Resistant Ovary Syndrome - Symptoms, Causes, Diagnosis, Treatment and Prevention

What Is the Role of Gonadotropins?

Ovarian dysfunction can occur due to antibodies against gonadotropin receptors due to a deficiency in the gonadotropin signaling that causes an elevation in the concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These gonadotropins receptors will bind a group of pituitary hormones called gonadotropins. Gonadotropins are responsible for inducing follicular development, which leads to ovulation and luteinization. The FSH is produced by the pituitary gland and will regulate both ovaries and testes. Low concentration or lack of FSH can lead to infertility or subfertility in both men and women.

Generally, a patient with resistant ovary syndrome will have primary amenorrhoea (an abnormal absence of menstruation), which stands for raised FSH and LH levels, despite a normal ovarian follicle pool.

These are the characteristic features of resistant ovary syndrome. Ovarian wedge resection is the procedure done to help patients with resistant ovary syndrome begin their menstruation.

What Is Resistant Ovary Syndrome?

Resistant ovary syndrome, also known as Savage syndrome, was also called gonadotropin-resistant ovary syndrome in the early days. It is the cause of ovarian failure that can lead to secondary amenorrhea. Resistant ovaries can occur due to a functional disturbance of the gonadotropin receptors in the ovarian follicles. Treatment of the syndrome involves estrogen replacement hormone therapy, and pregnancy is possible using ART (artificial reproductive technology) techniques.

What Are the Symptoms of Resistant Ovary Syndrome?

A typical manifestation of resistant ovary syndrome is:

1. Irregularity in menstruation.

2. Secondary amenorrhea.

3. Autoimmune pathology.

4. Frequent infections (severe viral infection).

5. Stress exposure.

6. Over ingestion of large doses of Sulfonamides or other drugs, etc.

7. Menstrual dysfunction by the type of oligomenorrhea (irregular menstruation) can exist in three years to ten years.

8. Absence of vegetative-vascular disorders like hot flashes, palpitations, sweating, etc.

The findings that are normal in a woman with resistant ovary syndrome are:

• Normal female body type.

• Properly developed secondary sexual characteristics.

• Normal development of mammary glands.

What Are the Causes of Resistant Ovary Syndrome?

The actual pathology behind the resistant ovary syndrome, which causes amenorrhea and infertility with normal secondary sexual characteristics, normal gonads, and a high gonadotropin level, is poorly understood. Among the various forms of amenorrhea, resistant ovary syndrome accounts for 1.9 % to 10 % of all cases. Its development may be due to genetic defects in the receptor apparatus of the follicles.

Iatrogenic factors like radiotherapy, the usage of immunosuppressants and cytostatics (medicine that inhibits cell division), and ovarian resection have also been proved to cause resistant ovary syndrome. The other common causes of resistant ovary syndrome are damage to ovarian tissue in mumps, tuberculosis, actinomycosis, and sarcoidosis.

How Does the Female Reproductive System Work?

• Due to the external and internal environment signals, the impulses are formed in the cerebral cortex and transmitted to the hypothalamus. This is the region in the brain where the gonadotropin-releasing hormones (GnRH) are produced, which triggers the production of gonadotropin hormones, namely, follicle-stimulating (FSH) and luteinizing (LH) in the neighboring area of ​​the brain substance known as the pituitary gland.

• Gonadotropic means the hormones that act on the gonads (the primary reproductive gland that produces reproductive cells). These gonadotropic hormones will affect the receptors (the sensitive nerve endings) located in the woman's gonads (ovaries). And the receptors, in turn, will transmit the corresponding signals to these organs (gonads) to secrete sex hormones like progesterone and estrogen.

• Hormones secreted by the ovaries will act on the uterus, mammary gland tissue, and other female reproductive organs, causing various body changes that distinguish a woman from a man. When the ovaries fail to receive gonadotropic stimulation will affect the production of sex hormones.

