Depleted ovary syndrome

Primary ovarian hypofunction of the ovaries includes the so-called syndrome of exhausted ovaries. Many terms have been proposed to characterize this pathological condition: "premature menopause", "premature menopause", "premature ovarian failure", etc. According to V. P. Smetnik, the term "syndrome of exhausted ovaries" is the most acceptable, since it indicates the ovarian genesis of the disease and the irreversibility of the process.

Epidemiology

Ovarian exhaustion syndrome is a complex of pathological symptoms (amenorrhea, infertility, hot flashes to the head, increased sweating, etc.). It is a rather rare disease, its exact frequency has not yet been established. It occurs in women under 37-38 years old, who had normal menstrual and generative functions in the past.

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Causes depleted ovarian syndrome

It has been established that many factors, both environmental and hereditary, play a role in the development of this disease. More than 80% of patients were found to have exposure to unfavorable factors during the period of intrauterine development, in the pre- and pubertal periods: toxicosis of pregnancy and extragenital pathology in the mother, a high infectious index in childhood. Analysis of genealogical data showed that in 46% of cases, relatives of the first and second degree of kinship had menstrual dysfunction and, comparatively often, early menopause (38-42 years). Apparently, against the background of an inferior genome, any exogenous effects (infections, intoxications, stress, etc.) can contribute to atresia of the follicular apparatus of the ovaries.

Sex chromatin fluctuates between 14 and 25%. Most patients have a normal female karyotype of 46/XX, and a mosaic set of chromosomes is rarely detected. One of the causes of early ovarian failure may be gene mutations, inherited or occurring de novo. The possibility of autoimmune disorders is not excluded. Ultimately, the pathogenesis of the disease is associated with pre- and postpubertal destruction of ovarian germ cells.

Pathological anatomy of ovarian failure syndrome

Hypoplastic ovaries are typical for the syndrome of exhausted ovaries. They are small in size (1.5-2x0.5x1-1.5 cm), weighing no more than 1-2 g each. Such ovaries are correctly formed, the cortex or medulla layers are clearly distinguished in them, but the number of primordial follicles in the first layer is sharply reduced. These follicles are usually enough for 5-15 years of reproductive life. The existing primordial follicles undergo normal growth and development.

They reach the stage of a mature Graafian follicle and ovulate with the formation of mostly full-fledged yellow and then white bodies. Follicles that have not reached the stage of mature Graafian follicles are subject, as in physiological conditions, to cystic and then fibrous atresia. By the period of completion of the reproductive function of the ovaries, a sterile cortex with atrophic interstitial tissue is found in them, since the fates of its cells and follicles are linked. The disappearance of the latter is accompanied by a sharp decrease in the number of cells in the interstitial tissue.

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Symptoms depleted ovarian syndrome

As a rule, menarche in patients with ovarian depletion syndrome occurs on time, menstrual and generative functions are not impaired for 12-20 years. The disease begins with either amenorrhea or oligoopsomenorrhea, lasting from 6 months to 3 years. 1-2 months after the cessation of menstruation, "hot flashes" to the head appear, then weakness, headaches, rapid fatigue, heart pain join in, and work capacity decreases. Disturbances in lipid metabolism, as a rule, are not observed. All patients with ovarian depletion syndrome have a normal physique. Anthropometry reveals a female phenotype. Hypoplasia of the mammary glands is not observed. Gynecological examination reveals severe hypoplasia of the uterus, a decrease in the estrogen reaction of the mucous membranes, and the absence of the "pupil" symptom.

Diagnostics depleted ovarian syndrome

When studying the ovarian function, its sharp decrease is revealed: the "pupil" symptom is always negative, colpocytological examination (CI) is within 0-10%, basal and parabasal cells of the vaginal epithelium are present in the mucus examination (ME). Rectal temperature is monophasic.

Pneumopelvigraphy or ultrasound scanning reveals a sharply reduced size of the uterus and ovaries. This data can be confirmed by laparoscopy, which reveals small, wrinkled, yellowish ovaries, no corpora lutea, and no visible follicles. Histological examination of ovarian biopsies reveals no follicles.

Hormonal examination shows low (usually lower than in the early follicular phase) estrogen levels. When determining gonadotropic hormones, a noticeable increase in FSH is noted, the content of which is 3 times higher than the ovulatory level and 15 times higher than the basal level of this hormone in healthy women of the same age. The content of LH in patients with the syndrome of exhausted ovaries approaches its level during the ovulatory peak and is 4 times higher than the level of basal secretion of luteinizing hormone. The prolactin level is reduced by 2 times compared to its content in healthy women. The progesterone test is negative in all patients, which reflects insufficient estrogen stimulation of the endometrium. Against the background of the estrogen-gestagen test, all patients experience an improvement in their well-being and the appearance of a menstrual-like reaction 3-5 days after its completion. These data indicate pronounced ovarian hypofunction and preservation of the sensitivity and functional activity of the endometrium.

A test with clomiphene (100 mg for 5 days) does not lead to stimulation of ovarian function. When introducing MCG (menopausal human gonadotropin) or hCG (chorionic gonadotropin), activation is also not observed.

