Traditional medicine

Ovarian and adrenal hyperandrogenism - how can the female body cope with male hormones? Idiopathic hyperandrogenism. Treatment and symptoms of hyperandrogenism in women Presence of a predisposition to hyperandrogenism in women with metabolic syndrome

– 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 of gynecological pathology is explained by its wide distribution among women of childbearing age (4–7.5% in teenage girls, 10–20% in patients over 25 years old).

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 of cosmetic defects (seborrhea, acne, alopecia, hirsutism, virilization), but also causes disorders of metabolic processes (metabolism of fats and carbohydrates), menstrual and reproductive function (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 with normal levels of 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 medications with androgenic activity.

Symptoms of hyperandrogenism in women

The clinical picture of hyperandrogenism in women depends on the severity of the disorders. In non-tumor hyperandrogenism, such as PCOS, clinical signs slowly progress 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 on 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 with dysfunction of the pituitary gland is accompanied by a high degree of virilization and massive obesity of the android type. High androgen activity contributes 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 an increased level of DHEA-S, and ovarian hyperandrogenism is 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.

With ovarian hyperandrogenism, a woman’s hormonal levels are assessed: 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 are estrogen-gestagen oral contraceptives with an 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 of subclinical hypothyroidism, hyperprolactinemia and other disorders is carried out. To treat women with hyperinsulism and obesity, insulin sensitizers (metformin) and weight loss measures (hypocaloric diet, physical activity) are used. 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 if they are identified, surgical removal is mandatory. 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.

Hyperandrogenism in women is a condition in which an increased level of androgens is determined in the blood, and clinical data of an excess of male sex hormones are also recorded.

Occurs in different age groups. The main causes of hyperandrogenism are adrenogenital syndrome (AGS) and polycystic ovary syndrome (PCOS). Treatment of hyperandrogenism is aimed at correcting hormonal levels and preventing the consequences of excess androgens. Normally, a woman’s hormonal status allows for a certain level of androgens in the blood. From them, under the influence of aromatase, some estrogens are formed.

Excessive amounts lead to reproductive dysfunction and increase the risk of cancer. There is no classification of this syndrome in ICD-10, since it is not a disease.

What is it?

Causes

Hyperandrogenism is a manifestation of a wide range of syndromes. Experts name the three most likely causes of hyperandrogenism:

increased levels of androgens in blood serum;
conversion of androgens into metabolically active forms;
active utilization of androgens in target tissues due to abnormal sensitivity of androgen receptors.

Excessive synthesis of male sex hormones is usually associated with ovarian dysfunction. The most common is polycystic ovary syndrome (PCOS) - the formation of multiple small cysts against the background of a complex of endocrine disorders, including pathologies of the thyroid and pancreas, pituitary gland, hypothalamus and adrenal glands. The incidence of PCOS among women of fertile age reaches 5–10%.

Androgen hypersecretion is also observed in the following endocrinopathies:

adrenogenital syndrome;
congenital adrenal hyperplasia;
galactorrhea-amenorrhea syndrome;
stromal thecomatosis and hyperthecosis;
virilizing tumors of the ovaries and adrenal glands that produce male hormones.

Hyperandrogenism due to the transformation of sex steroids into metabolically active forms is often caused by various disorders of lipid-carbohydrate metabolism, accompanied by insulin resistance and obesity. Most often, testosterone produced by the ovaries is transformed into dihydrotestosterone (DHT), a steroid hormone that stimulates sebum production and the growth of body hair, and in rare cases, scalp hair loss.

Compensatory hyperproduction of insulin stimulates the production of ovarian cells that produce androgens. Transport hyperandrogenism is observed with a lack of globulin that binds the free fraction of testosterone, which is typical for Itsenko-Cushing syndrome, dyslipoproteinemia and hypothyroidism. With a high density of androgen receptor cells in the tissues of the ovaries, skin, hair follicles, sebaceous and sweat glands, symptoms of hyperandrogenism can be observed with normal levels of sex steroids in the blood.

The severity of symptoms depends on the cause and form of endocrinopathy, concomitant diseases and individual characteristics.

The likelihood of manifestation of pathological conditions associated with the hyperandrogenism symptom complex depends on a number of factors:

hereditary and constitutional predisposition;
chronic inflammatory diseases of the ovaries and appendages;
miscarriages and abortions, especially in early youth;
metabolic disorders;
excess body weight;
bad habits – smoking, alcohol and drug abuse;
distress;
long-term use of medications containing steroid hormones.

Idiopathic hyperandrogenism is congenital or occurs in childhood or puberty for no apparent reason.

Classification

Depending on the cause, level and mechanism of development of the pathology, the following types of hyperandrogenism are distinguished.

Ovarian. Characterized by disorders of genetic or acquired origin. Ovarian hyperandrogenism is characterized by rapid development and sudden onset of symptoms. In the ovaries, androgens are converted to estrogens by the enzyme aromatase. If its functioning is disrupted, a deficiency of female sex hormones and an excess of male hormones occurs. In addition, ovarian hyperandrogenism can be provoked by hormonally active tumors of this localization.
Adrenal. This hyperandrogenism is caused by adrenal tumors (most often androsteromas) and adrenogenital syndrome. The latter pathology is caused by genetic abnormalities of the gene that is responsible for the formation of the enzyme C21-hydroxylase. The deficiency of this substance over a long period of time can be compensated by the work of other hormone-producing organs, so the condition has a hidden course. With psycho-emotional stress, pregnancy and other stress factors, the enzyme deficiency is not covered, so the AGS clinic becomes more obvious. Adrenal hyperandrogenism is characterized by ovarian dysfunction and menstrual irregularities, lack of ovulation, amenorrhea, and insufficiency of the corpus luteum during egg maturation.
Mixed. A severe form of hyperandrogenism combines ovarian and adrenal dysfunction. The trigger for the development of mixed hyperandrogenism is neuroendocrine disorders and pathological processes in the hypothalamus. It manifests itself as disorders of fat metabolism, often infertility or miscarriage.
Central and peripheral. Associated with dysfunction of the pituitary gland and hypothalamus, disruption of the nervous system. There is a deficiency of follicle-stimulating hormone, which impairs the maturation of follicles. As a result, androgen levels increase.
Transport. This form of hyperandrogenism is based on a deficiency of globulin, which is responsible for binding sex steroids in the blood and also blocks excessive testosterone activity.

Based on the site of origin of the pathology, the following types of hyperandrogenism are distinguished:

primary - originates in the ovaries and adrenal glands;
secondary - the center of origin in the pituitary gland.

According to the method of development of pathology, the following are distinguished:

hereditary;
acquired.

According to the degree of concentration of male hormones, hyperandrogenism occurs:

relative - the level of androgens is normal, but the sensitivity of target organs to them is increased, and male sex hormones tend to convert into active forms;
absolute - the permissible norm for androgen content is exceeded.

Symptoms

Symptoms of hyperandrogenism in women can range from mild (excessive body hair growth) to severe (development of secondary male sexual characteristics).

The main manifestations of pathological disorders are:

acne – occurs when the skin is too oily, which leads to blockage and inflammation of the sebaceous glands;
seborrhea of the scalp;
hirsutism - the appearance of heavy hair growth in places atypical for women (face, chest, abdomen, buttocks);
thinning and loss of hair on the head, the appearance of bald patches;
increased muscle growth, formation of male-type muscles;
deepening of voice timbre;
menstrual irregularities, scant discharge, sometimes complete cessation of menstruation;
increased sexual desire.

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

One of the most severe consequences of hyperandrogenism is virilization or virile syndrome. This is the name for the pathology of the development of the female body, in which it acquires pronounced male characteristics. Virilization is a rare disorder; it is diagnosed in only one patient out of 100 who experience excessive body hair growth.

The woman develops a masculine figure with increased muscle growth, menstruation stops completely, and the size of the clitoris increases significantly. Very often, such signs develop in women who uncontrollably take steroids to increase endurance and physical strength when playing sports.

Hyperandrogenism during pregnancy

Among all the possible causes of spontaneous abortion in a pregnant woman in the first trimester, hyperandrogenism occupies a leading position. Unfortunately, when detecting signs of hyperandrogenism in a woman during an existing pregnancy, it is extremely difficult to determine whether this pathology is congenital or acquired. In this period, determining the genesis of the disease is not so important, since it is necessary to take all measures to maintain pregnancy as a priority.

The phenotypic signs of hyperandrogenism in a pregnant woman are no different from the manifestations of this pathological condition in any other female, with the only difference being that in some situations hyperandrogenism manifests itself in the form of early termination of pregnancy, which is not always regarded by the woman as a miscarriage. The development of spontaneous miscarriage in the early stages is due to insufficient attachment of the fertilized egg to the wall of the uterus and its rejection even with the slightest traumatic influence. A striking clinical manifestation of this condition is the detection of vaginal bleeding, which, by the way, may not be so intense, nagging pain in the suprapubic region and leveling of signs of early toxicosis.

After the 14th week of pregnancy, physiological conditions are created to prevent abortion, since during this period there is an increase in the activity of female sex hormones secreted by the placenta in large quantities.

