R.A.MANUSHAROVA, Doctor of Medical Sciences, Professor, E.I. CHERKEZOVA, Candidate of Medical Sciences, RMAPO, Moscow

Hyperandrogenism syndrome

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

It is necessary to distinguish between hirsutism and hypertrichosis - excessive hair growth on any part of the body, including those where hair growth does not depend on androgens.

Hypertrichosis can be either congenital (autosomal dominantly inherited) or acquired as a result of anorexia nervosa, porphyria, and can also occur with the use of certain medications: phenotoin, cyclosporine, diazoxide, anabolic steroids, etc.

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

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

The severity of hirsutism is often arbitrarily defined and graded as mild, moderate, or severe. One of the objective methods for assessing the severity of hirsutism is the Bettapp and Gallway scale (1961). According to this scale, the growth of androgen-dependent hair is assessed in 9 areas of the body with points from 0 to 4. If the sum of points is more than 8, a diagnosis of hirsutism is made.

Hyperandrogenism is an increase in the level of male sex hormones in the blood of women, leading to

leads to menstrual irregularities, excessive hair growth, virilization, and infertility.

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

The main androgens include testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and its sulfate, androstenedione, L5 - androstendiol, L4 - androstenedione.

Testosterone is synthesized from cholesterol that enters the human body with animal products or synthesized in the liver, and is delivered to the outer mitochondrial membrane. Transport of cholesterol to the inner mitochondrial membrane is a gonadotropin-dependent process. On the inner membrane of mitochondria, cholesterol is converted into pregnenalone (the reaction is carried out by cytochrome P450). In the smooth endoplasmic reticulum, which follows two pathways for the synthesis of sex hormones: L5 (mainly in the adrenal glands) and L4 (mainly in the ovaries), subsequent reactions are carried out. Free and albumin-bound testosterone is biologically available.

■ Women with hyperandrogenism belong to the group increased risk on the occurrence of complications of childbirth. The most common of them are untimely rupture of amniotic fluid and weakness of labor.

In women, testosterone is produced in the ovaries and adrenal glands. In the blood, 2% of testosterone circulates in a free state, 54% is bound to albumin, and 44% is bound to globulin-binding sex steroids. The level of GSPS is increased by estrogens, and lowered by androgens, so in men the level of GSPS is 2 times lower than in women.

A decrease in the level of SHPS in blood plasma is observed with:

■ obesity;

■ excessive formation of androgens;

■ treatment with corticosteroids;

■ hypothyroidism;

■ acromegaly.

An increase in the level of GSPS occurs when:

■ treatment with estrogens;

■ pregnancy;

■ hyperthyroidism;

■ liver cirrhosis.

Testosterone associated with GSPC performs some functions on the cell membrane, but cannot penetrate inside. Free testosterone can convert into 5a-DHT or bind to the receptor and penetrate target cells. Biologically available is the sum of the fractions of free and albumin-bound testosterone.

Dehydroepiandrosterone (DHEA) is produced in the testes, ovaries and adrenal glands. It was first isolated in 1931 and is a weak androgen. Once converted to testosterone in peripheral tissues, it has effects on the cardiovascular and immune systems.

Table. Scale for quantitative characteristics of hirsutism according to 0. Ferrimaní Galway, 1961

Zone Points Description

Upper lip 1 Individual hair on outer edge

2 Small antennae on the outer edge

3 Whiskers extending half the distance to the midline upper lip

4 Whiskers reaching the midline

Chin 1 Individual hair

2 Individual hairs and small clumps

3, 4 Continuous hair coverage, sparse or dense

Breast 1 Hair around nipples

2 Hair around the nipples and on the sternum

3 Merging of these zones with coverage up to 3/4 of the surface

4 Continuous coating

Back 1 Scattered hair

2 Lots of scattered hair

3.4 Continuous hair coverage, dense or sparse

Lower back 1 Tuft of hair on the sacrum

2 Tuft of hair on the sacrum, expanding to the sides

3 Hair covers up to 3/4 of the surface

4 Complete coverage with hair

Upper abdomen 1 Individual hairs along midline

2 Lots of hair along the midline

3, 4 Covering half or the entire surface with hair

Lower abdomen 1 Individual hairs along midline

2 Stripe of hair along the midline

3 Wide band of hair along the midline

4 Hair growth in the form of the Roman numeral V

Shoulder 1 Sparse hair covering no more than 1/4 of the surface

2 More extensive but incomplete coverage

3.4 Continuous hair coverage, sparse or dense

Hip 1, 2, 3,4 Values ​​are the same as on the shoulder

Forearm 1, 2, 3, 4 Continuous hair coverage of the dorsal surface: two points for sparse hair and two for dense hair coverage

Shin 1, 2, 3, 4 Values ​​are the same as on the shoulder

Androstenedione, a precursor to testosterone, is produced in the testes, ovaries and adrenal glands. The transition of androstenedione to testosterone is a reversible process.

Androgens exert their action at the cellular level through high-affinity nuclear receptors. Under the action of the aromatase enzyme, androgens are converted into estrogens.

Free testosterone enters the target cell and binds to the androgen receptor on the DNA of the X chromosome. Testosterone or DHT, depending on the activity of 5a-reductase in the target cell, interacts with the androgen receptor and changes its configuration, resulting in a change in receptor dimers that are transmitted to the cell nucleus and interact with the target DNA.

