syndrome are reduced by 20-25% after the appointment of long-acting gonadoliberin analogues, although normalization of adrenal androgens against the background of such treatment is rarely observed. The secretion of adrenal androgens, especially dehydroepiandrosterone sulfate, can be increased with an excess of extra-adrenal androgens, further exacerbating hyperandrogenism.

Obesity

Obesity and hyperandrogenism are closely related, especially in polycystic ovary syndrome. It is not known which of these conditions develops first. In polycystic ovary syndrome, the amount of androgens that can be converted to estrogens in peripheral tissues increases, resulting in an increase in estradiol levels. In a prospective study, ten normal-weight young men undergoing female-to-male gender reassignment surgery underwent MRI scans: before testosterone, after a year of taking the drug, and after three years of taking the drug. In the course of treatment, the weight changed slightly, but the distribution of subcutaneous adipose tissue changed significantly. After a year of treatment, her thickness in the abdomen, pelvis, and thighs decreased significantly compared to baseline, but after three years of treatment, these differences were no longer statistically significant. Adipose tissue mass internal organs, on the contrary, in the first year of treatment practically did not change, although it increased in those who gained weight during this period. However, after three years of testosterone supplementation, this figure increased by 47% compared to baseline, and, as before, it was highest in those who gained weight.

All these data confirm that an excess of androgens or estrogens formed from them contributes to the development of male-type obesity, which leads to an increase in insulin resistance and a further increase in androgen levels in patients with hyperandrogenism. An indirect effect of androgens on weight gain through the central nervous system is not excluded. The role of androgens in the development of obesity is not entirely clear, but in favor of their influence is the fact that among men the prevalence of overweight is higher than among women.

Anabolic action of androgens and virilization

With severe and prolonged hyperandrogenism, virilization can be observed - the appearance of bald patches in the parietal part of the head and above the forehead, clitoral hypertrophy and severe hirsutism. In the future, especially if hyperandrogenism has developed before the onset of puberty, the physique (atrophy of the mammary glands, an increase in muscle mass) may change and the timbre of the voice may decrease. In women of childbearing age, virilization is almost always accompanied by amenorrhea. Most often, virilization indicates an androgen-secreting tumor. Moderate virilization also occurs in girls with severe insulin resistance (eg, with HAIR-AN syndrome).

Rare causes of hyperandrogenism

The clinical picture of hyperandrogenism is also observed in ACTH-secreting tumors - pituitary adenoma (Cushing's disease) or an ectopic tumor. However, Cushing's syndrome is extremely rare (1:1,000,000), and methods for its detection do not have one hundred percent sensitivity and specificity, so it is not necessary to examine all women with hyperandrogenism for Cushing's syndrome. Occasionally, hyperandrogenism can also be a consequence of the ingestion of androgens. In pregnancy, severe hirsutism or even virilization may have a benign ovarian cause, such as thecalutein cysts, pregnancy luteomas, or the extremely rare aromatase deficiency, in which the placenta is unable to synthesize estrogens from androgens, resulting in hyperandrogenism.

Examination for hyperandrogenism

To establish the cause of hyperandrogenism, the anamnesis and physical examination are primarily important, while laboratory studies are necessary mainly in order to confirm or refute the various diagnoses that arise during the examination.

Examination for suspected hyperandrogenism

Anamnesis

• Taking medications or other androgen-containing drugs
• Skin exposure to irritants
• Information about the menstrual cycle, pregnancy and childbirth
• Time of onset and progression of hirsutism, acne, and alopecia
• Enlargement of the limbs or head, changes in the contours of the face, weight gain
• Lifestyle information (smoking, drinking)

Physical examination

• Assessment of hirsutism, such as the modified Ferriman-Galloway scale
• Androgenetic alopecia
• Black acanthosis and soft fibromas
• Signs of Cushing's Syndrome
• Obesity and its type
• Clitoral hypertrophy
• Other signs of virilization

Laboratory research

• TSH (measured by a highly sensitive method)
• 17-hydroxyprogesterone in the follicular phase of the menstrual cycle
• Prolactin
• Total and free testosterone, dehydroepiandrosterone sulfate (usually in cases where symptoms of hyperandrogenism are mild or questionable)
• Fasting and postprandial insulin levels

Anamnesis

Collect a detailed history: taking drugs and other drugs containing androgens: exposure to the skin of irritants; data on the menstrual cycle, pregnancy and childbirth; time of onset and progression of hirsutism; an increase in the size of the limbs or head, a change in the shape of the face, weight gain; the presence of bald patches, hair loss and acne; find out also whether there are similar diseases in the next of kin. Diabetes in the next of kin is an important predictor of β-cell dysfunction in a patient. History should also include lifestyle information (smoking, drinking).

Physical examination

Pay attention to the signs of Cushing's syndrome, the presence of black acanthosis, bald patches, acne, the nature and distribution of hair on the body. The scale for assessing the degree of hirsutism is widely used, which is a modification of the scale proposed in 1961 by Ferriman and Gallway. Look for signs of virilization and masculinization (as a rule, they are clearly visible). Clitoral hypertrophy is usually referred to if the product of the longitudinal and transverse diameters of the clitoral head exceeds 35 mm 2 (normally both diameters are approximately 5 mm). Pay attention to the signs of insulin resistance: obesity, especially male type, the presence of acanthosis nigricans and soft fibromas. In women with male-type obesity, dyslipoproteinemia is noted, which is increased compared to obesity in terms of female type insulin resistance, higher risk cardiovascular disease and higher overall mortality. The type of obesity is most easily assessed by waist circumference, measured at the narrowest part of the abdomen, usually just above the navel. Waist circumference in women greater than 80 cm indicates the presence of excess visceral fat and is considered a deviation from the norm, although morbidity and mortality increase markedly at an indicator of 88 cm or more.

Laboratory research

The goal is an exception certain diseases with similar manifestations and, if necessary, confirmation of hyperandrogenism. In addition, it reveals the presence metabolic disorders. Diseases that should be ruled out if hyperandrogenism is suspected - pathology thyroid gland, hyperprolactinemia, HAIR-AN syndrome, and androgen-secreting tumors. Thyroid pathology is excluded by determining TSH level using a highly sensitive method.

As already mentioned, even if a patient with hirsutism claims that her menstrual cycle is regular, you need to make sure that there are no ovulation disorders; usually make a schedule basal body temperature. With ovulation disorders, polycystic ovary syndrome is possible. It is also necessary to determine the level of prolactin to rule out hyperprolactinemia, and the level of insulin and fasting glucose to rule out HAIR-AN syndrome.

Identification of metabolic disorders

Metabolic abnormalities are common in PCOS, but always in HAIR-AN syndrome. In HAIR-AN syndrome, the presence of insulin resistance is obvious, but in polycystic ovary syndrome this is not always the case. Unfortunately, there are no accurate, inexpensive, and reproducible assays for assessing insulin sensitivity in routine practice. In research settings, stimulation and suppression tests, such as the euglycemic test, and intravenous glucose tolerance testing are commonly used, with frequent blood sampling, but everyday conditions when examining patients with hyperandrogenism, they are rarely used.

Radiation diagnostics

Ultrasound of the small pelvis with hyperandrogenism allows you to clarify the presence of anovulatory disorders and polycystic changes in the ovaries. It must be remembered that polycystic ovaries can be found in many diseases that cause hyperandrogenism, and not only in polycystic ovary syndrome. The value of ultrasound using a vaginal probe increases with obesity, since it is difficult to identify pathological formations in the ovaries in such women during examination.

