Perimenopausal dysfunctional uterine bleeding

　　1. Etiology

　　Perimenopausal dysfunctional uterine bleeding is mostly of an anovulatory type, which is due to the decline in ovarian function at this time, with a significant decrease in the number of eggs in the ovaries, even exhaustion, losing the positive feedback effect of sex hormones on the hypothalamus and pituitary, leading to an increase in the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the pituitary (FSH is usually higher than LH), lack of LH mid-cycle peak, and inability to ovulate. On the other hand, growing follicles become insensitive to the stimulation of gonadotropins due to aging, which is also an important reason for the failure of follicular development to reach maturity and ovulation. In anovulatory cycles, the ovaries cannot normally produce progesterone, and the level of estrogen fluctuates with the development of the follicles. After a long-term single estrogen stimulation without progesterone, the endometrium becomes thickened, glands increase, glandular cavities expand, glandular epithelium abnormally proliferates. When the level of estrogen in the body decreases, the endometrium loses support, causing necrosis and shedding, leading to bleeding. However, due to the aggregation and gelation of acidic mucopolysaccharides (AMPS) induced by estrogen, the permeability of the stroma's blood vessels is reduced, affecting substance exchange, causing local endometrial tissue ischemia and necrosis, leading to bleeding. At the same time, the aggregation of AMPS also hinders the shedding of the endometrium, causing asynchronous shedding of the endometrium, resulting in long-term irregular bleeding. The amount of bleeding is often related to the degree of endometrial hyperplasia and the amount of necrosis and shedding.

　　Although dysfunctional uterine bleeding during the perimenopausal period is often caused by ovarian failure, anovulation, and imbalanced secretion of sex hormones, not every pre-menopausal woman experiences dysfunctional uterine bleeding. Therefore, the exact mechanism of uterine bleeding caused by anovulatory cycles still needs further in-depth research. Recent research suggests that perimenopausal dysfunctional uterine bleeding may also be related to various local factors of the endometrium. Some of the main factors include:

　　1. Abnormal vascular morphology Observation of the structure and morphology of spiral arteries in dysfunctional uterine bleeding patients shows that in the group with hyperplastic endometrium, 80% have abnormal spiral arteries. Abnormal vascular morphology, according to the frequency of occurrence, includes perivascular fibrosis, subendothelial hyaline change, vascular smooth muscle hyperplasia or hypertrophy, and elastin tissue degeneration, etc. Abnormal spiral arteries interfere with the microcirculatory function of the endometrium, affect the shedding and stripping of the functional layer of the endometrium and the repair of the vascular and epithelial surfaces, and affect the vasodilation and constriction function and local coagulation and fibrinolysis function, leading to abnormal uterine bleeding.

　　2. Enhanced fibrinolytic activity In cases of dysfunctional uterine bleeding, the activator substances of endometrial plasminogen increase, resulting in enhanced activity and activation of plasminogen to form plasmin. Plasmin cleaves fibrinogen, causing an increase in fibrin degradation products (FDP), a decrease in plasma fibrinogen, and the formation of a defibrinogenated state in the uterine cavity, thereby affecting the coagulation and hemostasis processes of the normal endometrial spiral arteries and vascular lakes, leading to long-term and large-scale bleeding.

　　3. Abnormal production of local prostaglandins Recent experimental results show that a large amount of estrogen without the counteraction of progesterone can lead to an increase in the secretion of prostacyclin (PGI2) by the capillary endothelium of the cultured endometrium. This results in a balance disorder between PGI2 and thromboxane A2 (TXA2), which are the main regulators of uterine local blood volume, spiral arteries, muscle contraction activity, and coagulation factors. Under the action of a large amount of PGI2, the uterine spiral arteries and microvessels dilate, thrombosis is blocked, and the uterine bleeding time is prolonged.

　　4. The number and function of lysosomes in abnormally proliferated endometrial cells are regulated by sex hormones and directly affect prostaglandin synthesis, thus being related to endometrial shedding and bleeding. Observation of the ultrastructure of the endometrium confirms that from the follicular phase to the luteal phase, the number of lysosomes and enzyme activity progressively increase. Progesterone plays a role in stabilizing the lysosome membrane, while estrogen destroys the stability of the lysosome membrane. Therefore, when the level of progesterone decreases before menstruation or in dysfunctional uterine bleeding, the imbalance between estrogen and progesterone will disrupt the stability of the lysosome membrane, causing phospholipase A2 to be released from lysosomes and enter the cytoplasmic bodies, leading to the activation of arachidonic acid and the formation of a large amount of prostaglandins (PGs). On the other hand, the rupture of the lysosome membrane causes destructive hydrolytic enzymes to be released, which will cause the破裂 of endometrial cells, collapse of the endometrial layer, necrosis, and bleeding.

　　Second, pathogenesis

　　1. Pathophysiological changes of the ovary in perimenopausal women: The weight of the ovary in the stage of sexual maturity is 5 to 6g, and after the perimenopausal period, its weight is only 1/2 to 1/3 of that in the stage of sexual maturity. The observation of the ovarian area by transvaginal ultrasound: the ovarian area of the perimenopausal group, postmenopausal group, and normal menstrual cycle control group is 3.4cm2±2.0cm2, 2.1cm2±1.2cm2, and 5.0cm2±1.2cm2, respectively. The average reduction of the ovarian area in the first two control groups is 32% and 56%, respectively, indicating that the ovarian area is significantly reduced since the perimenopausal period. The ovarian cortex becomes thin, the surface becomes creased, and the primordial follicles gradually decrease to exhaustion. The remaining few follicles are insensitive to gonadotropins, the development of follicles is impaired, and ovulation stops.

　　2. Pathological changes in the endometrium of perimenopausal dysfunctional uterine bleeding patients: Due to the lack of the action of progesterone (P) that restricts the growth of the endometrium, which is only stimulated by a single estrogen (E), the endometrium can present different degrees of hyperplasia due to the high and low levels of E in the blood, the duration of E action, and the sensitivity of the endometrium to E. A few show atrophic changes.

