Endometrial hyperplasia

　　Endometrial hyperplasia patients may have complications such as infection, shock, and so on due to continuous bleeding. The disease affects the daily life of female patients and endangers health, so it is important for high-risk populations to have regular screening and timely treatment.

　　Menstrual irregularity is one of the prominent symptoms of this disease, often manifested as irregular vaginal bleeding, oligomenorrhea, amenorrhea, or continuous bleeding after amenorrhea for a period of time. It is generally referred to as anovulatory dysfunctional uterine bleeding. Patients with anovulatory dysfunctional uterine bleeding during the reproductive period, in addition to vaginal bleeding, infertility is also a major symptom.

　　The methods of preventing endometrial hyperplasia include:

　　1. Eating soybean health products for more than five years can increase the risk of endometrial hyperplasia, and the thickening of the uterus can lead to cancer. Therefore, do not overeat.

　　2. Perimenopausal (menopausal) women are a high-risk population for endometrial hyperplasia. If there are menstrual irregularities or irregular vaginal bleeding, seek medical attention promptly. Do not arbitrarily choose hormone replacement therapy or take hemostatic drugs on your own, as this may conceal the condition.

　　3. Women with obesity, hypertension, diabetes, unmarried and childless women, and women with delayed menopause, especially those with a family history of endometrial cancer, should be highly vigilant and have regular gynecological examinations, which is very important for the prevention of endometrial hyperplasia.

　　Diagnosis relies on histological diagnosis of endometrial tissue. The methods of sampling include: endometrial biopsy, dilatation and curettage, vacuum aspiration, and hysteroscopy. Due to the atypical hyperplasia of the endometrium often presenting as scattered or solitary focal lesions, the entire uterine cavity may simultaneously have various degrees of hyperplasia. It is not possible to reflect all the changes of the endometrium by taking only a few tissue biopsies. For women with atypical hyperplasia of the endometrium during menopause, 30%-50% may have well-differentiated adenocarcinoma at the same time. Therefore, it is crucial to obtain a comprehensive endometrial tissue for pathological examination. Compared with simply taking a few pieces of endometrial tissue, the tissue obtained by dilatation and curettage is more comprehensive, but there is still a possibility of missing some areas, especially at the double uterine horns and the fundus. Vacuum aspiration, due to the effect of negative pressure aspiration, causes the endometrium to fall off more completely, making the diagnosis more comprehensive and reliable. Hysteroscopy not only allows for the observation of the endometrial appearance but also allows for curettage or vacuum aspiration under direct vision, making the examination and diagnosis more detailed and comprehensive.

　　Diet should be light and delicious. Fresh vegetables such as green vegetables, cabbage, radish, carrots, tomatoes, etc., can provide a variety of vitamins and inorganic salts, which are beneficial to the repair of the body's metabolic function. Soy products contain high-quality protein, which can supplement the tissue protein lost due to inflammation, and a small amount of lean meat rich in protein can also be added appropriately. The dishes should avoid being too salty, and steaming and boiling should be the main methods, not fried or stir-fried.

　　1. Treatment principles

　　The treatment of atypical endometrial hyperplasia should first be to make a clear diagnosis, investigate the cause of the atypical hyperplasia, whether there are polycystic ovaries, ovarian functional tumors, or other endocrine disorders, etc. Those with any of the above conditions should receive targeted treatment. At the same time, symptomatic treatment can be started for atypical endometrial hyperplasia, using either medication or surgery. The choice of treatment plan should be different according to age, the type of endometrial hyperplasia, and the requirement for fertility.

　　(1)Considerations for different ages:

　　①Young women eager to have children should prevent over-diagnosis and over-treatment. Over-diagnosis of adenocarcinoma and over-treatment in this group of endometrial lesions is not uncommon, and it would be very wrong to remove a woman's uterus without a definite diagnosis. In clinical practice, such errors are not uncommon. If the pathologist is not aware of the patient's desire to have children, and the clinician has not emphasized it, misdiagnosis and mis-treatment may be inevitable. Therefore, when there is a suspicion in the diagnosis of endometrial biopsy in young women who have not given birth, there should be a consultation with several experts, and a clear differential diagnosis between endometrial hyperplasia and endometrial adenocarcinoma should be made within the scope that is as comprehensive as possible.

　　②Perimenopausal or postmenopausal women should be vigilant about the possibility of atypical endometrial hyperplasia associated with cancer, and should consider hysterectomy more. Pay attention not to be overly conservative; do not perform endometrial resection alone without excluding the possibility of cancer, as this may lead to adverse consequences. When a hysterectomy is performed due to atypical endometrial hyperplasia, the removed uterus should be examined on the operating table for the presence of concomitant cancer, and attention should be paid to the presence of cancer infiltration into the myometrium to select an appropriate surgical range.

　　(2) Different types of endometrial hyperplasia have different principles of treatment:

　　① Simple and complex endometrial hyperplasia:

　　A. Young patients: Most are anovulatory dysfunctional uterine bleeding. Basal body temperature should be measured to confirm that they are uniphasic and anovulatory, and ovulation induction therapy can be adopted.

