1. What is menopause? Menopause can be categorized into natural menopause and artificial menopause. The former refers to either (1) natural menopause: due to the loss of follicular function, depletion of follicles in the ovary, or the loss of response of the remaining follicles to gonadotropins, the follicles will no longer develop and secrete oestrogen, and will not be able to stimulate the growth of the uterine endothelium, which will result in menopause, i.e., the permanent cessation of menstruation. In the absence of other obvious pathologic and physiologic causes, the last menstrual period is considered to be natural menopause. The judgment of menopause is retrospective, 12 months after menopause can be judged as menopause. (2) Pathological menopause: refers to the surgical removal of both ovaries or the cessation of ovarian function by other methods, such as radiation therapy and chemotherapy. Removal of the uterus alone while preserving one or both ovaries is not considered as artificial menopause. The determination of menopause is based primarily on clinical manifestations and hormone measurements. Artificial menopause is more likely to occur menopause syndrome. 2.What is the average age of menopause? The average age of menopause is 49.5 years for urban women in northern China and 47.5 years for rural women, while the average age of menopause for women in southern China is 48.99 years; the median age of menopause in the United States is 51.3 (48-55) years. The age of menopause is related to factors such as having taken contraceptives, nutrition, region, environment, smoking, etc., and there is no significant relationship with education level, body shape, age at menarche, number of pregnancies, age at last pregnancy and other factors. 3.What is perimenopausal (menopausal) syndrome? (1) Perimenopausal period (menopause): It is the stage of transition from regular menstruation during the reproductive period to menopause, which includes the appearance of endocrine, biological and clinical features related to the decline of ovarian function until one year after the last menstruation. Regarding the starting point of perimenopause, in China, it is marked by the occurrence of 2 changes in the length of the menstrual cycle of 7 days or more in a 40-year-old woman (who used to have regular menstruation). (2) Menopause syndrome (menopausal syndrome): refers to a series of menopause-related symptoms that appear before and after a woman’s menopause. In the 10 years before menopause, ovarian function gradually declines and changes occur in all systems of the woman’s body, which is called pre-menopause. (3) The average duration of menopausal symptoms is 3-5 years, with a few occurring within 1 year and others lasting longer. Menopausal symptoms can occur in almost every woman experiencing menopause, to varying degrees, with about 50%-75% of women having a noticeable feeling of menopause, and usually only 10%-15% of women experiencing more severe menopausal symptoms that require medication. (4) Fertility: The likelihood of obtaining a pregnancy during a menstrual cycle. It can be used as a tool for targeted analysis of fertility potential. Women under 30 years of age, the clinical pregnancy rate per cycle is about 0.25; nearly 30 years of age, the ovarian pregnancy rate per cycle gradually declined, and its significant decline from the age of 40; over 40 years of age, the ovarian pregnancy rate per cycle is about 0.12, compared with less than 30 years of age, a decline of more than 50%. 4.What are the clinical manifestations of menopausal syndrome? (1) menstrual disorders: prolonged or shortened menstrual cycle, excessive or insufficient menstrual flow, or spotting, often women feel uneasy. Therefore, women with contraceptive rings before and after the age of 40, irregular bleeding is recommended to be removed from the ring at the same time diagnostic scraping, to exclude malignant changes and then give drugs to regulate menstruation. Specifically can be manifested in the following patterns: 1, scanty transition: that is, the menstrual cycle is longer than 35 days, the menstrual period is shortened, the amount of menstruation is reduced, and then gradually stop; 2, disorganized transition: the menstrual cycle is irregular, can be manifested as frequent menstruation, that is, the menstrual cycle is shorter than 21 days, or scanty menstruation. Serious this appears anovulatory dysmenorrhea, and even anemia; 3, instant transition: menstruation suddenly stops, and then no longer come. Only 10% of women. (2) vasodilatory symptoms: the most common symptoms in postmenopausal women. The incidence of paroxysmal hot flashes and sweating is about 75%-85%, and the degree may vary. It is a manifestation of unstable vasodilatory function. The hot flashes start from the chest, surge to the head and neck, and then spread to the whole body. In a few women it is limited to the head, neck and breasts. In the area of the hot flashes the patient feels a burning, reddening of the skin, followed by an outbreak of sweating. It lasts from a few seconds to a few minutes and occurs several times a day to 30-50 times a day. The condition can last up to a year, sometimes up to 5 years or more. It is generally recognized that thin women are more likely to experience heavy, frequent hot flashes than obese women. In perimenopausal women, vasodilatory symptoms, genitourinary symptoms, and irritability, mood swings, and sleep are associated with FSH and testosterone epithelial and fluctuations. (3) Psychoneurological symptoms: such as restlessness, crying, irritability, depression, nervousness, tinnitus, inability to self-control, depressed mood, etc. Memory loss, inattention and sleep disorders may also occur. Estrogen deficiency may be potentially dangerous for the development of Alzheimer’s disease (dementia). 