If an androgen-secreting tumor is suspected, CT or MRI of the adrenal glands is indicated to exclude an adrenal tumor larger than 5 mm and to detect bilateral adrenal hyperplasia in the case of an ACTH-secreting tumor. However, since 2% of the population has asymptomatic adrenal adenomas (detected by chance), the discovery of a tumor does not always mean an androgen-secreting tumor and may provoke invasive and unnecessary procedures. Therefore, CT and MRI of the adrenal glands are performed only when the symptoms clearly indicate an adrenal cause. In rare cases, in order to establish the localization of an androgen-secreting tumor, selective adrenal catheterization or scintigraphy with,3β-cholesterol is performed.

Treatment of hyperandrogenism

Treatment of hyperandrogenism is mainly symptomatic.

It has four main goals:

1. normalization of the menstrual cycle;
2. elimination of skin manifestations;
3. elimination and prevention of concomitant metabolic disorders;
4. treatment of infertility caused by anovulation.

Treatment methods are aimed at suppressing the synthesis of androgens, blocking their peripheral action, correcting insulin resistance and dyslipoproteinemia (if any), eliminating skin manifestations of the disease using local, mechanical or cosmetics. In most cases, several methods are used. Ways to normalize the menstrual cycle and eliminate skin manifestations, primarily hirsutism, are discussed below.

Main goals in the treatment of hyperandrogenism

Regulation of the menstrual cycle

• Glucocorticoids
• Lifestyle changes

Elimination of skin manifestations (hirsutism, acne, alopecia)

• Decreased androgen levels
• Long acting gonadoliberin analogues
• Androgen receptor blockers
• Spironolactone
• Flutamide
• Cyproterone
• 5α-reductase inhibitors
• Finasteride
• Suppression of hair growth with local remedies
• Ornithine decarboxylase inhibitors
• Mechanical and cosmetic methods of hair removal
• Electrolysis
• Laser Hair Removal
• Cosmetic procedures (shaving, chemical hair removal, bleaching)

Elimination and prevention of concomitant metabolic disorders

• Drugs that increase insulin sensitivity
• Lifestyle changes

Treatment of infertility caused by anovulation

• Clomiphene
• Preparations of gonadotropic hormones
• Gonadoliberin analogues in pulsed mode
• Surgery (coagulation of the ovaries)
• Lifestyle changes

Normalization of the menstrual cycle

Normalization of the menstrual cycle reduces the risk of dysfunctional uterine bleeding and the anemia caused by these disorders. As a rule, COCs, progestogens are prescribed in a cyclic or continuous mode.

Combined oral contraceptives

COCs reduce the level of gonadotropic hormones and, consequently, the production of ovarian androgens. The estrogens contained in COCs simulate the synthesis of SHBG and, as a result, reduce the level of free testosterone. Progestogens in COCs can inhibit 5α-reductase and block the binding of androgens to receptors. Finally, COCs are able to suppress the synthesis of adrenal androgens, although the mechanism of this action is not yet clear. COCs normalize the menstrual cycle and reduce the risk of endometrial hyperplasia and cancer of the uterine body with hyperandrogenism of any origin. It is best (although not necessary) to choose a COC containing a progestogen with an antiandrogenic effect: cyproterone, chlormadinone (Belara), dienogest, drospirenone. When COCs are used by women with polycystic ovary syndrome, activation of the renin-angiotensin-aldosterone system can adversely affect metabolism, and in this regard, drugs such as Midiana and Dimia, which include drospirenone, which, in addition to antiandrogenic, antimineralocorticoid activity, have certain advantages. Endogenous progesterone, the deficiency of which is inevitable in anovulatory conditions, has a small antiandrogenic and antimineralo-corticoid effects.

Although it has not been specifically studied, COCs containing 30-35 micrograms of ethinyl estradiol are generally less likely to cause breakthrough bleeding. This statement does not apply to adolescents, who are more sensitive to sex steroids than adult women. Microdoses of ethinyl estradiol are better tolerated, but skipping a tablet of such a COC is more likely to lead to ineffective contraception.

Cyclic or continuous use of progestogens

It is also possible to normalize the menstrual cycle with hyperandrogenism, especially in the case of amenorrhea, by prescribing progestogens in a cyclic mode. Since sometimes progestogens can stimulate ovulation, and since not all patients ovulate completely, women leading sexual life, it is better to prescribe micronized progesterone (100-200 mcg twice a day) or dydrogesterone (10 mg twice a day) orally, rather than synthetic progestogens, derivatives of nortestosterone.

Drugs that increase the sensitivity of peripheral tissues to insulin

Originally developed for the treatment of type 2 diabetes, these drugs are now also used for polycystic ovary syndrome. These include metformin and thiazolidinedione derivatives. Encouraging results have also been obtained for a number of other drugs (for example, acarbose).

Metformin

Metformin, a biguanide, inhibits gluconeogenesis in the liver. Side effects - diarrhea, nausea and vomiting, bloating, flatulence, loss of appetite - they are observed in 30% of cases. In rare cases, lactic acidosis may develop; in predisposed persons, it can be provoked by the intravenous administration of iodine-containing radiopaque agents, although this mainly happens with decompensated diabetes mellitus or impaired renal function. In polycystic ovary syndrome, metformin normalizes the menstrual cycle, leading to regular menstruation, according to various sources, in 40 or even 100% of cases. There are several explanations for the positive effect of metformin on steroidogenesis: a decrease in CYP17 activity, suppression of androstenedione production due to a direct effect on thecocytes, a decrease in FSH-stimulated 3β-hydroxysteroid dehydrogenase activity, StAR protein levels, and CYP11A1 activity in granulosa cells. The molecular mechanisms of action of metformin on the ovary are not fully understood, but recent studies have shown that metformin increases the expression of AMP-activated protein kinase in granulosa cells. The use of metformin leads to a decrease in the level of androgens and, with a duration of therapy of at least 6 months, anti-Müllerian hormone. Interestingly, a significant decrease in the level of anti-Müllerian hormone was observed in women in whom a regular menstrual cycle was restored during metformin therapy, while the ineffectiveness of metformin was associated with the maintenance of an increased concentration of anti-Müllerian hormone. In polycystic ovary syndrome, metformin is taken at a dose of 1500-2000 mg / day, although in 15-30% of cases complications from the gastrointestinal tract may develop. Initial administration of metformin at a lower dose and then gradually increased to the full dose over 2-4 weeks, as well as use in the form of long-acting drugs, may reduce the incidence of side effects.

Thiazolidinedione derivatives

Thiazolidinedione derivatives are PPAR-γ receptor agonists (nuclear receptors activated by peroxisome inducers).

Thiazolidinediones (pioglitazone) and metformin have been compared in randomized controlled trials. The effect of these drugs on fasting plasma glucose levels, testosterone levels, Ferriman-Galloway score did not significantly differ, however, metformin, unlike pioglitazone, was accompanied by weight loss.

Weight loss

According to preliminary data, the type of diet (for example, 15-25% carbohydrates instead of 45%) is less important compared to the total calorie content. However, a low-carbohydrate (25%) diet is better at normalizing fasting insulin levels, glucose-to-insulin ratios, and triglycerides and appears to be the preferred diet for those with insulin resistance. Clear recommendations regarding dietary preferences in PCOS can only be made after prospective studies.

Surgical intervention

Ovulatory function can be normalized after wedge resection or laparoscopic coagulation of the ovaries and persist for 10-20 years. But if a woman does not aspire to have a baby, with polycystic ovary syndrome, laparoscopic coagulation does not have any particular advantages over taking COCs and currently as a method of normalizing the menstrual cycle not used.

Hyperandrogenism in women is a disorder hormonal balance, which increases the concentration of male sex hormones (androgens). The sex hormones are active substances, which perform a regulatory function and provide the appearance of secondary sexual characteristics and the difference between men and women. Sex hormones play a key role in the process of human reproduction: the maturation of germ cells, pregnancy and childbirth.

