Polycystic ovary syndrome (PCOS). clinic (symptoms), diagnosis and treatment of PCOS

Polycystic ovary syndrome (PCOS) is a pathology of the structure and function of the ovaries, characterized by ovarian hyperandrogenism with menstrual and generative dysfunction.

SYNONYMS OF POLYCYSTIC OVARIAN SYNDROME

Polycystic ovary disease, primary polycystic ovaries, Stein-Leventhal syndrome, scleropolycystic ovaries.

ICD-10 CODE E28.2 Polycystic ovary syndrome.

EPIDEMIOLOGY OF POLYCYSTIC OVARIAN SYNDROME

The frequency of PCOS is approximately 11% among women of reproductive age, in the structure of endocrine infertility it reaches 70%, and in women with hirsutism, PCOS is detected in 65–70% of cases.

ETIOLOGY AND PATHOGENESIS OF POLYCYSTIC OVARIAN SYNDROME

The etiopathogenesis of PCOS is not fully understood, despite the large number of proposed theories. At the same time, most researchers consider PCOS to be a heterogeneous disease, hereditarily caused, characterized by menstrual irregularities, chronic anovulation, hyperandrogenism, an increase in the size of the ovaries and features of their morphological structure: a bilateral increase in the size of the ovaries by 2–6 times, stromal and theca cell hyperplasia, and a multitude of cystic atresia follicles. 5–8 mm in diameter, thickening of the ovarian capsule.

Cardinal symptom of PCOS- ovarian hyperandrogenism. Summing up the available scientific works on this problem, it is possible to determine the following mechanisms of pathogenesis.

Violation of gonadotropic function. The era of synthesis and application of GnRH in the 80s. provided not only the possibility of ovulation induction, but also a more in-depth study of the role of gonadotropic dysfunction in the pathogenesis of PCOS. A hypothesis was put forward about the primary violation of the circoral rhythm of GnRH release from the period of puberty as the cause of PCOS, possibly genetically determined. An important role is assigned to environmental (stress) factors that disrupt neuroendocrine control in the regulation of GnRH secretion, resulting in an increase in the basal level of LH synthesis and a relative decrease in FSH production. It is known that puberty is a critical period in a girl's life, against which genetic and environmental factors contribute to the manifestation of various neuroendocrine syndromes.

As a result of excessive stimulation of LH, the production of androgens in theca cells increases, cystic atresia of follicles with hyperplasia of theca cells and stroma is formed, there is no selection and development of the dominant follicle. As a result of the relative deficiency of FSH, which is necessary for the synthesis of cytochrome P450, which activates enzymes for the metabolism of androgens into estrogens, androgen accumulation and estradiol deficiency occur. By negative feedback mechanisms, a decrease in the level of estradiol stimulates the synthesis of LH, which is the second factor for increasing the basal level of LH. In addition, estrogens (mainly estrone), synthesized extragonadally from testosterone in large quantities, increase the sensitivity of pituitary cells to GnRH, which contributes to chronic hypersecretion of LH. Hyperproduction of androgens leads to atresia of the follicles, hyperplasia of the theca cell stroma and albuginea. In addition, elevated androgen concentrations are positively correlated with inhibin B levels, which suppress FSH secretion.

On the other hand, an increase in GnRH secretion may not be primary, but secondary in response to androgen hyperproduction and a decrease in estradiol synthesis in the ovaries. At the same time, ovarian hyperandrogenism is the result of a violation of autoparacrine regulation of growth and maturation of follicles, as well as dysregulation of cytochrome P450c17. As a result of these disorders, the synthesis of estradiol decreases, which, by a feedback mechanism, stimulates the secretion of GnRH. Ovarian hyperandrogenism is noted in patients with normal levels of gonadotropins. This shows hyperreaction of theca cells of polycystic ovaries to normal levels of LH.

insulin resistance and hyperinsulinemia. The combination of hyperandrogenism and insulin resistance in PCOS was first reported in 1980, which contributed to the hypothesis that obesity and hyperinsulinemia should play a major role in the pathogenesis of PCOS in patients with insulin resistance. However, hyperinsulinemia is also noted in patients with normal body weight and PCOS. Therefore, obesity contributes to, but is not a major factor in the development of insulin resistance in PCOS. The frequency of insulin resistance is 35-60%. Pathogenetic mechanisms Insulin resistance is not fully known, it is multifactorial, and in the vast majority of patients with PCOS, it is caused not by a defect in the insulin receptor, but by disorders at the receptor and post-receptor levels of insulin signal transduction into the cell.

Normally, insulin binds to the transmembrane insulin receptor, activating several processes, in particular tyrosine autophosphorylation and successive reactions of glucose transport into the cell. As a result of the ongoing cascade mechanisms, insulin-mediated transport of glucose into the cell is triggered. An important role in the formation of insulin resistance is assigned to a genetically determined violation of the tyrosine kinase pathway of insulin receptor phosphorylation. Serine phosphorylation of the receptor inhibits the activity of the insulin receptor tyrosine kinase. In patients with PCOS, inhibition of insulin signal transduction into the cell as a result of the prevalence of serine phosphorylation has been proven. The same mechanisms enhance the activity of cytochrome P450c17, which is key in the synthesis of androgens both in the ovaries and in the adrenal glands.

A certain role in peripheral insulin resistance belongs to hyperandrogenism, since androgens change the structure muscle tissue towards the prevalence of type II muscle fibers, less sensitive to insulin. Concomitant obesity, more often visceral, in about 50% of patients exacerbates the existing violations of insulin sensitivity, providing a synergistic effect.

Normally, not insulin, but more insulin-like growth factor I plays an important role in steroidogenesis. But the action of insulin in concentrations above the norm is realized not only through insulin receptors, but also through receptors for insulin-like growth factor I. Insulin and insulin-like growth factor I enhance LH-dependent androgen synthesis in theca cells and stroma, stimulate excess LH secretion. Insulin also increases the activity of cytochrome P450c17, thus increasing the production of ovarian and adrenal androgens. Hyperandrogenism also contributes to an increase in the concentration of free biologically active testosterone due to a decrease in the formation of SHBG in the liver. Insulin has been shown to regulate SHBG production. With hyperinsulinemia, SHBG synthesis is reduced, which leads to an increase in the concentrations of free fractions of both testosterone and estradiol. In addition, insulin inhibits the production of proteins that bind insulin-like growth factor I, increasing their biological activity, and consequently, the synthesis of androgens in the ovaries.

The role of obesity is reduced to extragonadal synthesis of testosterone and estrone. This process is autonomous and does not depend on gonadotropic stimulation. Estrone, synthesized in adipose tissue, closes the "vicious circle" in the pathogenesis of PCOS formation, increasing the sensitivity of the pituitary gland to GnRH.

ovarian factors. Recent studies explain the overproduction of androgens by a genetically determined dysregulation of cytochrome P450c17, a key enzyme in the synthesis of androgens in the ovaries and adrenal glands. The activity of this cytochrome is regulated by the same mechanisms that are involved in the activation of the insulin receptor, i.e. there is a genetic determinant of ovarian, adrenal hyperandrogenism and insulin resistance. It has been shown that in patients with PCOS, the concentration of an apoptosis inhibitor is increased in the blood, i.e. the process of atresia of follicles that persist is reduced.

It is known that approximately 50% of patients with PCOS have adrenal hyperandrogenism. The mechanisms of increased DHEAS production in normal and overweight patients are different. In patients with normal body weight (approximately 30%), there is a genetically determined dysregulation of cytochrome P450c17, which leads to increased production of adrenal and ovarian androgens by a single mechanism. In patients with obesity, activation of the androgenic function of the adrenal glands is due to excessive production of corticoliberin and, accordingly, ACTH, therefore, the synthesis of not only DHEAS, but also cortisol increases.

Based on the analysis of the results of numerous studies, two variants of the pathogenesis of PCOS in patients with normal body weight and in insulin-resistant patients can be proposed (Fig. 181, 182). On genetic causes adrenal and ovarian hyperandrogenism in patients with normal body weight is also indicated by the anamnesis and clinical picture, since the frequency of past diseases is not higher than in the population, and, apart from menstrual and generative function disorders, the patients are not bothered by anything. Whereas in patients with obesity, the frequency of acute respiratory viral infections and many diencephalic symptoms are increased, which indicates a central, hypothalamic genesis of the formation of PCOS - a violation of the neuroendocrine control of GnRH secretion.

The pathogenesis of PCOS in insulin resistant patients is as follows (Fig. 18-2). Puberty is characterized by insulin resistance due to increased production of growth hormone. Insulin is an important mitogenic hormone, necessary in puberty in elevated concentrations for normal physical development and maturation of organs and tissues. reproductive system. As already noted, this is a critical period in life, when there may be a manifestation of any genetically determined pathology, especially under the influence of various environmental factors.

Rice. 18-1. Pathogenesis of PCOS in patients with normal body weight.

Fig.18-2. Pathogenesis of PCOS in insulin resistant patients.

Thus, the pathogenesis of PCOS is multifactorial, with involvement in pathological process ovarian, adrenal and extraovarian factors and has different mechanisms in patients with normal body weight, obesity, insulin resistance.

CLINICAL PICTURE OF POLYCYSTIC OVARIAN SYNDROME

Clinical picture PCOS characterized by a violation of the menstrual cycle, primary infertility, excessive hair growth, acne. AT last years more and more often (about 50%) there are women with normal body weight, mild androgen-dependent dermatopathies, the so-called hirsute-free patients. Menarche timely - 12-13 years. Violation of the menstrual cycle from the period of menarche - according to the type of oligomenorrhea in the vast majority of women (70%), less often dysfunctional uterine bleeding(7–9%). Secondary amenorrhea (up to 30%) occurs in untreated women over 30 with concomitant obesity, and in patients with normal body weight observed with menarche and does not depend on the duration of anovulation.

DIAGNOSIS OF POLYCYSTIC OVARIAN SYNDROME

Currently, most researchers have accepted the diagnostic criteria proposed at the Rotterdam Consensus in 2004: oligomenorrhea and / or anovulation, hyperandrogenism (clinical and / or biochemical manifestations), echographic signs of polycystic ovaries. The presence of two of these three signs diagnoses PCOS with the exclusion of other causes of PCOS formation.

ANAMNESIS

In anamnesis, in patients with normal body weight, the frequency of past diseases is not higher than in the population; with obesity - a high frequency of neuroinfections, extragenital pathology, aggravated heredity for non-insulin-dependent diabetes mellitus, obesity, arterial hypertension.

PHYSICAL EXAMINATION

On physical examination, the morphotype is female, with overweight, most patients have a visceral type of distribution of adipose tissue; the severity of hirsutism from meager to pronounced. The body mass index is determined: overweight is considered when the body mass index is more than 26 kg/m2, and obesity is considered when the body mass index is more than 30 kg/m2. Depending on the nature of the distribution of adipose tissue, obesity can be of the female type, or gynoid (even distribution of adipose tissue), or of the male type (central, cushingoid, android, visceral) with a predominant deposition of adipose tissue in the area of ​​the shoulder girdle, anterior abdominal wall and mesentery internal organs. The visceral type of obesity is more often accompanied by insulin resistance and is observed in 80% of patients with PCOS and overweight. It is recommended to determine not only the body mass index, but also the ratio of the waist to the hips. This index characterizes the type of obesity and the risk of metabolic disorders. The ratio of the waist to the volume of the hips more than 0.85 corresponds to the visceral type, and less than 0.85 - to the female type of obesity.

The clinical manifestation of insulin resistance is the presence of "acanthosis nigroid": areas of hyperpigmentation of the skin in places of friction (inguinal, axillary, etc.). On palpation of the mammary glands, in most patients, signs of fibrocystic mastopathy are determined. In a gynecological examination in patients with normal body weight, enlarged ovaries are determined.

LABORATORY RESEARCH

When examining the level of hormones in the blood, most patients determine an increased concentration of LH, testosterone, 17-OP, an increase in the ratio of LH / FSH more than 2.5; in 50-55% of cases - a decrease in the concentration of SHBG, an increase in the concentration of DHEAS, in 25% of patients - an increase in the concentration of prolactin. A sensitive method for diagnosing hyperandrogenism is the determination of the free androgen index, which is calculated using the following formula:

Free Androgen Index = Total T x 100 / SHBG

A significant increase in the levels of 17-OP and DHEAS requires the elimination of CAH in the first place. For this, in modern clinical practice, a test with ACTH is used. An increase in the level of 17OP and DHEAS (more than 8–10 times) in response to the administration of ACTH indicates CAH, the cause of which is a genetically determined deficiency of the enzyme 21hydroxylase.

The participation of the ovaries and adrenal glands in the synthesis of testosterone is approximately the same - 30% each. Therefore, an increased concentration of testosterone cannot differentiate between adrenal and ovarian hyperandrogenism. In this connection, for the purpose of differential diagnosis, practitioners can recommend the determination of DHEAS in blood plasma, the main marker of adrenal hyperandrogenism, before and after the test with dexamethasone. The study of 17 corticosteroids and the steroid profile of urine is not very informative, since it reflects the metabolism of all androgens and cannot accurately identify their source even after a test with dexamethasone.

Diagnosis of metabolic disorders is primarily aimed at identifying insulin resistance using the oral glucose tolerance test. At the same time, the basal and stimulated by the intake of 75 g of glucose levels of insulin and glucose are determined in the blood. If after 2 hours the blood glucose level returns to the original values, but there is no insulin, this indicates insulin resistance. If after 2 hours the level of not only insulin, but also glucose is increased, this indicates impaired glucose tolerance. At the same time, there is an increase in basal insulin concentration. At the next stage of metabolic disorders, non-insulin dependent diabetes mellitus develops, which is diagnosed with an increased basal concentration of both glucose and insulin. However, a glucose tolerance test is not recommended.

