Ovarian amenorrhea

Ovarian forms of amenorrhea are due to functional, organic changes and congenital ovarian pathology. The most common cause of functional and morphological disorders at the ovarian level of the regulation of the menstrual cycle is polycystic ovary syndrome (PCOS). A decrease or depletion of the hormonal function of the ovaries is observed in resistant ovarian syndrome (SAD) and ovarian depletion syndrome (SIA). Organic changes in the ovaries, accompanied by menstrual dysfunction, are caused by hormonally active ovarian tumors (see “Ovarian tumors”).

PCOS is a pathology of the structure and function of the ovaries with a very diverse clinical picture, the most permanent component of which is anovulation. PCOS consists in significant morphological changes in the ovaries. This is a smooth and dense protein shell, proliferation of connective tissue, an increase in the number of cystic-modified follicles in the absence of a dominant follicle. Polycystic ovaries are enlarged (> 9 cm3) as a result of proliferation of connective tissue, the protein shell is pearly white. On the cut, the cortical layer resembles a honeycomb, because the follicles of different diameters.

PCOS is accompanied by chronic anovulation, infertility, frequent metabolic disturbances, decreased glucose tolerance, and hyperandrogenism and, consequently, virilization. Excessively high production of androgens contributes to the growth of interstitial tissue in PCOS.

According to the results of numerous hormonal and clinical studies, there are distinguished primary (Stein-Leventhal syndrome, described in 1935) and secondary polycystic ovaries, the latter developing with adrenal hyperandrogenism, hyperprolactinemia, and neuroexchange – endocrine syndromes.

The most convenient for use in clinical practice proposed by M.L. Crimean classification, including three forms: • typical form, mainly associated with ovarian hyperandrogenism, – primary polycystic ovaries; • sonnet or mixed form with both ovarian and adrenal hyperandrogenism; • central form with hyperandrogenism and severe dysfunction of the central reproductive system with a predominance of secondary polycystic ovaries.

Etiology and pathogenesis. Etiology and pathogenesis depend on the form of PCOS. In the 60s of the 20th century, the pathogenesis of typical PCOS (Stein-Leventhal syndrome) was associated with a genetically determined deficiency of ovarian enzymes that block the conversion of androgens into estrogens. However, it was subsequently shown that the activity of granulosa cells depends on FSH. Disruption of the process of aromatization of androgens in estrogen leads to the accumulation of testosterone (active androgen) and a decrease in the level of estrogen in the ovaries. As a result, the cyclic secretion of gonadotropins is disturbed by the feedback mechanism, which, in turn, leads to stromal and ovarian cell cell hyperplasia, and excessive or increased production of androgens. Androgens are partially converted to estrone, and part of estrone to estradiol. However, this is not enough for the occurrence of preovulatory and luteal peak. The menstrual cycle becomes monophasic.

In the pathogenesis of a mixed form of PCOS, the trigger mechanism may be primary dysfunction of the adrenal cortex or a transient excess of adrenal androgens during the adrenarche period. In peripheral tissues, androgens are partially converted into estrogens. When critical body weight is reached, peripheral conversion of androgens in adipose tissue increases. This is accompanied by an increase in the synthesis of LH in the pituitary gland and a violation of the LH / FSH ratio, which leads to hyperplasia of the cells and ovarian stroma. These structures synthesize androgens in excess. Hyperandrogenism interferes with the maturation of the follicles, leads to anovulation and further suppresses the secretion of FSH. So the vicious circle closes.

The participation of brain structures in the development of the central form of PCOS is confirmed by the chronological connection between the onset of the disease and the stress state (onset of sexual activity, mental trauma, childbirth, abortion). Impaired function of the central nervous system may be the result of acute or chronic infection or intoxication. This increases the synthesis and secretion of endogenous opioids, which violates the dopaminergic regulation of GnRH secretion, leads to an increase in the basal level of LH secretion, a relative decrease in FSH production and a violation of folliculogenesis. Increased excretion of LH in PCOS is due to both a primary impairment of GnRH synthesis and chronic anovulation; these effects are mutually potentiated.

