Hyperandrogenism of adrenal origin. Treatment of hyperandrogenism syndrome and PCOS Ovarian hyperandrogenism

– a group of endocrinopathies characterized by excessive secretion or high activity of male sex hormones in the female body. Manifestations of various syndromes, similar in symptoms but different in pathogenesis, include metabolic, menstrual and reproductive disorders, and androgenic dermopathy (seborrhea, acne, hirsutism, alopecia). The diagnosis of hyperandrogenism in women is based on examination, hormonal screening, ultrasound of the ovaries, CT scan of the adrenal glands and pituitary gland. Correction of hyperandrogenism in women is carried out using COCs or corticosteroids, and tumors are surgically removed.

General information

Hyperandrogenism in women is a concept that unites pathogenetically heterogeneous syndromes caused by increased production of androgens by the endocrine system or excessive susceptibility of target tissues to them. The significance of hyperandrogenism in the structure gynecological pathology due to its widespread prevalence among women childbearing age(4–7.5% in teenage girls, 10–20% in patients over 25 years of age).

Androgens - male sex hormones of the steroid group (testosterone, ASD, DHEA-S, DHT) are synthesized in a woman’s body by the ovaries and adrenal cortex, less - by subcutaneous fatty tissue under the control of pituitary hormones (ACTH and LH). Androgens act as precursors of glucocorticoids, female sex hormones - estrogens and form libido. In puberty, androgens are most significant in the process of growth spurt, maturation of tubular bones, closure of the diaphyseal-epiphyseal cartilaginous zones, and the appearance of female-type hair growth. However, an excess of androgens in the female body causes a cascade of pathological processes that disrupt general and reproductive health.

Hyperandrogenism in women not only causes the occurrence cosmetic defects(seborrhea, acne, alopecia, hirsutism, virilization), but also causes disorders of metabolic processes (metabolism of fats and carbohydrates), menstrual and reproductive functions (anomalies of folliculogenesis, polycystic ovarian degeneration, progesterone deficiency, oligomenorrhea, anovulation, miscarriage, infertility in women). Prolonged hyperandrogenism in combination with dysmetabolism increases the risk of developing endometrial hyperplasia and cervical cancer, type II diabetes mellitus and cardiovascular pathology in women.

Causes of hyperandrogenism in women

The development of the transport form of hyperandrogenism in women is noted against the background of insufficiency of sex steroid binding globulin (SHBG), which blocks the activity of the free fraction of testosterone (with Itsenko-Cushing syndrome, hypothyroidism, dyslipoproteinemia). Compensatory hyperinsulism with pathological insulin resistance of target cells promotes increased activation of androgen-secreting cells of the ovarian-adrenal complex.

In 70–85% of women with acne, hyperandrogenism is observed when normal indicators androgens in the blood and increased sensitivity of the sebaceous glands to them due to an increase in the density of hormonal receptors in the skin. The main regulator of proliferation and lipogenesis in the sebaceous glands - dihydrotestosterone (DHT) - stimulates hypersecretion and changes in the physicochemical properties of sebum, leading to the closure of the excretory ducts of the sebaceous glands, the formation of comedones, the appearance of acne and acne.

Hirsutism is associated with hypersecretion of androgens in 40-80% of cases, in the rest - with increased conversion of testosterone into more active DHT, which provokes excessive growth of hair shafts in androgen-sensitive areas of the female body or hair loss on the head. In addition, women may experience iatrogenic hyperandrogenism caused by taking medicines with androgenic activity.

Symptoms of hyperandrogenism in women

The clinical picture of hyperandrogenism in women depends on the severity of the disorder. With hyperandrogenism of non-tumor origin, for example, with PCOS, Clinical signs progress slowly over several years. The initial symptoms manifest during puberty, clinically manifested by oily seborrhea, acne vulgaris, menstrual irregularities (irregularity, alternating delays and oligomenorrhea, in severe cases - amenorrhea), excessive hair growth of the face, arms, legs. Subsequently, cystic transformation of the ovarian structure, anovulation, progesterone deficiency, relative hyperestrogenemia, endometrial hyperplasia, decreased fertility and infertility develop. In postmenopause, hair loss is observed first in the temporal regions (bitemporal alopecia), then in the parietal region (parietal alopecia). Severe androgenic dermatopathy in many women leads to the development of neurotic and depressive conditions.

Hyperandrogenism in AGS is characterized by virilization of the genitals (female pseudohermaphroditism), masculinization, late menarche, breast underdevelopment, deepening of the voice, hirsutism, acne. Severe hyperandrogenism due to dysfunction of the pituitary gland is accompanied by a high degree of virilization and massive obesity of the android type. High activity Androgens contribute to the development of metabolic syndrome (hyperlipoproteinemia, insulin resistance, type II diabetes), arterial hypertension, atherosclerosis, and coronary artery disease. With androgen-secreting tumors of the adrenal glands and ovaries, symptoms develop rapidly and progress rapidly.

Diagnosis of hyperandrogenism in women

In order to diagnose pathology, a thorough history and physical examination are carried out with an assessment of sexual development, the nature of menstrual irregularities and hair growth, signs of dermopathy; Total and free testosterone, DHT, DHEA-S, and GSPS in the blood serum are determined. Detection of excess androgens requires clarification of its nature - adrenal or ovarian.

A marker of adrenal hyperandrogenism is increased level DHEA-S, and ovarian - an increase in the amount of testosterone and ASD. With very high levels of DHEA-S >800 μg/dL or total testosterone >200 ng/dL in women, a suspicion of an androgen-synthesizing tumor arises, which requires CT or MRI of the adrenal glands, ultrasound of the pelvic organs, and if visualization of the tumor is difficult, selective catheterization of the adrenal glands and ovarian veins. Ultrasound diagnostics can also determine the presence of polycystic ovarian deformation.

For ovarian hyperandrogenism, indicators are assessed hormonal levels women: levels of prolactin, LH, FSH, estradiol in the blood; with adrenaline - 17-OPG in the blood, 17-KS and cortisol in the urine. It is possible to perform functional tests with ACTH, tests with dexamethasone and hCG, and perform a CT scan of the pituitary gland. A study of carbohydrate and fat metabolism (levels of glucose, insulin, HbA1C, total cholesterol and its fractions, glucose tolerance test) is mandatory. Women with hyperandrogenism are advised to consult an endocrinologist, dermatologist, or geneticist.

Treatment of hyperandrogenism in women

Treatment of hyperandrogenism is long-term, requiring a differentiated approach to patient management tactics. The main means of correcting hyperandrogenic conditions in women is estrogen-progestogen oral contraceptives with antiandrogenic effect. They provide inhibition of the production of gonadotropins and the ovulation process, suppression of the secretion of ovarian hormones, including testosterone, raising the level of GSPS, blocking androgen receptors. Hyperandrogenism in AGS is treated with corticosteroids; they are also used to prepare a woman for pregnancy and during gestation with this type of pathology. In case of high hyperandrogenism, courses of antiandrogenic drugs in women are extended to a year or more.

For androgen-dependent dermatopathy, peripheral blockade of androgen receptors is clinically effective. At the same time, pathogenetic treatment is carried out subclinical hypothyroidism, hyperprolactinemia and other disorders. To treat women with hyperinsulism and obesity, insulin sensitizers (metformin), weight loss measures (hypocaloric diet, physical exercise). During treatment, the dynamics of laboratory and clinical parameters are monitored.