Another critical period for the threat of miscarriage in a woman suffering from hyperandrogenism is the 20th week of pregnancy, when there is an active release of dehydroepiandrosterone by the fetal adrenal glands, which inevitably provokes increased androgenization of the pregnant woman. A complication of these pathological changes is the development of signs of isthmic-cervical insufficiency, which can provoke the onset of premature delivery. In the third trimester of pregnancy, hyperandrogenism provokes early rupture of amniotic fluid, as a result of which a woman can give birth ahead of schedule.

To determine hyperandrogenism in a pregnant woman, it is advisable to use only laboratory diagnostic methods, which are fundamentally different from the examination of the rest of the category of patients. In order to determine the concentration of male sex hormones, it is necessary to examine the urine of a pregnant woman to determine the “sum of 17-ketosteroids.”

It should be borne in mind that not all cases of detection of signs of hyperandrogenism in a pregnant woman should be subject to drug correction, even if the diagnosis is confirmed by laboratory methods. Drug therapy is used only if there is a threat to pregnancy. The drug of choice for the treatment of hyperandrogenism during pregnancy is Dexamethasone, the initial daily dose of which is ¼ tablet, the action of which is aimed at inhibiting the function of the pituitary gland, which has an indirect effect on the production of male sex hormones. The use of this drug is justified by the complete absence of a negative effect on the development of the fetus with a simultaneous positive effect in terms of leveling the signs of hyperandrogenism.

In the postpartum period, women suffering from hyperandrogenism must be under the supervision of not only a gynecologist, but also an endocrinologist, since this pathological condition tends to progress and provoke serious complications.

Complications

The range of possible complications for all the diseases described above is extremely large. Only a few of the most important ones can be noted:

With congenital pathology, developmental anomalies are possible, the most common of which are anomalies in the development of the genital organs.
Metastasis of malignant tumors is a complication more typical for adrenal tumors.
Complications from other organ systems that are negatively affected by changes in hormonal levels due to pathology of the adrenal glands, pituitary gland and ovaries: chronic renal failure, pathology of the thyroid gland, etc.

With this simple enumeration, the list is far from complete, which speaks in favor of timely consultation with a doctor in order to anticipate their onset. Only timely diagnosis and qualified treatment contribute to achieving positive results.

Diagnostics

In the diagnosis of hyperandrogenism, both complaints, anamnesis and data on the objective status of the patient, as well as laboratory and instrumental research methods, are important. That is, after assessing the symptoms and medical history, it is necessary not only to identify the fact of an increase in the level of testosterone and other male sex hormones in the blood, but also to detect their source - a neoplasm, polycystic ovary syndrome or other pathology.

Sex hormones are examined on days 5-7 of the menstrual cycle. The blood levels of total testosterone, SHBG, DHEA, follicle-stimulating hormone, luteinizing hormone, and 17-hydroxyprogesterone are determined.

To detect the source of the problem, an ultrasound of the pelvic organs is performed (if ovarian pathology is suspected, using a transvaginal sensor) or, if possible, magnetic resonance imaging of the area.

To diagnose an adrenal tumor, the patient is prescribed computed tomography, magnetic resonance imaging or scintigraphy with radioactive iodine. It is worth noting that small tumors (less than 1 cm in diameter) cannot be diagnosed in many cases.

If the results of the above studies are negative, the patient may be prescribed catheterization of the veins that carry blood from the adrenal glands and ovaries in order to determine the level of androgens in the blood flowing directly from these organs.

Treatment of hyperandrogenism in women

The main method of treating hyperandrogenism in women is taking estrogen-progestin oral contraceptives with an antiandrogenic effect, for example, Diane 35. The drugs slow down the synthesis of gonadotropins, suppress the secretion of ovarian hormones and normalize the menstrual cycle. Sometimes gestagenic agents, such as Utrozhestan, are used.

Other treatment principles:

If oral contraceptives are contraindicated for a woman, they are replaced with Spironolactone or Veroshpiron. They are used in severe premenstrual syndrome and polycystic ovary syndrome to block the intracellular dihydrotestosterone receptor and suppress testosterone synthesis.
Androgenization in women with adrenogenital syndrome is treated with glucocorticoids such as Dexamethasone and Prednisolone.
In case of hypothyroidism or high prolactin levels, the concentration of these substances is directly adjusted. The amount of androgens in this case normalizes itself.
For hyperinsulism and obesity, take the hypoglycemic drug Metformin, follow a diet and exercise.
Benign neoplasms of the ovaries or adrenal glands are an indication for surgical intervention.
To normalize the menstrual cycle, Duphaston is often used. It is taken even after pregnancy to reduce the risk of miscarriage.
Renin-angiotensin blockers (Valsartan) and ACE inhibitors (Ramipril, Perindopril) help eliminate arterial hypertension.

The form of hyperandrogenism also influences the treatment regimen. The patient may need help to combat hirsutism, reproductive dysfunction, or complete infertility. The goal of treatment in pregnant women who are at risk of miscarriage is to maintain the pregnancy.

Prevention

Hyperandrogenism has no specific preventive measures.

The main ones include adherence to a proper diet and lifestyle. Every woman needs to remember that excessive weight loss contributes to hormonal imbalances and can lead to both the described condition and many others. In addition, you should not get involved in sports, which also (especially when taking steroid drugs) can lead to hyperandrogenism.

Rehabilitation is required for patients with hyperandrogenism of tumor origin who have undergone surgical and chemotherapy treatment. In addition, consultation with a psychologist is mandatory, especially for young girls with severe hirsutism and gynecological problems.

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

Endocrinological Research Center of the Russian Academy of Medical Sciences, 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 for 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, and an increased risk of developing 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 heart disease.

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 was 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. A relatively low level of 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 of muscle tissue by increasing the number of type II muscle fibers, which are less sensitive to insulin compared to type I 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. The 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 insulin administration to women with PCOS increased circulating levels of 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 of healthy women, women with PCOS, 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 direct action of insulin/IGF-1 on steroidogenic enzymes, synergism between insulin and LH/FSH, and effects on the number of LH receptors.

Insulin/IGF-1, acting synergistically with FSH, stimulates aromatase activity in granulosa cell culture and thereby increases 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.

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

Moller et al. found that phosphorylation of human serine P450c17, a key enzyme 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 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 the resulting primary or secondary infertility, hirsutism, acne; 40% of patients have obesity of varying severity. A gynecological examination reveals a bilateral increase in the size of the ovaries, often against the background of a hypoplastic uterus.

Hormonal research methods play an important role in the diagnosis of PCOS. , aimed at identifying hyperandrogenism, its source and determining the level of gonadotropic hormones: LH and FSH. 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 more than 25 and WC/TB more than 0.85, as well as dyslipidemia.

Treatment

The modern approach to the pathogenetic treatment of PCOS is based on 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 gestagenic components derived from 19-norsteroids (norethisterone, levonorgestrel), which have androgenic effects to varying degrees, and therefore the use 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.

The most effective means of stimulating ovulation in PCOS is an anti-estrogenic drug clomiphene citrate . The main effects of antiestrogens are a decrease in pituitary hypersensitization to the action of GnRH, a decrease in LH production, induction of 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 functional diagnostic tests, but not 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 of 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 the reuptake of 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 of various drugs 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).

If conservative therapy is ineffective, after a year the question of surgical treatment can be raised - laparoscopy with wedge resection of the ovaries or their laser vaporization . The effectiveness of surgical treatment is high (up to 90-95% 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 5th ed. 1994.

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

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

Ethinyl estradiol + cyproterone acetate

Diane-35 (trade name)

(Shering AG)

Hyperandrogenism is an increase in the concentration of male sex hormones in women. Hyperandrogenic disorders can be explained by excessive secretion of androgens by the ovaries or adrenal glands.

General symptoms of hyperandrogenism

Characteristic signs of hyperandrogenism can range from mild unwanted excess hair growth and acne to alopecia (baldness), excessive hirsutism, masculinization and virilization. Hirsutism is characterized by male-like hair growth, which is associated with the transformation of vellus hair into terminal hair in areas such as the face, chest, abdomen, and upper thighs. Signs of masculinization include loss of body fat and a decrease in breast size. Virilization consists of the addition of temporal baldness, a decrease in the timbre of the voice and an enlargement of the clitoris in response to any previous excessive influence of the male hormone during hyperandrogenism in women.

Hyperandrogenic disorders are divided into functional and neoplastic adrenal or ovarian disorders.

Causes of hyperandrogenism

Diseases of the adrenal glands: adrenal hyperplasia; Cushing's syndrome; adenoma, adrenal carcinoma.
Ovarian diseases: polycystic ovary syndrome; HAIR-AN syndrome.
Ovarian tumors: Sertoli-Leydig cells; chyle cells; lipoid cell tumors.
Idiopathic hirsutism.