Normally, a certain amount of male sex hormones circulate in the body of a woman. However, in some cases, their concentration may exceed the permissible values, as a result of which the woman will begin to show male signs, and the normal functioning of the ovaries is disrupted. Of particular danger is the increase in the content of androgens during pregnancy. An increase in the amount of male sex hormones may be associated with their secretion in the ovaries or adrenal glands. To normalize the hormonal balance, you can use folk remedies. Such treatment of hyperandrogenism has a mild complex effect on the body, improves metabolism and normalizes the functioning of the ovaries. In order for the therapy to be effective, it is necessary to take medicinal drugs systematically.

Androgens in women

Normal in female body a certain amount of male sex hormones circulate. Androgens are produced by the adrenal glands, ovaries, and, to a lesser extent, subcutaneous adipose tissue. The regulation of the synthesis of male sex hormones is carried out with the help of pituitary hormones. Androgens are precursors to other hormones: corticosteroids and estrogens. Also, these substances are involved in the process of human growth and puberty. The ratio of androgens and estrogens forms the libido.

However, if the amount of androgens in a woman's body exceeds the norm, pathological processes develop in her, metabolic disorders occur and reproductive function. Also, this condition increases the likelihood of developing diseases of the organs of the reproductive system, in particular, erosion, dysplasia and cervical cancer.

Disease classification

Depending on the source of male sex hormones, it happens:

• hyperandrogenism of ovarian origin;
• adrenal hyperandrogenism;
• mixed.

Depending on the origin, two forms of the disease are poured;

• hereditary;
• acquired.

Depending on the amount of androgens, two types of the disease are distinguished:

• absolute hyperandrogenism - there is an increase in the concentration of male sex hormones in the blood;
• relative - the concentration of androgens remains normal, but their activity increases or sensitivity to hormones of target cells increases.

Causes of pathology

Hyperandrogenism is a complex of syndromes that have similar manifestations, but are caused by different reasons:

1. Adrenogenital syndrome.
   This disease is the most common cause of hyperandrogenism in women. In this case, the adrenal glands produce normal amount androgens, but their further transformation does not occur.
   Normally, male sex hormones are produced in the adrenal glands, and then, under the action of a special enzyme, they turn into glucocorticoids - other very important hormones. However, if a woman develops no enough of this enzyme or the enzyme itself is defective, androgens do not turn into glucocorticoids, but remain unchanged in the woman's body, binding to target cells and exerting a pathological effect.
2. Tumors of the adrenal glands.
   Tumor development increases the number of active cells of the adrenal glands, and therefore increases the production of male sex hormones.
3. .
   In this case, there is an increase in the number of ovarian cells that produce androgens. Violation of the normal functioning of the pituitary gland.
   Pituitary hormones regulate the production of other hormones, in particular androgens. Violation of the normal functioning of the pituitary gland causes complex endocrine disorders organism, including can cause hyperandrogenism in women.
4. Hypersensitivity target cells.
   Some women have individual features hyperandrogenism, in particular, (redundancy hairline) and acne, but the concentration of androgens in their body does not exceed the norm. Symptoms of this pathology appear in them, because skin cells in such women are overly sensitive to androgens, and even their slight concentration leads to the manifestation of pathological symptoms.

Symptoms of pathology

Signs of hyperandrogenism can be different. They depend on the form of the disease, the level of androgens and the woman's sensitivity to them. The first signs of a violation congenital form diseases are noted during puberty of the girl.

1. Hyperandrogenism is manifested by skin disorders: acne, oily seborrhea, profuse acne.
2. Excess hair growth on the face, arms and legs.
3. Also, the girl's menstrual cycle may be disturbed: menstruation is irregular, delays often occur, in some patients menstruation may be absent.

As the disease progresses and the accumulation of male sex hormones, the girl may develop pathological changes in the ovarian tissue, in particular, polycystic. There comes a state of amenorrhea, an insufficient amount of female sex hormones is produced. Hyperplasia of the endometrium of the uterus also develops. Emerging violations are often manifested.

Manifestations of hyperandrogenism continue after menopause. These women experience male-pattern hair loss. They also suffer from skin diseases. hormonal imbalance and external manifestations hyperandrogenism often leads to the development depression and neurosis.

In more severe cases of hyperandrogenism, violations of the structure of the genital organs and reproductive function occur. Against the background of this condition, a woman may develop pseudohermaphroditism, late start menstruation, masculine features, poor breast development, rough voice. Another symptom of this condition is male-pattern obesity.

An increase in the concentration of male sex hormones provokes systemic disorders of the body:

• metabolic diseases;
• increased blood pressure;
• heart failure.

With hyperandrogenism, the sensitivity of cells to the hormone insulin is impaired. This can lead to the development of type 2 diabetes mellitus, in which the cells of the pancreas produce enough insulin, but it cannot fully perform its functions. This condition is difficult to treat.

If the disease is not caused by a tumor, then the symptoms of this pathology gradually increase. This process can take several years. If hyperandrogenism is caused tumor process in the ovaries or adrenal glands, the symptoms of the disease are similar, but they increase very quickly.

Hyperandrogenism during pregnancy

An increase in the concentration of androgens affects the general hormonal background of a woman and reproductive function. Pathological changes in the body against this background can become a serious obstacle to conception and birth. healthy child. However, in some girls with this disease, pregnancy is still possible. It all depends on the form and severity of the disease.

Hyperandrogenism can cause a violation of the structure of ovarian tissue and the development of polycystic. Also, a dense capsule can form around the organ. This interferes with the normal functioning of the ovaries: the production of estrogen, ovulation. In the case when the amount of androgens exceeds a certain critical level, the patient experiences anovulation.

If the patient develops mild hyperandrogenism, conception may still occur. However, in this case, the likelihood of a miscarriage in the first or second trimester of pregnancy increases. Both an excess of male sex hormones and a decrease in the level of progesterone, a hormone that plays a key role in bearing a baby, can lead to this. A decrease in the amount of progesterone is often observed with hyperandrogenism in women.

It is also difficult for women with this disease to give birth. They may experience delayed withdrawal. amniotic fluid. Insufficient amount of female sex hormones can cause weak contractile activity uterus.

Diagnosis of the disease

For an accurate diagnosis, an anamnesis is collected, including a family history, in order to establish a hereditary tendency to this pathology. Also, a physical examination of the patient is carried out, which allows to identify external manifestations of hyperandrogenism: skin diseases, increased hair growth, developmental disorders of the genital organs. However, the main diagnostic criterion is an increase in the concentration of androgens in the blood. Conduct a laboratory study of blood for hormones. It is important to determine the concentration of all hormones, this will help to establish the cause of the pathology.

To exclude the possibility of a tumor, an ultrasound examination of the abdominal cavity and small pelvis is performed, as well as a more informative computed tomography of the adrenal glands. An ultrasound also reveals polycystic ovaries.

Treatment of the disease

Hyperandrogenism is a disease that has a complex negative effect on a woman's body and causes many disorders: endocrine and metabolic pathologies, impaired reproductive function. A systematic approach is essential for his therapy.

Traditional medicine proposes to correct the hormonal balance of a woman's body with the help of oral contraceptives. However, such treatment completely excludes the possibility of pregnancy. There are folk remedies that allow you to normalize the metabolism and hormonal balance of the body. This treatment is mild. To achieve a positive effect, it is necessary to apply folk remedies systematically and long time. Treatment of hyperandrogenism with folk remedies lasts at least six months.

Folk recipes:

Also, in addition to taking medicinal drugs, it is necessary to change the way of life. Women with hyperandrogenism often have overweight. Such a woman needs to fight obesity. For these purposes, it is useful to adjust the diet and exercise. Moderate exercise will help improve your well-being and metabolism. Weight correction is necessary not only to improve a woman's well-being, but also for her psychological comfort.