To determine the reserve capacity of the hypothalamic-pituitary system, a test with LH-RH (100 mcg intravenously) is performed. When LH-RH is administered, an increase in the initially elevated levels of FSH and LH is noted, which indicates the preservation of the reserve capacity of the hypothalamic-pituitary system in the syndrome of exhausted ovaries.

During the study of the nature of the electrical activity of the brain in patients with the syndrome of exhausted ovaries, a reduction of the alpha rhythm is noted. In some of them, EEG abnormalities are noted, characteristic of the pathology of the hypothalamic nuclei. When analyzing radiographs, no pronounced changes in the skull and sella turcica are revealed.

The estrogen test allows to clarify the pathogenetic mechanisms of the disorder of secretion of gonadotropic hormones. Its results indicate the preservation and functioning of the feedback mechanisms between the hypothalamic-pituitary structures and sex steroids, since after the introduction of estrogens, a regular decrease in the level of gonadotropins is noted. With the introduction of estrogens, the nature of the electrical activity of the brain is restored even with a fairly long course of the disease. In some patients, according to the same authors, the exhaustion of ovarian function may be a consequence of increased neurohormonal activity of the hypothalamic structures producing LH-RH. Its cause is obviously the insensitivity of the receptor mechanisms to estrogens, on the one hand, and to gonadotropic hormones, on the other.

According to G. P. Korneva, patients with primary ovarian failure, along with an increase in gonadotropic hormones, have a reduced level of dopamine (DA) in the blood and a slightly increased level of serotonin (ST). The DA/ST coefficient is 1.

Thus, the diagnosis of ovarian depletion syndrome is based on the occurrence of amenorrhea in women of reproductive age, infertility, hot flashes to the head, and increased sweating. Some of the main diagnostic criteria for ovarian depletion syndrome are a significant increase in gonadotropin levels, especially FSH, a sharp decrease in estrogen levels, a decrease in the size of the uterus and ovaries, and the absence of follicles in them. Progesterone and ovarian function stimulating tests with clomiphene, MCG, and hCG are negative. A distinctive feature of the disease is an improvement in the general condition of patients against the background of therapy with estrogen drugs.

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Differential diagnosis

Ovarian exhaustion syndrome should be differentiated from diseases that have similar symptoms. The main methods for excluding a pituitary tumor are craniography, as well as ophthalmological and neurological examination.

Unlike women with ovarian depletion syndrome, patients with hypogonadotropic hypogonadism have low levels of gonadotropins and no vasomotor disorders. When using agents that stimulate ovarian function (gonadotropins, clomiphene), its activation is observed, which is not observed in patients with ovarian depletion syndrome. During laparoscopy, the ovaries are small, but follicles are visible; they are also detected during histological examination of ovarian biopsy specimens.

The syndrome of exhausted ovaries should be differentiated from the syndrome of resistant or refractory ovaries, which is also characterized by primary or secondary amenorrhea, infertility, normal development of secondary sexual characteristics, hypergonadotropic state, moderate hypoestrogenism. The syndrome is rare. Morphologically, in this syndrome, the ovaries are hypoplastic, although correctly formed: the cortex and medulla are clearly distinguishable; in the cortex there is a sufficient number of primordial follicles and single small maturing follicles with 1-2 rows of granulosa cells. Cavity and atretic follicles, yellow and white bodies are practically not encountered. The interstitial tissue contains more cells than, for example, in hypogonadotropic hypogonadism.

The autoimmune nature of the disease with the formation of antibodies to gonadotropin receptors is assumed. An idiopathic form of primary ovarian failure with a high level of FSH and the presence of follicles in the ovary is described. Symptoms are heterogeneous.

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Treatment depleted ovarian syndrome

Treatment of ovarian exhaustion syndrome consists of replacement therapy with sex hormones. In case of initial or prolonged amenorrhea, it should be started with estrogenization. Microfollin 0.05 mg per day in courses of 21 days with seven-day breaks. As a rule, a menstrual-like reaction occurs after the first course. After 2-3 courses of microfollin or other estrogens, you can switch to combined estrogen-gestagen drugs such as bisecurin (nonovlon, rigevidon, ovidon). Vegetative symptoms (hot flashes, sweating) are quickly relieved, general well-being improves. Treatment should be carried out with minimal doses that have a positive effect. According to V. P. Smetnik, usually 1/4 of a tablet of the indicated drugs is enough, you should not achieve a menstrual-like reaction, but only strive to reduce the severity of vegetative-vascular disorders. Treatment should be carried out until the age of natural menopause. In the spring months, courses of vitamin therapy are recommended. Treatment of patients with primary ovarian insufficiency is a kind of prevention of atherosclerosis, myocardial infarction, osteoporosis.

Prevention

Prevention of ovarian exhaustion syndrome consists of avoiding the impact of such unfavorable factors as toxicosis of pregnancy and extragenital pathology in the mother, infectious diseases in childhood. It is necessary to take into account genetic factors.

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