Dehydrotestosterone, then testosterone, has a high affinity for androgen receptors, while adrenal androgens (DHEA, androstenedione) have a low affinity.

The effects of testosterone include: differentiation of male sexual characteristics; the appearance of secondary sexual characteristics; growth of male genital organs; pubic hair growth; hair growth in the armpits and on the face; growth spurt during puberty; closure of the epiphyses; growth of the Adam's apple; thickening of the vocal cords; increase muscle mass, thickening of the skin; functioning of the sebaceous glands. Testosterone also affects libido and potency, and increases aggression.

With hyperandrogenism it is noted:

■ hair growth on the face and body according to the male type;

■ appearance of acne on the skin;

■ hair loss on the head (alopecia);

■ change in physique (masculinization) with expansion of the shoulder girdle and narrowing of the hips.

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

■ neuroendocrine-metabolic syndrome with obesity and gonadotropic dysfunction;

■ corticotropinoma (Itsenko-Cushing's disease);

■ somatotropinoma (acromegaly);

■ functional hyperprolactinemia and against the background of prolactinoma;

■ gonadotropinomas, hormonally inactive pituitary adenoma, “empty” sella syndrome;

■ anorexia nervosa;

■ obesity and type 2 diabetes mellitus;

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

■ insulin resistance syndromes (including acanthosis nigricans type A (insulin receptor gene mutation) and leprechaunism);

■ secondary hypothyroidism.

There are ovarian and adrenal forms of hyperandrogenism, and each of them has tumor and non-tumor forms. PCOS, stromal hyperplasia and ovarian thecamatosis are indicated by non-tumor or functional hyperandrogenism of ovarian origin, and congenital adrenal cortex dysfunction (CAD) is indicated by functional hyperandrogenism of adrenal origin. The tumor form of hyperandrogenism causes androgen-producing tumors of the ovaries or adrenal glands. With corticosteroma, severe hyperandrogenism is observed.

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

In the absence of ovulation while taking glucocorticoid drugs in the non-classical form of CAH or in case of insufficiency of the luteal phase of the menstrual cycle, clomiphene citrate (clostilbegit (Egis, Hungary); clomid (Hoechst Marion Roussel, Germany)) is prescribed according to the generally accepted scheme from 5 to 9 or from 3 to 7 days of the menstrual cycle. Due to its similarity with estrogen receptors in target cells in the ovaries, pituitary gland and hypothalamus, the drug clomiphene citrate has two opposite effects: weak estrogenic and pronounced antiestrogenic. Due to the fact that the effectiveness of therapy is observed when the synthesis of adrenal androgens is suppressed, ovulation stimulation should be carried out while taking glucocorticoids.

■ With functional hyperandrogenism (polycystic ovary syndrome (PCOS), ovarian thecamatosis, etc.), hirsutism develops gradually, accompanied by the appearance of acne, weight gain and irregular menstruation. Sudden Appearance hirsutism with signs of rapidly developing virilization may indicate androgen-producing tumors of the ovaries or adrenal glands.

In women with combined therapy, ovulation often occurs and pregnancy occurs. Discontinuation of glucocorticoid treatment after pregnancy may lead to spontaneous miscarriage or cessation of development of the fertilized egg, so therapy should be continued.

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

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

Patients with CDCN over the age of 30 years with ineffective treatment of infertility for more than 3 years and the presence of an ultrasound picture of polycystic ovaries are indicated for surgical treatment - wedge resection using a laparoscopic approach, demedulation or electrocauterization of the ovaries. At the same time, treatment with glucocorticoids is continued.

Low- and micro-dose combination oral contraceptives(COCs) with antiandrogenic action are used to treat patients with CAH and severe hirsutism. The most effective among them are: Diane-35, Janine, Yarina, etc. These drugs contain estrogens and gestagens. Under the influence of estrogens, the production of sex steroid binding globulin (SHBG) in the liver increases, which is accompanied by increased binding of androgens. As a result, the content of free androgens decreases, which reduces the manifestation of hirsutism. The antigonadotropic effect of these drugs suppresses the formation of gonadotropins in the anterior lobe of the pituitary gland, and the gonadotropic function of the pituitary gland in CAH is suppressed by the high level of androgens circulating in the blood. Consequently, the effect of COCs can lead to an even greater decrease in the concentration of gonadotropins and aggravate menstrual irregularities. In this regard, the use of COCs for VDC should not be long-term.

Treatment of androgen-producing ovarian tumors. In order to identify metastases, the pelvis and omentum are examined. Chemotherapy is carried out when distant metastases are detected. In the absence of signs of malignant growth and dissemination in such patients of reproductive age, unilateral adnexectomy is performed, and in postmenopausal women, extirpation of the uterus and appendages is performed. After surgery, dynamic monitoring of patients is necessary, con-

monitoring of hormone levels, ultrasound of the pelvic organs. In the absence of metastases and dissemination, after removal of the ovarian tumor, patients of reproductive age experience complete recovery: symptoms of virilization disappear, the menstrual cycle and fertility are restored. Ten-year survival depends on histological features and tumor size and ranges from 60-90%.