Case Study on Resistant Ovary Syndrome:

In a case study of two women hospitalized with resistant ovary syndrome because of secondary amenorrhoea, the development of secondary sexual characteristics was normal with the presence of a normal female karyotype (46/XX). The X-ray of the sella turcica (it forms a bony caudal border for the pituitary gland) and the examination of the visual fields did not reveal any abnormalities. However, the plasmatic gonadotropin levels; especially FSH, were markedly increased.

Administration of GnRH elicited strong responses in FSH and LH, compared to what is usually seen in post-menopausal women. The serum's concentration of 17 beta-estradiol (hormone estrogen) was low, and prolactin (a hormone released by the anterior pituitary gland to stimulate milk production after childbirth) levels were normal. The ovaries were small without morphological abnormalities in the laparoscopic examination with ovarian biopsy. In both women, treatment with estrogen (Epimestrol) therapy showed normal ovulatory menstrual cycles after three months to seven months.

What Are the Disorders Associated With Resistant Ovary Syndrome?

Savage syndrome (resistant ovary syndrome) is often associated with disorders like:

1. Hashimoto's thyroiditis.

2. Myasthenia gravis.

3. Diabetes mellitus.

4. Hypoparathyroidism.

5. Platelet purpura.

6. Alopecia (hair loss).

7. Autoimmune hemolytic anemia.

How to Diagnose Resistant Ovary Syndrome?

The methods to diagnose resistant ovary syndrome are:

Gynecological Examination: It reveals the signs of hypoestrogenism (thinning and hyperemia of the mucous membranes of the vulva and vagina).

Ultrasound of the Pelvis: Uterus that is normal or slightly reduced in size with a thin layer of the endometrium with no change in the size of the ovary, multiple follicles up to 5 mm to 6 mm in diameter are visualized in the ultrasound of the pelvis.

Hormonal Study: The study of hormones is distinguished by the high levels of LH and FSH, a normal level of prolactin, and a low concentration of estradiol in the blood plasma. An increase in the level of prostaglandin E2 is three to four times higher, cortisol two times higher, and testosterone three to ten times higher than the normal level. The hormonal test is the most effective test for detecting resistant ovary syndrome.

Diagnostic Laparoscopy: Performing a laparoscopy will allow seeing translucent follicles in the ovaries. Following histological examinations, the biopsy of the ovarian tissue to confirm the presence of primordial and preantral follicles in the biopsy. An X-ray of the sella turcica, CT (computed tomography) scan, or MRI (magnetic resonance imaging) of the pituitary gland is performed to avoid confusion with pituitary adenoma.

How to Treat Resistant Ovary Syndrome?

The treatment of resistant ovary syndrome is extremely difficult since the etiopathogenesis is not clear enough to be treated. A two or three-phase HRT (hormonal replacement therapy) is prescribed in women with resistant ovary syndrome, which is given to fix estrogen deficiency, to regularize the menstrual cycle, and lower the level of gonadotropic hormones. Young patients have been prescribed hormones like Estradiol with Dydrogesterone, Medroxyprogesterone, Norethisterone, or Cyproterone. For menopausal women, HRT is performed continuously with hormones.

Alternative Methods to Treat Resistant Ovary Syndrome:

The non-drug method for treating resistant ovary syndrome are:

• Acupuncture.

• Intravaginal and peritoneal ultra phonophoresis with vitamin E.

• Spa therapy.

How to Prevent Resistant Ovary Syndrome?

Since the actual etiopathogenesis is unknown and knowledge about the mechanisms of the resistant ovary syndrome is unclear, the gynecological team cannot yet identify any specific preventive measures.

Conclusion

Eliminating adverse iatrogenic effects like infections, radiation, drug intoxication, etc., can prevent the symptoms of resistant ovary syndrome, which is unclear. But women with menstrual dysfunction are still advised to consult a gynecologist for a complete examination to avoid any menstrual problem in the future.