Treatment of moderate atypical endometrial hyperplasia

Gynecological diseases are very harmful to women. If many gynecological diseases are not treated in time, they may lead to cancer and affect women's life and health. However, the choice of treatment methods for gynecological diseases is also very important, especially for diseases such as atypical endometrial hyperplasia. We should pay more attention to it. Let's learn about the treatment methods of moderate atypical endometrial hyperplasia.

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Treatment of moderate atypical endometrial hyperplasia

1. Treatment principles

The treatment of atypical endometrial hyperplasia must first make a clear diagnosis and find out the cause of the atypical hyperplasia, whether there is polycystic ovary, functional ovarian tumors or other endocrine dysfunction, 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 drug therapy or surgical treatment. The choice of these two treatment options should be based on age, type of endometrial hyperplasia, requirements for fertility, etc.

(1) Different ages have different considerations:

① Young women who are eager to have children should avoid overdiagnosis and overtreatment. It is not uncommon for endometrial hyperplasia to be overdiagnosed as adenocarcinoma and even overtreated. It would be a great mistake to remove the uterus without a clear diagnosis. In clinical practice, there are many examples of such mistakes. If the pathologist is unaware that the patient has fertility requirements and the clinician does not emphasize it, misdiagnosis and mistreatment may be inevitable. Therefore, for the diagnosis of endometrial biopsy in young infertile women, if any doubts are found, multiple experts should be consulted to clarify the differential diagnosis of endometrial hyperplasia or endometrial adenocarcinoma to the greatest extent possible.

② Perimenopausal or postmenopausal women should be alert to the possibility of atypical endometrial hyperplasia and cancer coexisting. They should consider hysterectomy and be careful not to be overly conservative. Do not perform only endometrial resection without ruling out the possibility of cancer, which may cause adverse consequences. When the uterus is removed due to atypical endometrial hyperplasia, the removed uterus should be examined on the operating table to see if there is coexistent cancer, and pay attention to whether there is cancer infiltration into the muscle layer and choose the appropriate surgical scope.

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

① Simple and complex endometrial hyperplasia:

A. Young patients: Most of them suffer from anovulatory functional uterine bleeding. The basal body temperature should be measured. If it is confirmed to be monophasic anovulation, ovulation induction treatment can be used.

B. Reproductive period: Generally, one curettage can control bleeding. If bleeding still occurs after curettage, hysteroscopy and B-ultrasound should be performed to rule out submucosal myoma or other organic lesions. Patients with polycystic ovary syndrome who may be infertile during the reproductive period and have clinical manifestations of anovulation should be treated according to polycystic ovary syndrome.

C. Menopausal transition period: It is often anovulatory functional uterine bleeding. If menstruation is infrequent and the amount of blood is heavy or the bleeding time is long after curettage and hemostasis, progesterone treatment should be given every two months, and follow-up observation should be conducted after 3 cycles in total.

D. Late menopause: The patient should be asked whether to use estrogen replacement therapy alone. After curettage, the replacement therapy can be suspended or progestin can be added.

②Atypical endometrial hyperplasia:

A. Menopausal transition or postmenopause: Hysterectomy. Since age is the main risk factor for malignant transformation of endometrial hyperplasia, hysterectomy is appropriate for patients in this age group.

B. Young people or those who want to have children: drug treatment. Atypical hyperplasia is a potentially malignant precancerous lesion. If not treated, 20% will develop into cancer. However, cancer is rare in young patients. Moreover, drug treatment is effective for young and reproductive patients, so drug treatment can be chosen to preserve fertility.

2. Medication

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

(2) Progestogen drugs: Progestogen drugs can inhibit endometrial hyperplasia caused by estrogen. Its mechanism of action is:

① Inhibit ovulation and the secretion of pituitary gonadotropin through the hypothalamus and pituitary gland, causing the serum E2 level to drop to the equivalent of the early follicular stage.

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

③Inhibit endometrial DNA synthesis.

④ Increase the activity of estradiol dehydrogenase and isocitrate dehydrogenase, thereby increasing the conversion of estradiol to less active estrogens such as estrone.

Commonly used progestins include progesterone, hydroxyprogesterone caproate, medroxyprogesterone (progesterone acetate) and medroxyprogesterone acetate. The method of use and dosage vary according to the degree of endometrial atypical hyperplasia. For mild atypical hyperplasia, 30 mg of progesterone can be injected intramuscularly, starting on the 18th or 20th day of the cycle, and used together for 5 to 7 days to transform the endometrium into the secretory phase. After that, the hyperplastic endometrium will fall off during the complete withdrawal of bleeding and menstruation. For moderate or severe atypical hyperplasia, cyclical medication is not adopted, but continuous application is used. The hormone dosage reported by various authors is inconsistent. The small dose of medroxyprogesterone (progesterone acetate) is only 10 to 30 mg/d, and the large dose is 200 to 800 mg/d, medroxyprogesterone acetate is 40 to 160 mg/d, and hydroxyprogesterone caproate is 125 mg/every other day. Continuous medication must be insisted on. Intermittent interval medication will greatly affect the effect.