The main clinical and biochemical criteria for insulin resistance: visceral obesity, "Nigroid acanthosis", glucose-stimulated hyperinsulinemia, fasting insulin level of 12.2 mIU/l or more, HOMA index over 2.5 (fasting insulin x fasting glucose / 22.5).

INSTRUMENTAL STUDIES

The most important method in the diagnosis of PCOS is the echoscopic picture of polycystic ovaries.

Echoscopic criteria for polycystic ovaries:

• ovarian volume more than 8 cm3;
• increase in the area of ​​hyperechoic stroma;
• the number of anechoic follicles up to 10 mm in diameter is at least ten;
• increased blood flow and abundant vascular network in the stroma (with Doppler).

In contrast to the echoscopic picture of multifollicular ovaries, characteristic of early puberty, hypogonadotropic amenorrhea, resistant ovary syndrome, a specific manifestation of multifollicular ovaries on ultrasound is a small number of follicles with a diameter of about 10 mm, located throughout the ovary between a small amount of stroma with a weak echo signal, and the volume of the ovaries does not exceed 8 cm3.

According to the data of echographic and endoscopic examinations, two types of polycystic ovaries were distinguished depending on the location of the follicles in relation to the stroma: type I polycystic ovaries - diffuse - and type II - peripheral location of follicles in relation to the hyperechoic stroma. Type I is more often seen in patients with normal body weight, poor hirsutism, resistant to clomiphene, a high incidence of secondary amenorrhea and OHSS. Type II polycystic ovaries (classic), well known to all, are more often detected in obese patients. It was the patients with type I polycystic ovaries who had a history of pregnancies that ended in spontaneous abortion in the early stages. According to functional diagnostic tests, ovulatory cycles with NLF are periodically tested in them, while visual examination during laparoscopy reveals tecalutein cysts with a diameter of 10–20 mm, similar to the luteinization syndrome of an unovulated follicle. While the ovaries large sizes, the ovarian capsule is thin, but smooth without stigmas, indicating anovulation. This clinical and morphological variant of PCOS (normal body weight, poor hirsutism, high incidence of secondary amenorrhea, type I polycystic ovaries) is becoming more common. Among these patients, “ovulating polycystic ovaries” are observed (approximately 9-11%). Often, laparoscopy reveals OHSS without previous use of ovulation stimulants in the form of tecalutein cysts, sometimes multi-chambered, with a total size of 5 to 10 cm in diameter. This so-called endogenous hyperstimulation due to the influence of its own gonadotropins, the level of which may be normal, occurs in approximately 11-14% of patients with type I polycystic ovaries. This fact indicates a hyperreaction of theca cells to a normal concentration of LH.

Endometrial biopsy is indicated for women with acyclic bleeding due to the high prevalence of endometrial hyperplastic processes. Currently, there is no doubt that women with PCOS have a high risk of developing endometrial cancer. Aggravating factors include metabolic disorders and the duration of anovulation.

DIFFERENTIAL DIAGNOSIS OF POLYCYSTIC OVARIAN SYNDROME

Differential diagnosis carried out in patients with normal body weight with CAH, and with obesity - with secondary polycystic ovaries in patients with metabolic syndrome (Table 18-1, 18-2). As can be seen from the presented data, in the formation of secondary polycystic ovaries, the hormonal and echographic picture does not differ from that in PCOS with obesity. Only on the basis of anamnesis data (the presence of a period of regular menstruation, pregnancy, childbirth, secondary menstrual and generative dysfunction against the background of weight gain) can PCOS with obesity be distinguished from secondary polycystic ovaries. In our opinion, this is important for practicing physicians, since the duration of chronic hyperandrogenic anovulation will be significantly longer in patients with PCOS (with menarche) and obesity, which, first of all, will affect the effectiveness various methods ovulation stimulation.

Table 18-1. Differential diagnostic criteria for VDKN and PCOS with normal body weight

Table 18-2. Differential diagnostic criteria for secondary PCOS against the background of MS and PCOS with obesity

TREATMENT OF POLYCYSTIC OVARIAN SYNDROME

GOALS OF TREATMENT

Treatment of patients with PCOS is aimed at:

• normalization of body weight and metabolic disorders;
• restoration of ovulatory menstrual cycles;
• restoration of generative function;
• elimination of hyperplastic processes of the endometrium;
• elimination of clinical manifestations of hyperandrogenism - hirsutism, acne.

MEDICAL TREATMENT OF POLYCYSTIC OVARIAN SYNDROME

Regardless of the ultimate goal of treatment, at the first stage it is necessary to normalize body weight and correct metabolic disorders. Complex metabolic therapy, including the principles of rational nutrition and medications, is detailed in the Metabolic Syndrome section.

In insulin-resistant patients with normal body weight, metformin therapy, drugs from the biguanide class, is recommended at stage I. Metformin leads to a decrease in peripheral insulin resistance by improving the utilization of glucose in the liver, muscles and adipose tissue. The drug is prescribed at 1000-1500 mg per day under the control of a glucose tolerance test. The duration of therapy is 3-6 months, including against the background of ovulation stimulation.

Stimulation of ovulation is carried out in patients planning pregnancy, after the normalization of metabolic disorders. At the first stage of ovulation induction, clomiphene citrate is used. It should be noted that the long-used method of ovulation stimulation by prescribing estrogen-progestogen drugs, based on the rebound effect after their withdrawal, has not lost its popularity. Clomiphene citrate is a synthetic antiestrogen, a class of selective ER modulators. The mechanism of its action is based on the blockade of the ER at all levels of the reproductive system. After the abolition of clomiphene citrate, the feedback mechanism increases the secretion of GnRH, which normalizes the release of LH and FSH and, accordingly, ovarian folliculogenesis. Clomiphene citrate is prescribed from the 5th to the 9th day of the menstrual cycle, 50-100 mg per day. If there is no effect when prescribing 100 mg, then a further increase in the dose of clomiphene citrate is not advisable. In the absence of ovulation maximum dose within 3 months the patient can be considered resistant to clomiphene citrate. The criterion for evaluating the effectiveness of ovulation stimulation is the restoration of regular menstrual cycles with a hyperthermic basal temperature for 12–14 days, the level of progesterone in the middle of the second phase of the cycle is 15 ng/ml or more, as well as confirmation of ovulation by an individual test that determines the preovulatory LH peak in the urine.

Hyperinsulinemia reduces the effectiveness of ovulation stimulation, therefore, in insulin-resistant patients with PCOS, clomiphene citrate is prescribed while taking metformin, which increases the incidence of ovulation and pregnancy compared with clomiphene citrate alone. The duration of hyperandrogenic anovulation (more than 10 years), age over 28 years can also contribute to resistance to clomiphene citrate. The following criteria for clomiphene resistance can be distinguished: age over 30 years, body mass index> 25, ovarian volume> 10 cm3, LH level> 15 IU / l, estradiol level<150 пмоль/л.

Combined regimens for the treatment of clomiphene citrate. Administration of an ovulatory dose of 10,000 IU hCG may increase the chance of pregnancy in the absence of a response to clomiphene citrate alone. At the same time, ultrasound monitoring of the growing follicle is necessary, hCG is administered with a dominant follicle diameter of at least 18 mm, after which ovulation is noted after 34–36 hours. implantation process. In connection with the antiestrogenic effect of clomiphene citrate, there may be insufficient tension of the cervical mucus in the preovulatory period, a decrease in proliferative processes in the endometrium. Therefore, the effect of clomiphene citrate in terms of ovulation induction is higher than in the onset of pregnancy. In order to treat these undesirable effects, it is recommended to prescribe natural estrogens - estradiol at a dose of 2–4 mg from the 9th to the 14th day of the cycle. With NLF, you can increase the dose of clomiphene citrate or prescribe gestagens in the second phase of the cycle from the 16th to the 25th day. In this case, natural progesterone preparations (dydrogesterone 20 mg per day or progesterone 200 mg per day) are preferable.

Combination therapy with clomiphene citrate and gonadotropins is more effective. Clomiphene citrate is prescribed 100 mg from the 2nd–3rd to the 6th–7th day of the cycle, then on the 5th, 7th, 9th, 11th, 13th day, recombinant FSH is administered at 50–150 IU per day under ultrasound control of folliculogenesis. With a preovulatory follicle diameter of at least 18 mm, 10,000 IU of hCG is administered. The second phase can be supported by the appointment of gestagens (dydrogesterone, progesterone). In the absence of pregnancy against the background of ovulatory cycles, laparoscopy is indicated to exclude peritoneal factors of infertility. In recent years, GnRH antagonists have been used to obtain a rebound effect after their withdrawal (similar to estrogen-progestogen drugs). But against the background of GnRH antagonists, a more pronounced suppression of gonadotropic function occurs, therefore, the effect in stimulating ovulation after withdrawal is higher than after estrogen progestin drugs. 4–6 injections of GnRH antagonists are recommended. This method of ovulation stimulation is preferable to recommend in young patients with normal body weight with type I polycystic ovaries in order to avoid the development of OHSS.

At the second stage of stimulation of ovulation in clomiphene-resistant patients with PCOS who are planning pregnancy, gonadotropins are prescribed. The latest generation drugs are created by fundamentally new technologies. One of the first was a recombinant preparation of pure FSH - puregon ©, its analogue - gonalF ©, with the use of which there is a lower risk of developing OHSS. When prescribing gonadotropins, the patient should be informed about the risk of multiple pregnancy, the possible development of OHSS, as well as about high cost treatment. In this regard, treatment should be carried out only after the exclusion of the pathology of the uterus and tubes, the male factor of infertility. There are many gonadotropin treatment regimens (they are described in detail in the relevant guidelines). The main principle of treatment with gonadotropins is strict transvaginal ultrasound monitoring for the timely termination of stimulation in order to prevent the development of OHSS. The use of GnRH antagonists in ovulation induction protocols in patients with PCOS is increasingly being used as it suppresses the peaks of excess LH secretion, which improves oocyte quality and reduces the risk of developing OHSS.

SURGICAL TREATMENT OF POLYCYSTIC OVARIAN SYNDROME

Surgical laparoscopic ovulation induction is most popular in clomiphene-resistant women with PCOS due to the affordable cost of treatment. In addition, the advantages of laparoscopy include the absence of the risk of OHSS, the onset of multiple pregnancies and the possibility of eliminating the often associated peritoneal factor of infertility. In addition to wedge-shaped resection, laparoscopy offers cauterization of the ovaries using various energies (thermo, electro, laser), which is based on the destruction of the stroma. The absence of ovulation within 2–3 cycles requires the additional prescription of clomiphene citrate, and in insulin-resistant patients, metformin, which increases the pregnancy rate. As a rule, pregnancy occurs within 6-12 months, in the future, the frequency of pregnancy decreases.

The choice of method of surgical stimulation of ovulation depends on the type and volume of polycystic ovaries, the duration of anovulation. With a significant increase in the volume of polycystic ovaries, regardless of the type, a wedge resection is recommended. With a slight increase in the volume of polycystic ovaries, it is possible to carry out endocoagulation of the stroma by the type of demedulation. This tactic is based on the pathogenetic mechanisms of surgical stimulation of ovulation - the maximum removal (or destruction) of the androgen-secreting stroma of polycystic ovaries is carried out, as a result, the extragonadal synthesis of estrone from testosterone decreases, and the sensitivity of the pituitary gland to GnRH is normalized.

FURTHER MANAGEMENT

Despite the rather high overall effectiveness of various methods of ovulation stimulation (75–80%) in restoring ovulation and fertility in PCOS patients, most practitioners note a recurrence of symptoms. Mostly, relapse is observed in patients who have realized a generative function using conservative methods of treatment, as well as after cauterization of polycystic ovaries. Therefore, after childbirth, it is necessary to prevent the recurrence of PCOS, as well as the risk of developing endometrial hyperplastic processes and long-term consequences of insulin resistance - cardiovascular diseases, non-insulin-dependent diabetes mellitus. For this purpose, it is most expedient to prescribe COCs, preferably monophasic ones (Yarina ©, Zhanin ©, Marvelon ©, Diane ©, etc.), and in patients with obesity, the introduction of the intravaginal hormonal releasing system NovaRing © is recommended, when using which there is no weight gain. With poor tolerability of COCs, gestagens can be recommended in the second phase of the cycle.

Treatment of hyperplastic processes of the endometrium. If endometrial hyperplasia, confirmed by histological examination, is detected, at the first stage, therapy with estrogen progestogens, progestogens or GnRH antagonists is carried out, with obesity, progestogens are preferable. Hormone therapy of hyperplastic processes of the endometrium provides for the central and local mechanism of action of the drug, which consists in suppressing the gonadotropic function of the pituitary gland, which inhibits folliculogenesis and, as a result, reduces the endogenous synthesis of steroids; local action of hormonal drugs contributes to the atrophic processes of the endometrium. Hormonal treatment of endometrial hyperplasia in insulin-resistant patients with PCOS is carried out against the background of metabolic therapy. Without correction of metabolic disorders (hyperinsulinemia, hyperglycemia, dyslipidemia), a relapse is natural, which is associated with the role of adipose tissue in steroidogenesis, as well as hyperinsulinemia in exacerbating existing endocrine disorders in PCOS.

For the regulation of the menstrual cycle and the treatment of androgen-dependent dermatopathies, COCs with antiandrogenic action are recommended. The prolonged regimen of taking COCs is more effective in reducing hirsutism, since the gonadotropic function of the pituitary gland is restored in a seven-day break, and, consequently, the synthesis of androgens.