　　(1) proliferative endometrium: There is no difference between the endometrium observed and the proliferative endometrium in the normal menstrual cycle, but it still shows the morphological characteristics of the proliferative phase in the latter half of the menstrual cycle or even during the menstrual period.

　　(2) Endometrial hyperplasia: According to the classification of the International Society of Gynecological Pathologists (ISGP, 1998) as follows:

　　① Simple hyperplasia with mild to moderate structural abnormalities: refers to the hyperplasia of glands with mild to moderate structural abnormalities. The endometrium may be locally or entirely thickened, or present as polypoid hyperplasia. Under the microscope, the characteristics are an increase in the number of glands, cystic expansion of the glandular cavities, varying in size, resembling the appearance of Swiss cheese, hence also known as Swiss cheese-like hyperplasia; or irregular gland outlines, glands are more crowded, and the ratio of glands to stroma increases; but there is no back-to-back glandular phenomenon and cellular atypia. The glandular epithelial cells are tall columnar, which can hyperplasia to form pseudostratified layers, nuclei are elliptical, chromatin is dense, and nucleoli can be seen; the cytoplasm is rich in RNA, slightly blue-stained, and transparent cells can be seen, which are caused by cells stopping at the prophase or metaphase of division. DNA synthesis is active, and glycogen droplets and lipid granules are often present in the cells, and the glands contain more mucus, especially acidic mucopolysaccharides at the apical margin. The stroma often appears edematous, necrotic, accompanied by a small amount of hemorrhage and leukocyte infiltration.

　　②Complex hyperplasia (adenomatous hyperplasia): refers to the proliferation of glands being crowded and structurally complex. The endometrial glands are highly proliferative, growing in a budding manner, forming daughter glands or protruding into the gland lumen, with irregular gland outlines, which may be saw-toothed or papillary, glands are crowded and dense, forming a back-to-back phenomenon, and only a small amount of connective tissue between glands. The gland epithelial cells are highly active, presenting as tall columnar, stratified or pseudostratified, with an increase in translucent cells; the cytoplasm is rich in RNA, the nucleus contains abundant deoxyribonucleic acid, active division, and an increase in mitotic figures; gland cells may undergo ciliary metaplasia, eosinophilic metaplasia, serous papillary metaplasia, etc.; mature squamous cells may appear in the stroma, or small nodular, less mature squamous cells, even protruding into the gland lumen to form a mulberry-like structure; foamy cells containing lipids may also be seen in the stroma. In summary, in the endometrium with complex hyperplasia, the glands have various structural abnormalities and hyperplasia of gland epithelium, but the morphology of gland epithelial cells remains normal, the nuclei of various metaplastic cells are regular, and do not have the characteristics of malignant cells, still belonging to benign lesions.

　　③Atypical hyperplasia: that is, 10% to 15% of the precancerous lesions can transform into endometrial cancer. The endometrium with atypical hyperplasia is based on the simple and complex types of hyperplasia mentioned above, with the gland epithelium showing cell atypia, small areas of glands may appear with a sieve-like structure, gland cells present as stratified or pseudostratified, arranged in disorder, cell size and shape vary, nuclei become larger, deeply stained, and polarity is lost, nuclear-cytoplasmic ratio increases, nucleoli are prominent, chromatin is irregularly aggregated, parachromatin is translucent, and giant cells may be present, with inflammatory exudation in the cytoplasm and gland lumen. The differentiation between complex hyperplasia and atypical hyperplasia mainly lies in the changes of the cell nuclei. Mildly atypical cells have enlarged nuclei, fine chromatin, and uniform distribution; moderately atypical cells have enlarged nuclei with polymorphism and prominent nucleoli; chromatin is clustered and unevenly distributed. Cells with atypical appearance in simple hyperplasia are called simple hyperplasia with atypical hyperplasia of cells (simple atypical hyperplasia); cells with atypical appearance in complex hyperplasia are called complex hyperplasia with atypical hyperplasia of cells (complex atypical hyperplasia).

　　④Atrophic endometrium: detection rate is 1.9% to 21.9%. The endometrium is thin and atrophic, with few and small glands, narrow and straight gland ducts, gland epithelium being single-layer cuboidal or low columnar cells, less and dense stroma, and relatively increased collagen fibers.

　　Perimenopausal dysfunctional uterine bleeding is mostly of the anovulatory type, which is due to the decline in ovarian function at this time, a significant decrease in the number of eggs in the ovaries, and even exhaustion, losing the positive feedback effect of sex hormones on the hypothalamus and pituitary. The pituitary secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), with FSH being higher than LH, and the lack of LH mid-cycle peak, leading to an inability to ovulate. Severe bleeding or prolonged bleeding can lead to anemia, shock, and infection.

　　Patients have irregular menstrual cycles, amenorrhea, or frequent menstruation; the amount of bleeding is not fixed, and it is related to the degree of endometrial hyperplasia and the amount of necrotic shedding; the duration of menstruation is not uniform, which is called 'three irregularities'. Ovulatory dysfunction menorrhagia often has several weeks or months of amenorrhea followed by heavy bleeding, or it can start with irregular vaginal bleeding. Clinical manifestations can include menorrhagia, frequent menstruation, irregular uterine bleeding, and excessive uterine bleeding.

　　Increase the awareness of perimenopausal women about this disease, actively treat early conditions, and prevent the occurrence of perimenopausal menorrhagia and its complications.

　　Recent research suggests that perimenopausal menorrhagia may also be related to local factors of various endometria, including several main factors:

　　1. Abnormal vascular morphology Observations of the structure and morphology of spiral arteries in patients with menorrhagia show that in the group with hyperplastic endometrium, 80% have abnormal spiral arteries. Abnormal vascular morphology includes perivascular fibrosis, subendothelial hyaline change, smooth muscle hyperplasia or hypertrophy, and elastin tissue degeneration, etc. Abnormal spiral arteries interfere with the microcirculatory function of the endometrium, affect the shedding and stripping of the functional layer of the endometrium, and affect the vascular contraction and relaxation function and local coagulation and fibrinolysis function, leading to abnormal uterine bleeding.