Hyperandrogenism syndrome is a whole group of pathologies that combines an increase in the amount or activity of androgens in the body of women. It is observed mainly in adolescence and childbearing age, occurs for various reasons. The most common is polycystic ovaries, and adrenal hyperandrogenism, congenital, idiopathic, associated with pituitary or ovarian tumors also occurs. Manifested by hirsutism (excessive male pattern hair growth), hyperfunction of the sebaceous glands, abdominal obesity, androgenic alopecia, in severe cases, atrophy of the mammary glands, uterus, ovaries. Treatment of hyperandrogenism syndrome depends on the ego etiology, the degree of manifestations, and can be conservative or operative.

Hyperandrogenism in women - causes

Hyperdrogenia in women, its symptoms, may be manifestations of the following diseases:

• Polycystic ovary syndrome
• Hirsutism idiopathic
• Congenital adrenal hyperandrogenism
• Tecomatosis of the stroma of the ovaries
• Tumors with androgen overproduction
• Other reasons

The most common cause of hyperandrogenism syndrome is PCOS (polycystic ovary syndrome). It can be primary (Stein-Leventhal syndrome), or secondary, which develops against the background of hypothalamic syndrome, hyperprolactinemia, primary hypothyroidism. At the same time, in women, the level of cytochrome P increases in the blood, which stimulates the production of androgens in the adrenal glands. In parallel, tissue resistance to insulin increases, its production in the pancreas and blood levels increase. This leads to a violation of the metabolism of glucose, fats, purines. An increase in androgen synthesis is characteristic of tumors of the ovaries, hypothalamus, and pituitary gland.

In addition to the above mechanisms, a change in androgen activity is important in the occurrence of symptoms with hyperandrogenism. It may be due to insufficient binding of testosterone to plasma proteins or a decrease in the amount of these proteins. This condition is characteristic of hypothyroidism and androgen deficiency. At idiopathic hirsutism the rate of their conversion into testosterone and dihydrotestosterone increases, some tissues become more sensitive to their effects. Therefore, with hyperandrogenism, treatment is necessary even when the level of testosterone in the blood is not elevated.

Signs of hyperandrogenism

First of all, androgens act on the sebaceous glands, hair follicles, which leads to seborrhea, hirsutism, and baldness. They also target the genitals. Androgens also affect fat metabolism, muscle tissue growth, and the blood system. They stimulate erythropoiesis, increase blood clotting, increase the risk of blood clots, including in coronary vessels. When hyperandrogenism occurs in women: its causes may be different, but the clinical manifestations are always similar.

Hyperandrogenism in women has three types of symptoms:

• First- This dermatological manifestations, which may for a long time remain the only clinical sign of hormonal disorders.
• Second group- changes in secondary sexual characteristics.
• To the third group include symptoms associated with tertiary sexual characteristics, changes in organs and systems that are not directly related to the sexual sphere.

The most sensitive to the effects of androgens are the sebaceous glands, which begin to secrete under the influence of hormones. increased amount sebum. Because hyperandrogenism has symptoms such as seborrhea, acne, oily skin. fungal infection skin head leads to dandruff. Blockage of the sebaceous glands on the face is the main cause of acne, and as a result of their inflammation, acne appears.

The effect of androgens on hair follicles is the cause of hirsutism and androgenetic alopecia. The most sensitive to hormonal influences is the hair in the pubic part, on inside thighs, abdomen and face. Under the influence of testosterone and dihydrotestosterone, they turn from fluffy to hard, because the rest period hair follicles is sharply reduced. On the head (in the temporal and parietal parts), on the contrary, testosterone causes a lengthening of the rest period. Because of what there is a thinning of the hairs, a slowdown in their growth and increased loss. Often, hyperandrogenism in women has symptoms exclusively from the skin, while the level of androgens in the blood is normal. This is due to the high activity of 5α-reductase, which converts testosterone to dihydrotestosterone.

Hyperandrogenism can also have symptoms from the genital organs. They are mainly associated with an absolute increase in androgens in the blood. They are manifested by involution of the mammary glands, a decrease in the size of the uterus and ovaries, an increase in the size of the clitoris, and a coarsening of the voice. Often accompanied by a decrease in sexual desire, signs of depression. In the future, women begin to develop male-type obesity, with an emphasis on the stomach and upper half body, muscle hypertrophy. Blood clotting may increase, the number of red blood cells in it. All these symptoms are combined with skin manifestations. Most often, these common signs of hyperandrogenism are clinical manifestations polycystic ovary syndrome or tumors.

Adrenal hyperandrogenism has a congenital hereditary character. It is associated with a deficiency of the enzyme C21-hydroxylase in the adrenal cortex. It is responsible for the synthesis of steroids, with its decrease, the production of androgens increases. The disease can manifest itself at different ages. In severe cases, atrophy of the female genital organs is already observed in girls at birth, which often makes it difficult to determine the sex. With an average decrease in the level of the enzyme, the disease begins to progress in adolescence. Menstruation begins late, at 15-16 years old, they are irregular. The mammary glands are poorly developed, hirsutism is observed, the structure of the figure is masculine, with narrow hips and broad shoulders. Growth in girls is small, sometimes they form masculine facial features. Light degree Adrenal hyperandrogenism manifests itself at a young age with slight hirsutism, irregular periods. It often causes infertility.

Hyperandorogenia in women during pregnancy

Hyperandrogenism syndrome often causes infertility in women. It can be manifested both by the inability to conceive a child, and by habitual miscarriage. Ovarian hyperandrogenism can occur with PCOS and is the most common cause of increased hormone production. In such a situation, not only hormonal imbalance but also anovulatory cycles in women. The follicle does not develop to the end, and the cell does not come out of it, which means that conception is impossible. Adrenal hyperandrogenism, the treatment of which is rather complicated, can be manifested both by the absence of ovulation and by miscarriages at different times.

Hyperandrogenism in women during pregnancy, if conception has taken place, can lead to miscarriage at the end of the first trimester and to premature birth in the middle of the second. Under influence male hormones the corpus luteum develops poorly or its involution occurs. This leads to a decrease in the level of progesterone, insufficient proliferation of the endometrium. As a result, the embryo cannot attach itself to the uterine wall and the pregnancy is terminated at about 10-12 weeks.

When the placenta takes over the function of hormone synthesis, at 18-20 weeks, the risk of miscarriage decreases. But hyperandrogenism during pregnancy as a boy can worsen, since at the same time the adrenal glands of the fetus begin to produce their own androgens. The manifestation can be isthmic-cervical insufficiency, premature aging of the placenta. If all dangerous periods were completed successfully, there are no special risks for the unborn child. Sometimes hyperandrogenism during pregnancy in a boy can be manifested by an increase in the scrotum and penis after birth, and in girls - swelling of the external genital organs. But this phenomenon is temporary and passes quickly.

Hyperandrogenism syndrome - diagnosis

Hyperandrogenism in women has quite pronounced symptoms, especially on the part of the skin. Because first diagnostic event there will be a detailed inspection. The degree of hirsutism is assessed using the Ferriman-Gallway index. It shows the intensity of hair growth in the face, shoulders, abdomen, hips, back and buttocks. Normally, it should be less than 8, the maximum value is 36. Signs of hyperandrogenism are also detected with a standard gynecological examination, check the size of the mammary glands, the presence of colostrum (characterizes hyperprolactinemia), evaluate the body structure and type of fat deposition.

Ovarian hyperandrogenism

The characteristic symptoms of this form of hyperandrogenism are:

• infertility
• irregular menstruation up to amenorrhea;
• hirsutism (excessive growth of coarse and long hair in a male pattern).