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Polycystic ovaries (ICD-10 code: E28.2) is one of the main causes female infertility. This common disease contributes to the formation of disorders in the body of a woman: ovulation does not occur, the chances of conceiving a child are reduced to almost zero. With polycystic ovaries, they are enlarged, small growths (cysts) are formed in them, which are filled with fluid.

Often the disease is found in women with an excess of male sex hormones. The egg does not mature, there is no ovulation. The follicle does not rupture, but fills with fluid and becomes a cyst. For this reason, the ovaries enlarge.

Symptoms

It is possible to determine the disease by symptoms only in 10% of women of reproductive age. Quite often, such a disease is detected during puberty. The most reliable symptom is an irregular monthly cycle, its absence, long delays, up to several months, infertility (female infertility according to ICD-10). Often the disease accompanies diabetes mellitus, candidiasis. Associated with disorders thyroid gland, adrenal. Polycystic ovary syndrome is characterized by a sharp increase in weight (10 or more kg). According to studies, fat deposits in the center of the torso indicate increased levels of androgens, lipids and sugar. Excess weight is a common problem for women with this disease. With polycystic disease, many women cannot conceive for a long time. But not all patients report the presence of such symptoms.

Causes

There are several theories about the causes of the disease.

According to one theory, the disease appears due to the inability of the body to process insulin. The increased level of insulin produced by the pancreas promotes the production of androgens. Hormonal imbalance interferes with the ovulation process.

According to another theory, the thickening of the protein coat of the ovary leads to the intensive formation of androgens.

Also, doctors do not exclude the importance of heredity and the genetic factor.

Another cause of polycystic ovaries can be a pregnancy that occurs with severe toxicosis, the threat of miscarriage and other pathologies.

The disease can also manifest itself after the use of hormonal drugs during pregnancy.

Polycystic ovaries is possible with an infectious disease or regular colds in childhood. Frequent tonsillitis (ICD-10:J35.0) influence the formation of the disease: the ovaries and tonsils are interconnected.

Stress and excessive physical activity may well contribute to the development of polycystic disease.

Diagnostics

If there are characteristic symptoms, doctors can immediately make a diagnosis, which is confirmed after the examination. On examination, the specialist pays attention to the condition of the skin, the presence of excess weight, the nature of hair growth and the general condition of the body.

Clinical and laboratory examination is prescribed to determine the condition of the genital organs. Ultrasound of the small pelvis allows you to identify changes in the tissues of the ovaries, how much they are enlarged in size. There is an increase in connective tissue. An ultrasound examination may also show the presence of small cysts in one or two ovaries at once and a decrease in the size of the uterus.

Image by jk1991 at FreeDigitalPhotos.net

A biochemical blood test reveals metabolic disorders. Such a disease is usually characterized by elevated levels of cholesterol or glucose. They also examine the blood for lipid and insulin levels.

A blood test to determine hormones helps to determine how elevated the level of male sex hormones. With polycystic disease, usually the level of testosterone and insulin is increased, the level of progesterone is lowered.

Sometimes doctors resort to a biopsy. The endometrium is scraped and then examined under a microscope. The procedure is often prescribed for patients with dysfunctional bleeding.

Basal temperature readings can also indicate pathology. If the woman is healthy, the temperature will increase in the second half of the cycle. When the disease remains unchanged. It is also necessary to identify the likelihood of the influence of a genetic factor, to examine the flora of smears from the vagina, using tomography to exclude the possibility of a tumor.

The laparoscopic method is used for diagnosis and treatment. It reveals subcapsular cysts, ovarian size, capsule thickening.

Treatment

Along with getting rid of polycystic disease, treatment will help reduce the manifestation of other symptoms: hirsutism, acne, pain, and others. Polycystic ovaries are treated with conservative and surgical methods.

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Hormonal drugs are often prescribed. Their action is aimed at normalizing the work of hormones. Also, the patient can get rid of acne, alopecia, hair growth and other unwanted symptoms. Oral contraceptives are usually prescribed. They will help regulate the cycle and normalize ovulation. They also stimulate the growth of follicles in the ovaries and cause ovulation.

If a woman's main goal is pregnancy, but oral contraceptives have not worked, she should make sure that there are no other causes of infertility. To do this, you should be checked for obstruction of the fallopian tubes, the husband needs to donate sperm for analysis. If the results are good, the doctor will prescribe ovulation stimulation.

Endovaginal vibromassage can also be effective. The impact of low-frequency vibration contributes to the expansion of the vessels of the genital organs, stimulating ovulation. The access of medicines to the ovaries will improve, metabolic processes will accelerate. Vibromassage is contraindicated in pregnancy, menstruation, tumors, inflammation of the pelvic organs, thrombophlebitis.

The surgical method of treating the problem of polycystic ovaries is addressed in the following cases:

• if the medical method did not bring positive results;
• the disease proceeds with a long violation of the cycle;
• the woman is over thirty years old.

During surgery, they resort to the destruction of that part of the ovaries that synthesizes androgens. But the ovary is able to recover quickly, so the effect is short-lived. If the patient wants to become pregnant, she should try to conceive a few months after the operation.

Many surgeries for polycystic ovary syndrome are performed laparoscopically. All tests before laparoscopy should be normal. The presence of violations will lead to complications after surgery. Laparoscopy can be performed on any day of the cycle, except for the days of menstruation: there is a risk of large blood loss. Usually, doctors use the following methods of laparoscopy: wedge resection and electrocoagulation.

Wedge resection

This method of operation helps to reduce the level of testosterone and androstenedione. If polycystic ovaries is the main obstacle to conception, most women become pregnant after resection.

After the patient should drink a course of hormonal drugs to restore menstruation. Ovulation often occurs two weeks after resection. The patient can return home on the third day if complications do not follow. After this method of operation, there is a high probability of pregnancy in the first month and the first six months.

Gradually, the cysts may reappear. Some patients experience the cessation of stable menstruation 3 years after resection. Therefore, you should carefully monitor the cycles and see a doctor.

Possible negative consequences of wedge resection:

• adhesions;
• ectopic pregnancy;
• infertility.

The main contraindication to surgery is ovarian cancer.

Laparoscopic electrocoagulation

During laparoscopic electrocoagulation, notches are made on the ovary with an electrode, cauterization of blood vessels is done to avoid bleeding. This is a more gentle way. With this procedure, the chance of the formation of an egg increases. A laparoscopy usually takes 15 minutes. The patient is hospitalized for several days.

Patients are encouraged to move more within a few hours after laparoscopy. Women rarely need pain medication because there is little to no tissue damage. Before wedge resection, electrocoagulation has a number of advantages:

• minimal risk of adhesion formation;
• small blood loss;
• no seams on the abdomen.

The rehabilitation period provides for restrictions: sexual rest for up to one month, sports are contraindicated. Hormonal drugs will help to avoid relapse. Laparoscopy is able to regulate the monthly cycle and the work of the ovaries.

Diet

If overweight, a woman will have to lose weight. She should track the amount of carbohydrates and calories in her diet, and exercise regularly. Weight loss alone can lower androgen and insulin levels and restore ovulation. With the loss of even 10% of the initial weight, it is possible to restore the normal menstrual cycle and reduce the dangerous consequences in the future. But too strict diets and fasting are contraindicated.

From the diet should be excluded soda and fruit juices. They contain too much sugar. Preference should be given to freshly squeezed grapefruit juice diluted with water. It is necessary to exclude sweets, chocolate, sweet pastries. It is better to replace them with dried fruits, nuts, berries. Sweeteners are also harmful. They are almost completely calorie-free, but there are easily digestible carbohydrates. Steamed meat is much healthier than fried meat. White flour meals should be replaced with whole grains. Whole grains are a source of fiber, minerals, and vitamins. The work of the intestines improves, the structure of the skin is restored. Whole grains include whole grain buckwheat, coarse oatmeal, unprocessed wheat and barley flakes, brown and wild rice.

High-fat dairy products should be avoided. You need to consume about a kilogram of dairy products per week. You should also reduce your intake of caffeinated foods.

Folk remedies

Some folk remedies can improve the functioning of the hormonal system. But you should not use funds without the permission of a doctor.

With polycystosis, it is recommended to take an infusion of a boron uterus. Pour 2 tablespoons of grass with two cups of boiling water, cover, leave to infuse for 2 hours. When boiled, the plant loses its beneficial properties. After the liquid must be filtered and taken in a spoon per day. Licorice root has antiviral and antibacterial properties. The infusion is able to lower blood pressure, cholesterol levels. May lower testosterone production. Do not use continuously for more than 6 weeks. Pour one tablespoon of the root with a glass of boiling water, let it brew for an hour and drink once a day.

Folk remedies are useless outside the complex of drug treatment, and their unsystematic or excessive use can be harmful to health.

Consequences

Why is polycystic ovaries dangerous? Often it develops into serious and dangerous diseases. Women with this diagnosis have a predisposition to diabetes, strokes, other heart diseases and oncology. The main complication of polycystic disease is endometrial cancer (endometrial cancer according to ICD-10). With an irregular cycle, the absence of ovulation, only estrogen affects the uterus. Therefore, there is no monthly rejection of the uterine layer, and it grows. Without progesterone, the endometrium becomes thick, which can lead to cell changes and cancer.

Polycystic ovary syndrome is not always cured once and for all, and it should be constantly monitored. Women with this disease should immediately contact a gynecologist-endocrinologist. Polycystic ovaries contribute to the development of very serious ailments: diabetes, oncology and infertility. Women with symptoms of the disease should be screened. When the diagnosis is confirmed, it is necessary to start hormonal therapy or turn to other methods of treatment under the supervision of a specialist.

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What is polycystic ovaries and how to treat a gynecological disease, combined with dysfunctions of the endocrine system

Polycystic ovaries is a gynecological disease, combined with dysfunctions of the endocrine system. The absence of a full-fledged dominant follicle provokes problems with conception. Against the background of PCOS, obesity often develops, women complain about the irregularity of menstruation, the appearance of acne, and excessive body hair.

What should I do if I have polycystic ovaries? What treatments are effective? What measures for PCOS help to get pregnant? Answers in the article.

Polycystic ovaries: what is it

With polycystic ovary syndrome, many small, underdeveloped follicles appear. The number of bubbles can reach a dozen or more. In the absence of a full-fledged dominant follicle, there are failures in the process of ovulation, the egg does not mature, and the regularity of the cycle is disturbed.

In patients with PCOS, on the background of anovulation, doctors diagnose primary infertility. Conducting a full hormone therapy, stimulation of ovulation in many cases allows you to restore the level of fertility, increases the chance of a full conception and gestation.

Amenorrhea (absence of monthly bleeding) or oligomenorrhea (scanty, rare menstruation) often develops. Sometimes bleeding during rejection of endometrial tissue is accompanied by severe pain, the volume of blood is much higher than normal.

Causes of disorders and discomfort: long-term influence of estrogens on the inner layer of the uterus and anovulation. In combination with a decrease in the level of progesterone, the development of hyperplastic processes is possible, which sometimes leads to pathological uterine bleeding. In the absence of treatment, inattention to the symptoms of PCOS, for a long period there is a negative effect on the uterus and appendages, which can cause a malignant process.

Polycystic ovaries ICD code - 10 - E28.2.

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Reasons for the development of pathology

PCOS develops when there are severe disorders in the endocrine system. The pathological process develops when there is a malfunction in the functioning of the ovaries, pituitary gland, adrenal glands.

With the progression of chronic autoimmune pathology, the indicators of female sex hormones are noticeably reduced: estradiol and progesterone, testosterone production is above normal. Hormonal failure occurs against the background of excessive synthesis of luteinizing hormone and prolactin, which is produced by the pituitary gland.

Note! Autoimmune pathology is congenital, hormonal disorders during fetal development are often associated with maternal malnutrition. With a poor diet, the growing body lacks many important substances, without which the full formation of the endocrine and reproductive systems in the female embryo is impossible.

First signs and symptoms

The first menstruation in girls occurs on time - from 12 to 13 years, but the cycle is not established for a long time. Scanty periods or lack of bleeding for six months indicates ovulation. During puberty, excessive hair growth is noticeable, acne often appears, examination shows a bilateral increase in the size of the ovaries. A characteristic feature is the uniform accumulation of fat in different parts of the body, which leads to an increase in body weight, sometimes by 10–20% above the norm.

Dishormonal disorders can be detected not only during a gynecological ultrasound and according to the results of a blood test for hormones, but also by external manifestations. With PCOS, a woman often gains extra pounds, hirsutism increases psycho-emotional discomfort. As you grow older acne often disappears, but obesity and hairiness on the background of excess testosterone remains. Sometimes the values ​​of the male hormone are not much higher than normal, the manifestations of hirsutism are minimal.

Specific symptoms of polycystic ovaries:

• menstrual irregularities;
• the absence or rare occurrence of ovulation;
• primary infertility;
• obesity, development of prediabetes;
• increased levels of cholesterol in the blood;
• thinning hair or their active growth on the body;
• acne;
• during the examination, the doctor notes the appearance of multiple cysts and an increase in the ovaries.

Diagnostics

It is possible to confirm the presence of PCOS in a woman on the basis of a comprehensive examination, according to the totality of echoscopic and clinical symptoms. When making a diagnosis, a long absence of ovulation in combination with high testosterone levels and hyperandrogenism syndromes is taken as the basis.

On bimanual examination, paired organs are dense, larger than usual sizes. Multiple cysts in the body of the ovaries in the absence of a mature dominant follicle are a characteristic sign of polycystic disease (“poly” means “many”).