For hormonally active adrenal tumors, surgical intervention is indicated, since conservative treatment does not exist. A contraindication is only severe dissemination of the process. With decompensation of the cardiovascular system, purulent complications the operation is postponed. In this case, according to indications, cardiac, antihypertensive, and sedatives are prescribed; Before surgery, patients with diabetes mellitus are transferred to simple insulin therapy in fractional doses.

The surgical approach depends on the size and location of the tumor. IN Lately Surgical treatment of the adrenal glands is carried out laparoscopically. Flow postoperative period depends on the degree and type of hormonal activity of the tumor and the metabolic disorders caused by it. Therefore, patients need to be prescribed specific hormonal therapy.

Treatment of idiopathic hirsutism. To treat idiopathic hirsutism, antiandrogens are used - modern microdosed drugs containing estrogens and gestagens. Among these drugs, Diane-35 in combination with Androcur, as well as Zhanin, Belara, Yarina, have the greatest antiandrogenic activity.

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

■ spironolactone, which inhibits 5a-reductase at the cellular level and reduces the rate of conversion of testosterone to dehydrotestosterone;

■ cyproterone acetate - a progestin that blocks androgen receptors at the cellular level;

■ cimetidine - an antagonist of histamine receptors that block the action of androgens at the cellular level;

■ desogestrel, ketoconazole, metrodin - increasing the level of GSPS, binding testosterone and making it biologically inactive;

■ flutamide - a non-steroidal antiandrogen that binds to androgen receptors, suppressing testosterone synthesis to a lesser extent;

■ finasteride - has an antiandrogenic effect due to inhibition of 5a-reductase activity and does not affect androgen receptors;

■ ketoconazole - suppresses steroidogenesis;

■ medroxyprogesterone - suppresses the secretion of gonadoliberin and gonadotropins, reducing the secretion of testosterone and estrogens.

■ analogues of gonadotropin-releasing hormone (GnRH) - acting on the functional state of the ovaries, suppressing the secretion of estrogens and androgens;

■ glucocorticoids.

If there is no effect from the use of combined oral contraceptives, the administration of flutamide reduces hair growth, reduces the levels of androstenedione, dihydrotestosterone, LH and FSH. COCs and flutamide can cause the following side effects: dry skin, hot flashes, increased appetite, headache, dizziness, breast engorgement, decreased libido, etc.

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

Medroxyprogesterone acts on the level of sex hormone binding globulin, reducing the content of the latter. When using the drug, 95% of patients note a decrease in hirsutism. The following side effects may occur: amenorrhea, headache, edema, weight gain, depression, changes in biochemical indicators of liver function.

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

If the level of dehydroepiandrosterone or 17 OH-progesterone in the blood is elevated, glucocorticoids are prescribed. Of these, dexamethasone is the most effective. While taking the drug, hirsutism decreases in patients and other symptoms of hyperandrogenism disappear. When dexamethosone is prescribed to patients, the pituitary-adrenal system may be suppressed, so it is necessary to monitor the level of cortisol in the blood.

Treatment of polycystic ovary syndrome. When treating PCOS, it is necessary to restore the ovulatory menstrual cycle and fertility, eliminate the manifestations of androgen-dependent dermopathy; normalize body weight and correct metabolic disorders; warn late complications PCOS.

Insulin resistance (IR) and obesity, which potentiates it, are the most important pathogenetic link of anovulation in PCOS.

In the presence of obesity (BMI>25 kg/m2), treatment of PCOS should begin with weight loss.

Drugs that reduce body weight are prescribed against the background of a low-calorie diet containing no more than 25-30% fat, 55-60% slowly digestible carbohydrates, 15% protein of the total calorie intake. Salt intake is limited. Diet therapy must be combined with increased physical activity.

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

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

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

If there is no effect from conservative therapy, surgical stimulation of ovulation is resorted to. Laparoscopic access is used to perform wedge resection or demedulation or cauterization of both ovaries. The use of the endoscopic method of intervention made it possible to significantly reduce the incidence of adhesions compared to laparotomy.

Surgical method PCOS treatment is used in the following cases:

■ In patients with CAI, after taking adequate doses of dexamethasone, the menstrual cycle is usually restored, and in the majority it becomes ovulatory.

■ when PCOS is combined with recurrent dysfunctional uterine bleeding and endometrial hyperplasia, regardless of the presence or absence of obesity;

■ in women with normal body weight with a significant increase in the level of LH in the blood plasma;

■ in women over 35 years of age, even if they are obese. In this case, intensive obesity therapy is carried out immediately after surgery.

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

■ duration of anovulation and the woman’s age over 30 years;

■ large ovaries with a subcapsular arrangement of atretic follicles around a hyperplastic stroma;

■ pronounced IR and GI regardless of body weight;

■ menstrual cycle disorders such as amenorrhea.

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

Due to the fact that hirsutism is caused by hyperandrogenism, drugs that reduce androgen levels and suppress receptors are used for treatment.

androgen rye; reducing the formation of androgens; suppressive enzyme systems involved in the synthesis of androgens, in the production of (extragonadal) testosterone and its conversion to DHT.

Due to the fact that the treatment of hirsutism using medicinal methods- the process is long, many women use different kinds hair removal (electrical, laser, chemical, mechanical, photoepilation).