Approximately half of women with ovarian hyperandrogenism are obese, which confirms an increased body mass index (BMI) - 26.3 ± 0.8. They often have hyperinsulinemia and insulin resistance, which is due to obesity rather than hyperandrogenism. These patients often develop diabetes, so during pregnancy, monitoring of glucose tolerance is necessary. Normalization of carbohydrate metabolism is achieved by reducing body weight, while the level of androgens also decreases.

Methods for diagnosing ovarian hyperandrogenism are:

• Hormonal examination

The results of a hormonal examination for ovarian hyperandrogenism reveal:

• high levels of luteinizing hormone (LH),
• high concentration of testosterone (T),
• increased levels of follicle-stimulating hormone (FSH).

Ultrasound diagnostics for ovarian hyperandrogenism reveals:

• an increase in the volume of the ovaries,
• stromal hyperplasia,
• more than 10 atretic follicles 5-10 mm in size, located along the periphery under a thickened capsule.

Adrenal hyperandrogenism

Adrenal hyperandrogenism is the leading factor in miscarriage in 30% of women with hyperandrogenism. The cause of hyperandrogenism in this case is most often adrenogenital syndrome, which manifests itself as a lack or absence of glucocorticoid enzymes for hormonal synthesis in the adrenal cortex. In this regard, the development of the disease is possible already in childhood.

To diagnose adrenal hyperandrogenism, first of all, an examination is performed, which is aimed at determining possible deviations from the norm of the level of individual types of hormones and the hormonal background as a whole. The use of ultrasound and other special methods is mandatory. In the event that the patient was diagnosed during pregnancy, and hyperandrogenism was detected, then the treatment will require the appointment of drugs that will help lower the androgen in the blood. most suitable and best way selected in each case individually. If the treatment regimen is selected in a timely and competent manner, the conception of a child and childbirth will soon become acceptable.

Hyperandrogenism - treatment

Can hyperandrogenism be cured? It all depends on its cause, the severity of the symptoms. Correctly chosen tactics of therapy in many cases allows leveling the symptoms of the disease, as well as solving the problem of infertility. Adrenal hyperandrogenism treatment involves steroid drugs. They suppress excess production of androgens in the adrenal glands. During pregnancy in women with this syndrome, therapy is continued at least until the end of the first trimester.

Idiopathic hyperandrogenism in women is treated to reduce the peripheral effects of testosterone. It blocks the action of the hormone at the level of the sebaceous glands and hair follicles. Androgen receptor blockers such as flutamide are used. Finastreid, an inhibitor of the 5α-reductase enzyme, has a good effect. Spironolactone is not only an antagonist of aldosterone, but also partly of androgens. It reduces swelling and reduces the activity of male hormones. Hyperandrogenism is also treated with progestogens.

Ovarian hyperandrogenism associated with polycystic disease is treated by suppressing androgen synthesis in these organs. Combined contraceptives are used, for example, Diana 35. In case of ineffectiveness, drugs are used that suppress the synthesis of gonadotropic hormones in the pituitary and hypothalamus. If hyperandrogenism is caused by a tumor in women, the treatment is surgical.

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“Many women have uterine discharge (menstruation), but not all. They happen to light-skinned people with a feminine appearance, but not to those who are dark and masculine ... "
Aristotle, 384 -322 BC e.

The syndrome of hyperandrogenism is a fairly large group of endocrine diseases that occur due to very diverse pathogenetic mechanisms, but are combined according to the principle of similar clinical symptoms due to the excessive quantity and / or quality (activity) of male sex hormones in the female body. The following hyperandrogenic conditions are the most widespread.

• Polycystic ovary syndrome (PCOS):
  a) primary (Stein-Leventhal syndrome);
  b) secondary (within the neuroendocrine form of the so-called hypothalamic syndrome, with hyperprolactinemia syndrome, against the background of primary hypothyroidism).
• Idiopathic hirsutism.
• Congenital dysfunction of the adrenal cortex.
• Stromal tecomatosis of the ovaries.
• virilizing tumors.
• Other rarer variants.

In most cases, the causes of the formation of these diseases have been studied in sufficient detail, and there are specific effective methods their corrections. Nevertheless, the interest of scientists and clinicians of various specialties in the problem of hyperandrogenism does not dry out. Moreover, the object of incessant and most close attention, especially over the past decade, is PCOS, otherwise called the syndrome of hyperandrogenic dysfunction of polycystic ovaries, ovarian sclerocystosis, Stein-Leventhal syndrome. Such close interest in this problem is justified.

First, only in the 90s. In the twentieth century, it was possible to obtain irrefutable evidence that PCOS is not only the most common hyperandrogenic condition (about 70-80% of cases), but also one of the most common endocrine diseases in girls and women of childbearing age. Based on numerous publications recent years, extremely impressive high level frequency of PCOS, which is from 4 to 7% in the population. Thus, approximately every 20th woman at various stages of her life - from infancy to old age - consistently encounters various manifestations of this pathology, and not only from the outside reproductive sphere, but also many others functional systems and organs.

Secondly, the last decade has been marked by a number of events and discoveries that have served as the key to a new understanding of many issues in the pathogenesis of PCOS. This, in turn, became a powerful impetus for the rapid development of very original, effective and promising methods not only for the treatment and rehabilitation of an already formed pathology, but also for its long-term hormonal and metabolic consequences, and also became the basis for an attempt to create a preventive action program aimed at prevention of the development of the disease and its numerous somatic complications.

Therefore, in this article, special emphasis is placed primarily on the problems of diagnosis and advances in the treatment of PCOS.

Etiopathogenesis

Relatively recently - at the end of the last century - the latest scientific concept was proposed and thoroughly argued that two interrelated components take part in the pathogenesis of PCOS:

• increased activity of cytochrome P-450C17alpha, which determines the excessive production of androgens in the ovaries / adrenal glands;
• hyperinsulinemic insulin resistance leading to multiple defects in the regulation of carbohydrate, fat, purine and other types of metabolism.

These two components are connected in the same patient not in a random way, but quite naturally - through a single primary mechanism. A lot of fairly convincing information has been obtained about the existence of a single universal congenital enzyme anomaly in PCOS, which determines excessive phosphorylation of serine (instead of tyrosine), both in steroidogenic enzymes (17β-hydroxylase and C17,20-lyase) and in substrates of the β-subunit of the insulin receptor. (IRS-1 and IRS-2). But at the same time, the final effects of such a pathological phenomenon differ: the activity of steroidogenesis enzymes, on average, doubles, which leads to hyperandrogenism, while insulin sensitivity at the post-receptor level in peripheral tissues is almost halved, which adversely affects the state of metabolism as a whole. Moreover, reactive hyperinsulinism, which occurs compensatory in response to pathological resistance of target cells to insulin, contributes to additional excessive activation of androgen-synthesizing cells of the ovarian-adrenal complex, i.e., further potentiates the androgenization of the woman's body, starting from childhood.

Clinical characteristics

From the point of view of classical terminology, PCOS is characterized by two obligate signs: a) chronic anovulatory ovarian dysfunction, which determines the formation of primary infertility; b) a symptom complex of hyperandrogenism, which has distinct clinical (most often) and / or hormonal manifestations.

Along with this, the latest model of the pathogenesis of PCOS has made it possible to significantly clarify and expand the understanding of the “complete clinical portrait” of the disease. The palette of its symptoms, along with the classic signs of hyperandrogenism described by the Chicago gynecologists I. F. Stein and M. L. Leventhal almost 70 years ago (1935), taking into account the latest ideas in most patients, includes a variety of (dys)metabolic disorders due to hyperinsulinism, which were first identified more than 20 years ago, thanks to the pioneering work of researchers G. A. Burghen et al. (Memphis, 1980). Due to the abundance of such fundamental changes in the health status of women with PCOS, clinical picture this combined pathology (hyperandrogenism along with hyperinsulinism) received a very figurative and clear reflection not only in the statements ancient Greek philosopher(see epigraph), but also in articles by contemporary authors.

