Syndrome of depleted ovaries

To the primary-ovarian hypofunction of the ovaries is the so-called syndrome of exhausted ovaries. To describe this pathological condition, many terms are suggested: "premature menopause," "premature menopause," "premature ovarian failure," etc. According to VP Smetnik, the term "depleted ovarian syndrome" is most appropriate, since it indicates an ovarian genesis disease and irreversibility of the process.

Epidemiology

Syndrome of exhausted ovaries is a complex of pathological symptoms (amenorrhea, infertility, hot flushes to the head, excessive sweating, etc.). It is a fairly rare disease, as though its frequency has not yet been established. Occurs in women younger than 37-38 years old, who in the past had normal menstrual and generative functions.

[1], [2], [3], [4], [5], [6]

Causes of the syndrome of depleted ovaries

It has been established that a number of factors play a role in the onset of this disease, both environmental and hereditary. More than 80% of patients showed adverse effects during the pre-natal period, pre and pubertal periods: pregnancy toxicity 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 violations of menstrual function and relatively often early menopause (38-42 years). Apparently, against the background of an inferior genome, any exogenous effects (infections, intoxications, stresses, etc.) can contribute to atresia of the follicular apparatus of the ovaries. 

Sex chromatin ranges from 14 to 25%. Most patients have a normal female karyotype of 46 / XX, and a mosaic set of chromosomes is rarely found. One of the reasons for the early depletion of the function of the ovaries can be gene mutations, which are inherited or arisen de novo. No possibility of autoimmune disorders is excluded. In the final analysis, the pathogenesis of the disease is associated with pre- and post-puertata destruction of germinal ovarian cells.

Pathonatomy of the syndrome of exhausted ovaries

For the syndrome of emaciated ovaries hypoplastic ovaries are characteristic. They are small in size (1.5-2x0.5x1-1.5 cm), weighing not more than 1-2 g each. Such ovaries are properly formed, they clearly distinguish between the cortical or cerebral layers, but the number of primordial follicles in the first layer is sharply reduced. These follicles usually last for 5-15 years of reproductive life. The existing primordial follicles undergo normal growth and development.

They reach the stage of a mature graafa vesicle and are ovulated with the formation of mostly full yellow and then white bodies. Follicles that do not reach the stage of mature graaff vesicles undergo, as in physiological conditions, cystic, and then fibrous atresia. By the end of the reproductive function of the ovaries, a sterile cortex with an atrophic interstitial tissue is found in them, since the fate of its cells and follicles is related. The disappearance of the latter is accompanied by a sharp decrease in the number of cells in the interstitial tissue.

[7], [8], [9], [10], [11]

Symptoms of the syndrome of depleted ovaries

As a rule, menarche in patients with the syndrome of exhausted ovaries occurs in time, menstrual and generative functions are not violated within 12-20 years. The disease begins with either  amenorrhea, or with oligopesomenorei, lasting from 6 months to 3 years. After 1 -2 months after the termination of menstruation, there are "hot flashes" of heat to the head, then weakness, headaches, fatigue, pains in the heart, working capacity decrease. Disturbances of fat metabolism, as a rule, are not observed. All patients with the syndrome of exhausted ovaries of the right physique. Anthropometry reveals a female phenotype. Hypoplasia of mammary glands is not observed. Gynecological examination reveals a sharp uterine hypoplasia, a decrease in the estrogenic response of the mucous membranes, and the absence of the "pupil" symptom.

Diagnostics of the syndrome of depleted ovaries

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

With pneumopyroscopy or ultrasound scanning, the uterus and the ovaries are sharply reduced in size. These data can also be confirmed with laparoscopy, in which small wrinkled ovaries are yellowish, yellow bodies are absent, follicles do not appear translucent. When histological examination of ovarian biopsy specimens, follicles are not detected.

Hormonal examination shows a low (usually lower than in the early follicular phase) level of estrogens. When determining gonadotropic hormones, there was a marked increase in FSH, whose content is 3 times higher than ovulatory and 15 times 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 4 times higher than the level of basal secretion of luteinizing hormone. The level of prolactin is reduced by 2 times compared with its content in healthy women. Progesterone sample in all patients is negative, which reflects insufficient estrogenic stimulation of the endometrium. Against the background of the estrogen-progestogen test in all patients, there is an improvement in the state of health and the appearance of a menstrual-like reaction 3-5 days after its termination. These data indicate a pronounced hypofunction of the ovaries and the preservation of the sensitivity and functional activity of the endometrium.

A sample with clomiphene (100 mg for 5 days) does not lead to stimulation of the ovary function. With the introduction of MCH (menopausal human gonadotropin) or HG (chorionic gonadotropin), activation is also not observed.

To determine the reserve capacity of the hypothalamic-pituitary system, a test with LH-RG (100 mcg iv) is performed. With the introduction of LH-RG, there is an increase in initially elevated levels of FSH and LH, which indicates the preservation of the reserve capacity of the hypothalamic-pituitary system in the syndrome of depleted ovaries.