　　2. Increased fibrinolytic activity during menorrhagia leads to an increase in the number and activity of activators of endometrial plasminogen, which activate plasminogen to form plasmin. Plasmin breaks down fibrinogen, increasing the level of fibrin degradation products (FDP), reducing plasma fibrin, and forming a defibrinogenated state in the uterine cavity. This affects the coagulation and hemostasis process of the normal endometrial spiral arteries and vascular lakes, leading to prolonged and massive bleeding.

　　3. Experimental results show that a large amount of estrogen without the antagonism of progesterone can lead to an increase in the secretion of prostacyclin (PGI2) by the capillary endothelium of the cultured endometrium. This results in a disorder of the balance between PGI2 and thromboxane A2 (TXA2), the main regulators of the uterine local blood volume spiral arteries, muscle contraction activity, and coagulation factors. Under the action of a large amount of PGI2, the uterine spiral arteries and microvessels dilate, thrombosis is blocked, and the uterine bleeding time is prolonged.

　　4. The number and functional abnormality of lysosomes: The lysosomal function of abnormal endometrial cells is regulated by sex hormones and directly affects prostaglandin synthesis, thus related to the shedding and bleeding of the endometrium. The ultrastructural observation of the endometrial ultrastructure confirms that from the follicular phase to the luteal phase, the number of lysosomes and enzyme activity increase progressively, with progesterone playing a role in stabilizing the lysosomal membrane. Estrogen, on the other hand, disrupts the stability of the lysosomal membrane. Therefore, when the level of progesterone decreases before menstruation or in dysfunctional uterine bleeding, the imbalance between estrogen and progesterone will disrupt the stability of the lysosomal membrane, causing phospholipase A2 to be released from the lysosomes into the cytoplasmic cell, causing the activation of arachidonic acid and the formation of a large amount of prostaglandins (PGs). On the other hand, the rupture of the lysosomal membrane causes the destructive hydrolytic enzymes to be released and cause the endometrial cells to rupture, the endometrial layer to collapse, necrosis, and bleeding.

　　First, laboratory examination

　　1. Sex hormone measurement

　　It is the most accurate indicator reflecting the internal reproductive endocrine status and ovarian function. Before hormone treatment, or under the guidance of basal body temperature (BBT), blood is collected at an appropriate time, and the levels of FSH, LH, prolactin (PRL), estradiol (E2), progesterone (P), and testosterone (T) are measured to distinguish the types of dysfunctional uterine bleeding, differentiate from polycystic ovary syndrome and hyperprolactinemia, and thus guide the clinical formulation of treatment plans, making the treatment more targeted.

　　2. Vaginal shedding cell smear

　　Dynamically observe the vaginal shedding cells, understand the level of E in the body through the maturation index (MI) of vaginal epithelial cells, and use it as a monitoring index for diagnosis, classification, and treatment.

　　Second, auxiliary examination

　　1. Cervical mucus scoring

　　To understand the level of E in the body, if the cervical mucus is still in the form of fernlike crystals even before or during the menstrual period, it indicates a single E effect, without ovulatory function, which can be used as a simple index for the clinical classification, E level estimation, and observation of efficacy for dysfunctional uterine bleeding.

　　2. BBT

　　It is one of the simplest and most commonly used methods for the diagnosis of dysfunctional uterine bleeding. Based on the BBT phase, combined with other monitoring indicators, it is the simplest and most effective means for the classification of dysfunctional uterine bleeding, observation of efficacy, and guidance of treatment.

　　3. Diagnostic curettage

　　It can understand the functional status of the endometrium and ovary, and can directly stop bleeding. For those with perimenopausal bleeding and high-risk factors for endometrial cancer, it should be the first choice to perform fractional curettage to exclude malignant lesions. The diagnostic curettage must fully remove the functional layer of the endometrium, send the tissue for pathological examination, and also pay attention to the depth, shape, and smoothness of the uterine wall. The sensitivity of diagnostic curettage is 78.8% to 84.5%, and the specificity is 100%.

　　4. Type B ultrasound

　　Ultrasound can detect submucosal small fibroids that were overlooked during curettage, detect ovarian tumors, measure the thickness of the endometrium, and observe it dynamically, and due to its non-invasive and repeatable nature, it plays an important role in the diagnosis and differential diagnosis of dysfunctional uterine bleeding, in judging the therapeutic effect, and in guiding clinical treatment.

　　5. Hysteroscopy

　　Hysteroscopy can directly observe the appearance, shape, location, and extent of lesions in the uterine cavity and cervical canal, perform localization biopsy on suspicious lesions, so hysteroscopy is helpful for discovering uterine lesions and selecting points for sampling under direct vision in patients with long-term treatment failure of dysfunctional uterine bleeding, reducing misdiagnosis. The sensitivity of hysteroscopy is 94.1%, and the specificity is 95.5%.

　　First, therapeutic diet for perimenopausal dysfunctional uterine bleeding

　　1. Ginseng and jujube chicken soup: 10 grams of Shendao ginseng (sliced), 30 grams of jujube (with seeds removed), and 1 chicken (with feathers and internal organs removed) cleaned. Put them together in a stewing pot and stew until the chicken is tender and then take it.

　　2. Pomegranate peel decoction: 50 grams of sour pomegranate peel, 30 grams of Codonopsis pilosula, 30 grams of Astragalus membranaceus. Boil, remove the residue, and add a proper amount of honey to drink. Take twice a day.

　　3. Ginseng stewed with turtle: One turtle (cleaned and with the intestines and viscera removed), 3 grams of ginseng. Put them together in a stewing pot and stew until the turtle is tender and then take it.