Congenital adrenal hyperplasia

CAH is a general term used to describe various disorders resulting from congenital adrenal enzyme deficiency accompanied by oversynthesis of steroids. The most common cause of CAH is 21-hydroxylase deficiency. CAH is represented by a spectrum of disorders, ranging from severe forms of salt wasting to virilization and non-classical CAH. Both salt wasting and simple virilization are called classic forms of hyperandrogenism in women because their symptoms (eg, salt wasting or hermaphroditic genitalia in newborn girls) are noticeable at birth or occur shortly thereafter. On the other hand, there is a non-classical form called late-onset, usually manifesting at puberty or later. Such patients do not have genital abnormalities due to hyperandrogenism, but may develop hirsutism, acne, as well as ovulatory and menstrual disorders.

Since 21-hydroxylase is responsible for converting 17-hydroxyprogesterone to 11-deoxycortisol, its deficiency leads to excessive accumulation of 17-hydroxyprogesterone. As a result, an increase in 17-hydroxyprogesterone in the blood is detected, as well as an increase in the synthesis of androstenedione and testosterone in the D4 metabolic pathway. The disease hyperandrogenism is inherited in an autosomal recessive manner.

Cushing's syndrome

Another serious disease of the adrenal glands that leads to excessive androgen production and hyperandrogenism is Cushing's syndrome, or persistent hypercortisolism. Characteristic Cushingoid signs include trunk obesity, moon face, hypertension, tendency to bruise, impaired glucose tolerance, loss of muscle mass, osteoporosis, stretch marks on the skin of the abdomen, fat deposition in the supraclavicular region and on the back of the neck. Other signs may be detected: hirsutism, acne, irregular menstruation. This disorder can develop with a cortisol-producing adrenal tumor or an ACTH-producing pituitary adenoma (Cushing's disease). It may be a rare cause of menstrual dysfunction in women with hyperandrogenism.

Adrenal tumors

Adrenal tumors leading to hyperandrogenism, in the absence of symptoms and signs of excess glucocorticoids, occur extremely rarely. Adenomas that synthesize only androgens tend to secrete large amounts of DHEAS. Adrenal carcinoma can synthesize large amounts of glucocorticoids.

Polycystic ovary syndrome

About 6% of women of reproductive age suffer from PCOS. This is a chronic disease characterized by anovulation or oligoovulation with clinical or laboratory signs of hyperandrogenism, as well as the absence of symptoms of any other pathological condition. As a rule, it develops during puberty. There is a hereditary predisposition to PCOS. First generation relatives are more likely to develop PCOS.

The most common symptoms of PCOS are: hirsutism (90%), menstrual irregularities (90%) and (75%). Women who have used combined hormonal contraceptives for most of their lives and women of Asian descent are less likely to experience hirsutism. Many patients with PCOS suffer from abdominal obesity, and the prevalence of hyperandrogenism varies widely depending on the woman's country of origin. In the United States, the prevalence of obesity is highest among women with PCOS (about 60%).

In the ovaries of most patients, many inactive follicular cysts are found with delayed follicular development at the mid-antral stage. Cysts are localized in the peripheral part of the ovarian cortex. The ovarian stroma is hyperplastic and usually contains islands of luteinized theca cells that produce androgens. In approximately 20% of women with normal hormonal status, polycystic ovary syndrome can also be detected.

Hyperandrogenism in women with PCOS occurs as a result of excessive synthesis of male sex hormones by the ovaries and often the adrenal glands. The pathophysiological basis of hyperandrogenism in PCOS is unknown. Patients exhibit an increased frequency of lutropin release, usually leading to an increase in the concentration of this hormone in the bloodstream. This is probably due to increased secretion of GnRH by the hypothalamus and increased sensitivity of the pituitary gland to it.

An increase in lutropin content promotes the secretion of androgens by theca cells, which increases the concentration of androstenedione and testosterone produced by the ovary. This in turn causes atresia of many developing follicles and often prevents the development of the dominant or preovulatory follicle. The conversion of androgens to estrogens during hyperandrogenism in the periphery leads to an increase in the concentration of estrogens (compared to that at the beginning of the follicular phase), suppressing the release of FSH from the pituitary gland. All this causes a disruption in the normal functioning of the ovary, so in the middle of the cycle there is no release of lutropin and anovulation occurs with hyperandrogenism in women. In some patients suffering from PCOS, excess androgen synthesis is detected by both the adrenal glands and the ovaries. The mechanism for the development of excess production of androgens by the adrenal glands in PCOS is unknown.

In PCOS, there is a relationship between abnormal androgen production, insulin resistance, and hyperinsulinemia. In approximately 60-70% of patients with PCOS, sensitivity to insulin decreases and hypersecretion occurs. Hyperinsulinemia is associated with direct stimulation of insulin production by theca cells, which leads to androgen secretion. Increased concentrations of androgens and insulin in PCOS also contribute to a decrease in the liver's synthesis of sex hormone-binding globulin and its secretion. In this case, the content of free testosterone may increase significantly, although the increase in the concentration of total testosterone will be moderate or insignificant. Thus, the severity of somatic symptoms of hyperandrogenism in PCOS depends on the content of total testosterone.

In the long term, insulin resistance associated with PCOS may lead to an increased risk of metabolic syndrome in women with hyperandrogenism (diabetes and heart disease). The action of estrogens during hyperandrogenism can lead to endometrial hyperplasia, and sometimes to endometrial cancer.

The diagnosis of PCOS continues to be somewhat uncertain due to inconsistency in diagnostic criteria. PCOS is considered a diagnosis of exclusion. Moreover, it is a syndrome, not a specific and easily diagnosed disease. The European Society of Human Reproduction and Embryology defines PCOS as a syndrome in which patients experience irregular ovulation, usually accompanied by oligomenorrhea, hyperandrogenism, or polycystic ovaries, after excluding other causes of these symptoms.

Hyperandrogenic insulin resistance with acanthosis nigricans syndrome

Hyperandrogenism with acanthosis nigricans syndrome (HAIR-AN syndrome) is a hereditary hyperandrogenic disorder characterized by severe insulin resistance, different from that of PCOS. In HAIR-AN syndrome, extremely high concentrations of circulating insulin are found (basal content - more than 80 IU / ml, after oral glucose - more than 500 IU / ml), associated with severe insulin resistance. Since insulin is a hormone with mitogenic activity, its extremely high content leads to hyperplasia of the basal layer of the epidermis of the skin, which causes the development of acanthosis nigricans - hyperpigmentation of skin folds. In addition, as a result of the action of insulin on the theca cells of the ovaries, many patients with HAIR-AN syndrome exhibit their hyperplasia. Patients with this disease may develop severe hyperandrogenism and even virilization. In addition, these women are at significant risk of developing dyslipidemia, type 2 diabetes, hypertension, and cardiovascular diseases. Such patients are especially difficult to treat, although the use of long-acting GnRH analogues is considered promising.

Ovarian neoplasms

Androgen-producing ovarian tumors occur in approximately one in 500 women with hirsutism. They include Sertoli-Leydig cells, chyle and lipoid cells. Virilization in hyperandrogenism is accompanied by hyperplasia of the stroma of surrounding non-hormone-producing ovarian tumors. These tumors include cystic teratomas, Brenner tumors, serous cystadenomas and Krukenberg tumors.

Idiopathic hirsutism

In some women, hirsutism is mild or moderate and is not accompanied by an increase in the concentration of androgens in the blood. This condition is called idiopathic hirsutism, also erroneously referred to as “constitutional hirsutism.” Idiopathic hirsutism with hyperandrogenism in women can develop due to increased tissue conversion of testosterone into the biologically more active DHT. Almost all diseases that lead to hirsutism (for example, PCOS, HAIR-AN syndrome or CAH) are hereditary. True hirsutism is rarely constitutional and almost always indicates a predominantly androgenic disorder in women.

Diagnostics

History: Functional disorders such as PCOS or late-onset CAH usually first appear during puberty and tend to progress slowly. In such disorders, symptoms of excessive androgen influence develop after several years. In contrast, tumor diseases can occur at any time. More often they develop after puberty and begin suddenly. Hyperandrogenism progresses at a rapid pace, and is often preceded by virilization. Sometimes a combination with functional disorders is recorded. Thus, 15% of patients with HAIR-AN syndrome exhibit symptoms of virilization due to hyperandrogenism, in particular severe hirsutism, temporal baldness, and even some enlargement of the clitoris.

Physical examination

The severity of hyperandrogenism, hirsutism, acne or androgenetic alopecia should be assessed and the thyroid gland should be palpated. Patients should be actively questioned about excessive facial hair, as they may be hiding hirsutism by regularly waxing and may be embarrassed to volunteer information. Pay attention to Cushingoid signs. Acanthosis nigricans often indicates insulin resistance and hyperinsulinemia. Using a bimanual gynecological examination, it is possible to detect enlarged ovaries with hyperandrogenism in women. Asymmetrical enlargement associated with rapid onset of virilization may indicate a rare androgen-producing tumor.

Laboratory tests for hyperandrogenism

Laboratory testing in patients with virilization and/or severe hirsutism is performed mainly to exclude serious diseases.

Measuring the basal concentration of 17-hydroxyprogesterone helps exclude 21-hydroxylase deficiency in CAH. When the content of this hormone is more than 2 ng/ml, the ACTH stimulation test, which determines the concentration of 17-hydroxyprogesterone, is considered the main diagnostic method. If Cushing's syndrome is suspected, either a measurement of daily urinary free cortisol or a dexamethasone suppression test should be performed. The last test for hyperandrogenism is to take 1 mg of dexamethasone orally at night, followed by determining the concentration of cortisol in the blood on an empty stomach at 8 a.m. (the normal value is less than 5 g/dL).