Symptoms of pathological androgenization

The clinic of hyperandrogenism consists of a few symptoms (only about ten signs), but, depending on the severity of the process, the general appearance of patients can vary significantly. And with PCOS, which is formed due to a relatively low hyperproduction of predominantly not the most aggressive androgens, the semiotics of only hyperandrogenic dermopathy, without virilization, attracts attention. This fundamentally distinguishes it from cases of extremely severe androgenization in virilizing tumors of the ovaries and adrenal glands, which have a completely different nosological origin.

hirsutism- this is not only a sign of PCOS, the most striking and "catchy" when it comes to medical diagnostics, but also a factor that most traumatizes the psyche of the patient. The Ferriman-Gallway scale allows you to assess the severity of hirsutism in points within a minute. This technique has been used for more than 40 years and has won universal recognition in world practice. The scale easily calculates the indicator of the so-called hormonal number (a four-point score in nine androgen-dependent zones). It reflects the androgen saturation of the patient, as a rule, much more accurately than the indicator of testosterone concentration in blood serum, which is available in domestic laboratory practice for measurement only in the total amount - in the form total testosterone. It is well known that the latter, even with severe pathology, can remain within the reference norm (due to a decrease in the level of the biologically inactive fraction of the hormone associated with the TESH transport protein), while the result of visual screening diagnostics by the hormonal Ferriman-Gallway number deserves more confidence. , since a direct correlation of the value of this marker with the concentration of free androgens has been repeatedly shown. It is the free fraction of testosterone that determines the severity of the process, therefore, in practice, the hormonal score for assessing hirsutism may well be considered as a reliable “mirror” of hyperandrogenism. In our own work, we have long been using the original gradation of the severity of hirsutism according to the hormonal number: I degree - 4-14 points, II - 15-25 points, III - 26-36 points. Experience shows that the oncological alertness of the doctor should be extremely high in any case - even in the absence of viril signs - especially if a woman goes to the doctor with long-standing hirsutism of the III degree, as well as with the II degree of severity of the disease, which quickly formed due to the "galloping" course illness.

Androgenetic alopecia- reliable diagnostic marker viril variants of SGA. Like other types of endocrine alopecia, it is diffuse rather than focal (nested) in nature. But unlike alopecia in other diseases of the endocrine glands (primary hypothyroidism, polyglandular insufficiency, panhypopituitarism, etc.), androgenetic alopecia there is a certain dynamic. As a rule, it manifests itself in hair loss in temporal areas(bitemporal alopecia with the formation of the symptoms of "temporal bald patches" or "privy councillor's bald patches" and "widow's peak"), and then spreads to the parietal region (parietal alopecia, "baldness"). The peculiarities of the synthesis and metabolism of androgens in the perimenopausal period explain the fact that up to 13% of women at this age have a "widow's peak" or more pronounced forms of baldness in the absence of other signs of SGA. On the other hand, baldness as a formidable indicator of the severe course of SGA is more often observed and forms faster (sometimes ahead of hirsutism) in this age group, which requires the exclusion of an androgen-producing tumor.

Symptoms of insulin resistance and hyperinsulinism

• Classic manifestations of the pathology of carbohydrate metabolism (impaired glucose tolerance or type 2 diabetes mellitus). In PCOS, the combination of hyperandrogenism and insulin resistance, named by R. Barbieri et al. in 1988, HAIR syndrome (hyperandrogenism and insulin resistance), occurs most often. Even among adolescents with developing PCOS, insulin resistance is detected by a standard glucose tolerance test with 75 g of glucose in about a third of cases (mainly by the type of IGT), and at an older age - in more than half of patients (55-65%), and by 45 years the frequency diabetes can be 7-10% versus 0.5-1.5% in the peer population. It should be noted that recently, according to the results of six prospective studies, it is precisely in patients with PCOS and IGT, first diagnosed at a young age, that the "acceleration" of diabetes has been clearly proven. Especially often, intolerance to carbohydrates progresses towards obvious pathology in those who reach the extreme degree of obesity and have a family history of diabetes (D.A. Ehrmannet al., 1999).
• Relatively rarely (only in 5%), the combination of HAIR is supplemented with a third element - the most typical clinical stigma of insulin resistance in the form of acanthosis nigricans and is designated as the HAIR-AN syndrome. Black acanthosis (acanthosis nigricans) is a papillary-pigmentary dystrophy of the skin, manifested by hyperkeratosis and hyperpigmentation (mainly on the neck, in the axillary and inguinal areas). This feature is especially pronounced against the background extreme degrees obesity, and, conversely, as weight loss and correction of insulin sensitivity, the intensity of acanthosis weakens.
• Massive obesity and/or redistribution of subcutaneous fat according to android type (abdominal "apple" type): body mass index more than 25 kg/m², waist circumference more than 87.5 cm, and its ratio to hip circumference more than 0.8.
• The presence in the pre-pubertal history of an isolated pubarche is the first sign of the onset of androgenization in the form of sexual hair growth before the onset of estrogenization of the mammary glands, especially in combination with a lack of body weight at birth.

Laboratory and instrumental diagnostics

Paradoxical as it may seem, but despite the colossal breakthrough in theoretical medicine in understanding the molecular biological and genetic mechanisms of PCOS development, the world has not yet made an agreed decision on the criteria for diagnosing PCOS, but the only document that at least partly regulates the examination process. and designed to prevent overdiagnosis of the disease rather than to ensure its detection in the early stages, are the recommendations of the US National Institutes of Health, adopted at a conference in 1990.

According to this document, which still guides the vast majority of researchers involved in this problem, the diagnosis of PCOS is a diagnosis of exclusion. For its verification, in addition to the presence of two clinical criteria inclusions mentioned above (anovulation + hyperandrogenism), a third one is also needed - the absence of other endocrine diseases ( congenital dysfunction adrenal cortex, virilizing tumors, Itsenko-Cushing's disease, primary hyperprolactinemia, thyroid pathology). Fully sharing this point of view, over the past 15 years, we consider it necessary for each patient to complete the diagnosis of PCOS with three additional examinations. This is extremely important not only and not so much for confirming the diagnosis, but for further use as criteria when choosing a differentiated therapy on an individual basis. It's about about the next research.

1. On the seventh to tenth day of the menstrual cycle - "gonadotropic index" (LH / FSH) >> 2, PRL is normal or slightly increased (in about 20% of cases).

2. On the seventh to tenth day of the menstrual cycle, ultrasound reveals characteristic signs:

• bilateral increase in the volume of both ovaries (according to our data, more than 6 ml/m² of body surface area, i.e., taking into account individual parameters physical development by height and body weight at the time of pelvic ultrasound);
• ovarian tissue of the "polycystic" type, i.e. 10 or more small immature follicles up to 8 mm in diameter are visualized from both, as well as an increase in the area of ​​the hyperechoic stroma medulla both ovaries;
• ovarian-uterine index (mean ovarian volume/uterine thickness)> 3.5;
• thickening (sclerosis) of the capsule of both ovaries.

3. Laboratory signs of insulin resistance:

• an increase in the basal (fasting) level of insulin in the blood serum or an increase in the calculated HOMAIR glucose-insulin index.

However, in April 2003 experts American Association clinical endocrinologists developed a new document, according to which it was decided to rename the complex of clinical and biochemical disorders, known since 1988 as (dys)metabolic syndrome X, into insulin resistance syndrome. And when verifying it, it was proposed to focus not on hormonal indicators, but on surrogate biochemical parameters.

