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Isolated hypogonadotropic ovarian hypofunction
Last reviewed: 23.04.2024
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It occurs as a result of insufficient stimulation of ovarian function by gonadotropic hormones (GH) of the pituitary gland. Reduced or inadequate secretion of HG by the pituitary gland can be observed with the defeat of its gonadotrophs or with a decrease in the stimulation of gonadotrophs by the lyuliberin of the hypothalamus, i.e., secondary hypofunction of the ovaries can be of hypophyseal genesis, hypothalamic and, more often, mixed - hypothalamic-pituitary. Reduction of the gonadotropic function of the hypothalamic-pituitary system (GGS) can be primary or dependent, ie, arising against the background of other endocrine and nonendocrine diseases.
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Causes of the isolated hypogonadotropic ovarian hypofunction
At the first reduction of the gonadotropic function of the GHS, a clinical symptom complex, called isolated hypogonadotropic ovarian hypofunction (IGGN), is formed. The frequency of this disease is low. Women often suffer from a young age.
The cause and pathogenesis of isolated hypogonadotropic ovarian hypofunction. Isolated hypogonadotropic hypofunction of the ovaries is congenital or acquired. IG Dzenis and EA Bogdanova revealed the essential role of hereditary factors. In the analysis of pedigrees and early history data, it was shown that in girls with various forms of hypogonadism in 76.9% of cases mothers suffered from reproductive system disorders, the same violations were noted with high frequency in relatives of the II-III degree of kinship both in the mother's line and in lines of the father.
Reduction in the level of GH may be associated with a violation of regulation at the level of catecholamines of the central nervous system. GP Koreneva believes that in patients with low LH excretion, but with increased release of dopamine, it can be assumed that there is either a primary abnormality at the level of neurosecretory cells of the hypothalamus that do not respond to sufficient dopaminergic stimuli or a disorder at the pituitary level.
The role of inhibin in the pathogenesis of central forms of ovarian hypofunction has not been fully studied. Inhibits - peptides isolated from the follicular fluid and granulosa cells, inhibit at the level of the pituitary gland the synthesis and secretion of FSH, and at the hypothalamus level - the secretion of lyuliberin.
Sex chromatin in patients with isolated hypogonadotropic ovarian hypofunction positive, karyotype 46 / XX.
Patanatomy of isolated hypogonadotropic ovarian hypofunction. Secondary hypogonadotropic hypofunction is characterized by the presence of properly formed ovaries with a normal number of primordial follicles, which, if developed, only up to the stage of small maturing forms with 1-2 rows of granulosa cells. It is extremely rare to form cavitary follicles, which are rapidly exposed to atresia. Yellow and white bodies, as a rule, are not found. In the interstitial tissue of the cortex, the number of cellular elements decreases. All these features lead to ovarian hypoplasia. With a deficiency of predominantly LH, hypoplasia is less pronounced than if both GTs are deficient; in them there are cavitary and atretic follicles.
Symptoms of the isolated hypogonadotropic ovarian hypofunction
Symptoms of isolated hypogonadotropic ovarian hypofunction. Complaints of patients are reduced to primary or secondary amenorrhea with consequent infertility. "Tides" heat, as a rule, is not observed. Somatic anomalies are not detected. The growth of patients is medium or high. The constitution of a woman, rarely with eunuchoid proportions.
When gynecological examination, the external genitalia of a normal structure, sometimes with signs of hypoplasia. Uterus and ovaries are reduced in size, which is confirmed by objective research methods (pneumopelvigraphy, ultrasound). Secondary sexual characteristics are well developed, and mammary hypoplasia is rarely observed. Body weight is more often normal.
Peculiarities of the course of the disease are mainly due to the turn-off time of the gonadotropic function and the degree of decrease in GH. With the admirably variant of the syndrome of isolated hypogonadotropic ovarian hypofunction, the symptoms of hypogonadism are most pronounced, up to eunuchoidism, the absence of development of secondary sexual characters, and the phenomena of osteoporosis. With late manifestation of the disease, clinical symptoms tend to be poorly expressed. In this case, both the degree of hypoestrogenism and the degree of decrease in the GH level also appear less. These differences largely determine the therapeutic tactics and prognosis of the disease. There are no complications leading to a decrease in working capacity.
On the roentgenogram, the skull of the pathology either does not appear, or signs of an increase in intracranial pressure and the phenomenon of endocrianiosis appear in the form of areas of calcification of the dura mater in the frontotemporal region and behind the back of the Turkish saddle, its small size and straightening of the back ("juvenilization"). The most frequent radiologic sign of hypogonadism is hypertrophic osteoporosis, which is common in the bones of the wrist and spine.
EEG reveals signs of organic brain pathology, diencephalic disorders, features of immaturity. However, the absence of changes in the EEG does not exclude the diagnosis of isolated hypogonadotropic ovarian hypofunction.
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Diagnostics of the isolated hypogonadotropic ovarian hypofunction
Diagnosis of isolated hypogonadotropic ovarian hypofunction. In the study of cervical mucus, hypoestrogenia is noted, the "pupil" symptom is negative and weakly expressed. OI fluctuations from 0 to 10%, the IC reveals mainly the intermediate cells of the vaginal epithelium, basal and parabasal cells are found (for example, 10/90/0). Rectal temperature monophasic.
A hormonal examination reveals a moderate, less pronounced hypoestrogenism. The level of estrogen is low and monotonous. Levels of GH (LH and FSH) either decreased, or are at the lower boundary of the normal basal level and are monotonous. The content of prolactin is not changed.
The test with progesterone, as a rule, is negative, which indicates the degree of hypoestrogenism. The sample with estrogen-progestogen is positive and indicates the functional preservation of the endometrium.