　　B. Reproductive period: Generally, one curettage is enough to control bleeding. If there is still bleeding after curettage, hysteroscopy and ultrasound should be performed to exclude submucosal fibroids or other organic lesions. In the reproductive period, there may also be infertility and clinical manifestations of anovulatory polycystic ovary syndrome. In such cases, treatment for polycystic ovary syndrome should be followed.

　　C. Perimenopausal period: It is often due to anovulatory dysfunctional uterine bleeding. If menorrhagia occurs after curettage, with oligomenorrhea and excessive blood volume or prolonged bleeding, then every two months of cyclic progestin therapy, for a total of 3 cycles, followed by follow-up observation.

　　D. Postmenopausal period: Ask whether estrogen-only replacement therapy is used. After curettage, alternative therapy can be temporarily suspended or progestin can be added.

　　② Atypical endometrial hyperplasia:

　　A. Perimenopausal or postmenopausal period: Hysterectomy. Since age is the main high-risk factor for malignant transformation of endometrial hyperplasia, it is advisable to perform hysterectomy for this group of patients.

　　B. Young or reproductive age patients seeking fertility: Medication therapy. Atypical hyperplasia is a potential malignant precancerous lesion. If not treated, 20% will develop cancer. However, cancer is relatively rare in young patients, and for young and reproductive age patients, medication therapy is effective. Therefore, medication therapy can be chosen to preserve fertility.

　　2. Medication therapy

　　(1) Ovulation-inducing drugs: Ovulation-inducing drugs include clomiphene and chorionic gonadotropin. They are generally used for patients with mild atypical endometrial hyperplasia. The dosage of clomiphene is 50 to 100mg, once a day, from the 5th to the 9th day of the cycle, and can be extended for 2 to 3 days if necessary.

　　(2) Progestin drugs: Progestin drugs can inhibit the endometrial hyperplasia caused by estrogen. The mechanism of action is:

　　① Inhibit ovulation and the secretion of pituitary gonadotropins through the hypothalamus and pituitary, causing the serum E2 level to decrease to the level of early follicular phase.

　　② Reduce the level of estrogen nuclear receptors in the endometrium.

　　③ Inhibit the synthesis of endometrial DNA.

　　④ Increase the activity of estradiol dehydrogenase and isocitrate dehydrogenase, thereby increasing the conversion of estradiol to estrone and other weaker estrogens.

　　Common progestins include progesterone, hydroxyprogesterone caproate, medroxyprogesterone acetate (Anagon), and acetate of medroxyprogesterone.

　　The method and dosage of medication vary according to the degree of atypical endometrial hyperplasia. For mild atypical hyperplasia, 30mg of progesterone can be administered intramuscularly, starting from the 18th or 20th day of the cycle, for a total of 5 to 7 days, to convert the endometrium to the secretory phase. Subsequent withdrawal bleeding should cause the hyperplastic endometrium to shed. For moderate or severe atypical hyperplasia, continuous application should be used instead of periodic medication. The hormone dosage reported by different authors is inconsistent. The low-dose medroxyprogesterone acetate (Anagon) is only 10 to 30mg/d, while the high-dose is 200 to 800mg/d. Acetate of medroxyprogesterone is 40 to 160mg/d, and hydroxyprogesterone caproate is 125mg every other day. It is necessary to adhere to continuous medication, as intermittent medication will greatly affect the efficacy.

　　(3)Danazol is a derivative of ethinyl-testosterone, a commonly used drug for the treatment of endometriosis. It has a strong antiproliferative effect on the endometrium. A dose of 200mg/d for 3 months has a significant effect on endometrial hyperplasia.

　　(4)Tribulus terrestris is an effective drug used in China to treat functional uterine bleeding due to endometrial hyperplasia and endometriosis. Its mechanism of action is to inhibit the ovary and also has a specific inhibitory effect on the endometrium. After treatment, the pathological morphology of the endometrium shows significant atrophy, and the ultrastructure shows obvious degenerative changes. Peking Union Medical College Hospital has observed preliminary effects in the treatment of atypical hyperplasia of the endometrium with tribulus terrestris. There was one case of atypical hyperplasia, after the use of Shujingfen, the atypical hyperplasia of the endometrium improved, but there were relapses. After 8 months of treatment with tribulus terrestris, the endometrium atrophied, and pregnancy occurred quickly afterward, giving birth to a healthy boy.

　　(5)GnRH agonists first cause a significant increase in blood gonadotropin levels, followed by the exhaustion of gonadotropin reserves in the pituitary, and inhibit the pituitary, reducing the level of estradiol to the postmenopausal level. Therefore, it can also be used for atypical hyperplasia of the endometrium.

　　All the above drugs are taken for a course of 3 months. After completing a course, the uterine cavity is scraped or endometrial tissue is taken for histological examination. According to the reaction to the drug, treatment may be stopped or the dosage of the drug may be adjusted appropriately. The duration of treatment is not consistent. It can be 3 months, 6 months, 9 months, or 12 months, with an average of 9 months. The difference is related to the severity of the potential etiology of the disease. The dosage and duration of medication can be guided according to the results of regular endometrial biopsy.