Treatment of complications of PCOS. To prevent the development of metabolic disorders, it is necessary to reduce body weight. To prevent the development of endometrial hyperplasia, it is necessary to conduct ultrasound monitoring of the condition of the endometrium and, if necessary, treat with progesterone derivatives. In the presence of GE (endometrial thickness more than 12 mm), curettage of the uterine mucosa is prescribed under the control of hysteroscopy, and a histological examination is also performed.

In addition to restoring fertility, treatment of PCOS must be carried out in order to correct metabolic disorders that are the background to the occurrence of type 2 diabetes mellitus, early atherosclerosis, hypertension, as well as a high risk of developing endometrial hyperplasia and adenocarcinoma.

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

Hyperandrogenism syndrome is a fairly large group endocrine diseases, which arise due to very diverse patho genetic mechanisms, but are combined on the basis of similar clinical symptoms due to excess quantity and/or quality (activity) of male sex hormones in the female body. The most common hyperandrogenic conditions are:

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

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

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

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

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

Etiopathogenesis

Relatively recently - at the end of the last century - the newest scientific concept that two interrelated components take part in the pathogenesis of PCOS:

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

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

Clinical characteristics

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

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

Symptoms of pathological androgenization

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

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

Androgenetic alopecia is a reliable diagnostic marker for virile variants of GAS. Like other types of endocrine alopecia, it is diffuse and not focal (clustered) in nature. But unlike baldness with other glandular diseases internal secretion(primary hypothyroidism, polyglandular insufficiency, panhypopituitarism, etc.), androgenic alopecia is characterized by certain dynamics. As a rule, it manifests itself as hair loss in the temporal areas (bitemporal alopecia with the formation of symptoms of “temporal receding hairline” or “receding hairline of the Privy Councilor” and “widow’s peak”), and then spreads to the parietal region (parietal alopecia, “baldness”). The peculiarities of the synthesis and metabolism of androgens in the perimenopausal period explain the fact that up to 13% of women at this age have a “widow’s peak” or more pronounced forms of baldness in the absence of other signs of GAS. On the other hand, baldness, as a serious indicator of severe GAS, is more often observed and develops faster (sometimes ahead of hirsutism) in this age group, which requires the exclusion of an androgen-producing tumor.

Symptoms of insulin resistance and hyperinsulinism

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

Laboratory and instrumental diagnostics

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

According to this document, which still guides the vast majority of researchers working on this problem, the diagnosis of PCOS is a diagnosis of exclusion. To verify it, in addition to the presence of two clinical inclusion criteria discussed above (anovulation + hyperandrogenism), a third is also necessary - the absence of other endocrine diseases (congenital adrenal dysfunction, virilizing tumors, Itsenko-Cushing's disease, primary hyperprolactinemia, thyroid pathology ). Fully sharing this point of view, over the past 15 years, we have considered it necessary for each patient to complete the diagnosis of PCOS with three additional examinations. This is extremely important not only and not so much for confirming the diagnosis, but for further use as criteria when choosing differentiated therapy on an individual basis. We are talking about the following studies.

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

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

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

3. Laboratory signs of insulin resistance:

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

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

Identification of insulin resistance syndrome

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

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

Treatment

Individual management tactics for patients with PCOS often depend not only on the established nosological variant of the pathology, but also on the situation in the family where pregnancy is planned. Taking this into account, therapy for PCOS can be conditionally divided into two groups: basic - when a comprehensive rehabilitation program is carried out for a long time and a young woman is systematically prepared for pregnancy, and situational - when, at the request of the patient, the issue of restoring fertility is urgently resolved.

Basic therapy

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

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

Modern powerful search systems for scientific and medical literature make it possible to track the appearance of the latest data even in remote corners of the planet within a few weeks after their appearance in print or on the World Wide Web. Ten years have passed since the publication in 1994 of an article by a team of authors from Venezuela and the United States about the first experience of using metformin in PCOS. Over the years, about 200 more works on this issue have appeared. Most of them report on non-randomized, uncontrolled, and generally small trials. This level of scientific analysis does not meet today’s stringent requirements for evidence-based medicine. Therefore, publications of systematic analytical reviews and the results of meta-analyses based on summary data from similar trials are of exceptional interest. Similar works appeared only during the last six months, and their discussion is important both for practice and for the development of theory. A summary of the most obvious systematically reproducible effects of metformin in PCOS is given below.

Clinical effects

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

Laboratory effects

• Reduced levels of insulin, insulin-like growth factor type 1 (IGF-1).
• Reducing cholesterol, triglycerides, LDL and VLDL levels, increasing HDL concentrations.
• Reduced levels of androgens, LH, plasminogen activator inhibitor.
• Increased levels of testosterone-estradiol-binding globulin, a binding protein for IGF-1.

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

Dosage regimen: first week = 1 table. at night, second week = + 1 table. before breakfast, third week = + 1 table. before lunch. Average daily dose— 1.5-2.5 g.

Duration of admission: minimum six months, maximum 24 months, average duration one year.

A break/cancellation in taking the drug should be carried out for several days in case of any acute illness and when conducting X-ray contrast studies for other conditions (risk of lactic acidosis).

Conclusion

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

For questions about literature, please contact the editor

D. E. Shilin, doctor medical sciences, Professor
Russian medical Academy postgraduate education Ministry of Health of the Russian Federation, Moscow

is a pathological condition that is associated with excessive production of male sex hormones. The syndrome is manifested by changes in menstrual function, infertility, metabolic disorders, and dermatological symptoms. The disease is usually caused by disorders of the reproductive and endocrine systems, including tumors.