Androgen-secreting tumors of the ovaries and adrenal glands are usually benign in nature, but when they are identified, it is necessary to surgical removal. Relapses are unlikely. In case of hyperandrogenism, clinical observation and medical support of the woman are indicated for successful planning of pregnancy in the future.

No matter how paradoxical it may sound, every female body produces androgens - male sex hormones. This occurs in the female ovaries, which are the sex glands, and in the adrenal glands, the organs of the endocrine system. The diagnosis of hyperandrogenism is indicated if an excessive amount of androgens is produced in the adrenal glands or ovaries.

The main “targets” of male sex hormones are the skin, ovaries, sweat and sebaceous glands, and hair.

Hyperandrogenism of adrenal origin. Treatment of this form

This disease may be a consequence of dysfunction of the adrenal glands in the presence of a congenital form of adrenogenital syndrome (in in this case hyperandrogenism is observed in children and men). Also, the disease can make itself felt in the postnatal period secondarily as a result of exposure to any unfavorable factors that disrupt the function of the adrenal cortex (various infections, intoxication, administration of exogenous hormones). Moreover, the pathogenesis of these conditions is the same as the congenital form of adrenogenital syndrome.

Adrenal hyperandrogenism is characterized by early manifestation of virile symptoms.

The first menstruation may appear late. In the future, menstruation with hyperandrogenism in a girl becomes quite rare (the so-called hypomenstrual syndrome). Almost all patients experience acne vulgaris in the back, chest, and face. Some patients may have dark skin or pigmented areas on the skin. Hypoplasia of the mammary glands is noted. The male body structure is characteristic: a fairly narrow pelvis, broad shoulders, shortened limbs. With adrenal hyperandrogenism, an increased concentration of androgens in the blood causes accelerated closure of bone growth zones, which causes body growth to stop prematurely. With an anomaly, the genitals develop according to the female type. There may be moderate hypertrophy of the clitoris and some reduction in the size of the uterus with completely normal ovarian sizes

Tests with dexamethasone (or prednisolone), as well as ACTH, are of great importance in the diagnosis of adrenal hyperandrogenism. In our clinic, all these studies are carried out using the latest equipment, which guarantees their maximum accuracy.

Adrenal hyperandrogenism - treatment. Replacement therapy with glucocorticoid drugs in a maintenance dosage is recommended, as in the presence of a congenital form of adrenogenital syndrome.

Hyperandrogenism of ovarian origin

The main cause of ovarian hyperandrogenism is considered to be polycystic ovary syndrome. How does the deviation manifest itself?

First of all, polycystic ovary syndrome itself occurs due to a deficiency of enzymes contained in the ovaries. In this case, we are talking specifically about the presence of a hereditary deficiency. It interferes with the conversion of exclusively male androgens into female sex hormones. Therefore, androgens accumulate, and eventually this pathology is formed.

Mild hyperandrogenism of ovarian origin is associated with the development of hormonal disorders in the pituitary gland and hypothalamus. In addition, imbalances in some other hormones usually occur in female body, in particular, FSH, LH, estradiol and prolactin.

Another reason for the development of ovarian hyperandrogenism is an androgen-producing tumor. Also, such tumors can cause a significant increase in the content of some other hormones taken separately.

Hyperandrogenism of mixed origin

Quite often there is a combination of the two types of hyperandrogenism discussed above. In addition, the adrenal form of hyperandrogenism is sometimes combined with some other diseases, since prolactin, which causes the production of androgens, simultaneously interferes with the production of other, exclusively female hormones.

Causes of the disease

Both the ovaries and the adrenal glands can produce excess androgens. In addition, excess androgens can appear as a result of metabolic disorders.

Adrenogenital syndrome is the most common cause of an increased amount of male sex hormones.

Hyperandrogenism is congenital, or this disease occurs due to diseases (including tumors) of the pituitary gland, which is the main endocrine gland located in the brain. In the presence of neuroendocrine syndrome (dysfunction of the pituitary gland and hypothalamus), signs of hyperandrogenism are accompanied by a significant increase in body weight.

In addition, the cause of the disease may be the presence of an adrenal tumor. As the number of cells that produce androgens increases, the number of these hormones also increases significantly.

Diagnosis of hyperandrogenism

To diagnose the disease, the woman’s age is taken into account, as well as the time when the first symptoms of hyperandrogenism appeared, which can appear with the onset of puberty of the girl or after reaching reproductive age. This makes it possible to assume a connection between the disease and a tumor of the adrenal glands or ovaries.

When diagnosing hyperandrogenism, the following examinations are carried out:

• Changes in hormonal status during the menstrual cycle.
• In case of hyperandrogenism, blood and urine tests are taken, which reveal male sex hormones, their breakdown products (FSH, LH, progesterone, estradiol, prolactin, testosterone, ketosteroids cortisol, as well as DEA-S - dehydroepiandrosterone sulfate), as well as some other hormones.
• Ultrasound of the pelvic organs.
• Examination of the adrenal glands using ultrasound, as well as MRI (magnetic resonance imaging).
• In some situations, laparoscopy is performed (the insertion of a specially designed device, a laparoscope, into an organ through a small incision in the skin, thanks to which one can examine the organ from the inside and take a segment of tissue for examination).

Our clinic is equipped with the most modern equipment, making all examinations as comfortable, painless and effective as possible.

Hyperandrogenism: treatment

The treatment methods used for hyperandrogenism will depend on the characteristics of the disease.

In case of increased production of male sex hormones by tumor tissue of the adrenal glands or ovaries, surgery. Tumors that contribute to the appearance of hyperandrogenism are often benign and in rare cases recur after removal.

In the case of neuroendocrine syndrome (dysfunction of the pituitary gland and hypothalamus) with obesity, one of the most important stages of therapy is weight loss, which is achieved by reducing the calorie content of food and sufficient physical activity. Such a diet for hyperandrogenism usually gives excellent results.

In the presence of adrenogenital syndrome - increased production of male sex hormones in the adrenal glands, which is associated with the absence of the enzyme that makes glucocorticoids from androgens, glucocorticoid drugs (metipred, dexamethasone) are used.

The same drugs are used to prepare for pregnancy and therapy during pregnancy for this form of hyperandrogenism.

For hirsutism, hormonal correction and various cosmetic measures, such as hair removal, are performed.

In patients suffering from infertility due to ovarian or adrenal hyperandrogenism, the use of antiandrogens is effective - drugs that suppress the excessive secretion of androgens by the adrenal glands and ovaries, including Diane-35, as well as cyproterone acetate (androcur).

As a therapy for infertility, which is associated with hyperandrogenism of ovarian or adrenal origin, drugs are used to stimulate ovulation, including clomiphene citrate.

Stimulation of ovulation in case of hyperandrogenism is carried out according to the same scheme as in other cases of endocrine infertility. But at the same time, the diversity and complexity of the causes of hyperandrogenism usually cause difficulties in restoring reproductive and menstrual function. In patients with hyperandrogenism, there is often no effect from treatment with clomiphene citrate, and the effect of stimulating ovulation with gonadotropins is almost half as much as in patients without the disease. Many women, in despair, begin treatment for hyperandrogenism folk remedies. However, such therapy is often completely ineffective.

Contact our clinic. Our specialists have accumulated vast experience in treating hyperandrogenism, and therefore will be able to do everything possible to rid you of this disease.

For quotation: Pishchulin A.A., Karpova E.A. Ovarian hyperandrogenism and metabolic syndrome // Breast cancer. 2001. No. 2. P. 93

Endocrinological science Center RAMS, Moscow

WITH ovarian hyperandrogenism syndrome of non-tumor origin or hyperandrogenic ovarian dysfunction, previously called Stein-Leventhal syndrome, is currently, according to the WHO classification, better known in the world literature as polycystic ovary syndrome (PCOS).