During the study of the electrical activity of the brain in patients with the syndrome of exhausted ovaries, a reduction in alpha rhythm is noted. Some of them have EEG disturbances, which are characteristic for the pathology of hypothalamic nuclei. When analyzing the radiographs of pronounced changes in the skull and the Turkish saddle is not revealed.

The test with estrogens allows to specify pathogenetic mechanisms of disturbance of secretion of gonadotropic hormones. Its results indicate the preservation and functioning of feedback mechanisms between the hypothalamic-pituitary structures and sex steroids, since after the administration of estrogens a regular decrease in the level of gonadotropins was noted. With the introduction of estrogens, the restoration of the character of electrical brain activity is observed even with a fairly long course of the disease. In some patients, according to the same authors, depletion of ovarian function may be a consequence of increased neurohormonal activity of hypothalamic structures producing LH-RG. Its cause, apparently, is the insensitivity of the receptor mechanisms to estrogens, on the one hand, and to gonadotropic hormones, on the other.

According to GP Korneva, in patients with primary-ovarian insufficiency, along with an increase in gonadotropic hormones, a reduced level of dopamine (DA) in the blood and a slightly elevated serotonin (CT) was detected. The ratio of DA / ST is 1.

Thus, the diagnosis of the syndrome of exhausted ovaries is based on the appearance of amenorrhea in women of reproductive age, infertility, hot flushes to the head, excessive sweating. One of the main diagnostic criteria for the syndrome of exhausted ovaries is a significant increase in the level of gonadotropins, especially FSH, a sharp decrease in the content of estrogens, a decrease in the size of the uterus and ovaries and the absence of follicles in them. Progesterone and stimulating ovarian function of the sample with clomiphene, MCH and HG are negative. A distinctive feature of the disease is the improvement of the general condition of patients on the background of estrogen therapy.

[12], [13], [14], [15]

Differential diagnosis

The syndrome of exhausted ovaries should be differentiated from diseases that have a similar symptomatology. To exclude tumors of the pituitary gland, the main methods are craniography, as well as ophthalmological and neurological examination.

Unlike women with the syndrome of exhausted ovaries, patients with hypogonadotropic hypogonadism have a low level of gonadotropins, no vasomotor disorders. When using agents that stimulate ovarian function (gonadotropins, clomiphene), its activation is noted, which is not observed in patients with the syndrome of exhausted ovaries. With laparoscopy, the ovaries are small, but the follicles show through; they are also found in the histological examination of ovarian biopsy specimens.

Syndrome of depleted ovaries should be differentiated with a syndrome of resistant or refractory ovaries, which is also characterized by primary or secondary amenorrhea, infertility, normal development of secondary sexual characteristics, hypergonadotropic condition, mild hypoestrogenism. The syndrome is rare. Morphologically, in this syndrome, the ovaries are hypoplastic, although they are correctly formed: the cortical and cerebral layers are clearly distinguishable; in the cortex a sufficient number of primordial follicles and single small ripening follicles with 1-2 rows of granulosa cells. Cavity and atretic follicles, yellow and white bodies practically do not occur. Interstitial tissue contains more cells than, for example, hypogonadotropic hypogonadism.

Assume the autoimmune nature of the disease with the formation of antibodies to receptors for gonadotropins. Idiopathic form of primary-ovarian insufficiency with a high level of FSH and presence of follicles in the ovary is described. Symptoms are heterogeneous.

[16], [17]

Treatment of the syndrome of depleted ovaries

Treatment of the syndrome of exhausted ovaries consists in replacement therapy with sex hormones. With initial or prolonged amenorrhea, it should begin with estrogenation. Microfollin at 0.05 mg per day with courses of 21 days with seven-day breaks. As a rule, after the first course, a menstrual reaction occurs. After 2-3 courses of microfollin or other estrogens, you can switch to combined estrogen-progestogen preparations such as bisecurine (novovalon, rigevidon, ovidon). Vegetative symptoms (hot flushes, sweating) quickly docked, overall well-being improves. Treatment should be done with minimal doses that have a positive effect. In the opinion of VP Smetnik, one-fourth of the tablets of these drugs are usually enough, one should not seek a menstrual reaction, but only seek to reduce the severity of vegetovascular disorders. Treatment should be carried out until the age of natural menopause. In the spring months, courses of vitamin therapy are shown. Treatment of patients with primary ovarian failure is a kind of prevention of atherosclerosis, myocardial infarction, and osteoporosis.

Prevention

Prevention of the syndrome of exhausted ovaries consists in preventing the effects of such unfavorable factors as pregnancy toxemia and extragenital pathology in the mother, infectious diseases in childhood. It is necessary to take into account genetic factors.

[18], [19], [20], [21], [22]