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Isolated hypogonadotropic ovarian hypofunction
Medical expert of the article
Last reviewed: 04.07.2025
Occurs as a result of insufficient stimulation of ovarian function by gonadotropic hormones (GH) of the pituitary gland. Reduced or inadequate secretion of GH by the pituitary gland may be observed when its gonadotrophs are damaged or when stimulation of gonadotrophs by luteinizing hormone of the hypothalamus is reduced, i.e. secondary ovarian hypofunction may be of pituitary genesis, hypothalamic and, more often, mixed - hypothalamic-pituitary. A decrease in the gonadotropic function of the hypothalamic-pituitary system (HPS) may be primary or dependent, i.e. arising against the background of other endocrine and non-endocrine diseases.
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Causes of isolated hypogonadotropic ovarian hypofunction.
With the primary decrease in the gonadotropic function of the HGS, a clinical symptom complex is formed, called isolated hypogonadotropic ovarian hypofunction (IHGO). The frequency of this disease is low. Young women are more often affected.
Cause and pathogenesis of isolated hypogonadotropic ovarian hypofunction. Isolated hypogonadotropic ovarian hypofunction may be congenital or acquired. I. G. Dzenis and E. A. Bogdanova revealed a significant role of hereditary factors. When analyzing pedigrees and early anamnesis 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 disorders were observed with high frequency in relatives of the second-third degree of kinship both on the mother's and father's side.
A decrease in the level of LH may be associated with a disturbance in regulation at the level of catecholamines in the central nervous system. G. P. Koreneva believes that in patients with low excretion of LH, but with increased secretion of dopamine, one can assume the presence of either a primary disorder at the level of neurosecretory cells of the hypothalamus, which do not respond to sufficient dopaminergic stimuli, or a disorder at the level of the pituitary gland.
The role of inhibin in the pathogenesis of central forms of ovarian hypofunction has not been fully studied. Inhibins are peptides isolated from follicular fluid and granulosa cells, inhibiting the synthesis and secretion of FSH at the pituitary level and the secretion of luliberin at the hypothalamus level.
Sex chromatin in patients with isolated hypogonadotropic ovarian hypofunction is positive, karyotype 46/XX.
Pathological anatomy of isolated hypogonadotropic ovarian hypofunction. Secondary hypogonadotropic hypofunction is characterized by the presence of correctly formed ovaries with a normal number of primordial follicles, which, if they develop, only to the stage of small maturing forms with 1-2 rows of granulosa cells. Formation of cystic follicles, which quickly undergo atresia, is extremely rare. Yellow and white bodies are usually not detected. In the interstitial tissue of the cortex, there is a decrease in the number of cellular elements. All these features lead to ovarian hypoplasia. With a deficiency of predominantly LH, hypoplasia is expressed to a lesser extent than with insufficiency of both GTs; cystic and atretic follicles are found in them.
Symptoms of isolated hypogonadotropic ovarian hypofunction.
Symptoms of isolated hypogonadotropic ovarian hypofunction. Patients' complaints are limited to primary or secondary amenorrhea with resulting infertility. Hot flashes are usually not observed. Somatic abnormalities are not detected. Patients are of medium or tall height. Female build, rarely with eunuchoid proportions.
During a gynecological examination, the external genitalia are of normal structure, sometimes with signs of hypoplasia. The uterus and ovaries are reduced in size, which is confirmed by objective research methods (pneumopelvigraphy, ultrasound). Secondary sexual characteristics are well developed, hypoplasia of the mammary glands is rarely observed. Body weight is usually normal.
The features of the disease course are mainly determined by the time of switching off of the gonadotropic function and the degree of decrease in GG. In the prepubertal variant of the syndrome of isolated hypogonadotropic ovarian hypofunction, the symptoms of hypogonadism are most pronounced, up to eunuchoidism, absence of development of secondary sexual characteristics, osteoporosis. In the late manifestation of the disease, clinical symptoms, as a rule, are weakly expressed. At the same time, both the degree of hypoestrogenism and the degree of decrease in the GG level are also less pronounced. These differences largely determine the treatment tactics and prognosis of the disease. Complications leading to a decrease in working capacity are not observed.
On the X-ray of the skull, pathology is either not revealed, or signs of increased intracranial pressure and endocrianosis are detected in the form of areas of calcification of the dura mater in the frontal-parietal region and behind the back of the sella turcica, its small size and straightness of the back ("juvenilization"). The most common X-ray sign of hypogonadism is hypertrophic osteoporosis, which is usually found in the bones of the wrist joint and spine.
EEG reveals signs of organic brain pathology, diencephalic disorders, and features of immaturity. However, the absence of changes in EEG does not exclude the diagnosis of isolated hypogonadotropic ovarian hypofunction.
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Diagnostics of isolated hypogonadotropic ovarian hypofunction.
Diagnostics of isolated hypogonadotropic ovarian hypofunction. Cervical mucus examination reveals hypoestrogenism, the "pupil" symptom is negative and weakly expressed. CI fluctuates from 0 to 10%, IS reveals mainly intermediate cells of the vaginal epithelium, basal and parabasal cells are found (for example, 10/90/0). Rectal temperature is monophasic.
Hormonal examination reveals moderate, less often pronounced hypoestrogenism. Estrogen levels are low and monotonous. HG (LH and FSH) levels are either reduced or are at the lower limit of the normal basal level and are monotonous. Prolactin levels are unchanged.
The progesterone test is usually negative, indicating the degree of hypoestrogenism. The test with estrogen-gestagen drugs is positive and indicates the functional preservation of the endometrium.