Measuring prolactin and TSH levels allows us to exclude hyperprolactinemia and thyroid dysfunction. For patients with subtle signs of hyperandrogenism, assessing the concentration of total and free testosterone and DHEAS in the blood may be useful. A DHEAS content of more than 7000 ng/ml or total testosterone of more than 200 ng/dl gives reason to suspect an androgen-producing tumor of the adrenal glands or ovaries. However, the best indicator of this disease, no matter how rare it is, is clinical symptoms. Signs of virilization are present in 98% of patients with tumors, regardless of the concentration of testosterone in hyperandrogenism in women.

A pelvic examination to exclude an ovarian tumor should be performed for any risk factors. Androgen-producing adrenal tumors can be detected using CT or MRI. If clinical or laboratory results indicate an androgen-producing tumor in hyperandrogenism and its localization cannot be determined using tomographic methods, selective venous catheterization and measurement of androgen concentrations in venous blood from each adrenal gland and ovary are performed.

In patients suffering from PCOS and HAIR-AN syndrome, metabolic status should be assessed. Although measuring glucose levels in hyperandrogenism is sufficient for mass screening for diabetes, in patients with PCOS, glucose tolerance should be determined for a thorough check. In persons over 35 years of age, young patients with signs of metabolic disorders (for example, with HAIR-AN syndrome), the concentration of lipids in the blood should be determined.

Treatment

When choosing treatment for hyperandrogenism, one should be guided by the etiology of the disease, the severity of clinical symptoms and the wishes of the patient. In rare cases, if there is a tumor of the ovaries or adrenal glands, surgical removal is recommended. In premenopausal women with an ovarian tumor, unilateral salpingo-oophorectomy (removal of the ovary and fallopian tube) is sufficient, which allows preserving reproductive function. Treatment for postmenopausal women consists of total abdominal hysterectomy and bilateral salpingo-oophorectomy. In patients with Cushing's syndrome, surgical removal of the source (adrenal or pituitary tumor) that is excessively producing cortisol or ACTH is performed.

Of course, PCOS is the most common functional ovarian disease causing hyperandrogenism, and the management of PCOS depends on the patient’s description of the disease and his wishes. Treatment of hirsutism in patients with PCOS involves suppressing ovarian function. This is usually achieved by taking combined OCs. When treated with estrogens and progesterone, the release of gonadotropins (FSH and lutropin) is suppressed, which helps reduce the overproduction of testosterone and androstenedione by the ovaries. Estrogens also stimulate the synthesis of sex hormone binding globulin, which reduces the concentration of free testosterone.

For the effective treatment of hirsutism with hyperandrogenism, androgen blockers are additionally prescribed. Spironolactone is the most commonly used drug to treat hyperandrogenism and hirsutism in women in the United States. This aldosterone antagonist binds competitively to testosterone, exerting a direct antiandrogenic effect on target tissues. In addition, spironolactone affects steroid enzymes and reduces testosterone production. Since this drug for hyperandrogenism in women is an aldosterone antagonist, it is possible to increase the concentration of potassium in the blood. Other drugs that block the binding of androgens to their receptors include flutamide and cyproterone, while finasteride inhibits the conversion of testosterone to its more active metabolite, DHT. Cosmetic improvement may take up to 6 months to achieve, with maximum effect occurring within two years.

Suppressing excess androgen production or action usually prevents further hair growth, but the cause of hirsutism does not disappear immediately. To obtain a good cosmetic result for hyperandrogenism, removal of unwanted hair in some areas in combination with biochemical treatment is usually required. Topical treatments for hyperandrogenism include shaving, hair removal cream, electrolysis, and laser hair removal. Individual hairs should not be removed as this may stimulate the development of surrounding hair follicles.

All patients suffering from hyperandrogenism, PCOS and chronic anovulation are at risk of endometrial cancer. That is why, when treating women who are not taking combined OCs, discontinuation of progestin-inducing agents should always be planned to protect the endometrium and reduce risk. For these purposes, it is recommended to take oral medroxyprogesterone at a dose of 10 mg daily, micronized progesterone 100 mg 2 times a day or norethindrone 5 mg daily 12-14 days every other month.

Insulin resistance and hyperandrogenism in many PCOS patients may influence the risk of diabetes and possibly cardiovascular disease. Women with PCOS tend to have higher cholesterol. In addition, they are at high risk of developing arterial hypertension due to hyperandrogenism. Therefore, patients with PCOS and chronic anovulation should be advised on weight loss, nutrition, physical activity and other lifestyle changes to reduce the risk of diabetes.

Patients with functional adrenal hyperandrogenism (eg, CAH) are prescribed glucocorticoids (eg, dexamethasone 0.25 mg at bedtime every other day). Many of these women also require medications that suppress ovarian androgen secretion. For this purpose, combined OCs and antiandrogens are prescribed.

The article was prepared and edited by: surgeon

Hyperandrogenism is a general designation for a number of endocrine pathologies of different etiologies, characterized by excessive production of male hormones - androgens in a woman’s body or increased susceptibility to steroids on the part of target tissues. Most often, hyperandrogenism in women is first diagnosed at reproductive age - from 25 to 45 years; less often in girls in adolescence.

Source: klinika-bioss.ru

To prevent hyperandrogenic conditions, women and adolescent girls are recommended to have preventive examinations by a gynecologist and screening tests to monitor androgen status.

Reasons

Hyperandrogenism is a manifestation of a wide range of syndromes. Experts name the three most likely causes of hyperandrogenism:

increased levels of androgens in blood serum;
conversion of androgens into metabolically active forms;
active utilization of androgens in target tissues due to abnormal sensitivity of androgen receptors.

Androgen hypersecretion is also observed in the following endocrinopathies:

adrenogenital syndrome;
congenital adrenal hyperplasia;
galactorrhea-amenorrhea syndrome;
stromal thecomatosis and hyperthecosis;
virilizing tumors of the ovaries and adrenal glands that produce male hormones.

The severity of symptoms depends on the cause and form of endocrinopathy, concomitant diseases and individual characteristics.

The likelihood of manifestation of pathological conditions associated with the hyperandrogenism symptom complex depends on a number of factors:

hereditary and constitutional predisposition;
chronic inflammatory diseases of the ovaries and appendages;
miscarriages and abortions, especially in early youth;
metabolic disorders;
excess body weight;
bad habits – smoking, alcohol and drug abuse;
distress;
long-term use of medications containing steroid hormones.

Idiopathic hyperandrogenism is congenital or occurs in childhood or puberty for no apparent reason.

Species

In gynecological practice, there are several types of hyperandrogenic conditions, which differ from each other in etiology, course and symptoms. Endocrine pathology can be either congenital or acquired. Primary hyperandrogenism, not associated with other diseases and functional disorders, is caused by disorders of pituitary regulation; secondary is a consequence of concomitant pathologies.

Based on the specifics of manifestation, absolute and relative types of hyperandrogenism are distinguished. The absolute form is characterized by an increase in the level of male hormones in a woman’s blood serum and, depending on the source of androgen hypersecretion, is divided into three categories:

ovarian, or ovarian;
adrenal, or adrenal gland;
mixed - signs of the ovarian and adrenal forms are simultaneously present.

Relative hyperandrogenism occurs against the background of normal levels of male hormones with excessive sensitivity of target tissues to sex steroids or increased transformation of the latter into metabolically active forms. A separate category includes iatrogenic hyperandrogenic conditions that develop as a result of prolonged use of hormonal drugs.

The rapid development of signs of virilization in an adult woman gives reason to suspect an androgen-producing tumor of the ovary or adrenal gland.

Symptoms of hyperandrogenism

The clinical picture of hyperandrogenic conditions is characterized by a wide variety of manifestations that fit into a standard set of symptoms:

menstrual dysfunction;
metabolic disorders;
androgenic dermopathy;
infertility and miscarriage.

The severity of symptoms depends on the cause and form of endocrinopathy, concomitant diseases and individual characteristics. For example, dysmenorrhea manifests itself especially clearly with hyperandrogenism of ovarian origin, which is accompanied by abnormalities in the development of follicles, hyperplasia and uneven exfoliation of the endometrium, and cystic changes in the ovaries. Patients complain of scanty and painful menstruation, irregular or anovulatory cycles, uterine bleeding and premenstrual syndrome. In galactorrhea-amenorrhea syndrome, there is a deficiency of progesterone.

Severe metabolic disorders - dyslipoproteinemia, insulin resistance and hypothyroidism are characteristic of primary pituitary and adrenal forms of hyperandrogenism. In approximately 40% of cases, patients are found to have abdominal obesity of the male type or with an even distribution of adipose tissue. With adrenogenital syndrome, an intermediate structure of the genitals is observed, and in the most severe cases, pseudohermaphroditism. Secondary sexual characteristics are weakly expressed: in adult women, there is underdevelopment of the breasts, a decrease in the timbre of the voice, an increase in muscle mass and body hair; For girls, late menarche is typical. The rapid development of signs of virilization in an adult woman gives reason to suspect an androgen-producing tumor of the ovary or adrenal gland.