Identification of insulin resistance syndrome

• Triglycerides >150 mg/dL (1.74 mmol/L).
• High density lipoprotein cholesterol in women< 50 мг/дл (1,3 ммоль/л).
• Blood pressure > 130/85 mmHg Art.
• Glycemia: fasting 110-125 mg/dl (6.1-6.9 mmol/l); 120 minutes after a glucose load of 140-200 mg/dL (7.8-11.1 mmol/L).

Concluding the conversation about the technology for diagnosing PCOS in modern clinical practice, we especially emphasize that each of these symptoms in isolation from the others is no independent diagnostic value does not have. At the same time, the more paraclinical signs from the above list in the same patient with hyperandrogenic ovarian dysfunction, the more justified, justified, effective and safe will be the attempt of an endocrinologist/gynecologist to apply new technologies and modern protocols for differentiated treatment.

Treatment

Individual management of patients with PCOS often depends not only on the established nosological variant of the pathology, but also on the situation in the family where the pregnancy is planned. With this in mind, PCOS therapy can be conditionally divided into two groups: basic - when complex therapy is performed for a long time rehabilitation program and there is a systematic preparation of a young woman for pregnancy, and situational - when, at the request of the patient, the issue of restoring fertility is urgently resolved.

Basic Therapy

The arsenal of assistance to patients with PCOS is now represented by a large pharmacotherapeutic group of drugs that have specific and fundamentally different effects on different pathogenetic links. An individual set of measures is developed taking into account the presence / absence of indications of insulin resistance, eating behavior and bad habits. Basic Therapy provides for two main treatment scenarios: a) for thin people without hyperinsulinism - antiandrogenic +/- estrogen-progestogen drugs; b) for everyone who has overweight body, and for thin people with insulin resistance, insulin sensitizers combined with weight management measures.

The most tangible and significant consequence of the discovery of the role of insulin resistance in the formation of PCOS has been a new therapeutic technology using drugs that increase the sensitivity of insulin receptors. It should be noted right away that the group of metformin and glitazones is indicated, although for the vast majority of patients, but not for all. It is clear that when selecting individuals for whom therapy with insulin-sensitizing drugs is indicated, women who meet the criteria for peripheral refractoriness to the hormone have a clear advantage.

Today's powerful search engines for scientific and medical literature allow you to track the appearance of the latest data, even in remote corners of the planet, within a few weeks of their appearance in print or on the World Wide Web. 10 years have passed since the publication in 1994 of an article by a team of authors from Venezuela and the United States on the first experience of using metformin in PCOS. Over the years, about 200 more papers on this issue have appeared. Most of them provide information on non-randomised, uncontrolled and usually small trials. This level of scientific analysis does not meet the modern stringent requirements for evidence-based medicine. Therefore, the publication of systematic analytical reviews and the results of meta-analyses based on pooled data from similar trials are of exceptional interest. Such works have appeared only during the last half a year, and their discussion is important both for practice and for the development of theory. A summary of the most apparent systematically reproducible effects of metformin in PCOS is given below.

Clinical Effects

• Improvement menstrual function, induction of spontaneous and stimulated ovulation, increased frequency of conception.
• Reduction in the frequency of spontaneous miscarriages, reduction in the incidence of gestational diabetes, improvement in pregnancy outcomes in the absence of a teratogenic effect.
• Reducing hirsutism, acne, oily seborrhea, and other symptoms of hyperandrogenism.
• Decreased appetite, body weight, blood pressure.

Laboratory Effects

• Decreased levels of insulin, insulin-like growth factor type 1 (IGF-1).
• Decrease in cholesterol, triglycerides, LDL and VLDL levels, increase in HDL concentration.
• Decreased levels of androgens, LH, plasminogen activator inhibitor.
• Increased levels of testosterone-estradiol-binding globulin, a binding protein for IGF-1.

Russian doctors of various specialties are most familiar with the drug Siofor 500 and 850 mg (Berlin-Chemie / Menarini Pharma GmbH), belonging to the group of insulin sensitizers. It has become familiar not only for endocrinologists (in the treatment of type 2 diabetes mellitus), but also for gynecologists-endocrinologists - it was with this drug that the story began treatment of PCOS sensitizers in our country (M. B. Antsiferov et al., 2001; E. A. Karpova, 2002; N. G. Mishieva et al., 2001; G. E. Chernukha et al., 2001).

Dosing regimen: first week = 1 tab. at night, the second week = + 1 tab. before breakfast, third week = + 1 tab. before lunch. The average daily dose is 1.5-2.5 g.

Reception duration: minimum six months, maximum 24 months, average duration- one year.

A break / cancellation in taking the drug should be carried out within a few days at any acute illness and when conducting radiopaque studies for other conditions (risk of lactic acidosis).

Conclusion

The syndrome of hyperandrogenism is widespread, and the most common cause of its development at any age is polycystic ovary syndrome. The formation of PCOS in children and adolescents is a high risk factor for not only reproductive disorders, but also a complex of very serious dysmetabolic disorders in childbearing and perimenopausal age. Modern views on the pathogenesis and natural evolution of ovarian hyperandrogenism serve as the basis for expanding the indications for therapy with insulin sensitizers, including Siofor.

For literature inquiries, please contact the editor

D. E. Shilin, doctor medical sciences, Professor
Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation, Moscow

Hyperandrogenism is caused by increased secretion of male sex hormones in a woman's body. Androgens are produced by the ovaries and adrenal cortex. Depending on the primary cause pathology, clinical symptoms may differ.

Hyperandrogenism in women causes increased secretion in the pituitary gland, which blocks the release of follicle-stimulating hormone and estradiol. As a result, the process of maturation of the follicle is disrupted, the release of the egg (anovulation) does not occur. High levels of androgens contribute to the formation of multiple cysts in the ovaries (polycystic ovary syndrome).

Male hormones reduce the susceptibility of peripheral tissues to, this leads to an increase in blood glucose levels, impaired glucose tolerance, carbohydrate metabolism and the development of type 2 diabetes mellitus.

Classify true and idiopathic hyperandrogenism. In the first case, the level of androgens in the woman's blood is increased, and in the second, the sensitivity of peripheral tissue receptors to male hormones is increased.

Causes of pathology

What is hyperandrogenism and why does it occur? The main causes of the disease are:

• tumors, adrenal metastases;
• violation of the hypothalamic-pituitary regulation caused by injuries, tumors, inflammatory diseases brain;
• ovarian tumors: luteoma, thecoma;
• androgenital syndrome - congenital pathology adrenal cortex, in which there is an increased production of testosterone.

In women, the causes of hyperandrogenism cause a violation of the hormonal balance, the functioning of the reproductive system, and metabolic processes in the body.

Symptoms of ovarian hyperandrogenism

The disease is of ovarian and adrenal genesis - depending on the organ, which begins to intensively produce androgens. Ovarian hyperandrogenism in most cases develops against the background of polycystic ovary syndrome, less often pathology is caused by hormone-producing tumors.

PCOS is characterized by irregular menstruation, infertility, and increased levels of androgens in the blood. The figure of the girl changes according to the male type, hair on the face and body begins to grow, the volume of the waist and chest increases, the fat layer is deposited in the lower abdomen. The work of the sebaceous glands is disrupted, seborrhea appears, an acne rash that cannot be treated. Stretch marks appear on the skin of the thighs and buttocks. Sleep apnea (holding your breath) leads to insomnia.

The photo shows a woman with characteristic signs of hirsutism.

The characteristic symptoms of hyperandrogenism in PCOS are the appearance of premenstrual syndrome. Women become irritable, their mood often changes, they are worried about migraine, intense pain in the lower abdomen, swelling, soreness of the mammary glands.

The ovaries increase in size by 2-3 times, their capsule thickens. Multiple cystic formations are found inside the organ. Hormonal imbalance causes thickening and hyperplasia of the endometrium of the uterus, menstruation becomes longer, more abundant, with the release of blood clots.