Features of the pathology

Under the term “hyperandrogenism in women,” experts combine pathological conditions that have different origins and lead to an increase in the concentration of male hormones in the blood or an increase in the susceptibility of target tissues to these substances. This syndrome is widespread among women of reproductive age. It is detected in approximately 5–7% of adolescents and 10–20% of adults over 25 years of age.

With hyperandrogenism, women begin to grow hairs where they should not be

Androgens include male sex hormones of a steroid nature:

• testosterone;
• dihydrotestosterone;
• DHEA-S.

Normally, in women, these substances are synthesized by the cells of the ovaries and adrenal glands. A small amount of these hormones is also synthesized by fatty tissue. Regulation of this process is carried out by the pituitary gland through luteinizing and adrenocorticotropic hormones (LH and ACTH).

The level of androgens in a woman’s body determines the severity of libido. During puberty, these hormones contribute to the girl’s growth by increasing the length of the tubular bones and are involved in the formation of hair growth. female type. In cases where the content of androgens in the blood becomes too high, diseases of the endocrine and reproductive systems develop.

This is manifested not only by cosmetic disorders in the form of acne, seborrhea, changes in hair growth, hair loss, but also by significant changes in metabolism. The metabolism of carbohydrates and fats, the process of formation of eggs in the ovaries, and the menstrual cycle are disrupted.

In advanced cases of hyperandrogenism, infertility develops.

Long-term hyperandrogenism can contribute to the occurrence of cervical cancer, an increase in endometrial volume, heart and vascular diseases, and type 2 diabetes. If this condition occurs during pregnancy, then in most cases a miscarriage occurs.

Classification of hyperandrogenism in women

According to the source of occurrence, this syndrome can be ovarian or adrenal - in the medical literature these diseases are designated by the terms “ovarian” and “adrenal” hyperandrogenism. Also, the syndrome can be primary or secondary in nature, that is, develop against the background of complete health or be a consequence of some pathology. In some cases, a hereditary factor plays a role in the occurrence of pathology.

Hyperandrogenism is also divided into the following forms:

• absolute;
• relative.

The first is associated with an increase in the production of male sex hormones and an increase in their concentration in the patient’s blood. The second is with increased susceptibility of target tissues to the action of these biologically active substances. The relative form of the disease is more common.

Causes of hyperandrogenism

Increased production of male sex hormones is usually observed in diseases of the reproductive and endocrine systems. The following pathologies can lead to the development of this condition.

• Polycystic ovary syndrome, which can be primary or secondary. In the second case, the disease is often preceded by hypothyroidism, hyperprolactinemia, and hypothalamic pathology.
• Congenital adrenal hyperplasia, or adrenogenital syndrome. In this case, androgen synthesis increases due to increased ACTH levels.
• Galactorrhea-amenorrhea– this pathological condition is accompanied by an increase in the concentration of prolactin in a woman’s blood, which also stimulates the production of steroids.
• Virilizing tumors of the ovaries and adrenal glands. This group of oncological diseases includes thecoma, androsteroma, and luteoma.
• Ovarian stromal thecomatosis– benign pathology associated with an increase in the volume of the ovarian stroma.

The transport form of hyperandrogenism develops with insufficient activity of proteins that bind steroid hormones. This leads to insufficient blocking of free testosterone and, as a result, excessive influence of this substance on target cells. This condition can develop with Itsenko-Cushing syndrome, dyslipidemia, and hypothyroidism.

In ¾ of patients with acne, the concentration of male sex hormones in the blood does not exceed the norm. Excessive activity of the sebaceous glands in these cases is associated with an increase in the number and sensitivity of androgen receptors in the skin.

Fat production is regulated by dihydrotestosterone, which also affects the composition and properties of the secretion. Therefore, a change in sensitivity to this hormone leads to the formation of comedones and acne.

The causes of male pattern hair are in most cases associated with the high content of androgens in the patient’s blood. In only 20–30% of women, this syndrome occurs due to excessive production of dihydrotestosterone, which stimulates hair growth in androgen-sensitive areas of the body and hair loss on the head. In some cases, this condition develops due to uncontrolled use of hormone-containing drugs.

Symptoms of hyperandrogenism

The clinical picture of the disease is determined by how much the woman’s hormonal levels are changed, and also depends on the cause of the pathology. For example, if the disease is not caused by a tumor of the reproductive system, the symptoms progress very slowly, and the duration of the disease can reach several years.

The first symptoms appear during puberty - acne, seborrhea, changes in the menstrual cycle up to the complete absence of periods, increased hair growth on the legs, arms and face. Gradually, cysts can form in the ovaries, which causes the impossibility of ovulation, decreased progesterone activity, impaired fertility and infertility. At a later age, after menopause, hair may begin to fall out on the temples, then on the parietal region.

The symptoms listed above, including changes in appearance and the inability to get pregnant, often lead to the development of neuroses and depression in patients.

With adrenogenital syndrome, the disease manifests itself much more clearly. The clinical picture in this case is characterized by general masculinization, late appearance of menstruation, and virilization of the genital organs. Hirsutism, acne and other dermatological phenomena are also almost always observed.

