(I) Definition
Abnormal uterine bleeding, manifested as heavy menstrual flow, prolonged menstrual period or irregular bleeding, is caused by the malfunction of the neuroendocrine mechanisms regulating reproduction in release or mutual regulation, and the abnormal bleeding is not related to organic lesions of the systemic and internal and external reproductive organs. It can occur at any age from the beginning of menstruation to pre-menopause.
Many internal and external factors, such as mental stress, fear, sadness, environmental and climatic changes, and certain systemic diseases, can affect the mutual regulation of the hypothalamic-pituitary-ovarian axis through the cerebral cortex and central nervous system. Malnutrition, anemia, and metabolic disorders can also affect the synthesis, functioning, and effects of hormones on target organs, resulting in menstrual disorders. Abnormal function of some endocrine glands (e.g. thyroid and adrenal cortex) can also lead to menstrual disorders. A proper understanding of the reproductive endocrine and its mutual regulation in all parts of the subthalamic-pituitary-ovarian axis of the menstrual cycle is fundamental to the understanding of menstrual bleeding.
(II) Classification
According to the functional status of ovaries, meritorious hemorrhage can be divided into ovulatory (sexual) meritorious hemorrhage and anovulatory (sexual) meritorious hemorrhage; anovulatory meritorious hemorrhage can be divided into adolescent meritorious hemorrhage and menopausal meritorious hemorrhage; ovulatory meritorious hemorrhage can be divided into luteal insufficiency (luteal insufficiency) and endometrial irregular shedding (luteal atrophy insufficiency) meritorious hemorrhage.
(C) Etiology, pathology and clinical manifestations of various types of functional hemorrhage
1.Anovulatory dysfunctional uterine bleeding
(1) Etiology It is caused by temporary changes in the release or balance of gonadotropin-releasing hormone, gonadotropin and ovarian sex hormones. Anovulatory uterine bleeding occurs mainly in adolescent and menopausal women, but the pathogenesis of both is not identical. During adolescence, the hypothalamic cycle regulation center and pituitary gland are not mature enough to establish a stable cycle regulation and positive and negative feedback between them and ovarian endocrine secretion. FSH secretion by the pituitary gland is continuously low during this period and there is no LH peak formation. As a result, there is no ovulation although there are batches of follicles growing in the ovaries, and follicular atresia occurs when follicles reach a certain level of development. In menopausal women, due to the gradual decline of ovarian function, the follicles are nearly exhausted and the remaining follicles are often unresponsive to pituitary gonadotropins, resulting in a decrease in estrogen secretion and a weakening of the negative feedback to the pituitary gland. Most anovulatory hemorrhage is either estrogen withdrawal bleeding or estrogen breakthrough bleeding.
Estrogen withdrawal bleeding: After follicle development, estrogen production, and excessive endometrial hyperplasia under the sustained stimulation of a single estrogen, a sudden drop in estrogen levels due to the inhibition of FSH by a large amount of estrogen (negative feedback) or if a group of follicles undergoes atresia, the endometrium peels off and bleeds due to loss of hormonal support, similar to withdrawal bleeding caused by withdrawal of exogenous estrogen after administration.
There are two types of estrogen breakthrough bleeding: the estrogen level is low for a long time, resulting in the endometrium not being able to repair well, causing long lasting intermittent small amount of bleeding; in the other case, the estrogen level is continuously high, the endometrium proliferates and thickens, which may even cause short-term amenorrhea, and because of the absence of progesterone on the endometrium, the endometrium is prone to breakthrough bleeding, with large amount of bleeding and long duration.
(2) Clinical manifestations Patients with anovulatory uterine bleeding can have a variety of different clinical manifestations. The most common clinical symptom is irregular uterine bleeding, characterized by disordered menstrual cycles, periods of varying length, bleeding that is sometimes more or less frequent, or even heavy bleeding. Sometimes there is menopause for weeks or months followed by prolonged and heavy bleeding or irregular bleeding. Gynecological pelvic examination does not reveal organic lesions. The uterus may be soft at the time of bleeding and the basal body temperature may be monophasic. High bleeding may be followed by anemia. Adolescent and menopausal uterine bleeding is mostly anovulatory.
(3) Endometrial pathological changes Depending on the level of estrogen and the duration of action, the endometrium may have different manifestations.