Symptoms of adrenal hyperandrogenism

This type of virilization develops against the background of androgenital syndrome. This is a hereditary disease that causes increased secretion of androgens in the adrenal cortex. Congenital deficiency of organ enzymes before a certain moment compensated by the body, but under the influence of a number of factors, a violation of the hormonal balance occurs. Pregnancy can provoke such a condition, severe stress the onset of sexual activity.

The cause of adrenal hyperandrogenism may be hormone-producing tumors,. Cancer cells mesh zone of the cortical layer produce "weak" androgens. In the process of metabolism, male hormones turn into a more active form and change the overall hormonal background of a woman. contributes to the acceleration of these processes.

Adrenal hyperandrogenism causes cyclic disturbances in the ovaries due to an increase in estrogen levels, suppression of the growth and maturation of the follicle occurs, the menstrual cycle is disturbed, and menstruation may completely stop. The process of ovulation does not occur, a woman cannot become pregnant and bear a child.

Symptoms of adrenal hyperandrogenism in girls:

• deformation of the external genital organs at birth, it is difficult to determine the sex of a child (female hermaphroditism);
• delayed sexual development, menarche begins at the age of 15–16, the menstrual cycle is irregular, accompanied by profuse blood loss;
• in girls in adolescence, signs of hirsutism are observed: hair grows on the face and body like in men;
• acne, seborrhea, skin pigmentation;
• partial atrophy of the mammary glands;
• an increase in the size of the clitoris;
• alopecia - hair loss on the head;
• the figure changes: narrow hips, broad shoulders, short stature;
• rough voice.

In women of reproductive age, adrenal hyperandrogenism leads to early abortion. This is caused by the cessation of growth of the uterus due to the formation of an inferior corpus luteum. Most girls have completely disrupted menstrual and childbearing function, infertility develops, sexual desire increases. Hirsutism is weakly expressed, physique does not change, metabolic processes are not disturbed.

Mixed type of hyperandrogenism

Hyperandrogenism of mixed origin is manifested by symptoms of the ovarian and adrenal forms of the disease. In women, polycystic ovaries and signs of androgenital syndrome are found.

Manifestations mixed type diseases:

• acne
• striae;
• elevated arterial pressure;
• violation of the menstrual cycle,;
• cysts in the ovaries;
• infertility, early termination of pregnancy;
• impaired glucose tolerance or high blood sugar;
• elevated levels of low density lipoproteins.

Hyperandrogenism can be caused systemic diseases that affect the adrenal cortex, ovaries or brain, disrupt metabolism. This , anorexia nervosa, schizophrenia, type 2 diabetes mellitus, acromegaly, prolactinoma.

Peripheral and central hyperandrogenism

With damage to the central nervous system, inflammatory, infectious diseases or intoxication of the body, the secretion of gonadotropic hormones of the pituitary gland, which are responsible for the production of luteinizing and follicle-stimulating hormone, can be suppressed. As a result, the process of maturation of the follicle in the ovary and the synthesis of sex hormones are disrupted, androgen production increases.

Women show symptoms, ovarian dysfunction, menstrual disorders, skin rashes, PMS.

Peripheral hyperandrogenism is caused by an increase in the activity of a skin enzyme, sebaceous gland 5-α-reductase, which converts testosterone into a more active androgen. This leads to varying degrees of severity, the appearance of acne vulgaris.

Hyperandrogenism during pregnancy

In pregnant women, an increase in androgen levels is the cause of spontaneous abortion. Most dangerous terms- the first 7-8 and 28-30 weeks. In 40% of patients, intrauterine fetal hypoxia is observed, most often this occurs in the third trimester. Another complication is late toxicosis, while kidney function worsens, blood pressure rises, and body edema appears.

Hyperandrogenism during pregnancy can lead to premature discharge of amniotic fluid, complicated childbirth. Changes in the hormonal background negatively affect the development of the child, infants may be disturbed cerebral circulation, there are signs of intrauterine malnutrition.

Hyperandrogenism and pregnancy are reasons for urgent hormone therapy to prevent abortion and other complications. Women who have previously had miscarriages, miscarriage, increased levels of male hormones should be thorough examination at the planning stage of pregnancy.

Diagnosis of the disease

Diagnosis - hyperandrogenism is established by the results laboratory research to hormone levels. With polycystic ovary syndrome, the level of testosterone, the luteinizing hormone, rises in a woman's blood. The concentration of FSH in the blood and 17-KS in the urine remains within the normal range. The ratio of LH/FSH is increased by 3-4 times. With hormone-dependent ovarian tumors, the level of testosterone and prolactin in the blood is significantly increased.

The mixed form of the disease is characterized slight increase levels of testosterone, LH, DHEA-S in the blood and 17-KS in the urine. The concentration of prolactin is normal, and FSH is reduced. The ratio of LH / FSH is 3.2.

To determine the primary cause of hyperandrogenism, tests with Dexamethasone and are carried out. A positive hCG test confirms polycystic ovarian disease, which causes a hormonal imbalance. A negative response indicates the adrenal nature of hyperandrogenism.

The Abraham test allows you to identify a disease of the adrenal genesis, with the introduction synthetic glucocorticoids synthesis in the anterior pituitary gland is suppressed, which stops the stimulation of the adrenal cortex. If the result is positive, it is adrenal hyperandrogenism, a negative response may be a sign of a cortical tumor.

Additionally, ultrasound of the ovaries is performed to detect cysts, changes in the size and structure of the organ. Electroencephalography, MRI, CT of the brain are indicated for suspected damage to the pituitary gland.

Treatment Methods

Therapy is prescribed individually for each patient. Androgen receptor blockers reduce the effect of male hormones on the skin, ovaries (Flutamide, Spironolactone). Androgen secretion inhibitors inhibit testosterone production endocrine glands(cyproterone acetate). These funds restore the balance of hormones, eliminate the symptoms of pathology.

Hyperandrogenism of the adrenal glands is compensated by glucocorticoids, which suppress the excess of androgens. Women are prescribed Dexamethasone, Prednisolone, they are also taken during pregnancy if the expectant mother has an increased level of testosterone. It is especially important to be treated in a timely manner for girls who have close relatives with congenital androgenital syndrome. The dosage and duration of the medication is prescribed by the doctor.

Hormonal treatment of hyperandrogenism is carried out with glucocorticosteroids combined oral contraceptives(Diana-35), GnRH agonists. Such drugs are treated with mild hyperandrogenism of ovarian origin, PCOS.

Non-drug treatment

To restore hormonal balance, women are advised to regularly engage in moderate physical activity, give up bad habits, and lead a healthy lifestyle. It is important to stick to a diet balanced diet excluding coffee, alcohol, carbohydrates, animal fats. It is useful to eat fresh fruits, vegetables, dairy products, diet varieties meat and fish. Pharmaceutical preparations are taken to compensate for the deficiency of vitamins.

Treatment with folk remedies can only be carried out in combination with the main therapy. You should first consult a doctor.

Hyperandrogenism causes disturbances in the work of many organs and systems, leads to the development of adrenal and ovarian insufficiency, infertility, and type 2 diabetes mellitus. To prevent the appearance of symptoms of hirsutism, skin rashes, hormone therapy is indicated.

Bibliography

1. Kozlova V.I., Pukhner A.F. Viral, chlamydial and mycoplasmal diseases of the genitals. Guide for doctors. St. Petersburg 2000.-574 p.
2. Miscarriage, infection, innate immunity; Makarov O.V., Bakhareva I.V. (Gankovskaya L.V., Gankovskaya O.A., Kovalchuk L.V.) - "GEOTAR - Media". - Moscow. - 73 p.-2007.