I. Clinical manifestations and etiology
Endometrial hyperplasia mainly occurs in women of childbearing age and mainly manifests as irregular vaginal bleeding, such as prolonged periods, excessive menstrual flow, scanty menstruation or heavy vaginal bleeding after a period of amenorrhea. Younger women may become infertile after marriage, and it is common in women over 35 years of age. The causes are mainly related to long-term estrogen stimulation.
1. Endogenous estrogen
(1) Non-ovulation: Adolescent and perimenopausal women, hypothalamic-pituitary-ovarian axis disorders, polycystic ovary syndrome, etc., can have non-ovulation, so that the endometrium is subject to long-term, continuous estrogen action and lack of progesterone counteracting, and is in a proliferative state for a long time.
(2) Obesity: androstenedione secreted by the adrenal glands of obese women is converted into estrone by the action of aromatase in adipose tissue; the more adipose tissue there is, the higher the plasma level of estrone, thus causing persistent estrogenic effects.
(3) Functional endocrine tumors: rare.
2. Exogenous estrogen
(1) Estrogen replacement therapy (ERT): Estrogen deficiency presents with menopausal syndrome, while osteoporosis, abnormal lipid metabolism and cardiovascular changes may also occur. Therefore, ERT is widely used and has achieved very good results. The use of estrogen alone for one year has resulted in endometrial hyperplasia in 20% of women. ERT, on the other hand, is often applied continuously over the years, even until the end of life.
(2) Tamoxifen: Tamoxifen (TAM) has an anti-estrogenic effect and is used in patients with advanced postmenopausal breast cancer. In conditions of low estrogen and weak estrogen-like effects, long-term use can also cause endometrial hyperplasia. cohen reported that in 164 cases of postmenopausal TAM users, endometrial lesions occurred in 20.7%, and the incidence was related to the duration of TAM use. For those who took TAM for >48 months, 30.8% had endometrial lesions.
Second, histological classification
1, endometrial simple hyperplasia: the uterus is slightly larger, the endometrium is obviously thickened, sometimes in the form of diffuse polyps. The amount of scraping material is large. The lesion is diffuse, involving the functional and basal layers of the endometrium, and the interstitium and glands are proliferating at the same time without showing glandular crowding. The glands are variable in size and unevenly distributed, with a smooth contour. The glandular epithelial cells are not heterogeneous.
2. Complex endometrial hyperplasia: The etiology is roughly similar to that of simple hyperplasia, but because the lesions are focal, they may also be related to the distribution of hormone receptors in the tissue. A small number of complex hyperplasia can develop into atypical hyperplasia, thus affecting the prognosis. The lesions are focal hyperplasia of glandular components without interstitial involvement. The amount of scrapings can be large or small. The glands are crowded and can be “back-to-back”, with a marked reduction in the interstitium. The outline of the gland is irregular, but there is no heterogeneity of glandular epithelial cells.
Endometrial atypical hyperplasia: The occurrence of atypical hyperplasia is similar to that of complex hyperplasia, and some cases can slowly develop into cancer. In severe atypical hyperplasia, the carcinoma rate can reach 30% to 50%. This type of hyperplasia is limited to the endometrial glands, and the heterogeneity of the glandular epithelial cells is the key to diagnosis. The lesions are focal or multifocal in distribution. There is an increase in the number of glands in the lesion area and a decrease in the interstitium. The hyperplastic glands are not only irregular in outline, but also have a heterogeneous pattern of glandular epithelial cells. According to the degree of lesion, it can be divided into mild, moderate and severe.
Third, the differentiation of clinical features
1. Response to drug therapy: atypical hyperplasia is sensitive to drugs, and the membrane is obviously reversed within a short period of time after the drug is administered, and the dose of the drug is small. For moderate or severe atypical hyperplasia, the dose of progestin must be increased and applied continuously without interruption for 3-6 months. After discontinuation of the drug, most of the recurrences occur only after a considerable period of remission. Endometrial adenocarcinoma is generally slow to respond to drug therapy and requires higher doses to bring about a transformative response in the endothelium. Once the drug is discontinued, recurrence occurs quickly.