Hormonal tests that stimulate ovarian function are positive. The introduction of MCG at a dose of 75-150 units IM or HG 1500 U / day for 2-3 days causes an increase in the level of estrogens in the blood, an increase in CI, a shift to the right of the IC (surface cells appear), a symptom of the "pupil" , arborization. There may be a subjective reaction in the form of a feeling of heaviness and soreness in the ovaries, an increase in whiteness.
Positive test with clomiphene (100 mg / day for 5 days). Along with an increase in the level of estrogens, an increase in the content of LH and FSH in the blood is determined. However, with a severe form of the disease with a sharp decrease in the level of estrogens, LH and FSH, a sample with clomiphene gives a negative result.
To diagnose the hypothalamic or pituitary level of the lesion with isolated hypogonadotropic hypofunction of the ovaries, a sample with LH-RG (luliberin) of 100 μg IV was given. Increased levels of LH and FSH in response to its introduction should indicate a hypothalamic genesis of the disease, the absence of a gonadotropic response indicates a pituitary genesis. However, it is known that the gonadotropic reaction of the pituitary gland is determined by a variety of factors and largely depends on the functional state of the ovaries, in particular, on the level of estrogens in the blood. This circumstance makes it possible to consider that in the case of deep hypoestrogenesis the absence of an increase in the secretion of gonadotropic hormones after the administration of lylyberyrin is not a reliable indicator of gonadotropic lesion damage at the level of gonadotrophs.
In some cases, laparoscopy with ovarian biopsy is used to clarify the diagnosis.
Differential diagnostics. The syndrome of isolated hypogonadotropic hypofunction of the ovaries should firstly be differentiated with secondary hypofunction of the ovaries on the background of various endocrine diseases (hypothyroidism, pituitary adenoma, Shien syndrome, functional forms of interstitial-pituitary insufficiency, etc.).
A very similar clinical picture has the so-called hyperprolacti- non-hypogonadism, which includes functional forms of hyperprolactinemia and tumor (micro- and macro-prolactinomas). The main differential diagnostic criterion is the level of prolactin and X-ray methods of investigation.
In addition, the syndrome of isolated hypogonadotropic ovarian hypofunction should be differentiated with all forms of primary ovarian hypofunction. Here the main diagnostic index is the level of FSH and LH.
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Treatment of the isolated hypogonadotropic ovarian hypofunction
Treatment of isolated hypogonadotropic ovarian hypofunction is to stimulate the hypothalamic-pituitary system in order to activate the gonadotropic function. To evaluate the extent of endogenous estrogenization, treatment should begin with a progesterone test: 1% drug 1 ml IM for 6 days. The subsequent menstrual-like reaction testifies to a sufficient level of estrogens in the body and the possibility of effective use of clostilbegite. The use of gestagens as monotherapy for isolated hypogonadotropic ovarian hypofunction is usually ineffective.
It should be noted that the use of synthetic estrogen-progestogen preparations such as bisekurin with a positive progesterone test with the calculation of the rebound effect also does not lead to the restoration of the ovulatory function of the ovaries. Therapy with these drugs is shown with a negative progesterone test for the preparation of endometrial receptors and the hypothalamic-pituitary system. For estrogen preparation of the receptor apparatus, it is possible to use microfoline at 0.05 mg 1 / 2-1 / 4 tablets per day) from the 5th to the 25th day of the induced cycle.
Usually there are 3-6 courses, after which it is possible to switch to stimulating therapy. To do this, the most commonly used is clostilbugite, which is used at a dose of 100-150 mg / day for 5-7 days, starting from the 5th day of the induced cycle. The effectiveness of treatment is monitored by tests of functional diagnostics (TDF). Restoration of a two-phase basal temperature indicates a positive effect. The appearance of a menstrual-like reaction against a background of single-phase and sharply hypolyutene temperature suggests a partial effect, which in this case can be strengthened by additional administration of CG at a dose of 3000-9000 units IM in the period of supposed ovulation on the 14-16th day of the cycle. Treatment is continued until full-fledged two-phase cycles are obtained (up to 6 courses can be conducted in a row). When the effect is achieved, treatment should be discarded and control of the action kept at rectal temperature. In case of relapse the treatment is repeated.
With ineffective therapy with clostilbugite and with a significant decrease in the level of GH, it is possible to use the menopausal human gonadotropin or its analogue - pergonal-500. From the 3rd day of the induced cycle, MCG is administered at a dose of 75-300 IU / m daily for 10-14 days until the pre-ovulatory estrogen peak reaches 1104-2576 pmol / L. It is effective to control the maturation of the follicle prior to the stage of the graafovaya vesicle by ultrasound. At the same time, observation is carried out on the TFD (symptom "pupil", arborization, CI, IP).
When the pre-ovulatory stage is reached, a break for one day is done, after which a large dose of HC is administered once (4500-12000 units), resulting in ovulation and a yellow body. Treatment of HMG is a known difficulty, since it is possible to hyperstimulate the ovaries, hormonal studies or ultrasound are required. When using MCH, daily gynecological control is necessary. The effectiveness of ovulation stimulation reaches 70-90%, the restoration of fertility - 30-60%. Perhaps the onset of a multiple pregnancy.
A promising and most effective method of treatment of isolated hypogonadotropic ovarian hypofunction is the use of lylyberyrin. Usually inject 50-100 μg of the drug in / m or IV, an intranasal route of administration is possible. Luliberin is administered within 10-14 days before the onset of ovulation, the timing of which is determined by TFD, ultrasound and hormonal studies.
Forecast
The forecast is favorable. Work ability is not violated. Patients are subject to dispensary registration to avoid the emergence of tumors of the hypothalamic-pituitary system and the timely detection of hyperplastic processes in the reproductive system on the background of hormonal therapy. In the case of pregnancy, they are at risk for her bearing.