　　4. Longan, jujube, and Chinese wolfberry decoction: 30 grams of longan, 20 grams of jujube, and 20 grams of Chinese wolfberry. Take in decoction.

　　5. Mussels, turtle shell, and lean pork soup: 50 grams of mussels, 20 grams of turtle shell, 50 grams of lean pork. Put the turtle shell in a pot, add water, boil for 20 minutes, then add the mussels and lean pork, cook until done, and season and eat.

　　6. Mussels and芡实soup: 30 grams of mussels, 30 grams of Euryale ferox, 50 grams of lean pork. Boil in water, season and eat with meals.

　　7. Burn the hooves of the horse (or cow) to charcoal and grind into fine powder. Take 9 grams each time, 3 times a day, taken with plain salt water. Take for 1-3 days.

　　8. Brown sugar and black fungus. 120 grams of black fungus (soaked), 60 grams of brown sugar. Boil the black fungus first, then add the brown sugar and mix well. Take it all at once. Take for 7 days as one course. It is suitable for functional uterine bleeding.

　　9. Corn silk pork soup. 15-30 grams of corn silk, 250 grams of pork. Boil the two ingredients together, eat the meat and drink the soup after the pork is cooked. Take one dose a day. It is suitable for functional uterine bleeding.

　　10. Chinese plum syrup. 1500 grams of clean Chinese plums. Add 3000 milliliters of water to the Chinese plums, boil over charcoal fire, wait until the water evaporates to half, then add water back to the original amount, and boil until thick. Filter the residue with clean gauze and pour into a bottle for use. Add sugar to taste when taking, 5-10 milliliters for adults each time, take with hot water, and take 3 times a day. It is suitable for functional uterine bleeding.

　　11. Pig Skin Jelly. Cut 1000 grams of pork skin into small pieces, place in a large pot, add an appropriate amount of water, and simmer over low heat until the skin is tender and the juice is thick and sticky. Add wine and sugar, mix well, and then turn off the fire. Pour into a porcelain bowl, cool and set aside. It can be eaten with meals as desired. It has the effects of nourishing Yin and blood, and stopping bleeding. It is suitable for excessive menstruation, functional uterine bleeding, and all kinds of bleeding symptoms.

　　12, Chinese plum sugar syrup. 15 grams of Chinese plum, 30-50 grams of brown sugar. Put Chinese plum and brown sugar in a pot, add half a bowl of water, boil until half a bowl remains, remove the residue, and take it warm. It has the effects of nourishing blood and stopping bleeding, and beautifying the skin. It is suitable for women with excessive menstrual bleeding or functional uterine bleeding. (6) Jujube and pork skin stew. 15-20 jujubes (with the kernel removed), 100 grams of pork skin. Clean and cut the pork skin into small pieces, clean and remove the kernel from the jujubes, and put them together in a stewing pot. Add a small amount of water, steam until the pork skin is tender. It has the effects of nourishing the spleen and blood, increasing skin luster and elasticity, and is suitable for treating spleen deficiency-type metrorrhagia and physical weakness.

　　13, Ginger juice rice wine clam soup. 3-5 milliliters of ginger juice, 20-30 milliliters of rice wine, 150-200 grams of clam meat, a proper amount of cooking oil and salt. Clean and halve the clam meat, fry it with peanut oil, add rice wine, ginger juice, and a sufficient amount of water, and cook until the meat is tender, then add salt for seasoning. It has the effects of nourishing yin and blood, clearing heat and detoxifying, and moisturizing and softening the skin. It is suitable for symptoms such as excessive menstrual bleeding and physical weakness.

　　14, Two fresh juices. Fresh lotus root nodes and fresh white radish, each 500 grams. Clean the above ingredients, crush them together, wrap them in clean gauze to extract the juice, and add a proper amount of rock sugar for drinking. It has the effects of clearing heat, cooling blood, stopping bleeding, and whitening the skin. It is suitable for symptoms such as excessive menstrual bleeding.

　　Second, what to eat for uterine bleeding caused by dysfunction during perimenopause

　　1, It is advisable to eat nutritious and easy-to-digest foods and eat more iron-rich foods: such as animal internal organs like liver, black-bone chicken, black fungus, longan meat, and fresh vegetables and fruits like spinach.

　　2, Those with属实热者 should eat more fresh vegetables, fruits, and low-fat foods, including milk, soy milk, eggs, lean meat, liver soup, shepherd's purse, black-bone chicken, persimmon cake, lotus root powder, purslane, watermelon juice, pear, water chestnut, hawthorn, crucian carp, black fungus, leek, etc.

　　3, Those with deficiency in the spleen and kidney should eat more astringent and nourishing foods: mung bean, jujube, pork stomach, yam, litchi, white fungus, black fungus, black, yellow croaker, leek, euryale, and pork kidney.

　　4, Good for nourishing the heart and spleen are: rice, millet, wheat, mung bean, yam, sesame, lotus seed, jujube, and longan; good for nourishing the liver and kidney are: millet, wheat, yam, sesame, chestnut, and walnut. For heat syndrome, choose millet, wheat, red bean, and mung bean; for cold syndrome, choose rice, sorghum, mung bean, and dried fruit. Poultry and livestock have strong nourishing power, and those with deficiency should eat them, and those with excess should not avoid them. Especially pork, beef, and chicken meat, milk, and eggs are neutral in nature and can be eaten regardless of cold or heat. Water buffalo meat is especially suitable for nourishing blood and stopping uterine bleeding.

　　5, Fruits are beneficial for promoting digestion without causing blood leakage, and they also have the function of nourishing the spleen and kidney, such as sugarcane, apple, cherry, fig, banana, grape, persimmon, and pomegranate can nourish the spleen, while mulberry can nourish the liver and kidney. When there is persistent and continuous bleeding for a long time, add sour plums and hawthorn to stop bleeding.