Be sure to test for hormones: it is important to know the level of progesterone, estrogen, FSH, testosterone, LH. Often, estrogens are practically normal, androgen values ​​are slightly elevated, which reduces the diagnostic value of a blood test in case of suspected PCOS. It is impossible to refuse tests: when choosing hormonal drugs, you need to see the indicators of the main regulators that affect the state of the reproductive and reproductive systems.

In difficult cases, laparoscopy of the ovaries is prescribed for an in-depth examination of the affected organs. If necessary, the doctor performs a tissue biopsy for examination.

Tasks and main directions of therapy

Treatment objectives for polycystic ovaries:

• restore the menstrual cycle;
• reduce negative symptoms that worsen the appearance and health of a woman;
• to achieve the onset of ovulation if a woman is planning a pregnancy;
• protect the walls of the uterus from excessive accumulation of endometrial cells that are not torn away during menstruation, which did not come on time;
• stabilize weight;
• prevent long-term complications associated with PCOS.

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The main methods of therapy:

• taking combined oral contraceptives to stabilize menstrual function. Depending on the level of testosterone, the gynecologist selects the optimal type of COC: Jazz, Jeanine, Diana 35, Yarina, Marvelon;
• to achieve pregnancy, ovulation is stimulated. There are several schemes, but the combination of Clomiphene in the first phase of the cycle and Duphaston tablets for 10 days in the luteal (second) phase is most effective and in demand. Ovarian hyperstimulation requires strict adherence to the drug regimen, timely testing, and an ovulation test on the recommendation of a doctor;
• Diet modification is an essential element of treatment. With polycystic ovaries, you need to stabilize the weight at levels that are optimal for height, age and body type. You can not starve, adhere to strict diets, eat only vegetables or buckwheat. An unbalanced diet increases fluctuations hormonal background that interfere with the healing process. You should not eat sugar, smoked meats, muffins, fatty foods, you need to limit salt, spices. It is useful to eat five to six times throughout the day, drink up to one and a half to two liters of water to maintain water balance;
• baths with coniferous elixir, herbal decoctions, sea salt are useful;
• according to the doctor's prescription, you need to take a complex of vitamins: tocopherol, ascorbic acid, riboflavin, biotin, cyanocobalamin. Vitamin therapy is needed to stimulate metabolic processes, normalize progesterone synthesis, strengthen immunity, improve the condition of blood vessels;
• surgical treatment with removal of multiple cysts is carried out with low efficiency of conservative therapy. Endoscopic surgery is less traumatic, the result after the procedure is in most cases positive - the probability of pregnancy against the background of the maturation of a full-fledged follicle increases several times.

Possible consequences

Against the background of long-term failure of the reproductive and endocrine systems, an increased risk of negative processes in various parts of the body was confirmed. The more attention a woman pays to health, the lower the likelihood of complications, but the development of pathologies cannot be completely excluded: diabetes mellitus, arterial hypertension, endometrial hyperplasia, oncopathology of the uterus and appendages.

Polycystic ovaries and pregnancy

Can you get pregnant with polycystic ovaries? Some "specialists" in their materials indicate inaccurate information: with PCOS, infertility necessarily develops, the probability of becoming pregnant is extremely low. After reading such articles, women who have been diagnosed with polycystic ovaries panic, despair, and become depressed. Nervous overload, taking tranquilizers, depressed mood causes even more active fluctuations in the hormonal background, which does not contribute to the restoration of the ability to conceive.

Reproductologists recommend that women with PCOS do not despair, go to the clinic with modern diagnostic equipment and qualified personnel. For the onset of a long-awaited pregnancy, you will have to undergo a course of drug therapy or undergo an endoscopic operation to remove multiple cysts. To achieve a positive result, time must pass: most often, conception occurs six months to a year after the start of treatment, sometimes therapy lasts longer. In some cases, it is possible to stabilize the menstrual cycle in a shorter time if ovulation occurs periodically.

A woman will need patience, accuracy in plotting a basal temperature chart. It is important to take antiandrogenic COCs strictly on schedule.

To stimulate the ovaries, in which a full-fledged egg should mature, on certain days a woman receives hormonal injections (hCG - human chorionic gonadotropin). Under the influence of regulators, a healthy follicle is formed in the ovary, which bursts and allows the prepared egg to be released. It is during this period that you need to do an ovulation test to confirm the optimal time for conception. Sexual intercourse is obligatory (also the next day) for the penetration of spermatozoa to a mature egg.

Before ovarian stimulation, you need to pass a test for tubal patency (a procedure called hysterosalpinography), which is important for free passage into the uterine cavity from the ovaries. A man should take a spermogram to confirm a sufficient number of mobile and healthy spermatozoa. Subject to the conditions, the absence of obstacles and pathological changes in the ejaculate and fallopian tubes, ovarian hyperstimulation can be performed.

If the ovaries are unresponsive to the standard dose, the reproductologist increases the rate of Clomiphene or, when the level of 200 mg is reached, drugs from another group are prescribed. It is important to monitor with ultrasound so that there is no excessive stimulation of the ovaries.

A positive result in the treatment of infertility against the background of PCOS gives "drilling" of the ovaries - a laparoscopic operation, during which the surgeon removes part of the thickened capsule with multiple cysts, freeing the passage for the follicle. After the operation, the production of testosterone decreases, with an excess of which it is often difficult to get pregnant. After laparoscopy of the ovaries, pregnancy can occur in the next full menstrual cycle. In most cases, conception occurs within a year after ovarian surgery.

After the onset of pregnancy, a woman with PCOS is under the supervision of a doctor. It is important to monitor the hormonal background in order to avoid spontaneous abortion, gestational diabetes, and other complications.

Prevention

The defeat of the endocrine system often occurs against the background of a genetic predisposition and endocrine pathologies. An autoimmune disease develops if the cells of the female fetus did not receive enough nutrients and hormones, without which the proper formation of the endocrine and reproductive system is impossible. Reasons: a poor diet during pregnancy, the impact of high doses of radiation, the expectant mother taking potent drugs, hormonal disruptions during the period of gestation, endocrine diseases.

You can reduce the risk of polycystic ovaries with a quality examination when planning a pregnancy. With deviations in the work of the endocrine system, you need to undergo a course of therapy under the guidance of an experienced doctor. It is important to reduce the impact of chronic pathologies, to ensure proper nutrition during pregnancy.

More information about the features of nutrition and diet in the treatment of polycystic ovaries can be found in the following video:

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polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a pathology of the structure and function of the ovaries, the main criteria of which are chronic anovulation and hyperandrogenism. The frequency of PCOS in the structure of endocrine infertility reaches 75%.

Symptoms of polycystic ovary syndrome

Violation of the menstrual cycle by the type of oligo-, amenorrhea. Since the violation of the hormonal function of the ovaries begins with the puberty, then the violations of the cycle begin with the menarche and do not tend to normalize. It should be noted that the age of menarche corresponds to that in the population - 12-13 years (in contrast to adrenal hyperandrogenism in adrenogenital syndrome, when menarche is late). Approximately in 10-15% of patients, menstrual irregularities have the character of dysfunctional uterine bleeding against the background of endometrial hyperplastic processes. Therefore, women with PCOS are at risk of developing endometrial adenocarcinoma, fibrocystic mastopathy and breast cancer, as well as problems with pregnancy.

anovulatory infertility. Infertility has a primary character, in contrast to adrenal hyperandrogenism, in which pregnancy is possible and its miscarriage is characteristic.

Hirsutism of varying severity develops gradually from the menarche period, in contrast to adrenogenital syndrome, when hirsutism develops before menarche, from the moment of activation of the hormonal function of the adrenal glands during the adrenarche period.

Excess body weight is observed in approximately 70% of women and corresponds to the II-III degree of obesity. Obesity often has a universal character, as evidenced by the ratio of waist to hip volume (WT / OB) less than 0.85, which characterizes the female type of obesity. The ratio of OT / OB more than 0.85 characterizes the cushingoid (male) type of obesity and is less common.

The mammary glands are developed correctly, every third woman has fibrocystic mastopathy, which develops against the background of chronic anovulation and hyperestrogenism.

In recent years, when they began to study the features of metabolism in PCOS, it was found that insulin resistance and compensatory hyperinsulinemia often occur - disorders of carbohydrate and fat metabolism of the diabetic type. There is also dyslipidemia with a predominance of lipoproteins of the atherogenic complex (cholesterol, triglycerides, LDL and VLDL). This, in turn, increases the risk of developing cardiovascular diseases in the second or third decade of life, i.e., in age periods in which these diseases are not characteristic.

Causes of polycystic ovary syndrome

There is still no consensus on the causes of the development of the disease.

PCOS is a multifactorial pathology, possibly genetically determined, in the pathogenesis of which the central mechanisms of regulation of the gonadotropic function of the pituitary gland from the puberty, local ovarian factors, extraovarian endocrine and metabolic disorders that determine clinical symptoms and morphological changes in the ovaries operate.

Diagnosis of polycystic ovary syndrome

• Stroma hyperplasia;
• hyperplasia of theca cells with areas of luteinization;
• the presence of many cystic-atretic follicles with a diameter of 5-8 mm, located under the capsule in the form of a "necklace";
• thickening of the ovarian capsule.

A characteristic history, appearance, and clinical symptoms facilitate the diagnosis of PCOS. In a modern clinic, a diagnosis can be made without hormonal studies, although they also have characteristic features.

The diagnosis of polycystic ovaries can be established with transvaginal ultrasound, as clear criteria for the echoscopic picture are described: ovarian volume is more than 9 cm3, hyperplastic stroma is 25% of the volume, more than ten atretic follicles up to 10 mm in diameter, located along the periphery under a thickened capsule.

The volume of the ovaries is determined by the formula: V \u003d 0.523 (L x Sx H) cm3, where V, L, S, H are the volume, length, width and thickness of the ovary, respectively; 0.523 is a constant factor. The increase in ovarian volume due to the hyperplastic stroma and the characteristic location of the follicles help to differentiate polycystic ovaries from normal (on the 5-7th day of the cycle) or multifollicular ones. The latter are typical for early puberty, hypogonadotropic amenorrhea, long-term use of COCs. Multifollicular ovaries are characterized by ultrasound with a small number of follicles with a diameter of 4-10 mm located throughout the ovary, a normal pattern of stroma and, most importantly, a normal ovarian volume (4-8 cm3).

Thus, ultrasound is a non-invasive, highly informative method that can be considered the "gold standard" in the diagnosis of PCOS.

Hormonal characteristics of PCOS. The diagnostic criteria are: an increase in the level of LH, an increase in the ratio of LH / FSH more than 2.5, an increase in the level of total and free T with a normal content of DEA-C and 17-OHP.

After the test with dexamethasone, the content of androgens slightly decreases, by about 25% (due to the adrenal fraction).

The test with ACTH is negative, which excludes adrenal hyperandrogenism, characteristic of adrenogenital syndrome. There was also an increase in insulin levels and a decrease in PSSH in the blood.

Metabolic disorders in PCOS are characterized by an increase in triglycerides, LDL, VLDL and a decrease in HDL.

In clinical practice, a simple and accessible method for determining impaired glucose tolerance to insulin is a sugar curve. Blood sugar is determined first on an empty stomach, then within 2 hours after taking 75 g of glucose. If after 2 hours the blood sugar level does not reach the initial values, this indicates impaired glucose tolerance, i.e., insulin resistance, which requires appropriate treatment.

Endometrial biopsy is indicated for women with acyclic bleeding due to the high frequency of endometrial hyperplastic processes.

The criteria for a diagnosis of PCOS are:

• Timely age of menarche;
• violation of the menstrual cycle from the period of menarche in the vast majority of cases by the type of oligomenorrhea;
• hirsutism and obesity since menarche in more than 50% of women;
• primary infertility;
• chronic anovulation;
• an increase in the volume of the ovaries due to the stroma according to transvaginal echography;
• increase in the level of T;
• increase in LH and LH/FSH ratio > 2.5.

Stages of treatment for polycystic ovary syndrome

As a rule, patients with PCOS go to the doctor with complaints of infertility. Therefore, the goal of treatment is to restore ovulatory cycles.

In PCOS with obesity and with normal body weight, the sequence of therapeutic measures is different.

In the presence of obesity:

• The first stage of therapy is the normalization of body weight. Weight loss on the background of a reduction diet leads to the normalization of carbohydrate and fat metabolism. The PCOS diet provides for a reduction in the total calorie content of food to 2000 kcal per day, of which 52% are carbohydrates, 16% are proteins and 32% are fats, and saturated fats should be no more than 1/3 of the total fat. An important component of the diet is the restriction of spicy and salty foods, liquids. A very good effect is noted when using unloading days, fasting is not recommended due to the consumption of protein in the process of gluconeogenesis. Raise physical activity is an important component not only to normalize body weight, but also to increase the sensitivity of muscle tissue to insulin. Most importantly, it is necessary to convince the patient of the need to normalize body weight, as the first stage in the treatment of PCOS.
• The second stage of therapy is the drug treatment of metabolic disorders (insulin resistance and hyperinsulinemia) in the absence of the effect of a reduction diet and physical activity. Metformin is a drug that increases the sensitivity of peripheral tissues to insulin. Metformin leads to a decrease in peripheral insulin resistance, improving the utilization of glucose in the liver, muscles and adipose tissue; normalizes the lipid profile of the blood, reducing the level of triglycerides and LDL. The drug is prescribed at 1000-1500 mg per day for 3-6 months under the control of a glucose tolerance test.
• The third stage of therapy is the stimulation of ovulation after the normalization of body weight and in PCOS with normal body weight. Stimulation of ovulation is carried out after the exclusion of tubal and male factors of infertility.

