What Is Premature Ovarian Failure?

Premature ovarian failure (POF) refers to the phenomenon of amenorrhea before the age of 40 caused by ovarian failure. It is characterized by primary or secondary amenorrhea accompanied by an increase in blood gonadotropin levels and a decrease in estrogen levels, and a series of low-estrogen symptoms such as hot flushes, sweating, facial flushing, and low libido. The average natural menopause age of women is 50-52 years old. There are differences in the distribution of menopause between races and regions, but the absolute values are not much different. Coulam et al. Summarized the natural amenorrhea of 1858 women. The incidence of POF was less than 1% when they were less than 40 years old, and the incidence of POF was less than 1 when they were less than 30 years old. POF accounts for 10% to 28% in primary amenorrhea, and POF accounts for 4% to 18% in secondary amenorrhea. Xu Ling and others found that the incidence of POF among women in Beijing was 1.8%. It can be seen that POF is not uncommon in clinical practice.

Basic Information

English name

premature ovarian failure, POF

Visiting department

Obstetrics and Gynecology

Common causes

Immune factors are a sure cause of premature ovarian failure

Common symptoms

Hot flushes, sweating, facial flushing, low libido, amenorrhea, infertility

Causes of premature ovarian failure

POF is a syndrome with multiple etiologies, and the etiology is unknown in most cases.

At present, the etiology of POF is mainly divided into the following aspects clinically, and each etiology can reduce the reserve of follicular pool in the ovary or cause follicular dysfunction from one of the above aspects and cause POF.

Genetic factor

Through careful analysis of family history, the incidence of familial POF is reported to be 4% to 31% in different populations, showing that genetic factors play a major role in POF. X chromosome abnormalities have been recognized as the main cause of POF. With the development of molecular biology, researchers have also found more and more candidate genes related to POF on autosomes.

2. Immune factors

Since the 1950s, researchers have found that 9% to 40% of patients with POF have other endocrine glands or systemic autoimmune diseases, such as autoimmune thyroiditis, systemic lupus erythematosus, myasthenia gravis, and parathyroid glands. Hypofunction, rheumatoid arthritis, idiopathic thrombocytopenic purpura, diabetes, etc. POF patients often have two or more autoimmune diseases. Among all autoimmune diseases accompanying POF, thyroid disease is the most common cause. 12% to 33% of POF patients can be detected with thyroid disease. In 18% of patients with POF, there is a genetic thyroid disease in the family, and the second most common is polyglandular autoimmune disease (PAGD, Addison disease with endocrine system dysfunction). In the PGAD type 1, the incidence of POF is 17% ~ 50%, PGAD type II, the incidence of POF is 3.6% to 7%, PGAD type II includes autoimmune Addison disease, thyroid autoimmunity and insulin-dependent diabetes mellitus, and other such as white spot, baldness, chronic atrophic gastritis, These syndromes, such as pernicious anemia, have many changes in the natural course, and symptoms of POF may appear before and after onset, such as Addison disease. POF usually occurs earlier than adrenal symptoms.

Clinical manifestations of premature ovarian failure

1. Amenorrhea is divided into primary amenorrhea and secondary amenorrhea. Secondary amenorrhea occurs before the age of 40. Investigation of a large sample of patients with POF found that there were no characteristic signs of menstrual abnormalities before menopause. Some people have sudden amenorrhea after regular menstruation, some stop contraceptives or amenorrhea after childbirth, and some show menstrual cycle and menstrual disorders before menopause.

2. Some patients with infertility found premature ovarian failure due to infertility. Infertility is the leading cause of medical problems and distress in patients with premature ovarian failure. There are primary and secondary infertility, so it is recommended that those with a family history of premature ovarian failure should plan pregnancy as soon as possible.

3. Low estrogen symptoms Low estrogen symptoms (hot flashes and / or dyspareunia, etc.) are rare in primary amenorrhea (22.2%). Most of them are related to previous estrogen replacement therapy. Hormonal symptoms are common (85.6%). This is consistent with the theory that hypoestrogen symptoms are caused by estrogen withdrawal. These low estrogen symptoms also include atrophic vaginitis and atrophic urethritis such as frequent urination and dysuria.

4. The manifestation of concomitant autoimmune diseases such as Addison disease, thyroid disease, diabetes, lupus erythematosus, rheumatoid arthritis, vitiligo and clonal disease. There are also hidden symptoms of adrenal insufficiency, such as recent weight loss, loss of appetite, unclear abdominal pain, weakness, increased skin pigmentation, and halophilia.

Premature ovarian failure

Medical history

A history of ovarian surgery and a history of radiotherapy and chemotherapy for tumors are iatrogenic factors that cause ovarian failure. Viral infection history is also one of the rare causes of ovarian failure, especially the history of mumps and AIDS. Because of the correlation between POF and autoimmunity, you need to ask your family or yourself if you have a history of autoimmune diseases, such as Addison disease, thyroid disease, diabetes, lupus erythematosus, rheumatoid arthritis, vitiligo, and clonal disease.

2. Medical examination

Turner syndrome has three typical manifestations of short stature, physical deformity, and sexual naivety. Other rare syndromes or autoimmune diseases associated with POF have their own characteristic physical examination results, which are not described in detail here. Idiopathic POF has few signs. Secondary sexual dysgenesis is more common in primary amenorrhea (88.9%) and rare in secondary amenorrhea (8.2%). Pelvic examination can reveal atrophic vaginitis and small uterus such as vulvar atrophy, vaginal atrophy, pale mucous membranes, thinning, punctiform hemorrhage, etc., but most patients with POF can intermittently produce enough estrogen to maintain normal vaginal mucosa .