　　Thirdly, it is best to avoid certain foods for Dysfunctional Uterine Bleeding During Perimenopause

　　1. Being deficient and cold in nature, when choosing food, it is advisable to use those that are slightly warm in nature to tonify, and avoid excessively hot or cold foods such as pepper, mustard, ginger, and cinnamon. For实证,热证, it is forbidden to use warm and hot substances.

　　2. Lamb, dog meat, and sparrow meat are warm in nature, so they should be used with caution for those with heat syndromes.

　　3. Avoid using spices like ginger, pepper, and garlic when there is excessive bleeding.

　　Firstly, Precautions Before Treatment for Dysfunctional Uterine Bleeding During Perimenopause

　　Before Treatment: It is necessary to have a detailed understanding of the symptoms of the disease and related contraindications.

　　Secondly, Traditional Chinese Medicine Treatment Methods for Dysfunctional Uterine Bleeding During Perimenopause

　　1. Blood Heat

　　(1) Treatment Method for Deficient Heat: Nourish Yin and Clear Heat, Stop Bleeding and Regulate Menstruation.

　　Herbal Medicine: Modified Bao-yin Decoction. Sheng-di 20g, Shu-di 15g, Bai-shao 20g, Shan-yao 15g, Xu-duan 15g, Huang-qin 15g, Huang-bai 15g, Gan-cao 10g. For those with continuous bleeding, add 15g of Ce-bai-ji-tan, 15g of Da-jì-tan; for those with red cheeks, heat in the palms and soles, add 15g of Mai-dong, 15g of Sha-shen, 15g of Qing-hao.

　　(2) Treatment Method for Excessive Heat: Clear Heat and Cool Blood, Reinforce the Spleen and Stop Bleeding.

　　Herbal Medicine: Modified Qing-renguo Decoction. Sheng-di 20g, Di-gu-pi 15g, Huang-qin 15g, Jiao-zhi-zi 15g, Zhì-gui-ban 15g, Ejiao (melting), Mu-li fen 20g, Di-yu 20g, Ou-jie 15g, Zong-tan 25g, Gan-cao 10g. For those with excessive bleeding, add 20g of Guan-zhong-tan, 15g of Jie-sui-tan; for those with blood clots, add 15g of Pu-huang-tan; for those with red face, thirst, restlessness, and sleeplessness, add 15g of Qing-hao.

　　2. Kidney Deficiency

　　(1) Treatment Method for Kidney Yang Deficiency: Tonify the Kidneys and Nourish Yin, Stop Bleeding and Regulate Menstruation.

　　Herbal Medicine: Modified Zuo-gui Pill. Shu-di 20g, Shan-yao 20g, Gui-qi 15g, Shan-zhu-yu 15g, Tu-si-zi 15g, Lu-jiao-jiang 15g, Du-zhong 20g, Gui-ban-jiang 15g, Nü-zhen-zi 15g, Han-lian-cao 20g. For those with continuous bleeding, add 15g of Qian-cao, 15g of Ce-bai-ji-tan, 15g of He ye-tan, 25g of Di-yu-tan; for those with restlessness of the five interiors and sleeplessness at night, add 15g of Mai-dong, 15g of Yin-chai-hu.

　　(2) Treatment Method for Kidney Yang Deficiency: Warm the Kidneys and Reinforce the Spleen, Stop Bleeding and Regulate Menstruation.

　　Herbal Medicine: Modified You-gui Pill. Prepared Fu-zi 10g, Shu-di 20g, Shan-yao 20g, Shan-zhu-yu 15g, Gui-qi 15g, Tu-si-zi 15g, Lu-jiao-jiang 15g, Du-zhong 20g, Huang-qi 30g, Fu-pen-zi 15g, Chi-shi-shi 10g. For those with continuous bleeding, add 15g of Qian-cao, 15g of Hai-ju, 25g of Zong-tan; for those with soreness in the lower back and knees, and clear urine, add 20g of Xu-duan, 15g of Zhi-yi-ren.

　　3. Spleen Deficiency

　　Treatment Method: Tonify Qi and Control Bleeding, Reinforce the Spleen and Stop Bleeding.

　　Herbal Medicine: Modified Gu-chong Decoction. Bai-zhu 20g, Huang-qi 30g, Long-gu 20g, Mu-li 20g, Bai-shao 25g, Qian-cao 15g, Hai-ju 15g, Zong-tan 25g, Di-yu-tan 25g. For those with fatigue, lack of speech, shortness of breath after exertion, and dizziness with palpitations, add 25g of Dang-shen, 20g of Shan-yao; for those with poor appetite and loose stools, add 15g of Li-zhi, 15g of Sheng-mu.

　　4、血瘀

　　治法：活血化瘀，止血调经。

　　方药：四物汤加味。熟地2Og，当归15g，川芎15g，白芍25g，炒蒲黄15g，桃仁15g，丹皮15g。血色暗有块者加红鸡冠40g，腹痛者加元胡15g，益母草30g。

　　三、专方验方

　　1、地榆苦酒煎：生地榆250g，苦酒(即米醋)1000ml，浸泡7天，去渣留液待用，每次30ml，1日3～4次口服。适用于久漏不止患者。

　　2、止血灵：补骨脂3g，赤石脂2g，共为细面，1次服用，每日3次口服。适用于肾阳虚久漏不止者。

　　3、复方四炭汤：棕炭25g，贯众炭25g，艾炭15g，蒲黄炭15g，当归15g，白芍15g，生地25g，阿胶15g(烊化)。加水2000ml，煎至600ml，每次200ml，日3次口服。适用于各型功血患者。

　　四、其他疗法物理疗法

　　用平流电刺激乳房、背部疗法，或红外线照射乳房部，通过神经反射至中枢，调整内分泌功能，改善月经周期。每日治疗1次，每次15～20分钟，停止流血后，再做2～3次。中药