Therapeutic methods of stimulation of ovulation in PCOS

After normalization of body weight and in PCOS with normal body weight, stimulation of ovulation is indicated. Stimulation of ovulation is carried out after the exclusion of tubal and male factors of infertility.

Most doctors start ovulation induction with Clomiphene. It should be noted that the long-used method of ovulation stimulation using estrogen-progestin drugs, based on the rebound effect after their cancellation, has not lost its popularity. In the absence of the effect of therapy with estrogen-gestagens and Clomiphene, the appointment of gonadotropins or surgical stimulation of ovulation is recommended.

"Clomiphene" refers to non-steroidal synthetic estrogens. Its mechanism of action is based on the blockade of estradiol receptors. After the abolition of Clomiphene, GnRH secretion increases by the feedback mechanism, which normalizes the release of LH and FSH and, accordingly, the growth and maturation of follicles in the ovary. Thus, Clomiphene does not directly stimulate the ovaries, but acts through the hypothalamic-pituitary system. Stimulation of ovulation with "Clomiphene" begins from the 5th to the 9th day of the menstrual cycle, 50 mg per day. With this mode, the increase in the level of gonadrtropins induced by the drug occurs at a time when the choice of the dominant follicle has already been completed. Earlier administration may stimulate the development of multiple follicles and increase the risk of multiple pregnancies. In the absence of ovulation according to ultrasound and basal temperature, the dose of Clomiphene can be increased in each subsequent cycle by 50 mg, until reaching 200 mg per day. However, many clinicians believe that if there is no effect when prescribing 100-150 mg of Clomiphene, a further increase in dose is inappropriate. In the absence of ovulation at the maximum dose for 3 months, the patient can be considered resistant to the drug.

The criteria for the effectiveness of ovulation stimulation are:

• Restoration of regular menstrual cycles with hyperthermic basal temperature within 12-14 days;
• progesterone level in the middle of the second phase of the cycle 5 ng / ml or more, preovulatory LH peak;
• Ultrasound signs of ovulation on the 13-15th day of the cycle:
• the presence of a dominant follicle with a diameter of at least 18 mm;
• the thickness of the endometrium is at least 8-10 mm.

In the presence of these indicators, it is recommended to administer an ovulatory dose of 7500-10000 IU of human chorionic gonadotropin - hCG ("Profazi", "Horagon", "Pregnil"), after which ovulation is noted after 36-48 hours. When treating with Clomiphene, it should be borne in mind that it has antiestrogenic properties, reduces the amount of cervical mucus (“dry neck”), which prevents sperm penetration and inhibits endometrial proliferation and leads to impaired implantation in case of fertilization of the egg. In order to eliminate these undesirable effects of the drug, it is recommended to take natural estrogens at a dose of 1-2 mg or their synthetic analogues (Microfollin) from the 10th to the 14th day of the cycle to increase the permeability of the cervical mucus and the proliferation of the endometrium after the end of the Clomiphene intake. .

The frequency of ovulation induction in the treatment of Clomiphene is approximately 60-65%, the onset of pregnancy is 32-35% of cases, the frequency of multiple pregnancies, mainly twins, is 5-6%, the risk of ectopic pregnancy and spontaneous miscarriages is not higher than in populations. In the absence of pregnancy against the background of ovulatory cycles, the exclusion of peritoneal infertility factors during laparoscopy is required.

With resistance to Clomiphene, gonadotropic drugs are prescribed - direct ovulation stimulants. Human menopausal gonadotropin (hMG) prepared from the urine of postmenopausal women is used. HMG preparations contain LH and FSH, 75 IU each (Pergonal, Menogon, Menopur, etc.). When prescribing gonadotropins, the patient should be informed about the risk of multiple pregnancy, the possible development of ovarian hyperstimulation syndrome, and the high cost of treatment. Treatment of polycystic ovary syndrome should be carried out only after the exclusion of the pathology of the uterus and tubes, as well as the male factor of infertility. In the course of treatment, transvaginal ultrasound monitoring of folliculogenesis and the state of the endometrium is mandatory. Ovulation is initiated by a single injection of hCG at a dose of 7500-10000 IU when at least one follicle with a diameter of 17 mm is present. If more than 2 follicles with a diameter of more than 16 mm or 4 follicles with a diameter of more than 14 mm are detected, the introduction of hCG is undesirable due to the risk of multiple pregnancies.

When ovulation is stimulated by gonadotropins, the pregnancy rate rises to 60%, the risk of multiple pregnancy is 10-25%, ectopic - 2.5-6%, spontaneous miscarriages in cycles ending in pregnancy reach 12-30%, ovarian hyperstimulation syndrome is observed in 5 -6% of cases.

Surgical methods of ovulation stimulation in PCOS

The surgical method of ovulation stimulation (wedge resection of the ovaries) in recent years has been performed laparoscopically, thereby ensuring minimal invasive intervention and reducing the risk of adhesion formation. In addition, the advantage of laparoscopic resection is the ability to eliminate the often associated peritoneal factor of infertility. In addition to wedge resection, during laparoscopy, it is possible to perform cauterization of the ovaries using various types of energy (thermo-, electro-, laser), which is based on the destruction of the stroma with a point electrode. Produced from 15 to 25 punctures in each ovary; the operation is less traumatic and lengthy compared to wedge resection.

In most cases, in the postoperative period, after 3-5 days, a menstrual-like reaction is observed, and after 2 weeks - ovulation, which is tested by basal temperature. The absence of ovulation within 2-3 cycles requires the additional appointment of Clomiphene. As a rule, pregnancy occurs within 6-12 months, in the future, the frequency of pregnancy decreases. The absence of pregnancy in the presence of ovulatory menstrual cycles dictates the need to exclude the tubal factor of infertility.

The frequency of ovulation induction with any laparoscopic technique is approximately the same and amounts to 84-89%, on average, pregnancy occurs in 72% of cases.

Despite a fairly high effect in ovulation stimulation and pregnancy, most clinicians note a recurrence of clinical symptoms after about 5 years. Therefore, after pregnancy and childbirth, it is necessary to prevent the recurrence of PCOS, which is important, given the risk of developing endometrial hyperplastic processes. For this purpose, it is most expedient to prescribe COCs, preferably monophasic ones (Marvelon, Femoden, Diana, Mercilon, etc.). With poor tolerability of COCs, which happens with overweight, progestogens can be recommended in the second phase of the cycle: "Dufaston" at a dose of 20 mg from the 16th to the 25th day of the cycle.

Women who do not plan pregnancy, after the first stage of ovulation stimulation with Clomiphene, aimed at identifying the reserve capabilities of the reproductive system, are also recommended to prescribe COCs or progestogens to regulate the cycle, reduce hirsutism and prevent hyperplastic processes.

Technique of wedge resection of the ovary

Indications: sclerocystic ovarian syndrome. At the same time, the ovaries are enlarged by 2-5 times, sometimes less than normal, covered with a dense thick fibrous membrane of a whitish or gray color.

Characteristic features are also the absence of corpus luteum in the ovaries, a very small number of small immature follicles.

In the syndrome of sclerocystic ovaries, despite their large mass, which is many times greater than the mass of normal ovaries, their hormonal function is often reduced. Clinically, this is often manifested by menstrual dysfunction, hypomenstrual syndrome, or amenorrhea. In some patients, maturation and rupture of follicles is sometimes observed. In these cases, the childbearing function may not be impaired, although, as a rule, menstrual dysfunction and infertility are observed with sclerocystic ovary syndrome.

generally accepted methodology surgical treatment syndrome of sclerocystic ovaries is a marginal wedge resection of both ovaries; it is recommended to excise two-thirds of the mass of each ovary.

The technique of the operation is simple. After laparotomy from abdominal cavity remove first one, then the second ovary. The tubal end of the ovary is sutured (taken on a "holder") for ease of manipulation and the main part of the operation is started.

Holding the ovary with the fingers of the left hand, a significant part of its tissues is excised along the free edge of the right hand - from half to two thirds. It is best to do this with a scalpel. It should be remembered that if the scalpel blade penetrates very deep in the direction of the hilum of the ovary, then the blood vessels, the ligation of which causes the development of ischemia of the remaining ovarian tissues. This will immediately negatively affect the results of the operation. If the injury to the ovarian vessels during the operation goes unnoticed, in postoperative period internal bleeding will occur, to stop which it will inevitably be necessary to perform relaparotomy and stitching of bleeding vessels. When suturing the ovary, one should not try to carefully connect the edges of the wound.

If they diverge a little in the future, ovulation will be easier.

After the toilet of the abdominal cavity, they begin to restore the integrity of the anterior abdominal wall by layer-by-layer stitching of the edges of the surgical wound and, finally, apply an aseptic bandage.

The main points of the marginal wedge resection of the ovary after laparotomy are as follows:

1. Inspection of the uterus, both ovaries and fallopian tubes;
2. flashing the tubal end of each ovary (taking them on "holds");
3. marginal wedge-shaped resection of two-thirds of the mass of both ovaries with their small cystic degeneration due to the persistence of follicles, or with sclerocystic degeneration of the ovaries (Stein-Leventhal syndrome);
4. if a tumor is detected during surgery, an excision is made within healthy tissues;
5. piercing or diathermopuncture of persistent follicles;
6. restoration of the integrity of the ovaries by applying a continuous catgut suture or knotted sutures;
7. abdominal toilet;
8. layer-by-layer suturing of the surgical wound;
9. aseptic dressing.

Treatment of hyperplastic processes in PCOS

Treatment of hyperplastic processes of the endometrium (see endometrial hyperplasia, as well as an article on its treatment). Recurrent endometrial hyperplastic processes in PCOS are an indication for ovarian resection.

Treatment of hirsutism

Treatment of hirsutism is the most difficult task, which is due not only to hypersecretion of androgens, but also to their peripheral metabolism.

At the level of the target tissue, in particular the hair follicle, T is converted into active dihydrotestosterone under the influence of the 5α-reductase enzyme. Of no small importance is the increase in fractions of free androgens, which aggravates clinical manifestations hyperandrogenism.

Treatment of hirsutism involves blocking the action of androgens in various ways:

• Inhibition of synthesis in endocrine glands;
• an increase in the concentration of PSSH, i.e., a decrease in biologically active androgens;
• inhibition of the synthesis of dihydrotestosterone in the target tissue due to inhibition of the activity of the enzyme 5α-reductase;
• blockade of androgen receptors at the level of the hair follicle.

Given the role of adipose tissue in the synthesis of androgens, an indispensable condition in the treatment of hirsutism in obese women is the normalization of body weight. A clear positive correlation has been shown between androgen levels and body mass index. In addition, given the role of insulin in hyperandrogenism in women with PCOS, insulin resistance therapy is needed.

Combined oral contraceptives are widely used to treat hirsutism, especially in mild forms. The mechanism of action of COCs is based on the suppression of LH synthesis, as well as an increase in the level of PSSH, which reduces the concentration of free androgens. Most effective in terms of clinical research, COCs containing desogestrel, gestodene, norgestimate.

One of the first antiandrogens was cyproterone acetate ("Androkur"), the mechanism of action of which is based on the blockade of androgen receptors in the target tissue and suppression of gonadotropic secretion. Diane-35 is also an antiandrogen, combining 2 mg of cyproterone acetate with 35 µg of ethinyl estradiol, which also has a contraceptive effect. Strengthening the antiandrogenic effect of "Diana" can be achieved by the additional appointment of "Androcur" - 25-50 mg from the 5th to the 15th day of the cycle. The duration of treatment ranges from 6 months to 2 years or more. The drug is well tolerated side effects sometimes at the beginning of the reception there is lethargy, pastosity, mastalgia, weight gain and a decrease in libido.

"Spironolactone" ("Veroshpiron") also has an antiandrogenic effect. Blocks peripheral receptors and androgen synthesis in the adrenal glands and ovaries, promotes weight loss. With long-term use of 100 mg per day, there is a decrease in hirsutism. Side effect: weak diuretic effect (in the first 5 days of treatment), lethargy, drowsiness. Duration of treatment - from 6 months to 2 years or more.

Flutamide is a non-steroidal antiandrogen used in the treatment of prostate cancer. The mechanism of action is based mainly on the inhibition of hair growth by blockade of receptors and a slight suppression of the synthesis of T. side effects not marked. It is prescribed 250-500 mg per day for 6 months or more. Already after 3 months, a pronounced clinical effect was noted without changes in the level of androgens in the blood.

Agonists of gonadotropic releasing hormones (Zoladex, Diferelin Depot, Buserelin, Decapeptil) are rarely used to treat hirsutism. They can be prescribed for high LH levels. The mechanism of action is based on the blockade of the gonadotropic function of the pituitary gland and, consequently, LH-dependent androgen synthesis in the cells of the ovarian theca. The disadvantage is the appearance of complaints characteristic of the climacteric syndrome, caused by a sharp decrease in ovarian function. These drugs are rarely used to treat hirsutism.

Medical treatment hirsutism is not always effective, so various types of hair removal (electro-, laser, chemical and mechanical) are widely used.

Hyperandrogenism and chronic anovulation are observed in endocrine disorders such as adrenogenital syndrome, neuroexchange-endocrine syndrome, Cushing's disease and hyperprolactinemia. At the same time, morphological changes similar to polycystic ovary syndrome develop in the ovaries, and hyperandrogenism occurs. In such cases, we are talking about the so-called secondary polycystic ovaries and the main principle of treatment is the therapy of the above diseases.

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How polycystic ovaries manifest and what happens: symptoms and causes

A woman's health is essential to her full life and Have a good mood. However, often patients are not aware that they have any disease.