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 menstrual dysfunction - opsomenorrhea, amenorrhea, but the development of metrorrhagia cannot be ruled out. Violations of folliculogenesis lead to the development of anovulatory primary or secondary infertility.

One of the main diagnostic criteria PCOS is hyperandrogenemia - increased levels of androgenic steroids in the blood (such as testosterone, androstenedione), which leads to the development of hirsutism and other androgen-dependent dermopathy.

Obesity or overweight often accompanies PCOS. Determination of body mass index (BMI) allows you to determine the degree of obesity. Measurement of waist (WC) and hip (HC) volumes and their ratio indicates the type of obesity (the abdominal type of obesity is prognostically unfavorable, in which WC/HC > 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, increased risk development of hyperplastic and tumor processes in the genitals. Dyslipidemia consists of increased levels of 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 changes in blood vessels, hypertension and coronary disease hearts.

Disorders of carbohydrate metabolism consist in the development of the insulin resistance-hyperinsulinemia complex, which has recently been 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 syndrome. However, in subsequent years it was shown that the aromatase activity of granulosa cells is an FSH-dependent function.

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

Until the mid-80s, it was believed (the theory of S.S.C. Yen) that the triggering mechanism in the pathogenesis of PCOS is excessive synthesis of androgens by the adrenal glands during the adrenarche period as a result of altered sensitivity of the adrenal glands to ACTH or excessive stimulation of the zona reticularis of the adrenal cortex by a non-ACTH-like factor or under the influence of b -endorphins, neurotransmitters, for example, dopamine. When a critical body weight is reached (especially when it is exceeded), the peripheral conversion of androgens to estrogens increases, primarily in the liver and adipose tissue. An increase in the level of estrogen, 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 increases, as a result of which the production of LH by the adenopituitary gland increases, the LH/FSH ratio is disrupted, and relative FSH deficiency occurs. The increased effect of LH on the ovaries promotes increased 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 into estrogens. Hyperandrogenism interferes with the normal growth of follicles and contributes to the formation of their cystic atresia. Lack of follicular growth and maturation further inhibits FSH secretion. 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.

Pathogenesis of PCOS according to S.S.C. Yen is presented 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 S.S.C. theory. Yen. PCOS has been found to be associated with hyperinsulinemia, and this syndrome is characterized by both reproductive and metabolic dysfunction.

The existence of a relationship between hyperinsulinemia and hyperandrogenism was pointed out back in 1921 by Achard and Thieris. They described hyperandrogenism in an obese woman with type 2 diabetes mellitus and called this condition “diabetes of bearded women.”

Subsequently, 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. A direct relationship has been found between insulin and androgen levels, and it has been suggested that hyperinsulinemia may be the cause of hyperandrogenism.

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

Hypotheses for the pathogenesis of hyperinsulinemia and hyperandrogenism

The mechanism of occurrence of hyperandrogenism and hyperinsulinemia has not been fully studied. Theoretically, three possible interactions are possible: hyperandrogenism (HA) causes HI; 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. Women who take oral contraceptives containing progestins with “androgenic properties” develop impaired glucose tolerance. Long-term administration of testosterone to transsexuals is accompanied by the occurrence of IR. Androgens have been shown to influence the composition muscle tissue, increasing the number of type 2 muscle fibers, which are less sensitive to insulin compared to type 1 fibers.

2. Most factors suggest that HI leads to GA. IR has been shown to persist in patients undergoing subtotal or total ovarian removal, as well as in women on long-term GnRH agonist use when there was significant androgen suppression. Administration of diazoxide, a drug that suppresses insulin secretion by the pancreas, caused a decrease in testosterone (T) levels and an increase in sexsteroid binding globulin (SSBG) levels in patients with PCOS, obesity and hyperinsulinemia. Intravenous administration insulin in women with PCOS resulted in increased levels of circulating androstenedione and T. Interventions aimed at increasing insulin sensitivity (weight loss, fasting and low-calorie diet) were accompanied by a decrease in androgen levels. There is evidence that insulin can directly suppress the production of CVD by the liver, and under conditions of hyperinsulinemia this effect is enhanced. It is believed that insulin, and not sex hormones, is the main regulator of CVS synthesis. A decrease in the level of SSSH 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 GA with hyperinsulinemia does not answer the question of how the ovary maintains sensitivity to insulin in an insulin-resistant state of the body. Several possible explanations have been proposed. Since insulin has many functions, a selective defect in some of them can be assumed. Organ-specific insulin sensitivity may occur. But a more likely assumption is that insulin acts on the ovary not only through insulin receptors, but also through insulin-like growth factor (IGF) receptors.

Insulin receptors and IGF-1 receptors have been identified in human ovaries (in ovarian stromal tissue healthy women, women with PCOS, in follicular tissue and granulosa cells). Insulin can bind to IGF-1 receptors, although with less affinity than to its own receptors. However, with HI, as well as in situations where insulin receptors are blocked or there is a deficiency, insulin can be expected to bind to IGF-1 receptors to a greater extent.

It is possible that the mechanisms of insulin/IGF-1 stimulation of steroidogenesis in the ovary can be divided into nonspecific and specific. Nonspecific are the classical effects of insulin on the metabolism of glucose, amino acids and DNA synthesis. As a result, cell viability increases and, consequently, hormone synthesis increases. Specific mechanisms include the direct effect of insulin/IGF-1 on steroidogenic enzymes, the synergism between insulin and LH/FSH, and the effect on the number of LH receptors.

Insulin/IGF-1, acting synergistically with FSH, stimulates aromatase activity in granulosa cell culture and thereby increases the synthesis of estradiol. 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 influence 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 predominantly in the form of hyperandrogenism.

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

There may also be a connection with the S.S.C. theory. Yen about the participation of adrenal steroidogenesis in the pathogenesis of PCOS (Scheme 2).

Scheme 2. Effect of insulin in polycystic ovary syndrome

V. Insler (1993), having conducted 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 causes excessive production of androgens through IGF-1 receptors, which, acting in synergy with LH, cause an increase in the activity of cytochrome P450c17a, the main controlling enzyme in the synthesis of androgens. In patients with normal body weight, a relative increase in the concentration of growth hormone stimulates excess production of IGF-1. From this point on, synergism with LH leads to hyperproduction of androgens according to 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 impaired 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 and HI patients develop hyperandrogenism and PCOS, a hypothesis has been put forward 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 makes 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 the field of 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 discovered a substitution of tryptophan for serosine at codon 1200. The researchers hypothesized that this 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 discovered the substitution of serine for arginine in the tetrameric structure of the insulin receptor. This mutation in the active locus led to the impossibility of combining the a- and b-subunits, as a result of which the functionally active receptor was not synthesized. The above studies are only the first attempts to identify the specific genetic etiology of ovarian stromal tecomatosis.

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

It cannot be ruled out that in PCOS-ser there is some serine phosphorylating factor. For example, a serine/threonine phosphatase inhibitor is isolated, which apparently disrupts the phosphorylation of iR in PCOS-ser. This compound is similar to the recently isolated membrane glycoprotein PC-1 (insulin receptor tyrosine kinase inhibitor), but the latter does not increase insulin-independent serine phosphorylation of iR.

The factor has similar properties tumor necrosis-a(TNF-a): phosphorylation of serine residues of IRS-1 (one of the secondary signal transducers of ir) under the influence of TNF-a leads to suppression of tyrosine kinase activity of ir.