Due to the high level of androgens in the blood, metabolic syndrome develops, which, if left untreated, contributes to the occurrence of type II diabetes mellitus. Along with this, persistent arterial hypertension, myocardial ischemia and other cardiac disorders are noted. As a rule, in the presence of pathology of the adrenal glands, symptoms progress very quickly.

Diagnosis of hyperandrogenism

A preliminary diagnosis can be made based on a general examination of the patient and anamnesis of the disease. An important role in this is played by symptoms associated with menstrual irregularities, changes in hair growth, and dermatological manifestations.

Before prescribing treatment for hyperandrogenism, check the level of hormones in the blood

To make a final diagnosis, it is necessary to carry out laboratory research in order to determine the level of total and free testosterone, dihydrotestosterone and other androgens. If an increase in the amount of DHEA-S is noted, the presence of adrenal hyperandrogenism should be suspected. A significant increase in the level of this hormone, together with a high concentration of testosterone, often indicates the presence of an adrenal tumor, which requires an ultrasound, CT scan or MRI.

At the same time, a study is carried out to determine the level of:

• prolactin, luteinizing hormone, FSH;
• cortisol, 17-KS and other adrenal hormones;
• blood glucose, glycated hemoglobin, insulin;
• performing a glucose tolerance test;
• cholesterol.

All patients are also advised to consult an endocrinologist and dermatologist.

Treatment of hyperandrogenism

Therapy for the disease is carried out over a long period of time – in courses of up to a year or more. The doctor selects treatment based on examination data and diagnosed pathology. For this purpose, medications are used to regulate a woman’s hormonal levels - oral contraceptives, which reduce the concentration of androgens in the blood. Such drugs reduce the activity of gonadotropin synthesis, inhibit ovulation and suppress the production of steroid hormones, testosterone. Additionally, oral contraceptives block androgen receptors in target tissues.

Self-treatment for this disease is unacceptable, as it can cause even greater problems in the woman’s reproductive system.

Treatment of a disease associated with adrenal dysfunction requires the use of corticosteroids. Also, such medications are used to detect hyperandrogenism during pregnancy or during preparation for gestation. Additionally, it is necessary to treat concomitant endocrine pathologies.

Hyperandrogenism is a serious condition that, if left untreated, can lead to infertility. Diagnosis and treatment of pathology is carried out by a gynecologist together with an endocrinologist. Only after undergoing a complete examination, which includes determining the level of sex hormones in the patient’s blood, can a treatment regimen be selected.

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

Normally, androgens are produced by the genitals in quantities that ensure the growth of pubic and armpit hair, the formation of the clitoris, and timely puberty and sexual desire. Androgens are responsible for normal work liver and kidneys.

Active production of androgens occurs in adolescence, during the formation of secondary sexual characteristics. In adulthood, androgens are necessary to strengthen bone tissue. However, excessive production of these hormones leads to pathological changes, which significantly worsen a woman’s quality of life. The most disastrous results include and. In these cases, treatment is necessary that will help normalize hormonal levels.

Types and causes of the syndrome

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

Depending on the origin of the pathology, there are several forms:

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

A number of patients are diagnosed with hyperandrogenism mixed origin. In this case, the functioning of the ovaries and adrenal glands is simultaneously impaired in the body. This pathology is caused by hypothalamic and neuroendocrine disorders. Disturbances in hormonal balance are aggravated by vegetative-neurotic disorders. In some cases, mild hyperandrogenism is diagnosed, in which androgen levels are normal, but does not reveal the presence of tumors in the internal organs.

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

Considering the degree of excess of the permissible level of androgens, absolute and relative forms of adrenogenital syndrome are distinguished. In the first case, the concentration of male hormones exceeds the permissible norms. Relative hyperandrogenism is diagnosed with acceptable levels of male hormones. At the same time it is noted increased sensitivity organs and glands of a woman to their effects.

To summarize, the following main causes of this syndrome can be identified:

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

For disorders of the ovaries, enlargement of the adrenal cortex, hypersensitivity of skin cells to the effects of testosterone, tumors of the genital and thyroid glands Pathology may also develop in childhood.

Congenital hyperandrogenism sometimes makes it impossible to accurately determine the sex of a born child. A girl may have large labia and a clitoris enlarged to the size of a penis. The appearance of the internal genital organs is normal.

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

In older age, hyperandrogenism causes excess hair growth throughout the body, delayed formation of mammary glands and the appearance of the first menstruation.

Clinical manifestations

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

Clinical manifestations of hyperandrogenism in women in the form of acne and male pattern hair growth

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;
• , scarcity of discharge, sometimes complete cessation of menstruation;
• increased sexual desire.

Occurring disruptions in hormonal balance cause the development of diabetes mellitus, the appearance excess weight, 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.

Establishing diagnosis

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

What tests need to be taken to determine androgen levels?

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

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

An ultrasound of the pelvic organs will determine the possible presence. Testing is necessary to determine the type of disease.

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

Principles of therapy

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

The choice of treatment methods depends on the form of the pathology and the goal pursued by the therapy (combat hirsutism, restore reproductive function, maintain pregnancy when there is a threat of miscarriage).

Main treatment measures include:

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

Conservative therapy

It is used to reduce the amount of male hormones produced and to block processes that contribute to their excessive activity. The presence of tumors in the genital organs, causing ovarian hyperandrogenism, is eliminated through surgery.