Hormonal tests stimulating ovarian function are positive. Administration of 75-150 U of MCG intramuscularly or 1500 U of hCG intramuscularly for 2-3 days causes an increase in the blood estrogen level, an increase in CI, a shift to the right of the SI (superficial cells appear), and the "pupil" symptom and ferning are noted. A subjective reaction may also occur in the form of a feeling of heaviness and pain in the ovarian area, and increased leucorrhoea.
Positive clomiphene test (100 mg/day for 5 days). Along with the increase in estrogen levels, an increase in LH and FSH levels in the blood is determined. However, in the severe form of the disease with a sharp decrease in estrogen, LH and FSH levels, the clomiphene test gives a negative result.
For diagnostics of hypothalamic or pituitary level of damage in isolated hypogonadotropic ovarian hypofunction, a test with LH-RH (luliberin) of 100 mcg intravenously, by jet stream, is proposed. An increase in the level of LH and FSH in response to its administration should indicate the hypothalamic genesis of the disease, the absence of a gonadotropic response indicates the pituitary genesis. However, it is known that the gonadotropic reaction of the pituitary gland is determined by many factors and largely depends on the functional state of the ovaries, in particular on the level of estrogens in the blood. This circumstance allows us to consider that in case of deep hypoestrogenism, the absence of an increase in the secretion of gonadotropic hormones after the administration of luliberin is not a reliable indicator of damage to the gonadotropic function 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 ovarian hypofunction should first of all be differentiated from secondary ovarian hypofunction against the background of various endocrine diseases (hypothyroidism, pituitary adenomas, Sheehan's syndrome, functional forms of interstitial-pituitary insufficiency, etc.).
The so-called hyperprolactinemic hypogonadism, which includes functional forms of hyperprolactinemia and tumors (micro- and macroprolactinomas), has a very similar clinical picture. The main differential diagnostic criterion is the level of prolactin and radiological examination methods.
In addition, the syndrome of isolated hypogonadotropic ovarian hypofunction should be differentiated from all forms of primary ovarian hypofunction. Here, the main diagnostic indicator is the level of FSH and LH.
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Treatment of isolated hypogonadotropic ovarian hypofunction.
Treatment of isolated hypogonadotropic ovarian hypofunction consists of stimulation of the hypothalamic-pituitary system in order to activate gonadotropic function. To assess the degree of endogenous estrogenization, treatment should be started with a progesterone test: 1% preparation, 1 ml intramuscularly for 6 days. The subsequent menstrual-like reaction indicates a sufficient level of estrogens in the body and the possibility of effective use of clostilbegyt. The use of gestagens as monotherapy for isolated hypogonadotropic ovarian hypofunction is usually ineffective.
It should be noted that the use of synthetic estrogen-gestagen drugs such as bisecurin with a positive progesterone test with the expectation of a rebound effect also does not lead to the restoration of ovarian ovulatory function. Therapy with these drugs is indicated with a negative progesterone test for the preparation of endometrial receptors and the hypothalamic-pituitary system. For estrogen preparation of the receptor apparatus, microfolin can be used at 0.05 mg (1/2-1/4 tablet per day) from the 5th to the 25th day of the induced cycle.
Usually 3-6 courses are carried out, after which it is possible to switch to stimulating therapy. For this purpose, clostilbegyt is most often used, which is administered at a dose of 100-150 mg / day for 5-7 days, starting from the 5th day of the induced cycle. The effectiveness of the treatment is monitored by functional diagnostic tests (FDT). Restoration of a two-phase basal temperature indicates a positive effect. The appearance of a menstrual-like reaction against the background of a single-phase and sharply hypoluteal temperature indicates a partial effect, which in this case can be enhanced by additional administration of hCG at a dose of 3000-9000 IU intramuscularly during the period of expected ovulation on the 14th-16th day of the cycle. Treatment is continued until full two-phase cycles are obtained (up to 6 courses can be carried out in a row). When the effect is achieved, the treatment should be discontinued and the preservation of the effect should be monitored by rectal temperature. In case of relapse, the treatment is repeated.
If clostilbegit therapy is ineffective and the HG level is significantly reduced, it is possible to use menopausal human gonadotropin or its analogue, pergonal-500. From the 3rd day of the induced cycle, HMG is administered at a dose of 75-300 IU intramuscularly daily for 10-14 days until the preovulatory peak of estrogens is reached at 1104-2576 pmol/l. Monitoring follicle maturation to the Graafian follicle stage using ultrasound is effective. In parallel, monitoring is carried out using TFD (the "pupil" symptom, arborization, CI, IS).
Upon reaching the preovulatory stage, a one-day break in treatment is taken, after which a large dose of hCG is administered once (4500-12000 IU), resulting in ovulation and the formation of a corpus luteum. Treatment with MCCG presents certain difficulties, since hyperstimulation of the ovaries is possible, hormonal studies or the use of ultrasound are required. When using MCCG, daily gynecological monitoring is necessary. The effectiveness of ovulation stimulation reaches 70-90%, fertility restoration - 30-60%. Multiple pregnancies are possible.
A promising and most effective method of treating isolated hypogonadotropic ovarian hypofunction is the use of luliberin. Usually 50-100 mcg of the drug is administered intramuscularly or intravenously, intranasal administration is possible. Luliberin is administered for 10-14 days before ovulation, the timing of which is determined by TFD, ultrasound and hormonal studies.
Forecast
The prognosis is favorable. Working capacity is not impaired. Patients are subject to dispensary registration to avoid the occurrence of tumors of the hypothalamic-pituitary system and timely detection of hyperplastic processes in the reproductive system against the background of hormonal therapy. In case of pregnancy, they are included in the risk group for its bearing.