So, neoplasms in the ovaries lead to many harmful consequences. Therefore, it is necessary to know the symptoms of polycystic ovaries and the causes that cause it. From what this pathology arises and what threatens we will consider later in the article.

What it is?

Polycystic ovaries is a disease of the female gonads of hormonal etiology, characterized by the multiple formation of cysts in their tissue.

Cysts are located both distantly from each other and in clusters. They also affect not only the surface of the organ, but also its internal space.

The ovaries are the reproductive organs of a woman in which eggs are formed. They consist of a body and a protein membrane. It is in the shell that follicles are formed, one of which becomes dominant, matures and subsequently bursts. An egg is released from such a follicle, which starts the process of ovulation.

Healthy ovaries have the following dimensions:

• width - about 25 mm;
• length - about three centimeters;
• thickness - about one and a half centimeters;
• volume - no more than 80 cubic meters. mm.

However, with polycystic disease, the dominant one does not stand out among the follicles, and therefore all the eggs remain immature. Ovulation does not occur, and the woman cannot become pregnant. In rare cases, when conception is successful, due to a hormonal imbalance, a natural termination of pregnancy occurs at an early stage.

With a disease, the volume of the ovaries becomes more than 9 cubic meters. see what helps in the diagnosis of polycystic disease.

(Image is clickable, click to enlarge)

By origin, polycystic disease is divided into the following types:

• Primary - has a genetic predisposition and is congenital or debuts in adolescent girls with the onset of the development of secondary sexual characteristics.
• Secondary - develops as a complication of other diseases and is more of a syndrome than a pathology. Its development occurs after the onset of menstruation.

This disease is often confused with multifollicular ovaries. It is important to understand that these are different states and there is a difference.

So, multifollicular ovaries are a kind of norm, treatment is not always required. This phenomenon is accompanied by the development of a large number of follicles, which is typical for the first week of the menstrual cycle. With polycystosis, it is not follicles that develop, but cysts - pathological formations filled with liquid contents.

This disease also differs from an ovarian cyst. With the latter, the formation in the gland is solitary and more often affects only one organ, while polycystic disease spreads to both sides. The causes of pathologies also differ.

According to statistics, 5-10% of women of reproductive age suffer from polycystic disease. It is this disease that leads to 25% of cases of female infertility. According to the International Classification of Diseases of the tenth edition of the ICD-10, polycystic ovaries refers to their dysfunction and has the code E28.2.

• Excess androgens and insulin prevent ovulation.
• Obesity increases the amount of estrogen. The body tries to restore balance and produces more testosterone.
• Chronic inflammation. Because of it, the body becomes insensitive to insulin, which leads to an increase in its level.
• Genetic predisposition for primary polycystic disease.

In addition to the causes, there are factors that trigger the development of the disease:

• excess weight;
• constant stress;
• irregular sex life;
• a large number of abortions.

In adolescence, polycystic disease is particularly affected by:

• smoking;
• unbalanced diet;
• early sexual life;
• little physical activity.

Psychosomatics in the development of the disease should not be excluded either. So, anxious and stressed women suffer more than others from polycystic disease. Psychological reasons are:

• problems with menstruation;
• dissatisfaction with their appearance;
• unhealthy relationship with a partner;
• inability to get pregnant, or loss of a child.

The last factor is the most important, since the feeling of losing such a loved one leads to functional changes in the body. With the death of a child, miscarriage or inability to become pregnant, the woman's body reacts to the feeling of loss by the formation of a cyst in the ovary.

With a large number of stresses and experiences, polycystic disease is formed.

• violation of the menstrual cycle;
• an increase in the amount of hair (hirsutism) in the perineum, on the abdomen and inner thighs, the appearance of antennae above upper lip(see photo);
• excess weight.

With the further development of polycystic disease, the patient's condition worsens. It is caused by an increase in the level of male hormones in the body. The disease is accompanied by the following symptoms:

• the scarcity or abundance of discharge during menstruation;
• different duration of menstruation;
• acne;
• low voice;
• bald patches of the male type;
• mastopathy;
• high insulin levels;
• uterine bleeding (may be perceived as menstruation);
• brown discharge (stained with blood);
• pain in the lower abdomen;
• mood lability;
• infertility.

This will help to diagnose the disease in a timely manner and prescribe therapy.

• type II diabetes;
• malignant tumors in the uterus and mammary glands;
• atherosclerosis;
• rheumatic diseases;
• hepatitis due to accumulation of fat in the liver;
• increased risk of heart attack and stroke.

In addition, the disruption of the work of the endocrine glands is aggravated, which further worsens the course of the disease:

• thyroid;
• hypothalamus;
• adrenal glands;
• pituitary.

Polycystic ovary syndrome is a disease that worsens a woman's well-being and self-perception. Along with unpleasant symptoms, it leads to harmful and even dangerous consequences and complications. This explains the need for its timely diagnosis and treatment.

How to treat polycystic ovaries read in our article.

Find out the main causes of polycystic ovaries from the video:

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2018 Women's Health Blog.

), adrenal cortex (hypersecretion of adrenal androgens), hypothalamus and pituitary gland.

Nomenclature Other names for this syndrome are as follows: polycystic ovary disease (incorrect, since this condition is not characterized as a disease, a separate nosological form, but as a clinical syndrome, the causes of which may be different); functional ovarian hyperandrogenism (or functional ovarian hyperandrogenism); hyperandrogenic chronic anovulation; ovarian dysmetabolic syndrome; polycystic ovary syndrome; polycystic ovaries. Definitions There are two most commonly used definitions of polycystic ovary syndrome in clinical practice. The first definition was developed in 2008 by consensus of an expert panel formed by the American National Institutes of Health (NIH). According to this definition, a patient should be diagnosed with PCOS if she also has: Symptoms of excessive activity or excessive secretion of androgens (clinical and / or biochemical); oligoovulation or anovulation The second definition was formulated in the year by the consensus of European experts formed in Rotterdam. By this definition, a diagnosis is made if the patient has any two of the following three signs at the same time: Symptoms of excessive activity or excessive secretion of androgens (clinical or biochemical); oligoovulation or anovulation; Polycystic ovaries on abdominal ultrasound and if other causes that can cause polycystic ovaries are excluded. The Rotterdam definition is much broader and includes significantly more patients in the group suffering from this syndrome. In particular, it includes patients without clinical or biochemical evidence of androgen excess (because any two of the three signs, not all three), while in the American definition, excess secretion or excess activity of androgens is a prerequisite for a diagnosis of PCOS. Critics of the Rotterdam definition argue that findings from studies of androgen-excess patients cannot necessarily be extrapolated to patients without androgen-excess symptoms. Symptoms Common symptoms of PCOS are as follows: Oligomenorrhea, amenorrhea - irregular, rare menstruation or complete absence of menstruation; those menstruations that do occur can be pathologically scanty or, on the contrary, excessively abundant, as well as painful; Infertility, usually the result of chronic anovulation or oligoovulation (complete absence of ovulation or ovulation does not occur in every cycle); Elevated blood levels of androgens (male hormones), especially free fractions of testosterone, androstenedione and dehydroepiandrosterone sulfate, which causes hirsutism and sometimes masculinization; Central obesity - "spider" or "apple-shaped" male-type obesity, in which the bulk of adipose tissue is concentrated in the lower abdomen and in the abdominal cavity; Androgenetic alopecia (significant baldness or male-pattern hair loss with bald patches on the sides of the forehead, above the forehead line, at the crown, occurring due to hormonal imbalance); Acanthosis (dark pigment spots on the skin, from light beige to dark brown or black); Acrochordons (skin folds) - small folds and wrinkles of the skin; Stretch marks (stretch marks) on the skin of the abdomen, usually as a result of rapid weight gain; Long periods of symptoms resembling those of premenstrual syndrome (swelling, mood swings, pain in the lower abdomen, lower back, pain or swelling of the mammary glands); Sleep apnea - stops breathing during sleep, leading to frequent nocturnal awakenings of the patient; Depression, dysphoria (irritability, nervousness, aggressiveness), often drowsiness, lethargy, apathy, complaints of "fog in the head". Multiple ovarian cysts. Sonographically, they may appear as a "necklace of pearls", a cluster of whitish vesicles, or "fruit pits" scattered throughout the ovarian tissue; Enlarged ovaries, usually 1.5 to 3 times normal, resulting from multiple small cysts; Thickened, smooth, pearly white outer surface (capsule) of the ovaries; Thickened, hyperplastic endometrium of the uterus as a result of a chronic excess of estrogen, not balanced by adequate progesterone influences; Chronic pain in the lower abdomen or lower back, in the pelvic region, probably due to compression of the pelvic organs by enlarged ovaries or due to hypersecretion of prostaglandins in the ovaries and endometrium; the exact cause of chronic pain in polycystic ovaries is unknown; Elevated LH or elevated LH/FSH ratio: When measured on day 3 of the menstrual cycle, the LH/FSH ratio is greater than 1:1; Decreased level of globulin that binds sex steroids; Hyperinsulinemia (increased levels of insulin in the blood on an empty stomach), impaired glucose tolerance, signs of tissue insulin resistance when tested by the sugar curve method. Health risks and complications Women with PCOS are at an increased risk of developing the following complications: Endometrial hyperplasia and endometrial cancer due to the absence or irregularity of menstruation and the "accumulation" of non-shedding endometrium, as well as due to the absence or insufficiency of progesterone influences, leading to prolonged unbalanced progesterone hyperstimulation of endometrial cells by elevated levels of estrogens; Insulin resistance and type 2 diabetes mellitus; Thrombosis, thromboembolism, thrombophlebitis due to increased blood clotting; Dyslipidemia (disorders in the metabolism of cholesterol and triglycerides with possible development vascular atherosclerosis); Cardiovascular disease, myocardial infarction, stroke. The data of a number of researchers indicate that women with polycystic ovaries have an increased risk of miscarriage or premature birth, miscarriage. In addition, many women with this syndrome are unable to conceive or have difficulty conceiving due to irregular menstrual cycles and no or infrequent ovulation. However, when proper treatment these women can normally conceive, bear and give birth to a healthy child. Epidemiology Although on ultrasound examination of the abdominal cavity, ovaries that look like polycystic are found in up to 20% of women of reproductive age (including those who do not present any complaints), only 5-10% of women of reproductive age are found Clinical signs for the diagnosis of polycystic ovary syndrome. Polycystic ovary syndrome is equally common in different ethnic groups. It is the most common hormonal disorder in women of childbearing age and one of the leading causes of female infertility. Etiology and pathogenesis The exact causes of the development of the syndrome are unknown, however, great importance is attached to the pathological decrease in insulin sensitivity of peripheral tissues, primarily adipose and muscle tissue (the development of their insulin resistance), while maintaining insulin sensitivity of ovarian tissue. A situation of pathologically increased insulin sensitivity of ovarian tissue is also possible, while maintaining normal insulin sensitivity of peripheral tissues. In the first case, as a consequence of the body's insulin resistance, there is a compensatory hypersecretion of insulin, leading to the development of hyperinsulinemia. A pathologically elevated level of insulin in the blood leads to hyperstimulation of the ovaries and increased secretion of androgens and estrogens by the ovaries and disruption of ovulation, since the ovaries retain normal sensitivity to insulin. In the second case, the level of insulin in the blood is normal, but the response of the ovaries to stimulation with a normal level of insulin is pathologically increased, which leads to the same result - hypersecretion of androgens and estrogens by the ovaries and impaired ovulation. Pathological tissue insulin resistance, hyperinsulinemia, and insulin hypersecretion in polycystic ovaries are often (but not always) the result of obesity or overweight. However, these phenomena themselves can lead to obesity, since the effects of insulin are an increase in appetite, an increase in fat deposition and a decrease in its mobilization. In the pathogenesis of polycystic ovaries, they also attach importance to violations of regulatory hypothalamic-pituitary influences: excessive LH secretion, abnormally increased LH / FSH ratio, increased "opioidergic" and reduced dopaminergic tone in the hypothalamus-pituitary gland. The condition may worsen and be more difficult to treat in the presence of concomitant hyperprolactinemia, subclinical or symptomatic thyroid insufficiency. Such combinations occur in these women much more often than in the general population, which may indicate a polyendocrine or polyetiological nature of the Stein-Leventhal syndrome. Some researchers attach importance to an increased level of prostaglandins and other inflammatory mediators in the thecal tissue of the ovaries and in the follicular fluid in patients with polycystic ovaries and believe that in the pathogenesis of polycystic ovary syndrome, the “cold” that occurs for reasons that are not yet clear can play a role. aseptic inflammation ovarian tissue transferred inflammatory diseases female genital area or autoimmune mechanisms. It is known that the introduction of prostaglandin E1 into the ovary or into the vessel feeding it causes a significant increase in the secretion of androgens and estrogens by the ovarian theca tissue in laboratory rats. Treatment History Historically, the very first attempts to treat polycystic ovary syndrome consisted of surgical intervention - decapsulation of the ovaries or their partial resection with the removal of the most cystic tissue areas, or excision of the ovarian bed ( ovarian wedge resection), or in the careful use of diathermy (heating) of the ovaries. In a number of cases, such operations were successful and made it possible to restore the woman's fertility, as well as to achieve a sharp decrease in ovarian androgen secretion, normalization of the menstrual cycle, etc. However, surgical intervention is not always possible, and did not always lead to success. In addition, complications are possible, for example, the formation of adhesions. Therefore, experts were looking for conservative, non-surgical treatments for polycystic ovaries. Traditional conservative treatment consisted in the appointment of antiandrogens, estrogens, progestins with antiandrogenic activity, or a combination of them (for example, in the form birth control pills Diane-35 type). Such treatment usually allowed to normalize the menstrual cycle, but had insufficient effectiveness in relation to skin manifestations(acne, greasiness of the skin, androgen-dependent alopecia), did not allow to restore ovulation and fertility, and did not eliminate the causes of polycystic ovaries themselves (impaired insulin secretion and insulin sensitivity of tissues, the function of the hypothalamus-pituitary axis, etc.). Moreover, treatment with estrogens, progestins and antiandrogens was often accompanied by a further increase in the weight of patients, aggravation of existing problems with carbohydrate metabolism and the thyroid gland, hyperprolactinemia, and depression. The next attempt to improve the methods of treatment of polycystic ovary syndrome was made with the advent of antiestrogenic drugs - clostilbegit (clomiphene citrate) and tamoxifen - in the arsenal of doctors. The use of clomiphene citrate or tamoxifen in the middle of the cycle allowed in approximately 30% of cases to successfully induce ovulation, restore female fertility and achieve a stable ovulatory menstrual cycle without the use of exogenous hormones (estrogens, progestins and antiandrogens). However, the effectiveness of clostilbegit and tamoxifen in relation to other symptoms of polycystic ovaries, in particular, manifestations of hyperandrogenism, was limited. The effectiveness of combination therapy (estrogens and progestins or antiandrogens in the cycle, clostilbegit or tamoxifen in the middle of the cycle) was higher, but also insufficient. Attempts to improve the effectiveness of the treatment of women with polycystic ovary syndrome by correcting known or suspected concomitant endocrine disorders (correction of concomitant hyperprolactinemia with bromocriptine, concomitant subclinical thyroid insufficiency by prescribing thyroid hormones, suppressing adrenal androgen hypersecretion by prescribing small doses of dexamethasone) have been partly successful, but success was individual and insufficiently constant and predictable. Real shifts in the effectiveness of the treatment of polycystic ovaries occurred when it was possible to penetrate deeper into the understanding of the pathogenesis of polycystic ovaries and when they began to attach primary importance to the development of this state of insulin hypersecretion and pathological insulin resistance of tissues with preserved insulin sensitivity of the ovaries. Since that time, for the treatment of polycystic ovaries, drugs have been widely used as first-line drugs that normalize tissue sensitivity to insulin and lower insulin secretion - metformin, glitazones (pioglitazone, rosiglitazone). This approach turned out to be very successful - in 80% of women with polycystic ovaries on monotherapy with metformin or one of the glitazones, ovulation was spontaneously restored, the menstrual cycle was normalized, androgen secretion by the ovaries decreased and the symptoms of hyperandrogenism disappeared or decreased, body weight decreased, carbohydrate metabolism normalized, improved mental condition. Most of these women were then able to carry and give birth to healthy children. An even higher success rate, exceeding 90%, was given by combination therapy - a combination of metformin or glitazones with previously known methods(estrogens, antiandrogens and progestins, and/or with antiestrogen in the middle of the cycle and/or possibly correction related disorders secretion of prolactin, thyroid hormones, adrenal androgens). The introduction of such a combined approach to the treatment of polycystic ovaries into the practice of gynecologists-endocrinologists has made it possible to almost completely eliminate, except for rare multidrug-resistant cases, the need for surgical intervention about polycystic ovaries, and also to make the need for induction of ovulation with gonadotropins and artificial insemination of women with polycystic ovaries much less frequent. The current state of the issue To date, the first-line drugs in the treatment of polycystic ovaries are metformin and glitazones (pioglitazone, rosiglitazone). Antiandrogenic drugs may be added to them, if necessary (