　　1、宫血宁胶囊：每次1～2粒，1日3次口服；出血严重者，1次3～4粒，每日4次口服，宜饭后服用。

　　2、人参归脾丸：每次1丸(9g)，每日3次口服。

　　3、云南白药：每次0.5～1g，每日2～3次口服。

　　针灸

　　1、患者双手取半握拳位，于双手第2、3掌指关节之间凹陷处取穴。针法：直刺1～1.5寸，捻转至有酸胀麻或电击感，每日1次。

　　2、取关元、三阴交、隐白为主穴。虚热者加内关、太溪穴；实热者加血海、水泉穴；脾虚者加膨俞、足三里穴。每日针1次。

　　五、围绝经期功能失调性子宫出血西医治疗方法

　　围绝经期功血患者多已无生育要求，故治疗的原则是迅速止血，预防出血过频、过多，纠正贫血，改善一般情况，遏制子宫内膜因持续无排卵造成的增生过长，诱导绝经，防止癌变。

　　1、一般治疗在明确功血的诊断后，应注意患者的全身情况。了解出血的时间和贫血的程度。对轻度贫血者(血红蛋白80～100g/L)，可给予口服铁剂，常用的制剂有硫酸亚铁，0.3g，3次/d；琥珀酸亚铁(速力菲)，0.1～0.2g，3次/d；辅以维生素C，0.1g，3次/d。伴有胃肠道疾病时，可采用铁剂注射，如右旋糖酐铁，50～100mg，肌内注射，1次/d。对重度贫血者(血红蛋白

　　2. Hemostasis The hemostatic methods applicable to perimenopausal dysfunctional uterine bleeding include curettage, progestin endometrial shedding method, hemostatic agents, and synthetic progestin endometrial atrophy method. The uterotonics are considered to have no significant hemostatic effect.

　　(1) Curettage: According to statistics, a certain number of patients with dysfunctional uterine bleeding naturally recover after curettage. Mock obtained an 83% cure rate with curettage alone, because after the degenerated and degenerative endometrium is scraped off, bleeding will stop naturally. Curettage is the fastest and most effective method of hemostasis, especially in cases of severe bleeding, long-term bleeding, and threatening the health of patients, it can stop bleeding quickly. Routine curettage should be given to perimenopausal patients with dysfunctional uterine bleeding, and segmental curettage can be adopted. Curettage should be thorough, not only to achieve hemostasis but also to understand the endometrial hyperplasia through pathological examination of the scraping material, and exclude endometrial malignancy. However, if the amount of bleeding is not much and the recent curettage pathological examination is negative, it is not necessary to repeat it.

　　(2) Progestin endometrial shedding method: Progestin hemostasis is suitable for patients who still have a certain level of estrogen in their bodies. At this time, the addition of the effect of progestin can cause the endometrium to undergo secretory phase changes and be completely shed, and then repair and stop bleeding under the influence of their own estrogen. This method of hemostasis is also called 'pharmacological curettage'. The disadvantage of this method is that a large amount of bleeding occurs on the second to third day of withdrawal, especially in patients with thickened endometrium and during the first use, sometimes hemoglobin can decrease by 20 to 30g/L. To compensate for the disadvantage of excessive bleeding, propionate testosterone can be added to reduce the amount of withdrawal bleeding. Testosterone can counteract the effect of estrogen, reduce congestion, and thereby reduce blood loss. Therefore, this method is suitable for patients with little uterine bleeding and not obvious anemia. If the hemoglobin of the patient has decreased to 60g/L due to uterine bleeding, it is not advisable to use the withdrawal method for hemostasis to avoid further decrease in hemoglobin causing severe anemia.

　　Progestin can be selected from progesterone or synthetic progestin derivatives. Progesterone 20mg/d for 3 days. Withdrawal bleeding usually occurs within 1 to 3 days after discontinuation of medication. If progestin occasionally causes ovulation, withdrawal bleeding may not occur until more than 10 days after discontinuation. Synthetic progestins can be selected from norethindrone (Fukang Tablets) 5 to 10mg/d, or medroxyprogesterone acetate (Medroxyprogesterone, Funing Tablets) 8 to 12mg/d, or hydroxyprogesterone (Angong Huangti) 10 to 16mg/d, or medroxyprogesterone acetate (Jiaoyun, Puwei) 50 to 100mg/d, for a total of 5 days, withdrawal bleeding will also occur after discontinuation. The injection method has a short medication time and reliable effects. To reduce blood loss, propionate testosterone 25 to 50mg/d can be used simultaneously for 5 days. Withdrawal bleeding should stop within 7 to 10 days; otherwise, the accuracy of the diagnosis of dysfunctional uterine bleeding should be suspected.

　　(3) Synthetic progestin endometrial atrophy method: This method of hemostasis is suitable for menopausal patients with severe anemia who have been excluded from uterine malignant lesions. The amount of synthetic progestin used should be large, taken for 20 consecutive days, and small amounts of estrogen can be added if breakthrough bleeding occurs. The principle is that through the action of a large amount of progestin, the endometrium synchronously secretes and stops bleeding. Continuous action of progestin can cause the endometrium to transform from secretion to atrophy, resulting in a concentrated withdrawal bleeding after drug discontinuation. Common methods include: 5-7.5mg of norethindrone, or 8-10mg of medroxyprogesterone acetate (medroxyprogesterone), or 8-10mg of medroxyprogesterone (Anjuning Huangti) every 4-6 hours. After 3-4 oral doses (24-36 hours), bleeding stops, and the dose is changed to every 8 hours. Then, the dose is reduced by 1/3 every 3 days until the maintenance dose is reached, 2.5-5mg of norethindrone, or 4-6mg/day of medroxyprogesterone acetate (medroxyprogesterone), or medroxyprogesterone (Anjuning Huangti) after stopping the bleeding. It is also possible to inject 1 vial of hydroxyprogesterone acetate (compound hydroxyprogesterone acetate): 250mg of hydroxyprogesterone acetate (hydroxyprogesterone) + 5mg of estradiol valerate, 1-2 days of blood stopping. After 7-10 days, another vial is injected, which is one cycle.