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

Scheme 4. Insulin resistance gene in PCOS

The role of leptin in PCOS

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 fully elucidated. For this reason, data on leptin levels in ovarian hyperandrogenism in combination with insulin resistance and ideas about 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 fully elucidated. For this reason, data on leptin levels in ovarian hyperandrogenism in combination with insulin resistance and ideas about its role in the development of these changes are very contradictory.

Thus, according to the results of a study conducted by Brzechffa et al. (1996), a significant proportion of women in the PCOS population have leptin levels higher than expected based on their BMI, free testosterone, and insulin sensitivity. On the other hand, recent work in this area has not shown significant differences in leptin levels between the PCOS study groups and the control groups. In addition, it was found that leptin levels are not affected by the basal level of insulin, the content of gonadotropins and sex steroids. However, Zachow and Magffin (1997), taking into account the presence of leptin receptor mRNA in ovarian tissue, demonstrated a direct effect of this hormone on the steroidogenesis of rat granulosa cells in vitro. At the same time, a dose-dependent inhibitory effect of leptin on IGF-1 was shown, potentiated by an increase in FSH-stimulated E2 synthesis by granulosa cells. These data support the hypothesis that increased 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 the 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, it can be assumed that high leptin levels may reduce the sensitivity of other target tissues to the action of endogenous insulin, leading to the development of IR in obesity.

Diagnosis

Diagnosis of ovarian hyperandrogenism syndrome with a typical clinical picture is not difficult. First of all, this is a violation of menstrual function such as oligo-, opso- or amenorrhea, anovulation and primary or secondary infertility caused by it, hirsutism, acne, 40% of patients have obesity varying degrees expressiveness. 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. In patients with PCOS, there is often a predominance of LH levels over FSH, their ratio is disturbed and increased (more than 2.5-3). Prolactin levels are normal, although in 30% of patients there is a slight increase.

The level of urinary excretion of total 17-CS 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 increased levels of dehydroepiandrosterone (DHA) and its sulfate (DHA-S) and 17-hydroxyprogesterone (17-OH-P) in the blood. To clarify the localization of the source of hyperandrogenism, various functional tests have been proposed, the most widespread of which are the test with dexamethasone and 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 determination of the level of glucose and immunoreactive insulin (IRI). Evidence in favor of insulin resistance is also a BMI over 25 and WC/TB over 0.85, as well as dyslipidemia.

Treatment

At the core modern approach pathogenetic treatment of PCOS lies principle of restoration of impaired ovarian function , that is, the elimination of anovulation, which in turn leads to a decrease in hyperandrogenism and restoration of folliculogenesis. However, studying the features of the etiopathogenesis of ovarian hyperandrogenism leads to the conclusion that choosing methods for adequate treatment of 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 synthesis of SSSH by the liver. After cancellation, a “rebound effect” is achieved, which consists in normalizing the hypothalamic-pituitary function, reducing the overproduction of androgens by ovarian tissue, normalizing folliculogenesis and restoring ovulation.

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

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

It is possible to use progestin drugs that lack androgenic properties in the form of monotherapy, especially for endometrial hyperplasia. Dydrogesterone is prescribed 1 tablet (10 mg) 2 times a day from 14-16 to 25 days of the cycle lasting from 3 to 6 courses.

Most effective means stimulation of ovulation in PCOS is an anti-estrogenic drug clomiphene citrate . The main effects of antiestrogens are a decrease in the hypersensitization of the pituitary gland to the action of GnRH, a decrease in LH production, induction of the ovulatory LH surge, and stimulation of ovulation. The drug is prescribed at 50 mg, 100 mg per day from days 5 to 9 of the cycle until ovulation is achieved according to tests functional diagnostics, but no more than 3 courses in a row. Recently, publications have appeared 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 (maximum by 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 administration of clomiphene was not found.

The emergence of drugs with antiandrogenic properties has significantly expanded the therapeutic options for PCOS. The most widely used drug is Diane-35, containing 35 mg of ethinyl estradiol 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 regimen, as an oral contraceptive, in courses of 6 or more cycles. However, it should be noted that these drugs have a negative effect on lipid and carbohydrate metabolism, manifested in increased levels of cholesterol, low-density lipoproteins, as well as increased hyperinsulinemia, which requires constant dynamic monitoring of these indicators in patients with PCOS. Spironolactone, which is widely used in the treatment of androgen-dependent dermopathy, also has antiandrogenic properties.

One of the main directions in modern therapy for 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 the reduction of excess body weight: a low-calorie diet (within 1500-2200 kcal/day) with limitation of fats and easily digestible carbohydrates, limiting salt intake to 3-5 g per day, moderate physical activity, normalization of work schedule and rest. It is possible to use drugs that help reduce BMI, for example, orlistat, which selectively inhibits gastrointestinal lipases (“fat blocker”) or sibutramine, which blocks recapture norepinephrine and serotonin at the synapses of the hypothalamic “saturation” center. Increased energy expenditure (thermogenesis) is also due to the synergistic interaction between the enhanced function of norepinephrine and serotonin in the central nervous system. This is expressed in the selective activation of the central sympathetic effect on brown adipose tissue due to indirect activation of b 3 -adrenergic receptors.

The next step is the use of drugs that improve impaired tissue sensitivity 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-Chemie). They potentiate the action of insulin at the receptor and post-receptor level and significantly improve tissue sensitivity to this hormone. Some studies have shown significant reductions in fasting insulin levels and 2 hours after a 75 g glucose load in women with PCOS using 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 reduces androgen levels. However, the revealed cytotoxic and hepatotoxic effects of this group of drugs limit the possibility of their widespread use. A search is underway for new drugs that selectively affect insulin sensitivity.

Despite the significant arsenal various means, used to treat ovarian hyperandrogenism, therapy for 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 excessive secretion of androgens and induce stability of monthly menstrual bleeding, which is best achieved by using drugs with antiandrogenic properties (Diane-35).

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

Literature:
1. Ovsyannikova T.V., Demidova I.Yu., Glazkova O.I. Problems of reproduction, 1998; 6:5-8.

2. Ginzburg M.M., Kozupitsa G.S. Problems of endocrinology, 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. Problems of endocrinology. 1998; 6:45-8.

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

8. Akmaev I.K. Problems of endocrinology. 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 resistance, acanthosis nigricans: a common endocrinopathy with unique pathophysiological 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 anovulation causes by peripheral endocrine disorders. In: Yen S.S.C., Jaffe R.B. Reproductive endocrinology: physiology, pathophysiology, and clinical management. Philadelphia: Saunders W.B. 1986; 462-87.

15. Moller D.E., Flier J.S. Detection of an alteration in the insulin-receptor 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 Publishing CO, Washington, DC. 1988; 293-317.

17. Speroff L., Glass R. H. Clinical gynecologic. Endocrinology and Infertility 5 th 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.

Ethinyl estradiol + cyproterone acetate

Diane-35 (trade name)

(Shering AG)

Adrenogenital syndrome or adrenal hyperandrogenism refers to a group of genetically determined enzymopathies (enzymopathies), which result in the manifestation of traits of the opposite sex in individuals of the same gender (virilization) and the formation of incorrect sexual orientation.

Quirks of heredity sometimes lead to the fact that a child turns out to be similar not to his parents, but to some distant ancestor. In general, there is nothing wrong with this, especially if the ancestor was a beautiful, healthy and worthy person. However, even in such cases, a man may suspect a woman and demand irrefutable evidence of fidelity.