Polycystic ovary syndrome is a multifactorial heterogeneous pathology characterized by menstrual irregularities, chronic anovulation, hyperandrogenism, ovarian cystic changes, and infertility. Polycystic ovary syndrome is characterized by moderate obesity, irregular periods or amenorrhea, and symptoms of androgen excess (hirsutism, acne). Usually the ovaries contain many cysts. Diagnosis is based on pregnancy tests, examination of hormonal levels, and examination to rule out a virilizing tumor. Treatment is symptomatic.

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ICD-10 code

E28.2 Polycystic ovary syndrome

Causes of polycystic ovary syndrome

Polycystic ovary syndrome - a common endocrine pathology of the reproductive system, occurring in 5-10% of patients; characterized by the presence of anovulation and an excess of androgens of unknown etiology. The ovaries may be normal sizes or enlarged, with a smooth, thickened capsule. As a rule, the ovaries contain many small, 26 mm in size follicular brushes; sometimes there are large cysts containing atretic cells. There is an increase in estrogen levels, which leads to an increased risk of endometrial hyperplasia and, ultimately, endometrial cancer. Increased androgen levels are often noted, which increases the risk of metabolic syndrome and hirsutism.

Pathogenesis

Women with polycystic ovary syndrome (PCOS) have abnormalities in androgen and estrogen metabolism, impaired androgen synthesis. The disease is accompanied by high serum concentrations of androgenic hormones such as testosterone, androstenedione, dehydroepiandrosterone sulfate and (DHEA-S). However, normal androgen levels can sometimes be detected.

PCOS is also associated with insulin resistance, hyperinsulinemia, and obesity. Hyperinsulinemia can also lead to suppression of SHBG synthesis, which in turn can increase signs of androgenicity.

In addition, insulin resistance in PCOS is associated with adiponectin, a hormone secreted by adipocytes that regulates lipid metabolism and blood glucose levels.

An increased level of androgens is accompanied by an increase in the stimulating effect of luteinizing hormone (LH), secreted by the anterior pituitary gland, which leads to an increase in the ovarian cell theca. These cells, in turn, increase the synthesis of androgens (testosterone, androstenedione). Due to decreased levels of follicle-stimulating hormone (FSH) relative to LH, ovarian granulosa cells cannot aromatize androgens to estrogen, resulting in a decrease in estrogen levels and subsequent anovulation.

Some evidence suggests that patients have a functional disorder of cytochrome P450c17, a 17-hydroxylase that inhibits androgen biosynthesis.

Polycystic ovary syndrome is a genetically heterogeneous syndrome. Studies of family members with PCOS prove autosomal dominant inheritance. A genetic link between PCOS and obesity has recently been confirmed. A variant of the FTO gene (rs9939609, which predisposes to overall obesity) is significantly associated with susceptibility to the development of PCOS. Polymorphisms of the 2p16 locus (2p16.3, 2p21 and 9q33.3) have been identified that are associated with polycystic ovary syndrome, as well as a gene that encodes luteinizing hormone (LH) and human chorionic gonadotropin (CG) receptor.

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Symptoms of polycystic ovary syndrome

Symptoms of polycystic ovary syndrome appear during puberty, their manifestation decreases over time. The presence of regular periods for some time after menarche excludes the diagnosis of polycystic ovary syndrome. Examination usually reveals abundant cervical mucus (reflecting high estrogen levels). The diagnosis of polycystic ovary syndrome can be suspected if a woman has at least two typical symptoms (moderate obesity, hirsutism, irregular periods, or amenorrhea).

The most common combination of the following clinical symptoms:

• violation of the menstrual cycle (oligomenorrhea, dysfunctional uterine bleeding, secondary amenorrhea);
• anovulation;
• infertility;
• hirsutism;
• violation of fat metabolism (obesity and metabolic syndrome);
• diabetes;
• obstructive sleep apnea syndrome.

Diagnosis of polycystic ovary syndrome

Diagnosis is based on the exclusion of pregnancy (pregnancy test), as well as the study of estradiol, FSH, TSH and prolactin in the blood serum. The diagnosis is confirmed by ultrasonography, which reveals more than 10 follicles in the ovary; follicles are usually found in the periphery and resemble a string of pearls. If ovarian follicles and hirsutism are noted, testosterone and DHEAS levels should be measured. Pathological levels are assessed as in amenorrhea.

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History and physical examination

Through a thorough history taking, hereditary factors development of polycystic ovary syndrome. On examination, the body mass index and the ratio of waist circumference to hip circumference (normally ≤ 0.8) are calculated to diagnose overweight and obesity.

Polycystic ovary syndrome is characterized by polymorphism of clinical and laboratory signs.

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Special methods for diagnosing polycystic ovary syndrome

Be sure to conduct a hormonal study on the 3rd–5th day of a menstrual-like reaction: the level of LH, FSH, prolactin, testosterone, adrenal androgens - DHEAS, 17-hydroxyprogesterone is determined in the blood. Polycystic ovary syndrome is characterized by a high LH / FSH index -> 2.5–3 (due to an increase in LH levels) and hyperandrogenism.

In order to clarify the source of hyperandrogenism, an ACTH test is performed for differential diagnosis with hyperandrogenism caused by a mutation of the gene encoding the enzyme 21-hydroxylase in the adrenal glands (diagnosis of obliterated and latent forms of adrenogenital syndrome). Technique: at 9 o'clock in the morning, blood is taken from the cubital vein, then 1 mg of the drug synakten-depot is injected intramuscularly, after 9 hours - repeated blood sampling. In both portions of blood, the concentration of cortisol and 17-hydroxyprogesterone is determined, then a coefficient is calculated using a special formula, the values ​​​​of which should not exceed 0.069. In these cases, the test is negative and the woman (or man) is not a carrier of the 21-hydroxylase gene mutation.

A test with difenin is carried out to identify the central forms of polycystic ovaries and the possibility of treatment with neurotransmitter drugs. Test technique: the initial concentration of LH and testosterone is determined in the blood, then difenin is taken 1 tablet 3 times a day for 3 days, after which the concentration of the same hormones is re-determined in the blood. The test is considered positive if the level of LH and testosterone decreases.

• With ultrasound of the genital organs, enlarged ovaries (10 cm 3 or more), many follicles up to 9 mm in diameter, thickening of the ovarian stroma, thickening of the capsule are determined.

• Additionally, if insulin resistance is suspected, a glucose tolerance test is performed to determine the level of insulin and glucose before and after exercise.
• If an adrenal genesis of polycystic ovary syndrome is suspected, genetic counseling and HLA genotyping are recommended.
• Hysterosalpingography.
• Laparoscopy.
• Fertility assessment of the spouse's sperm.

In November 2015, the American Association of Clinical Endocrinologists (AACE), the American College of Endocrinology (ACE), and the Androgen Excess and PCOS Society (AES) released new guidelines for the diagnosis of PCOS. These recommendations are:

1. Diagnostic criteria for PCOS should include one of the following three criteria: chronic anovulation, clinical hyperandrogenism, and polycystic ovaries.
2. In addition to clinical findings, serum levels of 17-hydroxyprogesterone and anti-Müllerian hormone must be measured to diagnose PCOS.
3. The analysis of free testosterone levels is more sensitive to the determination of androgen excess than the level of total testosterone.

Differential Diagnosis

Differential diagnosis is carried out with other diseases, in which menstrual disorders, hyperandrogenism and infertility are also observed: adrenogenital syndrome, tumors of the adrenal glands and ovaries, Itsenko-Cushing's syndrome.

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Treatment of polycystic ovary syndrome

Women who have anovulatory menstrual cycles (history of no or irregular menses and no evidence of progesterone production), in the absence of hirsutism and unwillingness to become pregnant, are given an intermittent progestin (eg, medroxyprogesterone 5–10 mg orally once a day for 10– 14 days of each month for 12 months) or oral contraceptives to reduce the risk of endometrial hyperplasia and cancer and reduce circulating androgens.

Women who have PCOS with anovulatory cycles, who have hirsutism and are not planning pregnancy, treatment is aimed at reducing hirsutism and regulating serum testosterone and DHEAS levels. Women who want to become pregnant undergo infertility treatment.

Treatment of infertility in polycystic ovary syndrome is carried out in 2 stages:

• 1st stage - preparatory;
• 2nd stage - stimulation of ovulation.

Therapy at the preparatory stage depends on the clinical and pathogenetic form of polycystic ovary syndrome.

• In polycystic ovary syndrome and obesity, the appointment of drugs that help reduce insulin resistance is indicated: the drug of choice, metformin, is used orally at 500 mg 3 times a day for 3-6 months.
• In the ovarian form of polycystic ovary syndrome and a high level of LH, drugs are used that help reduce the sensitivity of the hypothalamic-pituitary system to complete suppression of ovarian function (estradiol level in blood serum
• buserelin spray, 150 mcg in each nostril 3 times a day from the 21st or 2nd day of the menstrual cycle, a course of 1-3 months, or
• buserelin depot IM 3.75 mg once every 28 days from the 21st or 2nd day of the menstrual cycle, course 1-3 months, or
• leuprorelin s.c. 3.75 mg once every 28 days from the 21st or 2nd day of the menstrual cycle, a course of 1-3 months, or
• triptorelin s / c 3.75 mg 1 time in 28 days or 0.1 mg 1 time per day from the 21st or 2nd day of the menstrual cycle, the course is 1-3 months.

It does not matter from which (21st or 2nd) day of the menstrual cycle to prescribe GnRH agonists, however, the appointment from the 21st day is preferable, since in this case ovarian cysts do not form. When prescribed from the 2nd day of the cycle, the activation phase preceding the suppression phase in the mechanism of action of the GnRH agonist coincides with the follicular phase of the cycle and can cause the formation of ovarian cysts.

Alternative drugs:

• or
• ethinylestradiol / cyproterone acetate inside 35 mcg / 2 mg 1 time per day from the 5th to the 25th day of the menstrual cycle, the course is 3-6 months.
• In the adrenal form of polycystic ovary syndrome, the appointment of glucocorticoid drugs is indicated:
  • dexamethasone 0.25–1 mg orally once daily for 3–6 months, or
  • methylprednisolone 2–8 mg orally once daily for 3–6 months, or
  • oral prednisolone 2.5-10 mg once a day, course 3-6 months.
• In the central form of polycystic ovary syndrome, anticonvulsants are used:
  • difenin 1 tablet orally 1-2 times a day;
  • carbamazepine 100 mg orally 2 times a day, course 3-6 months.