① Endometrial glandular cystic hyperplasia: due to the continuous increase of estrogen level in the body, the endometrium is partially or completely thickened or may show polyp-like hyperplasia; the number of glands increases, the glandular cavity is cystically enlarged, the size varies, the glandular epithelium is highly columnar, the hyperplasia may form a compound layer or pseudo compound layer, without secretory manifestations. The interstitium is often edematous and necrotic, with a small amount of hemorrhage and leukocyte infiltration.
Endometrial adenomatous hyperplasia: The endometrial glands are highly hyperplastic, significantly increased in number, and form a glandular back-to-back phenomenon, resulting in a significant reduction of the interstitium. The glandular epithelium is arranged in a complex or pseudo-complex layer, or protrudes into the glandular lumen in a papillary pattern, with large deep-stained nuclei and nuclear division. If adenomatous hyperplasia is serious, it may develop into endometrial atypical hyperplasia, which is a precancerous lesion, and 10%-15% may be transformed into endometrial cancer.
③ Proliferative (proliferative) endometrium: the endometrium seen is no different from the proliferative endometrium in normal menstrual cycle, except that in the second half of the menstrual cycle, or even during menstruation, it still shows the proliferative phase pattern.
④ Atrophic endometrium: The endometrium is atrophied and thin, with few and small glands, narrow and straight glandular ducts, single-layer cuboidal or low columnar cells in the glandular epithelium, and little and dense interstitium. This reflects low estrogen levels.
2.Ovulatory dysfunctional uterine bleeding
It is less common than anovulatory uterine bleeding and occurs mostly in women of reproductive age. Although the patient has ovulatory function, the corpus luteum function is abnormal. There are two common types. (1) luteal insufficiency (luteal hypoplasia ), and (2) irregular shedding of endometrium (luteal atrophy insufficiency).
(1) Luteal insufficiency
①Etiology: Luteal insufficiency can be caused by a variety of factors, neuroendocrine regulation dysfunction can lead to a lack of FSH during the follicular phase, resulting in slow follicular development and reduced estrogen secretion; abnormal LH secretion, LH deficiency results in post-ovulatory luteal insufficiency and reduced progesterone secretion; abnormal LH/FSH ratio can also cause gonadal axis dysfunction, resulting in follicular dysplasia and post-ovulatory luteal insufficiency, i.e. There is follicular development and ovulation in the menstrual cycle, but the luteal phase progesterone secretion is insufficient or the corpus luteum declines prematurely, resulting in poor endometrial secretion response.
②Pathology: The morphology of the endometrium often shows poor glandular secretion and inconspicuous interstitial edema. It can also be observed that the glandular and interstitial development is not synchronized, or shows inconsistent secretory response in different parts of the endometrium. Sometimes the luteal function is normal but maintained for a short period of time.
(③) Clinical manifestations: Ovulatory type of gonorrhea usually still has a menstrual cycle. Sometimes the menstrual cycle is within the normal range, but the follicular phase is prolonged and the luteal phase is short. Patients are less likely to conceive or to miscarry early after conception.
(2) Irregular shedding of endometrium (luteal atrophy)
(1) Etiology: The corpus luteum usually atrophies after 14 days of survival. Irregular shedding of endometrium is due to dysfunction of hypothalamic-pituitary-ovarian axis regulation and continuous secretion of small amount of LH, which causes prolongation of luteal atrophy process and continuous progesterone influence on endometrium, resulting in irregular shedding of endometrium.
②Pathology: On the 3rd-4th day of normal menstrual cycle, the secretory endometrium has been completely shed and replaced by regenerated proliferative endometrium. However, in the case of irregular shedding of endometrium, secretory-responsive endometrium can still be presented on the 5th-6th day of menstruation. The endometrium shows a mixed type, both residual secretory phase endometrium mixed with bleeding necrotic tissue and newly regenerated endometrium.
(③) Clinical manifestations: It mostly occurs in women of reproductive age. The manifestation is prolonged menstrual period, up to 9-10 days, and may have more bleeding. Or there is a small amount of dripping bleeding after menstruation.
(iv) Diagnosis and differential diagnosis
1.It should be emphasized that before diagnosing gonorrhea, certain systemic or internal and external genital organ lesions caused by abnormal uterine bleeding must be excluded first.