1.Peri-menopausal and postmenopausal depression: incidence 8%-47%. 2, Sleep disorders: higher incidence. 3, Cognition and Alzheimer’s disease; the risk of Alzheimer’s disease in postmenopausal women is 2-3 times higher than in men of the same age. Estrogen protects central nervous system function through a variety of mechanisms. (4) Genitourinary tract symptoms: the main manifestations of the genitourinary tract atrophy symptoms, vulvar itching, vaginal dryness and pain, difficulty in sexual intercourse, low libido, uterine prolapse; vesicorectal bulge; urinary frequency, urinary urgency, tension urinary incontinence, repeated episodes of urinary tract infections. (5) Metabolic and cardiovascular diseases: postmenopausal body fat is centrally distributed with increasing age; elevated blood pressure or fluctuating blood pressure, significant weight gain, abnormal increase in glucose and lipid metabolism, coronary heart disease incidence and heart attack mortality rate increases faster. Bone and joint and muscle pain are common symptoms. Estrogen and cardiovascular relationship is close, age less than 60 years old and no cardiovascular system disease in recently menopausal women, hormone supplementation therapy does not cause early harm, and can reduce the incidence of cardiovascular disease and mortality rate, basic research suggests that estrogen has a protective effect on the cardiovascular system. (6) Osteoporosis: women from perimenopause, the rate of bone resorption is greater than bone production, prompting bone loss and osteoporosis. Osteoporosis appears about 9-13 years after menopause, and about 1/4 of women suffer from osteoporosis. The rapid loss of bone mass and degenerative changes in the bones and joints in early menopause can lead to pain in the lower back and extremities, and joint pain. Osteoporosis patients can develop a humpback, and in severe cases to fractures, most often in the concha, others such as the distal radius, femoral neck. The decline in estrogen levels after menopause is one of the main causes of osteoporosis. (7) Other symptoms, such as generalized aches and pains, headaches, muscle stiffness, cramps, etc., can be improved by appropriate exercise. There may also be dry mouth and low coarse voice. Significant decline in estrogen level may be an important factor for perimenopausal female patients to develop somatization symptoms. In clinical treatment, in addition to the use of antidepressant drugs for such patients, the appropriate use of estrogen replacement therapy according to the patient’s condition may better improve the patient’s clinical symptoms. 5. What are the changes in sex hormone secretion during menopause and postmenopause? After menopause, ovarian function declines, estrogen secretion decreases; FSH level increases; leptin level increases, positively correlated with obesity, negatively correlated with bone density; (1) estrogen: estrogen level fluctuates a lot in the early stage of menopausal transition period, and throughout the menopausal transition period estrogen does not show a trend of gradual decline, but in the follicular growth and development stops, the level of estrogen only declines. After menopause, the ovaries secrete very little estrogen, and the low level of estrogen in women’s bodies is mainly converted to estrone by the aromatase enzyme in the peripheral tissues, such as testosterone from the adrenal cortex and ovaries, and the level of estrone in the blood is higher than that of estradiol. (2) Progesterone: in the menopausal transition period, the ovary still has ovulation function, but the luteal function is not complete, and the amount of progesterone decreases. Very small amounts of progesterone may come from the adrenal glands after menopause. (3) Androgens: The ovaries mainly produce testosterone after menopause, and the production increases in the early postmenopausal period compared with the premenopausal period. As estrogen decreases after menopause, the ratio of circulating androgens to estrogens rises significantly; sex hormone-binding proteins decrease, increasing free free androgens, and thus mild hirsutism occurs in some postmenopausal women. (4) Gonadotropins: during the transition period of menopause, FSH may rise, but FSH/LH is still less than 1. After menopause, FSH and LH rise significantly, and the rise of FSH is more significant, and FSH/LH is more than 1. After 1 year of natural menopause, FSH rises by 13-fold, while LH rises by only 3-fold. Within 2-3 years after menopause, FSH/LH reaches the highest level, and then decreases with age, but still at a high level. 6.How to prevent and treat menopausal symptoms? (1) There is no way to prevent or delay the onset of natural menopause. However, perimenopausal women can strengthen self-care, actively participate in physical exercise, and actively prevent and control the occurrence of menopausal syndrome. Regarding the clinical question of whether to remove the ovaries when removing the uterus in premenopausal women, most scholars believe that premature removal of the ovaries should be avoided as much as possible, and that retaining the ovaries carries its own risks of malignant changes and pelvic pain, but they are unlikely to be significant, whereas the advantages of retaining the ovaries outweigh their dangers. (2) More perimenopausal women may develop the syndrome, but its severity varies greatly due to different mental states and living environments. Some women do not need treatment; some need only general treatment to make the