The current understanding of the pathogenesis of PCOS, in addition to disorders of the hypothalamic-pituitary complex, the ovaries and adrenal glands, includes metabolic disorders and autoparacrinous factors regulating steroidogenesis in the ovaries. Metabolic disorders are associated with the insulin – glucose system, since insulin is involved in the production of ovarian androgens. Obesity does not play a decisive role in the pathogenesis of PCOS, but as a result of hyperinsulinemia and insulin resistance, the existing endocrine disorders are aggravated. In patients with obesity and insulin resistance, chronic hyperinsulinemia stimulates the formation of insulin-like growth factor-1 (IPFR-1). The latter, through specific receptors, increases the formation of androgens in the telocell and interstitial ovarian tissue. In addition, insulin is able to inhibit the formation in the liver of globulins that bind sex hormones, as a result of which the free biologically active testosterone fraction increases in the blood.

According to the existing hypothesis, the stimulating effect of insulin on the synthesis of androgens in the ovary is due to a genetic predisposition.

PCOS develops in women and with a normal body weight. In the blood they have an increased level of growth hormone, which causes the formation of IPFR-1 in granulosa cells and increases the formation of ovarian androgens. The study of hormone biosynthesis in polycystic ovarian granulosa cells has indicated that luteinized cells lose their ability to synthesize progesterone. This is one of the possible mechanisms of anovulation in patients with PCOS.

Clinical symptoms. The clinical manifestations of PCOS are very different, but the main ones in all forms of PCOS are hypo, opso, oligo, and amenorrhea. Disturbance of the follicle gene leads to the development of anovulatory primary and secondary infertility. In typical PCOS, menstrual disorders begin with menarche. In a mixed form of PCOS, later menarche is combined with menstrual dysfunction in the future as a secondary amenorrhea. In the reproductive age, chronic anovulation and infertility are observed, often primary. With the central form of PCOS, the menarche is normal, but the menstrual cycle is unstable. Subsequently, this leads to hypo-, opso-, oligo- or amenorrhea. Reproductive dysfunctions consist in miscarriage at short periods and secondary infertility. In addition to menstrual dysfunction, dysfunction of the hypothalamic-pituitary system is noted. The onset of the disease may be associated with stress, adenovirus infection, brain injury.

The main reason for seeking medical attention from patients of a young age is excessive hair growth, the frequency of which during PCOS is, according to different authors, from 50 to 100%. Hirsutism with a typical form of PCOS develops gradually from the menarche period. There is excessive hair growth on the upper lip, chin, along the white line of the abdomen. Pronounced hirsutism and hypertrichosis for this form of PCOS are not typical, but with a mixed form, hirsutism is observed in all patients. Zones of excessive hair growth – inner and outer thighs, white line of the abdomen, upper lip, lower legs. Hair growth begins with menarche or earlier. In the central form of PCOS, hirsutism is detected in 90% of patients, occurs 3-5 years after menstrual dysfunction, already against obesity, and is more pronounced at reproductive age. In these patients, dystrophic changes can be seen: stretch bands on the chest, abdomen, thighs, brittle nails and hair.

The clinical picture of PCOS is largely determined by general metabolic disorders such as dyslipidemia, carbohydrate metabolism disorders, an increased risk of the development of hyperplasic genital processes. These disorders can cause early development of atherosclerotic vascular changes, hypertension, coronary heart disease. In 50% of patients with a typical form of PCOS since adolescence, an increased body weight is observed with an even distribution of subcutaneous fat. With a mixed form of PCOS, obesity is rarely observed. With the central form of the leading is a complaint of overweight. Obesity reaches And — III degrees; adipose tissue is localized mainly on the shoulder girdle, lower abdomen and thighs.