For some reason, when an unusual child is born, it is always customary to blame the woman, but meanwhile, parents have absolutely equal rights in transmitting their information to their offspring, since the child always receives half of the chromosomes with genes localized in them from the father, and half from the mother. “Bad” mutant genes responsible for the synthesis of sex hormones are the culprits of such disorders of the development of the human reproductive system as adrenogenital syndrome, in which it can be difficult to determine the gender of a barely born child. And, of course, one can imagine how such people suffer in later life, when their appearance involuntarily attracts the attention of others.

In addition, ovarian hyperandrogenism and hyperandrogenism of mixed origin are more often than others endocrine diseases are the cause of infertility, since they lead to insufficiency of the luteal phase (phase II of the cycle), which ensures the balance of progesterone and estrogens. Of course, correcting hormonal disorders in such cases requires a special approach and is a rather difficult task for a gynecologist.

A little about genetics

Many diseases are recessive and manifest themselves only when two identical genes meet, that is, in a homozygous state, while heterozygotes remain healthy and do not even suspect that they are carriers of a hereditary pathology. However, genes did not turn out to be 100% stable, so genetics is the science not only of heredity, but also of variability.

Genes, although not so often, change, and this phenomenon, called mutation, is reflected in changes in the characteristics of the body.

Mutagenesis (mutation process), in general, is considered a random process, but it has been proven that some factors can still influence it. These include:

• hard radiation, such as x-rays;
• chemicals with mutagenic properties;
• genetically modified food;
• stress, psycho-emotional stress;
• inadequate treatment with hormonal drugs;
• infectious viral agents.

The metabolism of any substance in the body consists of two enzymatic processes running in parallel, but interconnected:

• breakdown of complex compounds into simple molecules (catabolism);
• synthesis of complex substances, the precursors of which are simple molecules (anabolism).

Thousands of enzymes are involved in the metabolic transformations of metabolic products, each of which must be responsible for its own area and perform its job flawlessly. However, as a result genetic mutations, the enzyme can change its composition and properties, that is, become defective and lose the ability to cope with the task assigned by nature. Mutations of genes encoding enzymes responsible for the biosynthesis and functioning of substances important for the body, such as hormones, lead to endocrine defects affecting the production and transport of sex hormones.

Mutations of the genes that control the synthesis of androgens do not go away without a trace and lead to a pathological condition called adrenogenital syndrome (AGS) or adrenal hyperplasia (hyperplasia of the adrenal cortex).

Types of AGS

Clinical manifestations and their characteristic biochemical parameters make it possible to divide adrenogenital syndrome into five main types.

I. Rarely occurring lipid adrenal hyperplasia, in which blockade of steroidogenesis occurs even at initial stages, before the formation of enzymes that break down cholesterol. As a result, cholesterol accumulates in the adrenal glands, and ACTH (adrenocorticotropic hormone) accumulates in the blood. Clinically, this type is manifested by severe virilization in girls, hypospadias (congenital malformation of the urethra) and scrotal anomaly in boys. Loss of chlorides in urine is common in both sexes.

II. The biochemical basis of this type of AGS is the insufficient content of the enzyme 3β-ol-dehydrogenase, which ensures the synthesis of progesterone. As a result: in boys, feminization occurs, since the synthesis of steroids with androgenic effects is impaired.

III. The vast majority of patients with AGS (almost 90%) belong to this type, which occurs due to deficiency of the enzyme 2-hydroxylase. The two main forms of adrenogenital syndrome (simple and salt-wasting) are formed depending on the concentration of 21-hydroxylase, where in the partial form, virilization in girls occurs before birth, and puberty occurs with a significant delay. Boys, this type, on the contrary, are at risk of premature puberty, combined with short stature.

Complete loss of enzyme activity leads to severe and early manifestations of the syndrome:

• pylorospasm;
• loss of salts;
• metabolic acidosis;
• attacks of colloptoid state;
• changes in biochemical parameters of blood and urine (hormonal changes corresponding to the blockade).

IV. The clinical picture of this type is caused by a blockade of the conversion of 11-deoxycortisol to cortisol (decrease in the level of 11β-hydroxylase) and, in addition to virilization in both boys and girls, is manifested by progressive arterial hypertension, characterized by:

• changes in the blood vessels of the kidneys and fundus;
• hypertrophy of the heart muscle;
• retention of salt (NaCl) in the body;
• excretion of increased amounts of 11-deoxycortisol in the urine.

V. A very rare type of adrenogenital syndrome. Occurs when mutational blockade affects the stages of conversion of progesterone to 17α-hydroxyprogesterone.

Arterial hypertension, characteristic of type IV, begins to develop with might and main already in childhood, and is also difficult to treat.

Formation mechanism

The synthesis of androgens (male sex hormones) occurs in the testicles and adrenal glands. This process in the initial stages occurs equally in both organs and is common to androgens and other steroids produced by the adrenal glands: cortisone, corticosterone and aldosterone. The main enzymes that serve the stages of successive transformations of testosterone precursors are hydroxylases and dehydrogenases.

It would seem that since the matter concerns male sex hormones, then the pathology should be characteristic only of boys, but this is not so, since at the initial stages the biosynthesis of estrogens (female sex hormones) is no different from that in men, therefore these mutations are also possible in female individual.

And when a girl exhibits traits of the opposite sex, it is customary to talk about adrenogenital syndrome, which can be represented by three clinical forms:

• congenital;
• postnatal or prepubertal;
• post-pubertal.

Hormonal changes cause a violation of sexual differentiation, which often begins in the prenatal period and then continues in the postnatal period. Of course, if adrenogenital syndrome manifests itself in newborns, then one can hardly question its congenital hereditary nature. This form of hyperandrogenism is called classical, and it often puts neonatologists in a difficult position when determining the sex of the child.

Congenital adrenal hyperandrogenism

The excess production of androgens, which begins in the prenatal period, inevitably leads to hyperplasia of the adrenal cortex and the formation of false hermaphroditism. And since gender is initially determined by external sexual characteristics, the presence of a penis-shaped clitoris and fused labiosacral folds resembling a scrotum make one think that the child is male.

Congenital adrenogenital syndrome belongs to hereditary defects and is transmitted in an autosomal recessive manner. It is caused by congenital deficiency of enzyme systems and, in particular, 21-hydroxylase, which controls the synthesis of glucocorticoids in the adrenal cortex. If the deficiency of 21-hydroxylase is insignificant, then they speak of a simple form of AGS, but in the case of severe deficiency of the enzyme, a severe form of the syndrome develops. This occurs due to a lack of cortisol and aldosterone, which cannot be synthesized due to the failure of the adrenal cortex, or rather, its hyperplasia, which leads to a constant loss of salts by the body, therefore this variant of adrenogenital syndrome is called the salt-wasting form.

In addition, an excess amount of androgens significantly affects the formation of the external genitalia and leads to the development in girls of false male hermaphroditism of varying degrees of severity, which in the early stages of congenital AGS is manifested by abnormal formation of the skeleton with a predominance of male features.

It should be noted that the total frequency of such hyperandrogenism is quite high and occurs in the homozygous state in a ratio of 1: 5000-10000, in the heterozygous state - approximately 1: 50.

Congenital adrenogenital syndrome, in addition to impaired sexual differentiation even before the birth of a child, is more often than other types of hyperandrogenism characterized by a disorder of mineral metabolism and other severe disorders.