Androgenic dermopathy is usually associated with increased dihydrotestosterone activity. The effect of a hormone that stimulates the secretory activity of the skin glands changes the physicochemical properties of sebum, causing blockage of the excretory ducts and inflammation of the sebaceous glands. As a result, 70–85% of patients with hyperandrogenism have signs of acne - acne, enlarged skin pores and comedones.

Hyperandrogenic conditions are one of the most common causes of female infertility and miscarriage.

Less common are other manifestations of androgenic dermatopathy – seborrhea and hirsutism. Unlike hypertrichosis, in which there is excess hair growth throughout the body, hirsutism is characterized by the transformation of vellus hair into coarse terminal hair in androgen-sensitive areas - above the upper lip, on the neck and chin, on the back and chest around the nipple, on the forearms, lower legs and inner side of the thigh. In postmenopausal women, bitemporal and parietal alopecia are occasionally observed - hair loss on the temples and in the crown area, respectively.

Source: woman-mag.ru

Features of hyperandrogenism in children

In the pre-pubertal period, girls may develop congenital forms of hyperandrogenism caused by genetic abnormalities or exposure to androgens on the fetus during pregnancy. Pituitary hyperandrogenism and congenital adrenal hyperplasia are recognized by the pronounced virilization of the girl and abnormalities in the structure of the genitals. With adrenogenital syndrome, signs of false hermaphroditism may be present: hypertrophy of the clitoris, fusion of the labia majora and vaginal opening, displacement of the urethra to the clitoris and urethrogenital sinus. At the same time the following are noted:

early overgrowth of fontanelles and epiphyseal fissures in infancy;
premature body hair growth;
rapid somatic growth;
delayed puberty;
late menarche or absence of menstruation.

Congenital adrenal hyperplasia is accompanied by disturbances in water-salt balance, skin hyperpigmentation, hypotension and autonomic disorders. Starting from the second week of life, with congenital adrenal hyperplasia and severe adrenogenital syndrome, the development of adrenal crisis is possible - acute adrenal insufficiency associated with a threat to life. Parents should be alert to a sharp drop in blood pressure to a critical level, vomiting, diarrhea and tachycardia in the child. In adolescence, an adrenal crisis can be triggered by nervous shocks.

Moderate hyperandrogenism in adolescence, associated with a sharp growth spurt, should be differentiated from congenital polycystic ovary syndrome. The debut of PCOS often occurs at the stage of formation of menstrual function.

Congenital hyperandrogenism of adrenal origin in children and adolescent girls can suddenly be complicated by an adrenal crisis.

Diagnostics

Hyperandrogenism in a woman can be suspected by characteristic changes in appearance and based on medical history. To confirm the diagnosis, determine the form and identify the cause of the hyperandrogenic condition, a blood test is performed for androgens - total, free and biologically available testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate (DHEA sulfate), as well as sex hormone binding globulin (SHBG).

In hyperandrogenic conditions of adrenal, pituitary and transport etiology, the woman is referred to an MRI or CT scan of the pituitary gland and adrenal glands. If indicated, blood tests are performed for 17-hydroxyprogesterone and urine tests for cortisol and 17-ketosteroids. Laboratory tests are used to diagnose metabolic pathologies:

tests with dexamethasone and human chorionic gonadotropin;
determination of cholesterol and lipoprotein levels;
blood tests for sugar and glycogen, glucose tolerance test;
tests with adrenocorticotropic hormone.

To improve the visualization of glandular tissue, if a neoplasm is suspected, MRI or CT with the use of contrast agents is indicated.

Treatment of hyperandrogenism

Correction of hyperandrogenism gives lasting results only as part of the treatment of underlying diseases, such as PCOS or Itsenko-Cushing syndrome, and associated pathologies - hypothyroidism, insulin resistance, hyperprolactinemia, etc.

Hyperandrogenic conditions of ovarian origin are corrected with the help of estrogen-progestin oral contraceptives, which suppress the secretion of ovarian hormones and block androgen receptors. For severe androgenic dermopathy, peripheral blockade of receptors in the skin, sebaceous glands and hair follicles is performed.

In the case of adrenal hyperandrogenism, corticosteroids are used; with the development of metabolic syndrome, insulin synthesizers are additionally prescribed in combination with a low-calorie diet and dosed physical activity. Androgen-secreting neoplasms, as a rule, are benign in nature and do not recur after surgical removal.

For women planning a pregnancy, treatment of hyperandrogenism is a prerequisite for restoring reproductive function.

Prevention

To prevent hyperandrogenic conditions, women and adolescent girls are recommended to have preventive examinations by a gynecologist and screening tests to monitor androgen status. Early detection and treatment of gynecological diseases, timely correction of hormonal levels and competent selection of contraceptives successfully prevent hyperandrogenism and help maintain reproductive function.

If you have a tendency to hyperandrogenism and congenital adrenopathy, it is important to adhere to a healthy lifestyle and a gentle regime of work and rest, give up bad habits, limit the influence of stress, lead an orderly sex life, avoid abortions and emergency contraception; Uncontrolled use of hormonal drugs and anabolic drugs is strictly prohibited. Body weight control is of no small importance; Moderate physical activity without heavy physical exertion is preferable.

Most often, hyperandrogenism in women is first diagnosed at reproductive age - from 25 to 45 years; less often in girls in adolescence.

Consequences and complications

Hyperandrogenic conditions are one of the most common causes of female infertility and miscarriage. Long-term hyperandrogenism increases the risk of developing metabolic syndrome and type II diabetes mellitus, atherosclerosis, arterial hypertension and coronary heart disease. According to some data, high androgen activity correlates with the incidence of certain forms of breast cancer and cervical cancer in women infected with oncogenic papillomaviruses. In addition, aesthetic discomfort with androgenic dermopathy has a strong psychotraumatic effect on patients.

Congenital hyperandrogenism of adrenal origin in children and adolescent girls can suddenly be complicated by an adrenal crisis. Due to the possibility of death, at the first signs of acute adrenal insufficiency, the child should be immediately taken to the hospital.

Video from YouTube on the topic of the article:

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

The main types of hyperandrogenism in women

At the moment, depending on the causes of hyperandrogenism, there are two main forms. This is true and others. True ones include ovarian and adrenal hyperandrogenism. They can be functional or tumor in origin.

Functional true hyperandrogenism in women and their causes:

Ovarian hyperandrogenism. Associated with a deficiency of the aromatase enzyme, which ensures the conversion of testosterone into estrogens. As a rule, this is a congenital defect. Mild hyperandrogenism of ovarian origin is often encountered - erased forms (testosterone levels may be normal, ultrasound signs of sclerocystic ovaries may be absent).
Adrenal hyperandrogenism. Associated with a deficiency of the enzyme that converts testosterone precursors. Symptoms of adrenal hyperandrogenism: characterized by significantly increased levels of testosterone and, as a manifestation of this, hirsutism;

Other forms include:

Transport. Associated with deficiency of sex hormone binding globulin (SHBG). This globulin binds and prevents it from entering the target organ cell. SHBG is produced in the liver, its levels depend on the functioning of the thyroid gland and the amount of estrogen.
Metabolic hyperandrogenism. Associated with impaired carbohydrate and fat metabolism. The basis is insulin resistance;
Hyperandrogenism of mixed origin. A combination of various forms and causes causing hyperandrogenism syndrome in women;
Iatrogenic. Occurs as a result of the action of various medications.

Main symptoms of hyperandrogenism

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

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

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

Diagnosis of hyperandrogenism in women

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

Complaints about increased hair growth in places atypical for women, the appearance of acne, infertility, menstrual irregularities, often obesity;
History: manifestations of hyperandrogenism syndromes coincide with the period of puberty and reproductive age;
Examination data: obesity, hirsutism, the above-described skin manifestations;
Hormonal examination data: increased levels of free testosterone, adrenocorticotropic hormone, dehydroepistendinone, prolactin;
Ultrasound data: sclerocystic ovaries, increased volume of the ovaries or their tumors, adrenal tumors;
Decreased levels of sex hormone binding globulin;
Increased insulin levels and impaired glucose tolerance.

Treatment of hyperandrogenism in women

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

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

Dexamethasone is used in the treatment of adrenal hyperandrogenism.

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

Hyperandrogenism syndrome in women associated with increased prolactin levels requires the use of prolactin-lowering drugs (Alactin, Bromocriptine).

Treatment of hyperandrogenism of tumor origin consists of surgical removal of these formations on the ovaries, adrenal glands, and pituitary gland.

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

Hyperandrogenism during pregnancy

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

You have probably paid attention to women who have masculine features in their appearance. This could be a deep voice, the appearance of facial and body hair, a typical male body structure, and the like.

This situation is most often caused by excessive secretion of androgens or their increased effect on the woman’s body. In medicine, such a pathology is defined as hyperandrogenism.

We will look at the symptoms, causes and ways to combat it in this article.

What causes hyperandrogenism?