　　(4) Hemostatic agents: When there is a large amount of bleeding, general hemostatic agents can be added, including hemostatic drugs, antifibrinolytic drugs, prostaglandin synthase inhibitors, coagulation factors, etc. Hemostatic drugs are chosen for oral or intravenous administration based on the amount of bleeding. For less bleeding, oral vitamin C, K, carbacrol (Anluoxue), Yunnan Baiyao, etc. can be taken. For more bleeding, phenolsulfonate (hemostatic sens) 3-5g can be added to 500-1000ml of 5% glucose water for intravenous infusion. Enhanced fibrinolytic activity is considered to be one of the important factors in uterine bleeding, so antifibrinolytic drugs are also commonly used in clinical practice to reduce uterine bleeding. Research shows that antifibrinolytic drugs can reduce bleeding by about 50%. The commonly used drugs and administration methods are: 4-6g of aminocaproic acid added to 100ml of 10% glucose solution for rapid infusion (15-30 minutes), then changed to a rate of 1g/h to maintain, with a total daily dose of 6-12g; 0.3-0.5g of methamizole (hemostatic acid) added to 100-200ml of 10% glucose solution for infusion, with a total daily dose of 0.6-1g; 0.25-0.5g/day of tranexamic acid (hemostatic ring acid) infused into 5%-10% glucose solution. Such drugs have reports of intracranial thrombosis, so they should be used with caution in women with a history of thrombotic disease and risk factors.

　　Prostaglandin synthase inhibitors, also known as non-steroidal anti-inflammatory drugs (NSAIDs), reduce uterine local prostaglandin levels by inhibiting cyclooxygenase and changing the ratio between prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), prostacyclin (PGI2), and thromboxane (TXA2). Studies have shown that 1/3 of women can reduce bleeding by 20% to 30% after taking NSAIDs. Commonly used drugs include: indomethacin (消炎痛) 25mg, 3 times a day; mefenamic acid (甲灭酸) 250mg, 3 times a day; chlorfenac acid (氯灭酸) 200mg, 3 times a day. Usually used for 3 to 5 days. Common side effects include headache and gastrointestinal dysfunction.

　　In severe bleeding, coagulation factors can be supplemented, such as the input of frozen dried human fibrinogen (fibrinogen), platelets, fresh frozen plasma, and fresh blood.

　　3. Consolidation therapy and induction of menopause After the bleeding of patients with perimenopausal uterine bleeding has been stopped, further treatment is needed to prevent recurrence. There are many methods to reduce bleeding and induce menopause at present, which should be selectively applied according to the specific situation of the patient, such as the amount of bleeding, early or late menopause. Inducing patients to enter menopause too quickly or too early will lead to more menopausal symptoms and exacerbate osteoporosis. Entering menopause too slowly will prolong the bleeding stage, which is also unfavorable to the patients. The commonly used methods are as follows:

　　(1) Progesterone: With sufficient dosage and duration, all progesterones can convert estrogen-like endometrium into atrophic endometrium. Due to its definite efficacy, low cost, and minimal side effects, progesterone has become the most commonly used therapy in clinical practice. For patients with menopausal anovulatory uterine bleeding, a vaginal smear should be taken 7 to 10 days after the bleeding stops to understand the estrogen level. If the level of the vaginal smear is slightly to moderately affected, there is a possibility of recurrence of bleeding. Progesterone supplementation therapy should be given during the luteal phase (19 to 26 days of the cycle). Intramuscular injection of progesterone 20mg/d, or oral medroxyprogesterone acetate (Anogon) 8 to 10mg/d, or norethindrone 5 to 10mg/d, can make the endometrium retreat regularly. This method can reduce menstrual blood volume by 15%. If further reduction of the retreatment bleeding is desired, propionate testosterone 25 to 50mg can be added by intramuscular injection, once a day. However, it should be noted that propionate testosterone has the effect of inhibiting ovarian function and accelerating menopause, so the dosage and duration of use should be decided according to the individual condition of the patient.

　　The amount of bleeding in perimenopausal metrorrhagia is closely related to the degree of endometrial hyperplasia. If the endometrium grows thicker due to the influence of estrogen alone for 3 months, the withdrawal bleeding will necessarily be more, so 1 withdrawal should be performed every 1 to 2 months. If there is no withdrawal bleeding when using the withdrawal method, it indicates that the amount of estrogen secreted by the ovary is very little, which is not enough to prepare the endometrium, and therefore there is no withdrawal bleeding, marking the entry into menopause, and the withdrawal method can be discontinued, and clinical observation can be made. Generally, medication is about 3 to 6 times, shorter about 1 to 2 times, and longer about 10 or more times before entering menopause. For patients nearing menopause, progesterone can not only reduce menstrual blood volume but also inhibit the hyperplasia and cancer of the endometrium. Barrington recently reported that the use of a controlled-release intrauterine device containing levonorgestrel (18-methyl norethindrone) for 3 months can significantly reduce menstrual blood volume. Of course, before inserting this intrauterine device, it is necessary to exclude malignant lesions of the endometrium. He believes that if a 40-year-old woman places this intrauterine device, it only needs to be changed 1 to 2 times before menopause, and it also has the effect of contraception.

　　(2) Gonadotropin-releasing hormone agonists (GnRH-A): In recent years, many scholars have used the gonad-inhibitory effect of GnRH-A, that is, the drug castration effect, to treat perimenopausal metrorrhagia and achieved satisfactory efficacy. GnRH-A can bind to specific receptors in the pituitary gland, inhibit the release of gonadotropins, thereby reducing the levels of estrogen and progesterone to menopausal levels, leading to the atrophy of the endometrium. The inhibitory effect of GnRH-A takes about 3 weeks, so conventional treatment methods should be used first in cases of acute bleeding. After the bleeding stops, GnRH-A should be selected according to the specific condition of the patient. Currently, the long-acting preparation is generally used, 3.75mg per vial, injected once a month, and used for 2 to 3 cycles according to the condition. Most patients experience amenorrhea after 4 to 6 weeks of medication. Some late perimenopausal patients may enter menopause as a result.