At the 2nd stage, ovulation is stimulated.

The choice of drugs and the scheme of their administration is determined taking into account clinical and laboratory data. During ovulation induction, careful ultrasound and hormonal monitoring of the stimulated cycle is performed.

It is unacceptable to carry out the induction of ovulation by any medicines without ultrasound monitoring. It is not advisable to start ovulation induction in the presence of cystic formations in ovaries > 15 mm in diameter and > 5 mm thick endometrium.

Induction of ovulation with clomiphene is indicated for a short history of the disease in young women with sufficient estrogen levels (serum estradiol 15 IU / l).

Clomiphene is administered orally 100 mg 1 time per day from the 5th to the 9th day of the menstrual cycle at the same time of day.

A control ultrasound is performed on the 10th day of the cycle, the diameter of the dominant follicle and the thickness of the endometrium are assessed. Examinations are carried out every other day, in the periovulatory period - daily. It is not the day of the cycle that matters, but the size of the leading follicle: if its diameter is more than 16 mm, then ultrasound should be performed daily until a size of 20 mm is reached.

Alternative treatment regimens (with a pronounced antiestrogenic effect):

• clomiphene 100 mg orally once a day from the 5th to the 9th day of the menstrual cycle at the same time of day +
• ethinylestradiol (EE) 50 mcg orally twice a day from the 10th to the 15th day of the menstrual cycle or
• estradiol inside 2 mg 2 times a day from the 10th to the 15th day of the menstrual cycle.

• clomiphene 100 mg orally once a day from the 3rd to the 7th day of the menstrual cycle at the same time of day +
• menotropins IM 75-150 IU 1 time per day at the same time from the 7th-8th day of the menstrual cycle or
• follitropin alfa IM 75-150 IU once a day at the same time from the 7th-8th day of the menstrual cycle.

Ovulation induction with clomiphene citrate is not indicated in the following situations:

• with hypoestrogenism (the level of estradiol in the blood serum
• after preliminary preparation with GnRH agonists (as a result of a decrease in the sensitivity of the hypothalamic-pituitary-ovarian system, hypoestrogenism develops);
• in women of older reproductive age, with a long history of the disease and a high level of LH in the blood serum (> 15 IU / l). It is not advisable to increase the dose of clomiphene to 150 mg/day during repeated stimulation courses, as the negative peripheral antiestrogenic effect is enhanced.

Stimulation of ovulation by gonadotropins is indicated in the absence of adequate folliculogenesis after stimulation with clomiphene, in the presence of a pronounced peripheral antiestrogenic effect, and insufficient estrogen saturation. It can be performed both in young patients and in late reproductive age.

Drugs of choice:

• menotropins IM 150-225 IU 1 time per day from the 3rd-5th day of the menstrual cycle at the same time, course 7-15 days or
• urofollitropin / m 150-225 IU 1 time per day from the 3rd-5th day of the menstrual cycle at the same time, the course is 7-15 days.

• follitropin alfa IM 100-150 IU once a day from the 3rd-5th day of the menstrual cycle at the same time, the course is 7-15 days. serum LH level (> 15 IU/l).

Drugs of choice:

• buserelin in the form of a spray of 150 mcg in each nostril 3 times a day from the 21st day of the menstrual cycle or
• buserelin depot i / m 3.75 mg once on the 21st day of the menstrual cycle;
• leuprorelin s / c 3.75 mg once on the 21st day of the menstrual cycle;
• triptorelin s / c 3.75 mg once on the 21st day of the menstrual cycle or 0.1 mg 1 time per day from the 21st day of the menstrual cycle +
• menotropins / m 225-300 IU 1 time per day from the 2nd-3rd day of the subsequent menstrual cycle at the same time.

Alternative drugs (for high risk development of ovarian hyperstimulation syndrome):

• menotropins IM 150-225 IU once a day from the 2nd-3rd day of the menstrual cycle at the same time or
• follitropin alfa intramuscularly 150–225 IU once a day from the 2nd–3rd day of the menstrual cycle at the same time +
• ganirelix s / c 0.25 mg 1 time per day, starting from the 5-7th day of gonadotropin use (when dominant follicle size 13–14 mm);
• cetrorelix s / c 0.25 mg 1 time per day, starting from the 5th-7th day of the use of gonadotropins (when the dominant follicle reaches a size of 13-14 mm).

Ovulation induction in patients of late reproductive age(with a weak response of the ovaries to gonadotropic drugs).

Drugs of choice:

• menotropins IM 225 IU 1 time per day from the 3rd–5th day of the menstrual cycle at the same time +
• triptorelin s / c 0.1 mg 1 time per day from the 2nd day of the menstrual cycle.

Alternative drugs:

• triptorelin s / c 0.1 mg 1 time per day from the 2nd day of the menstrual cycle +
• follitropin alfa IM 200-225 IU once a day from the 3rd-5th day of the menstrual cycle at the same time.

In all schemes with the use of gonadotropins, the adequacy of the dose of the latter is assessed by the dynamics of follicle growth (normally 2 mm / day). With slow growth of follicles, the dose is increased by 75 IU, with too rapid growth, it is reduced by 75 IU.

In all schemes, in the presence of a mature follicle with a size of 18–20 mm, an endometrial thickness of at least 8 mm, therapy is stopped and chorionic gonadotropin is prescribed intramuscularly 10,000 IU once.

After ascertaining ovulation, the luteal phase of the cycle is supported.

Drugs of choice:

• dydrogesterone inside 10 mg 1-3 times a day, course 10-12 days or
• progesterone inside 100 mg 2-3 times a day, or into the vagina 100 mg 2-3 times a day, or intramuscularly 250 mg 1 time a day, course 10-12 days. Alternative drug (in the absence of symptoms of ovarian hyperstimulation):
• chorionic gonadotropin intramuscularly 1500–2500 IU once a day on days 3.5 and 7 of the luteal phase.

Other medicines used in the treatment of PCOS:

• Antiandrogens (eg, spironolactone, leuprolide, finasteride).
• Antidiabetic drugs (eg metformin, insulin).
• Selective estrogen receptor modulators (for example, clomiphene citrate).
• Acne medications (eg, benzoyl peroxide, tretinoin cream (0.02-0.1%)/gel (0.01-0.1%)/solution (0.05%), adapalene cream (0.1%) ) / gel (0.1%, 0.3%) / solution (0.1%), erythromycin 2%, clindamycin 1%, sodium sulfetamide 10%).

Side effects of treatment

When using clomiphene, most patients develop a peripheral antiestrogenic effect, which consists in lagging the growth of the endometrium from the growth of the follicle and reducing the amount of cervical mucus. With the use of gonadotropins, especially human menopausal gonadotropin (menotropins), the development of ovarian hyperstimulation syndrome (OHSS) is possible, with the use of recombinant FSH (follitropin alfa), the risk of ovarian hyperstimulation syndrome is less. When using schemes that include GnRH agonists (triptorelin, buserelin, leuprorelin), the risk of developing ovarian hyperstimulation syndrome increases, and the use of GnRH agonists can cause symptoms of estrogen deficiency - hot flashes, dry skin and mucous membranes.

Forecast

The effectiveness of infertility treatment in polycystic ovary syndrome depends on the clinical and hormonal characteristics of the course of the disease, the age of the woman, the adequacy of preparatory therapy, and the correct selection of the ovulation induction scheme.

In 30% of young women with a short history of the disease, pregnancy is achieved after preparatory treatment without ovulation induction.

The effectiveness of ovulation stimulation with clomiphene does not exceed 30% per 1 woman, 40% of patients with polycystic ovary syndrome are clomiphene resistant.

The use of menotropins and urofollitropin can achieve pregnancy in 45-50% of women, but these drugs increase the risk of developing ovarian hyperstimulation syndrome.

Polycystic ovaries(sclerocystic ovarian disease, polycystic ovary syndrome) is characterized by a state of chronic oligoovulation and/or anovulation, which is manifested by oligomenorrhea and/or amenorrhea, hypertrichosis, infertility and obesity. Statistical data. The syndrome is found in 3-7% of women of reproductive age.

Code by international classification ICD-10 diseases:

• E28.2

Etiology. Central pathology due to increased secretion of luliberin, LH and androgen levels.
Genetic Aspects. Deficiency of 17 -  - hydroxysteroid dehydrogenase (EC 1.1.1.62, testicular form - EC 1.1.1.63 and EC 1.1.1.64) is a familial form of polycystic ovarian disease (also violations of sexual differentiation in the form of male pseudohermaphroditism with gynecomastia [*264300, ]) . Identification of gene defects and specific clinical form is difficult.
Pathogenesis. The main link is an increase in the content of androgens in the blood.
. It is assumed that the main violation is localized in the hypothalamic - pituitary system (constant, not cyclic hyperproduction of LH) or there is an excessive secretion of androgens in the ovaries. Deviations in the synthesis of androgens in the adrenal glands were found, which may be a starting point; there are reports of the disappearance of polycystic ovary syndrome after removal of an androgen-secreting adrenal adenoma .. Elevated levels of androstenedione (turns into estrone in adipose and other tissues) and other androgens prevent the maturation of follicles, resulting in anovulation .. An increased level of circulating estrone leads to the secretion of excess LH by the pituitary gland and reduces the formation of FSH... Elevated levels of LH cause hyperplasia of the theca - and stromal cells of the ovaries, as well as additionally increased production of androgens... A reduced level of additional FSH prevents the maturation of follicles.
. Obesity already increases elevated levels sex steroids both by reducing the content of sex hormone-binding globulin, which increases the level of free testosterone, and by increasing the conversion of androstenedione to estrone.
. The cessation of the development of follicles leads to an increase in the ovaries, a thickening of the capsule, the appearance of multiple small follicular cysts.

Pathomorphology. The ovaries have a characteristic appearance - a smooth, thickened mother-of-pearl-colored capsule with multiple small cysts (formed by atretic follicles), clearly visible on the cut. The white membrane of the ovary is thickened.
Clinical picture. Allocate. Primary polycystic ovaries is a disease of polycystic ovaries. secondary polycystic ovaries - polycystic ovary syndrome.
. Primary polycystic ovaries.. Infertility and menstrual disorders (amenorrhea or oligomenorrhea) as a result of chronic anovulation.. Rare bleeding due to prolonged and non-cyclic estrogenic stimulation of the endometrium. an increase in the ovaries by 2-6 times compared to the norm.
. Secondary polycystic ovaries.. Increased oiliness of the skin, acne and hirsutism due to an excess of androgens.. Signs of true virilization (coarsening of the voice, enlargement of the clitoris).. The menstrual cycle is disturbed by the type of oligomenorrhea, anovulation and insufficiency of the luteal phase of the cycle often occur. often ends in miscarriage in the early stages.
. Obesity is observed in 40% of patients, regardless of the type of polycystic disease.
Laboratory research . Increased LH / FSH ratio (2 or more times). The content of LH is usually increased, FSH - at the lower limit of the norm. The content of testosterone and androstenedione in the blood is often increased. Seen less often increased content androgens, mainly of adrenal origin (dehydroepiandrosterone and dehydroepiandrosterone sulfate). The concentration of estrone in the blood is usually high, estradiol - within the normal range.
Special Studies- Ultrasound of the pelvic organs reveals enlarged ovaries with numerous small follicular cysts.

Treatment

TREATMENT
Goals. Reducing the severity of symptoms of hyperandrogenemia. Restoration of ovulation and fertility.
Reducing the severity of manifestations of hyperandrogenemia. Oral contraceptives with antiandrogenic properties (ethinylestradiol + cyproterone, ethinylestradiol + dienogest). HA preparations, such as dexamethasone 0.5 mg at night (because ACTH peaks in the early morning). Spironolactone 100 mg 1-2 r / day - reduces the synthesis of androgens in the ovaries and adrenal glands and inhibits the binding of androgens to receptors in hair follicles and other targets. The effects of hormone therapy in relation to unwanted hair growth on the face and body rarely develop quickly - improvement is observed no earlier than after 3-6 months. Artificial hair removal is often necessary: ​​shaving, electrolysis, chemical hair removal.
Restoration of ovulation and fertility. Clomiphene 50 mg 1-2 p / day from 5 to 9 days from the start of the progesterone-induced menstrual cycle, blocking the binding of estrogen to receptors in target cells (hypothalamus and pituitary gland), stimulates the formation of LH and FSH and the maturation of follicles and ovulation. Menotropins 75-150 U / day / m daily until an increase in the content of estrogen in the blood and confirmation by ultrasound of the maturation of follicles in the ovaries. 24-48 hours after the end of the injections of the drug, then to stimulate ovulation, HCG is administered at 1500-3000 IU / day / m for 3 days. Due to the risk of ovarian hyperstimulation and the occurrence of multiple pregnancies, such therapy is carried out only when other approaches are ineffective. For chronic anovulation and abnormal menstrual bleeding, progestin (eg, medroxyprogesterone 10 mg for 10 days every 1 to 3 months) or cyclic estrogen-progestin therapy (interrupt persistent endometrial proliferation).

ICD-10. E28.2 Polycystic ovary syndrome

Note. Stein-Leventhal syndrome (#184700, polycystic ovary syndrome with hyperandrogenemia, polymorphism of the CYP11A locus, ; heterogeneous). Multiple ovarian cysts, stromal and theca cell hyperplasia in atretic follicles; increased activity of 5 - liver reductase; usually presents with hirsutism, obesity, menstrual irregularities, infertility, and ovarian enlargement.