The described disease is the most common dysfunction of the endocrine system in women. As a result of research, it has been established that 20% of the fairer sex are diagnosed with hyperandrogenism.

In women, this condition is usually caused not only by an excess amount of male sex hormones produced by the ovaries or adrenal glands. Pathology is also provoked by increased conversion of androgen precursors into their even more active form (for example, testosterone becomes dihydrotestosterone, which is 2.5 times more active). The situation is also aggravated by an increase in androgen utilization, driven by the increased sensitivity of the organ (for example, skin) to this hormone.

Some features of the development of hyperandrogenism

Thus, hyperandrogenism in women, the symptoms of which are manifested, in particular, by acne (acne), develops with an increase in sensitivity to androgens in the sebaceous glands. Please note that the level of male sex hormones in the patient’s blood remains normal!

In addition, the development of hyperandrogenism is also influenced by a decrease in the amount of globulin, which binds sex hormones (normally it prevents free testosterone from entering the blood cell and interacting with androgen receptors).

Globulin synthesis occurs in the liver, so dysfunction of this organ can provoke the onset of hyperandrogenism or spur its development. A decrease in the level of estrogen produced by the thyroid gland has the same effect.

Signs of hyperandrogenism in women

Hyperandrogenism can manifest itself as virilization, that is, the appearance of male characteristics in a woman. As a rule, this is expressed in the growth of hair in the chest area, midline of the abdomen, inner thighs and increased hair growth on the face. But at this time, bald patches may appear in the hair on the head (so-called alopecia). In addition, the pathology is often accompanied by cosmetic defects: acne (acne), peeling and inflammation of the skin on the face (seborrhea), as well as atrophy of the abdominal muscles and limbs.

Women with hyperandrogenism are characterized by menstrual irregularities or amenorrhea (absence of menstruation), obesity, hypertension, myocardial hypertrophy and infertility.

In addition to all of the above, women suffering from the described pathology usually have increased susceptibility to various types of infections, a tendency to depression, and increased fatigue.

By the way, remember that this pathology has no age. Hyperandrogenism in women can manifest itself at any period of life, starting from birth.

How is hyperandrogenism diagnosed?

The diagnosis described cannot be made solely on the basis of the patient’s external signs. Even when they seem very eloquent. It is necessary to conduct a number of tests and ultrasound of internal organs. And the key method for diagnosing this pathology is a blood test for the amount of steroids.

Please note that the patient’s condition may also be manifested by the presence of diabetes mellitus, Cushing’s syndrome (which is externally expressed by obesity, a moon-shaped face and thinning of the limbs), polycystic ovary syndrome, adrenal tumors, etc.

As you can see, all this suggests a variety of methods by which hyperandrogenism in women will be diagnosed.

How to distinguish between hirsutism and hypertrichosis?

As mentioned above, one of the earliest and most persistent symptoms of the appearance of the described pathology in women is excess hair growth on the face and body (hirsutism).

But this symptom should not be confused with hypertrichosis - a condition in which hair growth occurs on any part of the body, including where hair growth does not depend on the action of androgens.

And hyperandrogenism syndrome in women provokes the appearance of hair in precisely these places, that is, according to the male type: on the face (beard and mustache), on the chest, inner thighs, on the stomach and lower back, as well as between the buttocks.

A patient with hirsutism is usually offered treatment, which includes both cosmetic measures (hair removal) and hormonal correction.

The effect of androgens on hair growth in women

How is hair growth related to the production of androgens in a woman’s body? The fact is that it is the amount of this hormone that determines how and where hair will grow on a woman’s body. So, during the onset of sexual development, it is under the influence of androgens that a girl develops small amounts of hair under her arms and on her pubic area.

But if the level of hormones begins to exceed the norm, then hair growth will appear on the face, chest, and stomach. And a very high level of androgens causes, in addition, a decrease in hair growth on the head, which is why bald spots appear above the forehead.

Moreover, please note that this hormone does not affect the growth of vellus hair, as well as eyelashes and eyebrows.

How does ovarian hyperandrogenism develop?

In medicine, there are three forms of the described disease: ovarian, adrenal and mixed.

The development of the first form of pathology is caused by a deficiency of enzymes contained in the ovaries (we are usually talking about hereditary pathology). This interferes with the conversion of androgens into female sex hormones - estrogens and, accordingly, causes their accumulation. As a result, the woman develops ovarian hyperandrogenism.

By the way, which androgens (testosterone, DHEA sulfate or androstenedione) will predominate in the patient’s blood directly depends on which enzymes are missing in her body.

How is the functioning of the ovaries impaired?

The ovarian form of the disease is most often characterized by polycystic disease and hyperthecosis (bilateral enlargement) of this organ. By the way, girls involved in strength sports have a high risk of acquiring this pathology.

This occurs because excess androgen levels stunt the growth of the follicles that make up the ovaries, eventually leading to their occlusion (called follicular atresia). In addition, it stimulates the development of pathological formation of fibrous connective tissue (fibrosis) and causes polycystic disease.

According to the feedback principle, this hyperandrogenism syndrome in women leads to a failure in the central regulation of androgen levels (at the level of the pituitary gland and hypothalamus), which, in turn, greatly changes hormonal levels.

Adrenal hyperandrogenism

Now let's talk about adrenal hyperandrogenism. You probably know that the adrenal glands are a pair of small endocrine glands that are located above the kidneys. They, by the way, produce 95% of the androgen called DEA sulfate.

A feature of the pathology of this organ is that adrenal hyperandrogenism in women is most often congenital. It occurs as a result of androgenital syndrome.

This syndrome is caused by the absence of enzymes that promote the production of glucocorticoid hormones, which are normally produced by the adrenal cortex. This leads to the accumulation of their precursors (progesterone, pregnenolone, etc.) in the blood, forcing the body to use them for excess androgen production.

Less common is hyperandrogenism caused by adrenal tumors that secrete androgens (this pathology is called Cushing's disease).

Mixed hyperandrogenism

Mixed hyperandrogenism also occurs periodically in women. The reasons for its occurrence lie in the simultaneous dysfunction of the ovaries and adrenal glands.

Due to the increase in the level of adrenal androgens, their formation in the ovaries also increases, and the increased content of the latter in the blood stimulates the pituitary gland, forcing it to increase the production of luteinizing hormone, which provokes the formation of hyperandrogenic syndrome.

The mixed form also occurs as a result of trauma, pituitary tumors or brain intoxication in a woman.

What are the dangers of hyperandrogenism during pregnancy?

In addition to the problems listed above, the described pathology is dangerous for women who want to conceive and bear a child. For example, hyperandrogenism during pregnancy is the cause of 20 to 40% of miscarriages or fetal deaths that occur in the early stages.

And note that this state of affairs is sad because pregnancy terminations themselves aggravate hormonal disorders. And in this case, against the background of existing hormonal changes, this ultimately leads to the fact that pregnancy becomes impossible in the future.

Prognosis for pregnancy with hyperandrogenism

If a woman turns to a specialist with specific complaints that were listed above, then she will definitely be prescribed an examination to exclude the described pathology.

With correct diagnosis and adequate treatment, hyperandrogenism during pregnancy does not prevent the patient from successfully carrying and giving birth to a child. This is helped by drugs that reduce the level of androgens in the blood. The patient must take them regularly throughout pregnancy.

How is hyperandrogenism treated?

Before starting treatment for hyperandrogenism in women, it is necessary to undergo a detailed examination to identify the type of disease and the reasons that triggered its development.

If a woman does not plan to have a child, then the doctor selects oral contraceptives for the patient, which have an antiandrogenic effect. In the opposite case, drugs are prescribed to stimulate the release of the egg, and sometimes wedge-shaped excision of the ovary is used to help the egg release.

If high levels of androgens are detected, which the body cannot utilize, patients are usually prescribed the drugs Dexamethasone and Metipret, which increase the amount of female hormones in the body.

If the disease is caused by the presence of a tumor, then the patient is indicated for surgical intervention. Polycystic ovary syndrome also forces specialists to do this. As a rule, most of it is removed.

For the adrenal form of the disease, hormonal therapy is used, including glucocorticoid hormones (for example, Dexamethasone). By the way, it is prescribed in a maintenance dose during pregnancy.

Medicines used to treat hyperandrogenism

To improve the condition of the skin in the described disease, the drug “Diane-35” is used, which suppresses the production of androgens by the adrenal glands and ovaries, as well as the release of luteinizing hormone into the woman’s blood by the pituitary gland. At the same time, cyproterone acetate, which is part of the drug, blocks skin receptors sensitive to androgens, preventing them from contacting them.

As a rule, to increase the effectiveness, the named drug is prescribed in combination with Androkur. These drugs help women with severe acne. But their effect can only be assessed 3 months after the start of treatment.

Therapy with antiandrogenic drugs “Yanina” and “Zhanin” is also very effective. Treatment of hyperandrogenism in women with the help of these drugs lasts at least six months. It does not cause weight gain and helps normalize the menstrual cycle.

Are there any folk remedies that help with hyperandrogenism?

There is a fairly wide range of medicinal herbs that are included in the metabolic processes of the female body and have a positive effect on the processes of regulating the balance of hormones.

