Resistant Ovarian Syndrome is a pathological symptom complex that develops due to insensitivity of the ovaries to gonadotropic stimulation. The syndrome of resistant ovaries is characterized by secondary amenorrhea and infertility in women under 35 years of age. In the diagnosis of resistant ovarian syndrome, the data of gynecological anamnesis and examination, hormonal studies and tests, ultrasound, ovarian biopsy are important. Treatment of the syndrome involves estrogen replacement hormone therapy; pregnancy is possible with the help of ART techniques.
General information
Resistant ovarian syndrome is a poorly studied pathology in which amenorrhea and infertility develop with normally formed secondary sexual characteristics, maro– and microscopically unchanged gonads and high levels of gonadotropins. In gynecology, among the various forms of amenorrhea, resistant ovarian syndrome accounts for from 1.9 to 10% of all cases. Synonyms of resistant ovary syndrome in the literature are Savage syndrome, the syndrome of refractory, paralyzed, “mute”, resting or insensitive ovaries.
Causes
The etiopathogenesis of resistant ovarian syndrome is not completely clear. It is possible that its development may be due to genetic defects in the receptor apparatus of the follicles. The data testifying to the autoimmune nature of the pathology are presented – in the syndrome of resistant ovaries, antibodies blocking the sensitivity of FSH receptors in the ovaries are detected in the serum. In addition, according to clinical observations, Savage syndrome is quite often combined with disorders such as Hashimoto’s thyroiditis, myasthenia gravis, diabetes mellitus, hypoparathyroiditis, platelet purpura, alopecia, autoimmune hemolytic anemia, etc.
The role of iatrogenic factors in the likelihood of developing the syndrome has also been proven – radiorentgenotherapy, the use of immunosuppressants and cytostatics, ovarian resection. Often, the syndrome of resistant ovaries is caused by damage to ovarian tissue in mumps, tuberculosis, actinomycosis, sarcoidosis.
Symptoms
A typical manifestation is irregularity, and then the cessation of menstruation in women under the age of 35 (secondary amenorrhea). In the anamnesis, hereditary burden in relation to menstrual and reproductive functions, the presence of autoimmune pathology, frequent infections are often noted. The onset of the disease is usually preceded by a severe viral infection, stress exposure, taking large dosages of sulfonamides or other drugs, etc.
The formation of menarche in patients with resistant ovarian syndrome is timely, childbirth and abortions are often noted in the past. Violation of menstrual function by the type of oligomenorrhea can exist from 3 to 10 years. An important informative feature characterizing Savage syndrome is the absence of vegetative-vascular disorders (hot flashes, palpitations, sweating, etc.) typical of menopause or depleted ovarian syndrome.
Patients with resistant ovarian syndrome have a female body type, correctly developed secondary sexual characteristics. The development of the mammary glands is normal, fibrocystic mastopathy is quite often detected in women. Episodic spontaneous menstrual-like bleeding is extremely rare.
Diagnostics
Only a comprehensive study of instrumental and laboratory data makes it possible to differentiate the syndrome of resistant ovaries from a similar pathology in terms of symptoms: gonadal dyskesia, ovarian depletion syndrome, prolactinoma, etc. Gynecological examination reveals signs of hypoestrogenism – thinning and hyperemia of the mucous membranes of the vulva and vagina, a weakly positive symptom of the “pupil”.
According to the ultrasound of the pelvis, a uterus of normal or somewhat reduced size with a thin layer of endometrium is determined; the dimensions of the ovaries are not changed, multiple follicles up to 5-6 mm in diameter are visualized in them (the phenomenon of multifollicular ovaries). The study of hormones is characterized by high levels of LH and FSH, normal prolactin levels and low concentrations of estradiol in blood plasma. Characteristic hormonal indicators in resistant ovarian syndrome are an increase in the level of prostaglandin E2 by 3-4 times, cortisol by 2 times, testosterone by 3-10 times.
Hormonal tests provide high diagnostic information in the case of resistant ovarian syndrome. The first gestagen test is usually positive, subsequent tests show a negative result. The syndrome of resistant ovaries is always characterized by a positive response to an estrogen-progestogen test in a cyclic mode, which indicates the preservation of feedback mechanisms between the hypothalamic-pituitary region and the ovaries.
Diagnostic laparoscopy allows you to see translucent follicles in the ovaries; ovarian tissue biopsy and subsequent histological examination confirms the presence of primordial and preantral follicles in the biopsy. In order to exclude pituitary adenoma, radiography of the Turkish saddle, CT or MRI of the pituitary gland is performed.
Treatment
Since the etiopathogenesis of resistant ovarian syndrome in most cases remains unclear, treatment can be extremely difficult.
With resistant ovarian syndrome, two- or three-phase HRT is prescribed, aimed at correcting the state of estrogen deficiency, normalizing the menstrual cycle, reducing the level of gonadotropins. In the mode of contraception, young patients are prescribed estradiol with didrogesterone, norethisterone, medroxyprogesterone or ciproterone. Women after 50 years of HRT is carried out in a continuous mode (tibolone, estradiol with dienogest or norethisterone).
From non-drug methods for resistant ovarian syndrome, acupuncture on the receptor areas of the ovaries, intravaginal and abdominal ultraphonophoresis with vitamin E, spa therapy is indicated.
Since there is no restoration of the normal ovulatory menstrual cycle, the implementation of generative function in women with resistant ovarian syndrome is possible only by IVF using a donor egg. Reports of the independent onset of pregnancy and childbirth after treatment with estrogens are rare.
After 40 years, patients require annual mammography, pelvic ultrasound, densitometry to exclude osteoporosis, blood cholesterol and lipoproteins.
Prevention
Due to the complexity and insufficient knowledge of the mechanisms of development of resistant ovarian syndrome, modern gynecology cannot yet identify specific measures for its prevention. It is recommended to exclude adverse iatrogenic effects – infections, radiation, drug intoxication, etc. It is advisable to consult a gynecologist in case of menstrual function disorders with a full examination.