2. Detailed medical history should be taken, physical examination and pelvic examination should be performed, and auxiliary diagnostic tests should be selected in a targeted manner.
3.Diagnosis and differential diagnosis should be made based on the medical history, pelvic examination and auxiliary diagnostic tests, and endometrial pathological diagnostic results. Pay attention to the analysis of doubtful points. And differentiate from pregnancy-related diseases and abnormal endometrial bleeding due to improper use of gonadal endocrine drugs or contraceptives.
4. In patients with long illness and poor results of standardized treatment, the possibility of organic lesions, especially small lesions in the uterine cavity, should be reconsidered.
5, diagnostic scraping has both the role of minimizing bleeding and aiding diagnosis and treatment. All the scraped endometrium should be sent for pathological examination, scraping away the abnormal endometrium, which can cause synchronous changes in the endometrium with gonadal endocrine therapy is beneficial. Diagnostic scraping should be performed in those who are married, have a long course of disease, and have a lot of bleeding.
(E) Treatment
How to develop the appropriate treatment plan is the key to achieve good results.
1.Treatment principles.
Consideration should be given to hemostasis, menstrual regulation, restoration of health and prevention of recurrence. It varies from person to person according to age, condition, endometrial pathological examination results and the requirement of fertility.
Adolescent meritorious bleeding: stop bleeding, regulate menstruation, and promote the establishment of cyclic regulation of the subthalamic-pituitary-ovarian functional axis and ovulation of the ovaries.
Menopausal hematemesis: hemostasis, menstrual regulation, induction of amenorrhea in women near menopause.
In women with fertility requirements, guidance should be given to increase pregnancy and reduce the chance of miscarriage. The selection of medication for menstrual regulation is based on the patient’s age and condition, with artificial cycles for the younger ones, contraceptive pills for those with contraceptive requirements, and synthetic progestins for those near premenopausal age.
2.Treatment methods.
(1) General treatment, including hemostatic drugs, contraction drugs, anemia to give blood supplements and rest as appropriate. For long-term bleeding secondary to infection, antibiotics should be given.
(2) Sex hormone medication: gonadal endocrine therapy is an effective treatment method, but it should be carefully planned, reasonable plan should be made, the lowest effective dose should be used as much as possible, and the dose should be reasonably adjusted in time when a large amount of medication is used to stop bleeding as soon as possible, and the treatment process should be closely observed. Avoid medical bleeding caused by improper application of sex hormones.
In addition, it is necessary to understand the pathogenesis of various gonorrhea and the pharmacological effects of the applied gonadal endocrine drugs, so that the appropriate drug can be selected according to the condition.
In addition to general treatment, a large amount of sex hormones can be used and the dose can be gradually reduced to a maintenance amount to treat the bleeding.
The function of estrogen to stop bleeding is to make the endometrium grow and cover the wound surface to stop bleeding, which is suitable for adolescent and fertile age.
The effect of progesterone on hemostasis is to make the endometrium change in the secretory phase based on the effect of estrogen on the endometrium, and the endometrium can be shed more completely after stopping the drug. It is also called “drug scraping” and is suitable for adolescent and childbearing age hematemesis. It is not suitable for those who have severe anemia.
The effect of decreasing doses of large amounts of synthetic progestins is to cause metaplasia of the proliferating and hyperplastic endometrium, followed by atrophy and shedding after discontinuation of the drug. It is indicated for menopausal uterine function hemorrhage or near premenopausal age fertility age uterine function hemorrhage. The application of male endocrine alone can only reduce bleeding, but the hemostatic effect is not satisfactory.
The purpose of adjusting the menstrual cycle is to enable the patient to “menstruate” on a monthly basis. This means that withdrawal bleeding occurs.
For adolescent and fertile age menstrual cycle adjustment, artificial cycle is available. Short-acting contraceptive pills can be used to regulate menstruation for those who require contraception. Menopausal menstrual bleeding can be regulated with synthetic progesterone or male endocrine. In cases of anovulation with fertility requirements, clomiphene or hCG (chorionic gonadotropin) can be given in increasing doses to stimulate ovulation when follicles reach a certain level of development, simulating the formation of an LH peak.
Luteinizing insufficiency or luteal atrophy can be treated with progesterone or hCG in the second half of the menstrual cycle to stimulate and maintain luteal function.