Adrenal hyperandrogenism

Despite the fact that adrenogenital syndrome includes several forms, what is common to all is a delay in the production of cortisol in the adrenal glands, leading to stimulation of the production of adrenocorticotropic hormone (ACTH) by the pituitary gland, which in turn stimulates the synthesis of 17-hydroxyprogesterone and leads to hyperproduction of androgens. Accumulation of ACTH in the blood leads to a decrease in cortisol levels and an increase in urinary excretion of 17-ketosteroids or 17-hydroxycorticosteroids. These indicators are very important diagnostic signs and are successfully used to establish the diagnosis of AGS. But since all these transformations are tied to the adrenal cortex, then such AGS is called hyperandrogenism of adrenal origin, which, in addition to the congenital form, has (as mentioned above) two more: postnatal and postpubertal. They are not always congenital, as they can develop as a result of hyperplasia of the adrenal cortex, which occurs for various reasons, or the formation of a tumor, which happens much less frequently.

The postnatal (prepubertal) form of AHS is characterized by early puberty and has the following features:

• virilization (growth of hair on the face and body according to the male pattern, enlargement of the clitoris, deepening of the voice);
• the presence of numerous rosacea on the face, chest and back;
• increased bone growth (before menarche, girls with the prepubertal form are significantly ahead of their peers);
• early closure of the epiphyseal zones of cartilage, so growth stops and children ultimately remain short. Short lower limbs are typical for the syndrome.

The clinical picture of the postpubertal form of AGS is characterized by:

• virial syndrome;
• signs of defeminization (breast glands become smaller, hypo- or amenorrhea occurs);
• hirsutism (voice becomes rough);
• enlargement of the clitoris.

Obviously, a diagnosis can be assumed based on a person’s appearance; moreover, all these disorders are clearly reflected in the blood and urine, so diagnosing adrenogenital syndrome does not present any special problems. The diagnosis is made based on:

• clinical symptoms;
• general examination;
• gynecological studies;
• studies of hormonal status (venous blood) using enzyme immunoassay;
• biochemical urine analysis (17-ketosteroids, 17-hydroxycorticosteroids).

Adrenogenital syndrome naturally affects reproductive function and casts doubt on pregnancy, however, there are other types of hyperandrogenism that should be distinguished, since they more often than AGS lead to infertility. For example, ovarian hyperandrogenism or adrenal and ovarian at the same time.

Hyperandrogenism of mixed origin

Hyperandrogenism of ovarian origin, called “polycystic ovaries” (PCOS), very often causes recurrent miscarriages and infertility. Structural and functional changes in the ovaries, occurring against the background of neurometabolic pathological processes, are caused by disorders of the hypothalamic-pituitary department nervous system. The cause of ovarian hyperandrogenism is functional disorders the activity of hypothalamic structures, which, starting from puberty, should regulate the release of luteinizing hormone releasing hormone (RLH). But since this pathology is characterized by increased secretion and release of RHLH, this leads to chronic anovulation (lack of ovulation), resulting from disorders:

• folliculogenesis;
• synthesis of steroids in the ovaries;
• metabolism.

Since these disorders began at puberty, the main symptom of the disease becomes primary infertility, although there are other manifestations of the disease that are important for diagnosis:

• enlarged ovaries;
• oligoamenorrhea (the menstrual cycle lengthens to 40 days or more, bleeding is insignificant) or acyclic bleeding (less often);
• weight gain;
• hypertrichosis (excessive hair growth).

It should be noted that ovarian hyperandrogenism can be combined with adrenal hyperandrogenism, that is, these two forms can occur simultaneously in one woman. This pathology is also caused by hypothalamic and neuroendocrine disorders, but in the formation of hyperandrogenism of mixed genesis, metabolic disorders of cortisol and insulin play a significant role, that is, the adrenal glands take an active part in this case. Hyperandrogenism of mixed origin is mainly associated with the presence of a genetic defect in 3α-hydroxysteroid dehydrogenase, leading to the accumulation of dehydroepiandrosterone, which undergoes further transformations. The result is an excess content of androgens in the tissues of the woman’s body.

Hormonal imbalance caused by pathological processes is manifested by inadequate functioning of other endocrine organs, for example, vegetative-neurotic disorders are often accompanied by abnormal behavior thyroid gland. Since insulin is involved in this process, the pancreas cannot stand aside.

The transformations occurring in the body lead to a significant disruption of hormonal balance and dysfunction of the endocrine system. This entails not only a change appearance women (acquisition of masculine traits), but also results in severe hormonal diseases, which prevent the onset and gestation of pregnancy.

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Treatment of adrenal hyperandrogenism

Considering the presence of various forms of hyperandrogenism and the close connection of endocrine disorders with all body systems, it is very difficult to treat the disease. Correction of the imbalance is carried out by prescription and individual selection hormonal drugs taking into account the origin and degree of hyperandrogenism, therefore treatment with folk remedies without the participation of a doctor is hardly appropriate. True, for some correction of hormonal levels, they resort to the use of alternative medicine - homeopathic preparations of plant origin, which, however, should be distinguished from tinctures and decoctions prepared at home. The use of antiandrogens of plant origin is quite acceptable and justified in adequate doses and for certain problems that do not require correction by their synthetic analogues.

Treatment of the congenital form of adrenogenital syndrome should be started as early as possible, given that the muscularization of the skeleton, which was acquired during the illness, will not go away, that is, it is impossible to eliminate it after the fact. Early treatment can save you from many other troubles.

The congenital form of adrenogenital syndrome is often the cause of incorrect sexual orientation and subsequently requires a change in the “passport” gender, which is very painful for the person himself and gives rise to condemnation of his behavior by people ignorant in this matter.

Adrenal hyperandrogenism can be treated for a long time (from one year to 15). During these years, the patient regularly receives individually selected doses of glucocorticosteroid drugs that suppress the synthesis of many sex hormones in the adrenal glands. During treatment, monitoring of 17-ketosteroids excreted in daily urine is mandatory. Glucocorticoid replacement therapy They are also carried out in patients with postnatal and postpubertal forms of AGS, but treatment here begins with large doses of hormones (15-20 mg of prednisolone or 2 mg of dexamethasone per day for a week) under the constant monitoring of 17-ketosteroids in daily urine. After 7 days of taking steroids, the dose begins to be gradually reduced, bringing it to maintenance. As soon as the level of 17-ketosteroids is normalized and the menstrual cycle is regulated, the dosage of the drugs is reviewed. In such cases, glucocorticosteroids are usually left only in the first phase of the menstrual cycle.

Treatment of polycystic ovaries and hyperandrogenism of mixed origin

Ovarian hyperandrogenism can be treated both conservatively and surgically.

The goal of conservative treatment of primary polycystic ovary syndrome is:

• stimulation of ovulation (infertility treatment);
• prevention of endometrial hyperplasia.

Prescription of combined estrogen-gestagen drugs (combined oral contraceptives - COCs) to suppress the increase in the concentration of gonadotropins and inhibit proliferative processes in the endometrium. However, the well-known drug (COC) Diane-25, which has an antiandrogenic effect, is prescribed only if the woman is not planning a pregnancy. Other options require a different approach (prescribing glucocorticoids in low doses).

Surgical treatment of PCOS can be carried out using several methods:

• wedge resection of the ovaries;
• demedulation of the ovaries with incision (or without it) of follicular cysts;
• electrocautery;
• thermocauterization.

The last two methods are an alternative to wedge resection of the ovaries and are performed laparoscopically.