Of course, with a disease such as hyperandrogenism, treatment with folk remedies is not a panacea at all, but, for example, a remedy such as cohosh (or, in other words, black cohosh) can help in cases of hormonal imbalance. No less effective is the sacred twig, on the basis of which the drug “Cyclodinone” is produced.

However, you can list a whole list of flora representatives that, along with medications prescribed by a specialist, will help regulate hormonal balance: licorice root, mint, angelica, evasive peony, etc. Ready-made collections of such plants are sold in the pharmacy chain and are always ready to alleviate a woman’s condition.

A few final words

Do not try to treat the pathology yourself! If you have been diagnosed with hyperandrogenism, reviews of friends or relatives about any “magic” remedies will not help solve the problem.

Incorrect treatment can have very serious consequences for a woman. Therefore, if you suspect a disease, you must first contact a gynecologist and endocrinologist. Their joint efforts and your patience and perseverance will help stop the development of pathology and prevent irreversible consequences.

Hyperandrogenism syndrome in women is an endocrine pathology that develops due to excessive activity of androgens (male sex hormones) in the body. This deviation occurs as often as pathology of the thyroid gland. There are many factors that can trigger this disease:

Cushing's syndrome (increased levels of hormones in the adrenal cortex);
Thyroid diseases;
Hormone-producing ovarian tumors;
Frenkel's disease (enlarged ovarian stroma);
The effect of hormonal drugs;
Liver diseases that have become chronic;
The presence of hyperandrogenism syndrome in close relatives;
Polycystic ovary syndrome;
A benign tumor of the pituitary gland (prolactinoma), which produces a hormone (prolactin) responsible for breast development and milk production;
Excessive production of androgens by the adrenal glands.

There are 3 types of hyperandrogenism: mixed, adrenal and ovarian. Hyperandrogenism is also divided into primary (impaired functioning of the adrenal or ovarian cortex) and secondary (malfunction of the hypothalamus and pituitary gland), congenital and acquired.

The clinical picture of the disease can be bright or mild. Main symptoms:

Acne is a skin disease caused by inflammation of the sebaceous glands. It is one of the factors in the origin and development of hyperandrogenism syndrome. This disease is typical for the puberty stage of development, therefore signs of acne (red painful acne, blackheads, comedones) are observed in most adolescents. If such skin inflammations do not go away even in adulthood, you should be tested for hyperandrogenism, which, in turn, may be a consequence of polycystic ovary syndrome. In some cases, acne is accompanied by seborrhea (excessive activity of the sebaceous glands in certain areas of the skin), which can be caused by androgens.
Alopecia is the name given to rapid baldness. With androgenetic alopecia, a change in the hair structure occurs. First, the hair becomes very thin and colorless, and then hair loss begins. This sign suggests that hyperandrogenism has been progressing for a long time.
Hirsutism is the appearance of an excessive amount of coarse and dark hair on the face, arms, and chest. This disease is almost always accompanied by infertility and scanty menstruation.

Virile syndrome. Virilization is a rare pathology in which a woman exhibits exclusively male characteristics. The causes of viril syndrome can be a neoplasm on the adrenal glands, adrenoblastoma and ovarian hyperplasia. The following symptoms are observed during virilization:

Irregular menstruation, amenorrhea;
Increased libido;
Acne;
Changing the timbre of the voice;
Increased muscle mass;
Enlargement and swelling of the clitoris;
Excess weight in the upper body;
Alopecia (baldness in the parting area);
Hair growth around the nipples, on the stomach, cheeks.

There are also symptoms that are much less common:

Arterial hypertension;
Obesity;
Diabetes mellitus type 2;
Sensitivity of cell receptors to male hormones.

Hyperandrogenism syndrome can occur at any age. Girls suffering from this disease are prone to depression, overwork and colds. Signs of pathology can also be caused by a lack of estrogens (female sex hormones) and a lack of protein that regulates the activity of androgens.

Diagnostics

Many inexperienced doctors diagnose hyperandrogenism only if there is a large amount of androgens in the body. For this reason, women with hyperandrogenism, whose androgen levels are normal, do not receive timely treatment. As a result, the signs of the disease become more pronounced, and the patient’s health worsens. In most cases, hyperandrogenism syndrome occurs with moderate amounts of androgens.

When diagnosing, they use: laboratory testing of genes, analysis of the concentration of dehydroepiandrosterone sulfate and instrumental examination methods (ultrasound, scintigraphy, CT, MRI), anamnesis (when symptoms first appeared, what medications the woman has taken recently). A clinical examination of the patient is carried out: skin rashes, excessive hair growth, deepening of the voice, body hair structure and gynecological examination (size of the clitoris and labia). At the same time, specialists determine the level of testosterone, follicle-stimulating and luteinizing hormones. But not all women need hormonal testing. With symptoms such as acne and seborrhea, the level of male sex hormones usually does not exceed the norm, so standard procedures will be quite sufficient.

Hirsutism is a more accurate diagnostic indicator of increased activity of male hormones than high levels of testosterone in the blood. The second indicator may be normal even though the signs of the disease have appeared for a long time.

Androgenetic alopecia is considered one of the most important diagnostic criteria. The important fact is that hair falls out first at the temples, and then at the parietal region.

Treatment and prevention

Treatment for a woman is prescribed taking into account the form of hyperandrogenism and the reasons that caused it. If the disease is caused by tumors of the adrenal glands and ovaries, they must be removed surgically. If the cause was not a tumor, but a malfunction in the functioning of the pituitary gland and hypothalamus, then the therapy will depend on the goal that the woman wants to achieve during treatment. These goals may include eliminating symptoms and signs of disease and restoring fertility. If these areas of the brain do not work properly, a woman becomes overweight, so normalizing it is the main stage of treatment. To do this, you need to adjust your diet and exercise.

If a woman is not planning a child, but wants to get rid of the unaesthetic manifestations of hyperandrogenism, she is prescribed antiandrogenic oral contraceptives (Diana is 35).

If the disease occurs due to the absence of an enzyme that transforms male sex hormones into glucocorticoids, drugs such as Metipred and Dexamethasone are prescribed.

If reproductive function is impaired, which is associated with ovarian or adrenal hyperandrogenism, the woman is prescribed drugs that force the egg to release from the ovary (Clomiphene).

If medications do not help completely get rid of the disease, surgical methods are used. The most popular of them is laparoscopy. It is carried out by introducing a special device into the abdominal cavity, which displays an image on the screen. After this, a second incision is made, through which, using surgical instruments, peculiar “notches” are made on the ovaries so that the egg can be released freely.

To prevent the disease, you should visit a gynecologist several times a year, monitor weight fluctuations, adhere to proper nutrition, give up bad habits, treat liver and thyroid diseases in a timely manner, and avoid stressful situations.

Traditional methods of treatment

Traditional methods will not help to completely cure hyperandrogenism syndrome in women, but they are very good as an aid. Here are some of the most effective recipes:

Basil tincture. Add 2 tablespoons to a glass of boiling water, then boil the mixture again, and keep it on low heat for another 10 minutes. After this, cool the broth and strain. You need to take 2-3 times a day, 100 ml.
Infusion of boron uterus. First you need to dry about 50 g of plant leaves. After this, crumble them and mix with 500 ml of vodka. Pour the mixture into a container and leave for a month. The tincture should not be exposed to light. You need to take 35 drops at least 4 times a day.
Licorice tincture. Add one tablespoon of licorice to a container of boiling water (200 ml). Leave the infusion for an hour and then strain. The entire infusion should be drunk on an empty stomach in the morning.
Herbal collection of red brush, motherwort, rowan, nettle, viburnum bark, chamomile, shepherd's purse. Grind all these herbs using a blender and mix. Add 2 tablespoons of the mixture to 500 ml of boiling water and leave to steep for 7–8 hours. You need to drink the tincture in one day. The collection must be consumed for 2–3 months.
Red brush tincture. Add one tablespoon of the peeled plant to a container of boiling water (200 ml). Leave the broth to steep (for one hour), then strain and cool. You need to take the infusion at least three times a day, half an hour before meals.
Collection of red brush and leuzea. Grind the herbs and mix them. Then pour one teaspoon of the mixture into water (one glass). Take the infusion 3-4 times a day half an hour before meals.

Please note that the use of red brush for hypertension is strictly contraindicated. In addition, any independent treatment, including traditional methods, without consulting a doctor can cause serious harm to health.

Hyperandrogenism (or hyperandrogenemia) - This is an increased level of male sex hormones androgens. Androgens are present in varying concentrations in both men and women. Hyperandrogenism in a woman brings many problems. This pathology is the most common cause of amenorrhea (lack of menstruation) and female infertility.

The ovaries in women consist of follicles - eggs, surrounded by layers of cells. Excessive levels of male sex hormones androgens inhibit the growth of follicles and ultimately contribute to their overgrowth (follicular atresia). In addition, it provokes the development of fibrosis of the ovarian capsule (fibrosis is a pathological formation of fibrous connective tissue) and leads them to a state of polycystic disease - the formation of multiple cysts (polycystic ovary syndrome).