　　The main side effects of GnRH-A are menopausal symptoms and bone loss caused by the low estrogen levels formed in the short term, hence it is not suitable for long-term use. Generally, it should not exceed 6 months. Since the inhibitory effect of GnRH-A on the gonads is reversible, the above side effects can disappear once the medication is stopped. To prevent osteoporosis, some people have tried to add a small dose of estrogen during the medication period, known as the 'backing' therapy. Whether this therapy is suitable for the treatment of metrorrhagia requires further research. Vercellini's research believes that GnRH-A, like other hormone drugs, can alleviate bleeding symptoms, and selective short-term application can avoid blood transfusion and emergency surgery, and can be used as the first step in treatment. After treatment, the hemoglobin level increases, followed by cyclic progesterone therapy.

　　(3) Danazol: It is a 17α-ethynyltestosterone isonazole derivative with a slight androgenic property, which acts by directly inhibiting the synthesis of steroid hormones through enzyme inhibition and competitively inhibiting the binding of steroid hormones to androgen and progesterone receptors. Higher doses can also change the release of pulsatile gonadotropin-releasing hormone and inhibit ovulation. Its mechanism of reducing uterine bleeding is to cause endometrial atrophy, making it suitable for the treatment of climacteric dysfunctional uterine bleeding. Studies have shown that 200mg/day of Danazol for three cycles can reduce bleeding by 58.9%, and its effect in reducing bleeding still persists for 4 months after discontinuation of the drug. If the dose is reduced to 100-50mg, the efficacy is correspondingly reduced, and it can lead to menstrual irregularities. Increasing the dose to 400mg/day can cause amenorrhea. Randomized controlled trials have shown that Danazol is more effective in reducing bleeding than mefenamic acid (mefenamic acid) and norethindrone. The latter two reduce bleeding by 22.2% and 10% to 15% respectively at a dose of 500mg, 3 times a day and 5mg, 3 times a day (from day 19 to 26 of the cycle). The side effects of Danazol include headache or cyclic migraine, bloating, muscle cramps, weight gain, acne, and depression. At a dose of 200mg/day, the side effects are minimal, and most patients can tolerate them. Some scholars recommend Danazol as the first-line choice for patients with dysfunctional uterine bleeding who require drug treatment.

　　4. Surgical treatment Although there are many drugs available for the treatment of perimenopausal dysfunctional uterine bleeding, some patients still need surgery for根治. For those with early onset of the disease, repeated treatment for many years, or unable to receive long-term treatment and observation due to living and working conditions, those over 40 years old can consider hysterectomy. Such patients often develop uterine fibroids at the age of 40, which is an indication for surgery. For women approaching menopause, repeated curettage indicates endometrial complexity and atypical hyperplasia, and those with uterine fibroids, adenomyosis, and severe anemia are also indications for hysterectomy. If the age reaches 54 to 55 years and the ovarian function does not decline, and the estrogen level in the vaginal smear is still high with continuous bleeding, hysterectomy and oophorectomy should be considered to avoid endometrial malignancy.

　　As for surgical methods, in addition to the traditional abdominal and vaginal hysterectomy, there are also laparoscopic total or subtotal hysterectomy, laparoscopic-assisted vaginal hysterectomy, hysteroscopic endometrial resection, and other methods. For patients with perimenopausal dysfunctional uterine bleeding, it is recommended to choose surgical approaches and methods with minimal trauma. For those without a history of pelvic or abdominal surgery, no history of pelvic inflammatory disease, and no adnexal tumors, vaginal hysterectomy should be chosen, which has significantly less trauma than abdominal hysterectomy, with less postoperative pain and faster recovery. For those with relative contraindications to vaginal surgery, laparoscopic assistance can be added before surgery to evaluate the pelvic condition under laparoscopy, remove factors affecting vaginal surgery, and then remove the uterus vaginally. This procedure, even with the addition of laparoscopy, is still less traumatic than open abdominal surgery. As for laparoscopic total hysterectomy, although it has the advantage of minimal trauma, it requires complex instruments and doctors with special training and experience, and takes more time, and is still in the development stage and not widely used.

　　In recent years, hysteroscopic endometrial resection for menorrhagia has gradually gained recognition due to its small injury, the ability to preserve the uterus, and a high success rate, and has become another effective method for treating menorrhagia, in addition to total hysterectomy.

　　(1) The surgical indications are:

　　①Conservative treatment is ineffective and the patient does not want to have the uterus removed, or the patient cannot tolerate hysterectomy due to severe systemic complications;

　　②Dilation and curettage or hysteroscopy has excluded the possibility of endometrial malignant changes;

　　③No longer desires childbearing;

　　④Uterus ≤ 10 weeks of pregnancy size;

　　⑤Cervical canal depth ≤ 12cm.

　　(2) The contraindications for surgery are:

　　①Acute pelvic inflammatory disease;

　　②Endometrial malignant changes or precancerous changes;

　　③There is still a desire for childbearing. Experience from both abroad and China shows that the success rate of menstrual improvement after hysterectomy can reach 95%. The effect is especially good for those over 35 years old. In patients approaching menopausal age, even if there is a small amount of menstruation after the operation, the proportion of those who transition to amenorrhea is significantly higher than that of younger individuals. This method is a very ideal treatment for dysfunctional uterine bleeding during perimenopause, although there are still some issues with the safety and long-term efficacy of the surgery itself. It is believed that these issues will gradually be overcome with further research.

　　In summary, there are various treatment methods for dysfunctional uterine bleeding during perimenopause. Doctors should choose and decide according to the specific condition of the patient to help the patient get rid of anemia as soon as possible and safely and smoothly transition to menopause.