The most difficult thing to treat is hyperandrogenism of mixed origin, especially if a woman is planning a pregnancy. In such cases, low doses of dexamethasone are usually taken for a year to suppress the production of dehydroepiandrosterone in the adrenal glands. At the same time, the level of cortisol in the patient’s blood is monitored, which should not exceed 5 μg%.

After a year, the woman’s hormonal status is subject to a comprehensive study and, if it is discovered that the vast majority of androgens are produced not by the adrenal glands, but by the ovaries, the treatment tactics are changed and combined oral contraceptives are prescribed (also in small doses).

There are other treatment regimens for hyperandrogenism, which are used by the doctor after establishing the form, origin and severity clinical manifestations diseases.

It should always be borne in mind that even small doses of glucocorticosteroid drugs can lead to the development of Cushing's syndrome, therefore individual dose selection and hormone testing once a month during therapy are mandatory measures.

Antiandrogens

Sex hormones are a very delicate and difficult thing to control. When they decrease, men experience unwanted sexual disorders, for example, such as impotence and decreased libido.

In women, an excess of male sex hormones leads to increased hair growth on the face, but loss on the scalp, the mammary glands become smaller, the voice changes, and the menstrual cycle is disrupted. In order to suppress the production of male sex hormones and reduce their concentration (and therefore activity) in the blood serum for hyperandrogenism, antiandrogen drugs are prescribed, which, as a rule, are oral contraceptives. However, given that their list and the given treatment regimens may be perceived by some readers as a guide to action, there is no point in dwelling in detail on this group, although it would not be superfluous to get to know plant-derived antiandrogens. Moreover, some cosmetic products contain them in their compositions, and they are very helpful for many women during menopause.

A substance such as Saw Palmetto, which is based on dwarf palm extract, is part of the drug for baldness Rinfaltil.

Cohosh (black cohosh) is known to women of “Balzac age”, as it is part of many herbal preparations intended to combat the unpleasant manifestations of menopause. In case of hormonal imbalance, Cyclodinone, which contains sacred twig, is often prescribed.

A very wide range of flora representatives, being involved in metabolic processes, can positively influence the process of regulating hormonal balance. Angelica, licorice root, peony, mint and many other plants that you don’t have to go far to find. Ready-made preparations are sold in every pharmacy, and how to prepare the medicine is written in the attached instructions.

Diagnosis and early treatment of hyperandrogenism (before the formation of irreversible clinical manifestations) is very justified from an ethical point of view, because an advanced case, when a girl has already acquired masculine traits that cannot be gotten rid of, will have a very negative impact on her future life. Wrong sexual orientation, the need to change gender when a person is already formed is a great grief for him and his family. But when modern methods treatment of such problems can be avoided if you do not ignore the warnings and recommendations of doctors, therefore a disease such as adrenogenital syndrome should never be left to chance.

Video: "Adrenogenital syndrome"

In medical terminology, hyperandrogenism of ovarian origin is called a disruption in the functionality of a woman’s endocrine system, causing excessive production of androgens. In a woman’s body, they are necessary to perform many important functions: puberty, hair growth intimate area, strengthening bone tissue, maintaining libido levels, etc. If the amount male hormones increases, this threatens the development of pathology that needs to be treated.

Types of hyperandrogenism in women

According to statistics, hyperandrogenism is diagnosed in 5-7% of women of reproductive age, of which about 20% experience problems with conception. This is due to the fact that an excess of androgens interferes with the natural maturation of follicles. The ovaries begin to become overgrown with a dense membrane, which prevents the release of the egg from the follicle during the menstrual cycle. In addition, some patients experience problems conceiving and carrying a pregnancy.
This disease can occur due to various reasons, but most often the cause of the disease is a failure in the functionality of the pituitary gland-hypothalamus. Depending on the factor that provoked the development of the pathology, the following forms of the disease can be distinguished:

• central – occurs against the background of abnormalities in the functioning of the hypothalamus and the formation of a pituitary tumor;
• adrenal – the cause is a tumor of the adrenal glands;
• ovarian – a disease of this form is associated with the development of polycystic and ovarian hyperthecosis. And also this type of pathology is characterized by androgen-producing ovarian tumors;
• mixed - this form of pathology is characterized by several disorders at once (failure in the functionality of the adrenal glands, deviations in the functioning of the ovaries, etc.);
• peripheral – occurs against the background diabetes mellitus and failure of metabolism (fat).

Experts note that the most common forms of hyperandrogenism are adrenal and ovarian.

Ovarian

Most often, ovarian hyperandrogenism develops against the background of polycystic ovary syndrome, which is characterized by a deficiency of enzymes contained in these organs. This disease is considered hereditary. Polycystic ovary syndrome interferes with the conversion of androgens into female hormones.

In addition, experts note that this form of hyperandrogenism is caused by dysfunction of the pituitary gland and hypothalamus. Such deviations cause increased production of LH and deviations in the proportions of LH/FSH. High levels of LH cause the development of hyperplasia of the outer layer of the follicles. Ultimately, this leads to increased production of androgens and the appearance of the first signs of masculinization. And the lack of FSH affects the maturation of follicles.
FLH is a type of hormone produced by the pituitary gland. In the human body, it is responsible for the functionality of the gonads and promotes the production of reproductive cells. In men, it controls testosterone levels and promotes the natural maturation of sperm, and in women it normalizes follicle maturation.
Another factor in the development of the ovarian form of pathology is considered to be androgen-producing tumors. These neoplasms provoke increased production of male hormones and the further development of hyperandrogenism.

Experts note that the ovarian form of the pathology may be associated with the central one. Such cases occur against the background of certain factors: trauma and intoxication of the brain, pituitary tumors. This disease is accompanied by an increase in the level of prolactin in the blood.

Adrenal

According to experts, adrenal hyperandrogenism is a hereditary disease, since the risk of developing this pathology with a complicated genetic background is significantly high. The disease can occur even in childhood.
Among the main factors in the development of the adrenal form of the disease, one can highlight androgenital syndrome. It manifests itself in insufficient production of enzymes responsible for the production of hormones, which are located in the adrenal cortex. In medicine, these enzymes are called glucocorticoids.
In the absence of necessary enzymes, human body begins to use substances that are normally processed to produce androgens. In this regard, an excess of androgens can also occur in children.
Typically, symptoms of the adrenal form of pathology appear early. Menstruation begins quite late, and later becomes scanty or may disappear altogether. Women have a masculine figure, in which the pelvis becomes narrower and the shoulders, on the contrary, become wider. In addition, other symptoms of pathology appear:

• underdeveloped mammary glands;
• skin pigmentation;
• acne that is localized in the back and chest;
• the clitoris hypertrophies slightly, and the size of the uterus decreases.

In the adrenal form of hyperandrogenism, patients are prescribed treatment with glucocorticoid drugs.