(3) Danazol is a derivative of ethynyl-testosterone and a commonly used drug for the treatment of endometriosis. It has a strong anti-proliferative effect on the endometrium. Treatment with a dose of 200 mg/d for 3 months has a significant effect on endometrial hyperplasia.

(4) Cottonpol is an effective drug used in my country to treat endometrial hyperplastic functional uterine bleeding and endometriosis. Its mechanism of action is to inhibit the ovaries and it also has a specific inhibitory effect on the endometrium. After treatment, the endometrial pathological morphology is highly atrophic and the ultrastructure has obvious degenerative changes. Peking Union Medical College Hospital has observed preliminary results in the treatment of atypical endometrial hyperplasia with cottonypol. There was one case of atypical hyperplasia. After using cottonypol, the atypical endometrial hyperplasia improved, but it still recurred. After 8 months of treatment with cottonypol, the endometrium atrophied and the patient soon became pregnant and gave birth to a boy.

(5) GnRH agonists first cause a sharp increase in blood gonadotropin levels, followed by a depletion of the gonadotropin reserve in the pituitary gland, thereby inhibiting the pituitary gland and reducing estradiol levels to postmenopausal levels. Therefore, they can also be used for atypical endometrial hyperplasia.

All of the above medicines have a course of treatment of three months. After each course of treatment, the uterus is scraped or the endometrium is taken for histological examination. Depending on the response to the medicine, the treatment is either stopped or the dosage of the medicine is increased or decreased as appropriate. The treatment period varies, ranging from 3 months, 6 months, 9 months, to 12 months, with an average of 9 months. The difference is related to the severity of the underlying cause of the disease. The dosage and duration of the medicine can be guided by the results of regular endometrial biopsy.

3. Monitoring of the condition during drug treatment

During drug treatment, it is important to monitor atypical endometrial hyperplasia during the treatment process.

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(2) Monitoring of the disease can assist in the differential diagnosis of endometrial atypical hyperplasia and well-differentiated adenocarcinoma: Although endometrial cancer and endometrial atypical hyperplasia have their own characteristics in terms of tissue pathological morphology, it is sometimes difficult to make a correct judgment on the difference between severe atypical hyperplasia and well-differentiated adenocarcinoma based solely on the results of endometrial examination obtained by curettage. The two conditions respond differently to drug treatment and can be used as a reference for differential diagnosis.

(3) Monitoring of the disease can help detect stubborn cases early and pay attention to canceration: Although the canceration rate of atypical endometrial hyperplasia is only about 10% to 15%, we should be more vigilant for stubborn cases that do not heal for a long time and detect and treat them early.

4. Drug efficacy

Lindahl (1990) reported 89 cases of endometrial hyperplasia. After treatment with high-dose progestin, 96.7% of the endometrium returned to normal. The disappearance rate of endometrial atypical hyperplasia and well-differentiated adenocarcinoma treated with drugs is shown in Table 4. The disappearance rate of endometrial lesions after progestin treatment is better for atypical hyperplasia, with a lesion disappearance rate of 70% to 94%. The response of well-differentiated carcinoma is poor, but its lesion disappearance rate can also reach 60% to 75%.

5. Pregnancy after progesterone therapy

After progestin treatment, when the endometrium improves and progestin is discontinued, ovulation induction or other medical techniques should be considered in a timely manner to prevent the recurrence of endometrial hyperplasia or well-differentiated cancer. According to the 6 groups of cases shown in Table 4, there were reports of pregnancy and delivery after treatment. Kimmig (1995) and Keike have each reported successful pregnancy after progestin treatment of well-differentiated endometrial cancer through in vitro fertilization or gamete implantation, one of which was a triplet. Kurman's group (1985) found that 25% of patients under 40 years old had full-term deliveries after treatment. There were 8 pregnancies after treatment in Peking Union Medical College Hospital, accounting for 30% of the preserved uterus. The severity of endometrial hyperplasia has a certain influence on the pregnancy rate. The success rate of pregnancy is high in patients with complex hyperplasia, followed by mild atypical hyperplasia, and the pregnancy rate is low in patients with moderate atypical hyperplasia and severe atypical hyperplasia.

The above is an introduction to the treatment of moderate atypical endometrial hyperplasia. I hope that after understanding the above content, female friends will be able to pay great attention to the disease. In fact, many diseases have a very high cure rate if they are treated in the early stages of the disease, and will not cause too much pain to the body.