To understand this complex topic, you need to remember the following terms:

Hypothalamus - part of the brain, the highest regulatory center that controls metabolism, the functioning of the endocrine and gonads, the place of interaction between the nervous and hormonal systems

Pituitary - the main endocrine gland, located at the base of the brain; under the guidance of the hypothalamus, regulates the action of the hormonal system.

Disorders of central origin - means dysregulation on the part of the brain, that is, on the part of the hypothalamus and pituitary gland. This is manifested by a violation of the release of hormones from the hypothalamus and pituitary gland, which act on the hormonal glands, disrupting the release of their hormones into the blood.

Adrenal glands - a pair of small endocrine glands located above the kidneys and consisting of two layers - the outer cortex and the inner medulla

Test with dexamethasone - administration of the drug followed by laboratory determination of the level of anlrogens in order to determine the source of hyperandrogenism

As well as hormones that are involved in the formation of hyperandrogenic syndrome:

Testosterone, androsterone, androstenedione - male sex hormones, androgens

DEA-sulfate (DEA-S, DEA-S ) - androgen, a hormone that is produced 95% in the adrenal glands and 5% in the ovaries

Estradiol - female sex hormone

Prolactin - pituitary hormone

Follicle stimulating hormone (FSH) - pituitary hormone

Luteinizing hormone (LH) - pituitary hormone

Adrenocorticotropic hormone (ACTH) - pituitary hormone

Cortisol - hormone of the adrenal cortex

17-hydroxyprogesterone - adrenal hormone

17-ketosteroids - a product of androgen metabolism, excreted in the urine; their concentration gives an idea of the concentration of androgens

SSG (sex-binding or steroid-binding globulin) - its function is to transport sex hormones to the organs

What are the reasons for the development of hyperandrogen syndrome? The source of increased androgen production may be

ovaries

adrenal cortex

Therefore, it is customary to distinguish between ovarian hyperandrogenism and adrenal hyperandrogenism.

I. Ovarian hyperandrogenism

The most common cause of ovarian hyperandrogenism is polycystic ovary syndrome. Much less commonly, it can be caused by an ovarian tumor that secretes androgens.

But whatever the origin of the increased level of androgens, it still leads to the development of polycystic ovary syndrome.

A. Polycystic ovary syndrome

It is also called Stein-Leventhal syndrome. It is based on a hereditary deficiency of ovarian enzymes. Androgens, undergoing a number of changes, must turn into the female sex hormones estrogens in a woman’s body. A lack of the enzyme blocks this transformation and, as a result, male sex hormones androgens accumulate in the woman’s body. Estrogen production decreases and this decrease directly depends on the degree of enzyme deficiency. Moreover, which particular androgens will predominate (testosterone, DEA sulfate, androstenedione) depend on which enzyme is missing.

Enzymes, the deficiency of which leads to polycystic ovary syndrome:

19 - hydroxylase (testosterone accumulates)

betaol dehydrogenase (very high levels of DHEA sulfate, androstenedione and less high testosterone)

3-betaol dehydrogenase (less serious changes, levels of female sex hormones estrogen are almost normal)

Violation of the production of female sex hormones in the ovaries according to the feedback principle leads to a failure of central regulation (at the level of the hypothalamus and pituitary gland).

As a result, the following hormonal levels are revealed in patients with Stein-Leventhal syndrome:

high level of androgens (testosterone, androstenedione with a predominance of androstenedione)

an increase in LH levels with normal levels of FSH and prolactin.

the LH/FSH ratio is significantly increased (up to 5 when the norm is less than 1.5)

estradiol levels are the same as in healthy women or reduced

when tested with dexamethasone, the level of 17-ketosteroids in the urine decreases by less than 50%, which confirms the ovarian origin of hyperandrogenism.

B. Ovarian hyperandrogenemia of tumor origin.

Hormonally active ovarian tumors secrete male sex hormones - testosterone, androstenedione, DHEA sulfate. The main manifestation of ovarian tumors that secrete hormones is a high level of testosterone in the blood (10-12 times higher than normal). There is usually no correlation between testosterone levels in the blood and tumor size. When tested with dexamethasone, the content of testosterone in the blood does not change significantly.

The level of the female sex hormone estradiol in the blood is usually normal or reduced. But if the tumor simultaneously secretes both male and female sex hormones, then the estradiol content is increased. The level of pituitary hormones LH and FSH in such patients is within normal limits. Rarely a decrease in FSH is detected. In isolated cases, the FSH content exceeds the norm. Prolactin levels in the blood are often elevated.

II Hyperandrogenism and polycystic ovary syndrome of central origin.

Polycystic ovary syndrome of central origin is caused by increased release of pituitary hormones LH and FSH into the blood. Often, such dysregulation in the brain occurs as a result of acute or chronic infection or intoxication (frequent sore throats, rheumatism, tuberculosis), as well as mental trauma. The LH level in the blood increases, the FSH content may decrease and, as a result, the LH/FSH ratio reaches 3 or more. For the growth and development of follicles and the onset of ovulation (the release of an egg from the ovary), this indicator should not exceed 1.5.

A significant role in the development of polycystic ovary syndrome of central origin has a high level of prolactin, which is found in 30% of patients with this syndrome.

A change in the content of FSH, LH and prolactin leads to impaired ovarian stimulation, as a result, the number of maturing follicles decreases, the production of sex hormones is disrupted - the production of the main male sex hormone testosterone increases and the production of the main female hormone estradiol decreases. Most patients have the following hormonal levels:

slight increase in LH levels

decreased FSH levels

the LH/FSH ratio is 4-5 times higher than normal

Prolactin levels are normal

testosterone levels are increased

estradiol levels are reduced or at the lower limit of normal

the level of DEA sulfate in the blood is within normal limits

III Adrenal hyperandrogenism

Causes of hyperandrogenism of adrenal origin:

adrenogenital syndrome (AGS) is the most common cause

Androgen-secreting adrenal tumors (rare)

Cause of adrenogenital syndrome - lack of enzymes that normally contribute to the production of adrenal hormones (glucocorticoids). Blockade of glucocorticoid production leads to the accumulation in the blood of precursors from which these adrenal hormones are produced (pregnenolone, progesterone, 17-hydroxyprogesterone). The body uses them to produce excess androgens.

Enzymes, the deficiency of which leads to the development of adrenogenital syndrome (AGS):

21-hydroxylase

11-beta-hydroxylase

3-beta-hydroxysteroid dehydrogenase

A block of these enzymes leads to the development of AGS already in childhood. In adult patients, as a rule, there is an incomplete, mild deficiency of enzymes, which does not entail clear manifestations of increased function of the adrenal cortex.

A combination of adrenal and ovarian causes of hyperandrogenism is often observed, because hyperandrogenism itself promotes increased production of androgens in the ovaries due to stimulation of the ovaries by the pituitary hormone LH. This was written about above.

Less common are cases of adrenal hyperandrogenism caused by tumors that secrete adrenocorticotropic hormone (ACTH). This pathology is called Itsenko-Cushing's disease.

For laboratory diagnosis of adrenal hyperandrogenism, the following hormones are prescribed:

Testosterone

Androsterone

DEA-sulfate (DEA-S, DEA-S

FSH

ACTH

Cortisol

17-hydroxyprogesterone

SSG

DEA sulfate is synthesized 95% in the adrenal glands and only 5% in the ovaries. Therefore, determining it in the blood will reveal the origin of androgens. A similar diagnostic function is performed by the determination of 17-hydroxyprogesterone. In addition, a test with dexamethasone is prescribed. Dexamethasone suppresses the release of ACTH from the pituitary gland, which means it turns off the stimulating effect of ACTH on the production of hormones in the adrenal cortex. Therefore, if androgens are of adrenal origin, laboratory diagnostics will reveal a drop in androgen levels in the blood.

IV Mixed form of hyperandrogenism and polycystic ovary syndrome.

A combination of ovarian and adrenal causes of hyperandrogenism is often found. An increased level of adrenal androgens entails increased formation of androgens in the ovaries. And the high content of ovarian androgens in the blood stimulates the pituitary gland to increased production of luteinizing hormone (LH). For those who want to understand the process more deeply, I will explain that it is not the high level of androgens itself that leads to an increase in LH. From androgens in the process of metabolism (especially in adipose tissue) female sex hormones estrogens are formed and it is their excess (especially one of them - the hormone estrone) that leads to stimulation of the pituitary gland and the release of LH.

Laboratory diagnosis of the combined form of polycystic ovary syndrome involves the study of a wide range of hormones:

testosterone

androsterone

DEA sulfate

prolactin

FSH

ACTH

cortisol

17-hydroxyprogesterone

17-ketosteroids

SSG

The level of LH in the blood is elevated, but its increase is less pronounced than in patients with Stein-Leventhal syndrome (polycystic ovary syndrome). FSH content is reduced. The LH/FSH ratio averages 3.2, with the norm being less than 1.5. Prolactin levels are normal. Testosterone levels are moderately increased and estradiol levels are decreased. The content of 17-CS in the urine and the level of DEA sulfate in the blood are increased. Determination of DHEA sulfate allows one to differentiate the origin of androgens (adrenal glands or ovaries).

Hyperandrogen syndrome in women is the main cause of hair loss and acne (rosacea).

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