Causes of pathology

Hyperandrogenism usually occurs in two forms: absolute (increased levels of androgens in the blood) and relative (androgen levels are normal, but with increased metabolism into other types of hormones that have a negative effect on target organs - epithelium, sebaceous and sweat glands, hair follicles ).
According to statistics, the number of people suffering from ovarian hyperandrogenism (of ovarian origin) is growing every year. Currently, every woman of reproductive age is diagnosed with this disease. To cure this pathology, it is important to identify the factor that provoked its appearance. Among the main causes of hyperandrogenism in women are the following:

• andrenogenital syndrome - in the process of producing androgens by the adrenal glands, there is an insufficient amount of enzymes to process the hormone. This leads to the accumulation of the hormone in the body;
• a tumor in the adrenal glands and ovaries - neoplasms that can provoke hormonal imbalance, in which there is increased production of androgen;
• polycystic disease is pathological process, in which the ovaries are covered with cysts;
• Cushing's syndrome - a deviation in the functionality of the adrenal glands, in which there is an increased production of glucocorticoids;
• pathologies of the thyroid gland - diseases there include hypothyroidism, which causes hormonal imbalance in the female body;
• increased body weight - excess weight can provoke hormonal imbalance. Obesity in childhood is especially dangerous;
• long-term use hormonal contraceptives and steroid drugs;
• disturbance in the functionality of the pituitary gland or hypothalamus - such disturbances cause increased production of LH, against the background of which the proportion of LH/FSH is disrupted;
• ovarian hyperplasia - usually develops in women in old age;
• diabetes mellitus – with metabolic disorders, there is an increased production of certain hormones, in which hyperandrogenism may develop;
• pregnancy – during this period, hormonal changes occur in a woman’s body, which can cause an increase in androgen levels;
• congenital diseases of the adrenal glands and ovaries - this factor is common and is observed in 50% of patients with hyperandrogenism. With a complicated genetic background, it is almost impossible to cure the pathology.

Read also Atrophy of female ovaries as a cause of infertility

If the functionality of the ovaries is impaired, the pathology can develop in childhood. With congenital hyperandrogenism, problems may arise with determining the sex of the child. Girls are diagnosed with large labia and an enlarged clitoris, which may be similar in size to the penis. The internal genital organs are not modified. Their size is normal. With the development of hyperandrogenism at an older age, girls experience increased body hair growth.

It is worth noting that despite normal level androgens, 70-85% of women show signs of hyperandrogenism.

Most patients suffer from acne on the body. Additionally, some women report hair loss on their scalp. In 40-80% of cases, this is due to increased production of androgens, and in the rest - increased processing of testosterone into a more active hormone that causes excess hair growth.

Symptoms of hyperandrogenism

Symptoms of ovarian hyperandrogenism in women of reproductive age are of two types: primary and secondary. The clinical picture of the disease depends on the severity of the pathology and the factor of its development.
Among the main ones, experts identify the following signs of androgen excess in women:

• increased hair growth on the limbs and other areas of the body (chest, abdomen, back. In advanced cases, facial hair growth is observed;
• formation of bald patches on the head;
• formation of acne and comedones on the face;
• cessation of mammary gland growth, the figure develops according to the male type;
• atrophy of muscle tissue.

Doctors also identify secondary signs of an increase in the amount of androgens, the appearance of which depends on the factor in the development of the pathology:

• high glucose content in physiological fluids (diabetes mellitus);
• rapid weight gain;
• increased libido;
• increased growth of muscle tissue;
• menstrual irregularities or amenorrhea;
• infertility or failure to bear a fetus.

Among the sexual signs of hyperandrogenism, one can highlight the development reproductive organs women of the intermediate type and disruption of the menstrual cycle (in some cases, amenorrhea may develop).
Increased activity of androgens causes the development of metabolic syndrome (hyperlipoproteinemia, type 2 diabetes), coronary heart disease, atherosclerosis, arterial hypertension.
Experts note that these failures lead to patients getting sick more often colds. This is due to deterioration in functionality immune system against the background of hyperandrogenism. Many women with these diseases are prone to depression.

Read also Signs of female ovarian hypertrophy

Diagnosis of pathology

Mild hyperandrogenism of ovarian origin usually occurs latently and is almost impossible to diagnose. As a rule, the level of androgens in mild hyperandrogenism of ovarian origin is within normal limits.
If the patient experiences one or more symptoms of hyperandrogenism, then it is necessary to immediately visit a specialist. As a rule, the problem is diagnosed by a gynecologist. In addition, the woman will have to visit an endocrinologist. The specialist will prescribe a number of examinations:

• interviewing the patient (to establish an anamnesis of the patient’s life);
• MRI and CT;
• external examination of the skin;
• gynecological examination;
• tests using dexamethosone (carried out in order to establish the source of increased androgen production);
• examination to determine genetic abnormalities;
• determination of globulin level;
• measurement of testosterone levels and 17 OP in urine;
• marker for the determination of hCG (prescribed if the androgen level is within normal limits.

If the presence of ovarian tumors is suspected, patients are referred for an ultrasound of the genital organs. All these examination methods will allow you to restore clinical picture illness and choose the optimal method of therapy.

Therapy used

If the patient is diagnosed with an ovarian form of pathology, she is prescribed complex therapy using several treatment methods:

• medicinal (based on hormonal treatment with drugs containing the hormone TSH);
• drug therapy traditional medicine;
• diet therapy.

If patients are diagnosed with a tumor of the ovaries or adrenal glands, surgical treatment is used. Such patients will undergo surgery to remove the tumor and further chemotherapy (if the tumor was malignant).

Conservative treatment methods

The principle of treatment for hyperandrogenism directly depends on the factor that provoked the development of the pathology. In addition, when prescribing therapy, the specialist must take into account the purpose of the therapy: elimination of signs of hirsutism, restoration of reproductive function, etc.
If an excess of androgens is caused by excess weight, then patients are prescribed diet therapy and physical activity in order to reduce body weight.
In addition, women are prescribed drug therapy using drugs of a certain group:

• for increased hair growth, Medroxyprogesterone is prescribed;
• To reduce the level of steroid hormones, patients are prescribed combination contraceptives. This therapy is prescribed only if the woman is not planning a pregnancy;
• steroid production can be suppressed with Ketonozole;
• for symptoms of hirsutism, Spironolactone is prescribed. The course of therapy can last up to 6 months.

When a tumor is detected on the female ovaries, hyperandrogenism cannot be cured using a conservative method. In such cases, surgical intervention is prescribed.

Folk remedies

According to experts, drug treatment Ovarian hyperandrogenism should be combined with taking traditional medicine. Despite the effectiveness of such therapy, it is important to remember that long-term use of medicinal infusions can cause the development of negative consequences. That's why herbal teas are taken only as prescribed by the attending physician.

1. Uterus Borovaya - has a weak therapeutic effect with hyperandrogenism. Therefore, this plant should be used in combination with other herbs. In order for the treatment to be more effective, the course of taking Uterus boron should last at least 6 months. The recipe for preparing this medicinal infusion is simple: pour 1 tbsp into a glass of boiling liquid. spoon of dry herb and let it brew for 60 minutes. Drink a glass in small portions throughout the day. It is important to remember that the shelf life of this medicinal infusion is very short.
2. Licorice root – helps reduce testosterone production in a woman’s body and has a calming effect. To make the treatment more effective, it is better to take licorice root in combination with Maryina root. Mix these ingredients in equal proportions (1 tablespoon each). Pour the resulting mixture with three glasses of boiling water and leave for 10-12 hours. Take 1 tbsp three times a day. spoon of decoction.
3. Dandelion root is actively used not only in the treatment of hyperandrogenism, but also to remove waste and toxins from the body. Grind the dandelion root. After this, 4-5 tbsp. spoons of root pour 1 liter of hot liquid. Simmer over low heat for 30-40 minutes. After the time has passed, let the broth brew for an hour, and then strain thoroughly. Take 1 tbsp. spoons of the product 3-4 times a day.
4. Mint – lowers androgen levels and has a relaxing effect. Add 1 teaspoon of the plant to tea. Pairs perfectly with any type of this drink.
5. Medicinal decoctions are great for helping with hyperandrogenism, but they are by no means a panacea. As a rule, the effect of such therapy is not noticeable immediately, but only 3-4 months after the start of treatment.