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

Such drugs not only eliminate unpleasant external signs, but also help normalize the menstrual cycle. For a cosmetic effect, anti-inflammatory ointments are prescribed that reduce sebum production.

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

An analogue drug is Veroshpiron. Its main active ingredient is also spironolactone. Taking Veroshpiron is highly undesirable without consulting your doctor about the duration of use and the required dosage.

If hyperandrogenism is caused by the lack of an enzyme that converts androgens into glucocorticoids, agents that normalize this process are indicated. The drug Metipred is very effective. Its release forms are tablets and powders for injection. The drug is contraindicated in the presence of infectious and viral diseases, tuberculosis, heart failure. The duration of the course of treatment and dosage are determined by the doctor.

Drugs used to treat hyperandrogenism

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

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

The diet indicated for hyperandrogenism involves the exclusion of fatty, salty and spicy foods, as well as alcohol, sauces and fatty gravy.

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

The fight against hirsutism is carried out using various cosmetic procedures: waxing, depilation, elimination unwanted hair laser.

Application of traditional medicine

Treatment with folk remedies is quite applicable in combination with drug therapy, but is not a complete replacement for traditional methods.

Popular recipes:

1. The herbs of sweet clover, sage, meadowsweet and knotweed are mixed in equal parts, poured with 200 ml of water, kept in a water bath for 20 minutes and filtered. Add 1.5 ml of Rhodiola rosea tincture to the resulting decoction. Take a third of a glass of the decoction several times a day before meals.
2. 2 tablespoons of chopped string, 1 spoon of yarrow and motherwort are poured with boiling water, left for about an hour, filtered. Take half a glass on an empty stomach in the morning and before bed.
3. A few tablespoons of dried nettle leaves are poured into a glass of water, infused in a closed container, and filtered. Take a tablespoon several times a day.
4. Rose hips and black currants are poured with boiling water and left for about an hour. Then add a little honey. The resulting cocktail is drunk several times a day after meals.

Among the most common folk remedies in the fight against gynecological diseases are hog queen. It is used in conjunction with other medicinal products in the form of a decoction or tincture.

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

Peppermint is used to reduce the amount of androgens produced. On its basis, tinctures and teas are prepared. For greater effectiveness, you can add milk thistle to mint. Regular intake of green tea normalizes female hormonal balance.

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

Hyperandrogenism and infertility

Excess androgen production often becomes an obstacle to a desired pregnancy.

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

Infertility treatment in this case is aimed at using drugs that stimulate the release of eggs from the ovaries. An example of this medicine Maybe Clomiphene.

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

If stimulation is ineffective, doctors advise resorting to surgical treatment. Modern medicine widely uses the method. During this procedure, the ovaries are excised to help the mature egg “release.” The chance of getting pregnant after laparoscopy is higher, the less time passes from the day of surgery. Maximum fertility is observed in the first three months.

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

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

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

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

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

Prevention

There are no specific measures to prevent hyperandrogenism, since this syndrome develops at the hormonal level.

To general preventive measures include:

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

Hyperandrogenism is not only problems with the skin, hair and menstrual cycle. This general disease an organism that does not allow a woman to lead a quality lifestyle and often deprives her of the joys of motherhood. Modern methods diagnostics and treatment allow to identify pathology in time and successfully eliminate its manifestations.

Diseases

IN healthy body In women, the amount of sex hormones is strictly balanced. However, a change in their ratio can lead to the appearance serious illnesses. For example, when the amount of male sex hormones increases significantly and their activity increases, hyperandrogenism occurs. This is one of the most common diseases of the endocrine system in women. According to medical statistics, the disease is detected in 10-20% of the fairer sex over 25 years of age. The disease is also diagnosed in 4-7% of girls during adolescence.

Symptoms of hyperandrogenism in women

Clinical signs of the disease can vary greatly, since their intensity depends on the severity of the disorders. Typically, the disease progresses slowly over several years. The following symptoms may indicate hyperandrogenism in women:

A woman can suspect hormonal imbalances from excessive hair growth on her face and body. She may have a mustache and beard. In addition, the hair on the chest, between the shoulder blades, and on the arms begins to darken. But the disease can also cause a completely opposite reaction in the body. A specific sign of hyperandrogenism may be. This term means:

• increased hair loss;
• baldness of the head;
• change in hair structure (thinning).

Baldness is most often observed in the parietal, frontal and temporal areas of the head. Virile syndrome is specific symptom a disease in which a woman develops male characteristics. Her menstruation may completely disappear, and her sexual desire may increase sharply. The patient has:

• increased growth of muscle mass;
• increasing the size of the clitoris;
• reduction of mammary glands;
• change in voice timbre.

Various factors can trigger the onset of the disease. Quite often, hormonal imbalances are associated with gynecological problems. Experts say that the following ailments can cause hyperandrogenism in women:

In addition, hormonal imbalances can also cause congenital disorders of the adrenal cortex. There is also a hereditary predisposition to hyperandrogenism. Tumor formations in the pituitary gland can also cause the disease. This area of ​​the brain is responsible for the production of a hormone that regulates:

• development of mammary glands;
• their growth;
• production and secretion of milk.