2. Age: It is very rare for patients with endothelial adenocarcinoma to be younger than 40 years of age. Among 1566 cases of endometrioid carcinoma collected by the Norwegian Cancer Registry, the average age was 62 years (36-91 years), of which 0.6% were <40 years and 8.4% were <50 years. Therefore, in young women, especially those who are eager to have children, if the scraping material does not definitely see the features of interstitial infiltration, the diagnosis of atypical hyperplasia should still be favored, despite the obvious hyperplasia of glands and cellular heterogeneity. However, this rule of age is for endometrioid carcinoma. Those less common endometrial carcinomas of other tissue types, such as non-estrogen-dependent type II endometrial carcinomas, including plasmacytoid papillary carcinoma and clear cell carcinoma, do not have the characteristics of young age. Some scholars have reported five cases of younger non-estrogen-dependent endometrial cancer in patients aged 28, 34, 37, 41 and 43 years old.
IV. Treatment principles
1. Simple hyperplasia and complex hyperplasia of endometrium.
(1) Young patients: Most of them are non-ovulatory gonorrhea. Basal body temperature should be measured, and those who are really monophasic non-ovulatory can be treated with ovulation promotion.
(2) Reproductive phase: bleeding can usually be controlled by scraping the uterus once. Those who are infertile and exhibit anovulation with polycystic ovary syndrome are treated as polycystic ovary syndrome.
(3) Transitional menopause: often non-ovulatory function hemorrhage. If menstruation is sporadic and the amount of blood or bleeding is prolonged after scraping to stop bleeding, periodic progesterone therapy is given every two months for a total of 3 cycles followed by observation.
(4) Late menopause: should ask if estrogen replacement therapy alone is used. Replacement therapy may be suspended or progestin may be added after curettage.
2. Endometrial atypical hyperplasia.
(1) Transitional or late menopause: hysterectomy. Since age is the main high-risk factor for malignant endothelial hyperplasia, hysterectomy is appropriate for this group of age patients.
(2) Young or reproductively expecting fertility: pharmacological treatment. Atypical hyperplasia is a potentially malignant precancerous lesion, and if left untreated, 20% will develop into cancer. However, cancer is less common in young patients. Moreover, drug therapy is effective for young and reproductive patients.
① Ovulation-promoting drugs: Ovulation-promoting drugs include clomiphene and chorionic gonadotropin. They are generally used in patients with mild endometrial atypical hyperplasia.
②Progestin drugs: Progestin drugs can inhibit estrogen-induced endometrial hyperplasia. Commonly used progestins include progesterone and methylhydroxyprogesterone. Mild atypical hyperplasia can be treated with progesterone 30mg intramuscularly, starting on day 18 or 20 of the cycle, for 5-7 days. In moderate or severe cases, it should be applied continuously.
③ Danazol: It is a derivative of ethynyl testosterone, which is commonly used in the treatment of endometriosis. It has a strong anti-proliferative effect on the endometrium. Treatment with a dose of 200mg/d for 3 months has a significant effect on endometrial hyperplasia.
④Cottonol: It is an effective drug used to treat endometrial hyperplastic functional uterine bleeding and endometriosis in China. Its mechanism of action is ovarian inhibition, and it also has a specific inhibitory effect on the endometrium.
⑤ GnRH agonist: It first causes a significant increase in blood gonadotropin levels, followed by depletion of gonadotropin stocks in the pituitary gland and suppression of the pituitary gland, causing estradiol levels to drop to postmenopausal levels.
A course of treatment is given in three months. The endometrium is taken for histological examination at the end of each course of treatment, and depending on the response to the drug, the treatment may be stopped or the dose of the drug may be increased or decreased. The duration of treatment varies from 3 months, 6 months, 9 months and 12 months, with an average of 9 months. The dose and duration of medication can be guided by the results of regular endometrial biopsies.
V. Pregnancy after progestin therapy
When the endometrium has improved and progestin is discontinued, ovulation promotion or other techniques to help pregnancy should be considered in time to prevent the recurrence of endometrial hyperplasia or highly differentiated cancer. The severity of endometrial hyperplasia has an impact on the rate of conception. Complex hyperplasia has a high conception success rate, followed by mild atypical hyperplasia, while moderate atypical hyperplasia and severe atypical hyperplasia have a lower conception rate.