3. Vaginal B-ultrasound

Visible small uterus and bilateral atrophic ovaries. It has been reported that 41% to 60% of patients have follicular-like structures in the ovaries through vaginal B-ultrasound. Biopsy confirmed that these are premature luteinized follicles, which have no normal function and are the result of hypoovarian failure and follicular failure. In addition, because the basal follicles are too small to be detected by B-ultrasound, B-ultrasound cannot help diagnose follicular POF (ovarian resistance syndrome) or non-follicular POF.

4. Blood hormone levels

Blood FSH persists above 40 IU / L, E2 is often below 100 pmol / L, and P is below 2 nmol / L. Elias et al measured blood androgen levels in patients with premature ovarian failure at the first visit and found that blood testosterone and dehydroepiandrosterone levels in patients with POF were similar to those of women of the same age, and androstenedione levels were lower than those of normal age women.

If accompanied by autoimmune diseases of the thyroid or adrenal glands and causing their hypofunction, cortisol, T ₃ , FT ₃ , T4, FT ₄ levels are low, ACTH and TSH levels are increased.

5. Laparoscopy

The ovary is reduced in size, it is difficult to see the follicles and ovulations during development, no corpus luteum is formed, and the uterus is reduced in size. Ovarian biopsy is not of great significance in diagnosing ovarian inflammation or determining follicular or follicular-free POF, because ovarian biopsies have been reported to show the possibility of pregnancy in the absence of follicles. The one-sided nature of ovarian biopsies can be seen. Therefore, most scholars do not advocate the use of ovarian biopsy to diagnose the etiology and condition of premature ovarian failure.

Diagnosis of premature ovarian failure

In 1967, Moraes-Reuhsen proposed that pre-menopausal, perimenopausal syndrome or menopausal symptoms, hypoestrogenemia and hypergonadotropinemia can be diagnosed as premature ovarian failure before the age of 40. In 1973, Goldenberg proposed that blood FSH³40IU / L is hypergonadotropinemia. However, multiple studies have confirmed that the evidence of follicular failure with a single FSH> 40IU / L is wrong. Therefore, the currently accepted diagnostic criteria for premature ovarian failure in the world are: age <40 years. Amenorrhea time 6 months. (3) Blood FSH> 40mIU / ml twice (with an interval of more than 1 month). Therefore, the diagnosis of premature ovarian failure is not difficult. The main thing is to make the cause of premature ovarian failure as clear as possible to guide clinical treatment.

Premature Ovarian Failure Treatment

1. Estrogen and progestin replacement therapy (HRT)

Estrogen and progesterone replacement therapy is very important for young patients with POF, which can alleviate low estrogen symptoms and urogenital atrophy (preparing for egg donor embryo transfer), and can prevent long-term complications (osteoporosis , Alzheimer's disease, etc.), the risk of colon cancer is reduced by 37%. But long-term HRT also has certain risks, such as the occurrence of endometrial cancer and breast cancer. However, studies have shown that estrogen and progestin replacement therapy with progestin applied for more than 10 days per month can reduce the risk of endometrial cancer to almost zero. The risk of breast cancer has increased slightly, but mortality has not increased. Sequential combination of estrogen and progestin is usually used. Prior to the application of HRT, individualized trade-offs should be made and necessary monitoring and follow-up performed.

2. Prevention of osteoporosis

With the exception of HRT, a daily calcium intake of 1200 mg is guaranteed. VitD400 800IU / day, perform necessary physical exercises, such as walking, yoga or tai chi.

3. Ovulation Promoting Treatment

There are many reports in the literature about the successful experience of ovulation promotion in patients with POF. The conditions for screening patients before treatment are mostly short amenorrhea, low blood FSH levels, and clinical judgment as follicular POF. In general, HRT or GnRHa is used to inhibit endogenous gonadotropins (mainly FSH) to a lower level (<20IU / L), and a sufficient amount of hMG / hCG is required to monitor ovulation and B-ultrasound, requiring a large amount of hMG and a long duration . The theoretical basis for the success of deregulation for ovulation promotion is that the level of endogenous FSH decreases after deregulation, the increase of FSH receptors on the surface of granular cells increases the sensitivity of the ovary.

4. Immunotherapy

Because immune factors are a definitive cause of premature ovarian failure, immunosuppressive treatment of this part of patients with premature ovarian failure with evidence of immune factors is effective. There have been multiple reports of pregnancy during immunosuppressive therapy. So far, there has been no clear method to identify the role of immune factors in POF, no clear indications for immunotherapy and standardized medication regimens, and immunosuppressive treatment can cause serious side effects, so blind application is not recommended Immunosuppressive agents for POF.

5.DHEA treatment

50% of DHEA is secreted by the adrenal cortex reticular zone, 20% is secreted by the ovary, and 30% is transformed by peripheral DHEAS. It produces 6-8 mg daily in the body and the blood concentration is 3-35 nmol / L. Its level decreases with age. DHEA is an important substance for the synthesis of androstenedione, testosterone, and estradiol. The level of DHEA affects the levels of these hormones.

6. Egg Donation and Embryo Transfer

In 1984, Lutjen et al reported that the world's first case of premature ovarian failure oocytes was donated to a viable newborn, providing a way for POF patients to obtain fertility. So far, egg-donating embryo transfer is still the most effective treatment for pregnancy in POF patients.

7. Ovarian transplant

In October 2004, DonnezJ et al. Reported for the first time a case of autologous transplantation of human ovarian tissue to restore ovarian function and deliver live births. In the following years, several reports of successful ovarian cryopreservation and transplantation and pregnancy and childbirth were reported. ^[1-5]