Most often, the disease occurs against the background of other disorders developing in the body, and is therefore considered acquired. For example, its appearance may be caused by a decrease in the production of hormones by the thyroid gland. The risk group includes women suffering from chronic liver diseases. In addition, incorrect intake can provoke the disease. hormonal drugs, namely:

• oral contraceptives;
• anabolic steroids;
• glucocorticoids.

The disease should not be ignored. In addition to pronounced cosmetic defects, it can cause serious problems with the reproductive system. The following can quickly identify the symptoms and causes of hyperandrogenism in women, as well as prescribe treatment:

At the first appointment, the doctor will carefully listen to the patient’s complaints and examine her. In order to understand how to properly deal with the disease, he must determine the causes of the pathology. To do this, he will conduct a survey. The patient will be asked to clarify:

1. How long ago did the first symptoms appear?
2. Are menstrual irregularities a concern?
3. Have there been any cases of hyperandrogenism in women in your family?
4. Is she taking oral contraceptives?
5. Have you undergone long-term drug treatment?
6. Have the mammary glands decreased in size?

Very often, during a conversation with a patient, the doctor discovers the root causes of the disease. Therefore, the survey plays an important role in diagnosing the disease. If the examination does not help determine what triggered it, then the doctor may prescribe the patient to undergo a genetic test. It will help identify hereditary diseases.

Treatment

The main goal of therapy will be to effectively combat the root causes of hormonal imbalance in the body. The doctor determines the treatment regimen. With conservative therapy, the patient is prescribed:

• hypocaloric diet to prevent obesity;
• playing sports to lose weight;
• taking estrogens-progestogens to correct hormonal balance.

The patient may also be prescribed antiandrogens. These are drugs that selectively suppress the activity of male sex hormones. The following may be recommended:

• progesterone;
• oral contraceptives;
• glucocorticoids.

Doctors' efforts will be aimed at combating diseases that provoke the development of hyperandrogenism. If the level of male sex hormones in a woman is increased due to hypothyroidism, then she needs:

• take hormones that are not sufficiently produced by the thyroid gland;
• replace table salt with iodized salt;
• eat more seafood.

Surgical intervention may be required if tumors that produce male hormones are detected in a woman’s body. Such tumors are excised even if they are benign. In the future, the patient is advised to undergo clinical observation and medical support when planning pregnancy.

Diagnostics

The doctor may suspect the disease based on the results of an external examination of the patient. But in order to confirm hyperandrogenism in women, it is necessary to conduct a comprehensive examination. It consists of:

• Blood test for hormones. The study can be completed in capital clinics for 500-700 rubles. The accuracy of the method is 85%.
• Ultrasound of the ovaries. In Moscow, the procedure costs from 1,500 to 2,000 rubles. The examination allows you to determine the condition of the ovaries with up to 90% accuracy.
• MRI of the adrenal glands and skull. The price of the study varies from 4,000 to 6,000 rubles. The method is distinguished by its high accuracy (up to 95%).
• Adrenal scintigraphy. For such a procedure in Moscow hospitals you will have to pay about 8,000 rubles. The accuracy of the method is 90%.

Sex hormones are examined on days 5-7 of the menstrual cycle. The analysis helps specialists determine the level of:

• testosterone;
• DHEA;
• SHBG;
• 17-hydroxyprogesterone and other hormones.

Ultrasound examination and magnetic resonance imaging of the patient are performed to identify tumors. If all of the above diagnostic methods do not give accurate results, then the patient is prescribed catheterization of the veins that extend from the ovaries and adrenal glands. This procedure allows doctors to determine the level of male hormones flowing from these organs.

How dangerous is the disease?

Hyperandrogenism in women causes significant cosmetic imperfections, which cause the patient to experience severe psychological stress. The following defects cause serious stress, depression and neuroses:

• excessive body hair of the male type;
• excessive oily skin;
• dandruff;
• loss of hair on the head.

In some cases, the disease can cause diabetes. The disease can lead to serious problems with fertility. Therefore, it is very important to start fighting the disease as early as possible. If you refuse treatment, the consequences can be very dire. The most common complications of the disease include:

• spontaneous termination of pregnancy;
• premature birth;
• infertility.

Some forms of hyperandrogenism completely disappear with timely initiation of treatment. This allows women to maintain or restore reproductive health. In severe cases, when the cause of the disorders is in tumor formations, reproductive function may be completely lost.

Prevention of hyperandrogenism in women

Hormonal disorders are a serious problem that requires long-term and complex treatment. It is much easier not to fight the disease, but to prevent its occurrence. You can prevent the occurrence of hyperandrogenism if you adhere to the following simple rules:

• Do not take hormone-containing medications without a doctor’s prescription. Consult a doctor when choosing oral contraceptives.
• Visit a gynecologist regularly for a medical examination. A woman of childbearing age needs to be examined at least 2 times a year.
• Quit smoking and drinking strong alcoholic drinks.
• Control body weight. A balanced diet helps to avoid a lot of diseases, including hormonal imbalance.
• Avoid stress, emotional stress and strain.

It is important to promptly treat all gynecological diseases and not ignore their symptoms. If a woman is at risk, that is, has serious problems with the thyroid, liver or adrenal glands, then it is especially important for her to strictly adhere to all of the above recommendations. If the disease cannot be avoided, treatment of hyperandrogenism should be started immediately.

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