symptoms disappear; some women need hormone replacement therapy to control the symptoms. (3) General and symptomatic treatment Perimenopausal women should understand that perimenopause is a natural physiological process and should adapt to this change with a positive attitude. Psychological adjustment can be made and some medications can be used to assist, such as nighttime valium if there are sleep disorders affecting the quality of life. To prevent osteoporosis, increase exercise, increase sun exposure, and consume adequate protein and calcium-containing foods. Participation in moderate to strong degree of exercise causes insulin resistance to be significantly reduced, and these changes in endocrine metabolism may reduce the risk of breast cancer in postmenopausal women. (4) Phytoestrogens are substances in plants with a structure similar to that of estrogen, which can bind to estrogen receptors and produce a series of estrogen-like and/or anti-estrogen-like activities. The more studied substance is soy isoflavones, which are mainly found in soybeans and their products. The available evidence is not yet sufficient to prove that isoflavones can be used as a substitute for estrogen therapy in perimenopausal women, and their possible negative effects have been repeatedly debated: e.g., stimulation of the development of estrogen-sensitive tumors, impairment of cognitive function, and effects on reproductive function. (5) Hormone Replacement Therapy (HRT) The use of individualized HRT can improve the quality of life. in postmenopausal women less than 60 years old, HTR prevents the risk of fracture and stops bone loss, and the continued use of HRT in women older than 60 years old may increase the risk of coronary artery disease events. the risks of HRT are mainly endometrial cancer, breast cancer, and blood clot. Contraindications and cautions for hormone supplementation are detailed in the Hormone Replacement Therapy (HRT) article. PRINCIPLE RECOMMENDATION: Hormone therapy is a medically necessary response to health problems associated with the menopausal transition and postmenopause, and is an effective method of preventing postmenopausal osteoporosis. Indications: Menopause-related symptoms, problems related to atrophy of the genitourinary tract, risk factors for osteoporosis (including low bone mass) and postmenopausal osteoporosis. Timing of treatment: it can be applied after the onset of ovarian decompensation and associated symptoms. Contraindications: known or suspected pregnancy, vaginal bleeding of unknown origin; known or suspected breast cancer, malignant tumors related to sex hormones or meningiomas (progesterone is contraindicated), etc.; active venous or arterial thromboembolic disease within the last 6 months, severe hepatic or renal dysfunction, hematoporphyria, otosclerosis, systemic lupus erythematosus. Caution: uterine fibroids, endometriosis, history of endometrial hyperplasia, hyperprolactinemia, uncontrolled diabetes mellitus, severe hypertension, thrombotic tendency, gallbladder disease, epilepsy, migraine, asthma, benign breast disease, family history of breast cancer, God’s courage. 1, hormone therapy related issues: pre-treatment assessment: the main assessment of whether there are indications, contraindications and caution. Weighing the pros and cons: according to age, ovarian function decline and pre-treatment assessment results for comprehensive evaluation to determine the necessity of applying hormone therapy. Hormone therapy should be individualized. Hormone therapy regimen selection: When applying hormone therapy, the lowest available small dose should be used under the premise of comprehensive evaluation of the therapeutic objectives and risks. Individualized risk/benefit assessment should be performed at least once a year during the treatment period to determine the duration of treatment and whether to continue. To prevent thrombosis, discontinue as appropriate in cases of prolonged bed rest due to illness or surgery. Hormonal regimens may include estrogen alone, progestin alone, and estrogen-progestin combinations. Estrogen alone: for women who have had their uterus removed and do not need protection of the endometrium. There is insufficient evidence that phytoestrogens can be used as an alternative to hormone therapy. Progestogens alone: Used cyclically for the menopausal transition and to adjust menstrual problems that occur during the decline of ovarian function. Combined estrogen-progestin application: for women with an intact uterus. The purpose of combined progestins is to counteract estrogen-induced endometrial overgrowth and, in addition, may have a synergistic effect on enhancing bone health. Side effects and risks a. Uterine bleeding: Abnormal bleeding during the use of drugs, mostly breakthrough bleeding, if necessary, scraping to exclude endometrial pathology. b. Side effects of sex hormones: excessive dosage can cause breast swelling, leukorrhea, headache, edema, hyperpigmentation, etc. Reducing the dosage as appropriate can reduce its side effects. c. Side effects of progesterone: including depression, irritability, breast pain and swelling, very few patients even intolerant to progesterone. d. Endometrial cancer: long-term application of estrogen alone increases the risk of endometrial cancer and endometrial hyperplasia by 6-12 times. When estrogen replacement therapy is given to women with a uterus, progesterone must be added, which can stop simple and complex hyperplasia of the endometrium, and the relative risk of endometrial cancer is reduced to 0.2-0.4. e. Breast cancer: replacement therapy for more than 5 years increases the relative risk of invasive breast cancer by 26%.