Women’s endocrine status is characterized by stability after birth, adolescence, fertility, transition, and postmenopause. -Psychological and physical changes are also in progress. In this process, changes and disorders of sex hormones play an important role, especially abnormalities of estrogen, which is the essence of women, can lead to various clinical symptoms and diseases. Since estrogen receptors are distributed in all tissues and organs of the body, abnormalities of estrogen can adversely affect patients’ quality of life and require estrogen supplementation and adjustment. 1. Classification and characteristics of estrogens To use estrogens, one should have an in-depth understanding of the changes and characteristics of endogenous estrogens in normal women, and one should also understand the classification and characteristics of exogenous estrogens. The level of endogenous estrogen in normal women has two characteristics: first, it changes with age; second, it changes monthly during the ovulation cycle. Hypothalamic gonadotropin-releasing hormone (GnRH) with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are already present in women at 10 weeks of embryonic life. When the placenta is delivered, all hormones of placental origin, mainly estrogen, disappear and the inhibition is lifted. Five days after birth, gonadotropins begin to rise, and within 3 months estrogen appears to increase temporarily, after which gonadotropins decline and remain at low levels until about 4 years of age. During childhood the hypothalamic-pituitary gland remains in a state of hyporegulation, and by the time puberty develops GnRH again begins to pulse at night, and there is a successive FSH and LH response, which in turn leads to a rise in estrogen levels. Puberty is the transition from anovulatory to ovulatory menstrual cycles in women, with a wide variation in estrogen level changes, from lower estradiol levels to ovulatory cycles with elevated estradiol levels. The main characteristic of estrogen during the fertile period is the monthly cyclic variation with ovulation, including two peaks of estrogen level changes. After reaching the menopausal transition, estrogen shows a fluctuating, gradual decline. After menopause, estrogen shows a more stable low level. Only by recognizing and keeping these characteristics in mind can we better regulate and treat patients. Only by fully grasping these patterns of estrogen changes can we clarify if, when, and how estrogen needs to be used to regulate the menstrual cycle. Gynecological endocrine treatment is usually carried out and observed with a cycle as a unit, and drug treatment also varies with the normal menstrual cycle, the ultimate goal of treatment is to be able to restore the normal physiological cyclicity of women. The endogenous estrogen in women of reproductive age comes mainly from the follicles that develop in the ovaries and the corpus luteum after ovulation, with a very small amount secreted by the adrenal cortex. There are four types of endogenous estrogens in humans: estradiol (E2), estrone (E1), estriol (E3) and estriol (E4), the first three being the most common. E2 is the most biologically active, while E1 is equivalent to 30% of the activity of E2, but E2 and E1 can be freely converted in the body, so when E1 is converted to E2, its activity is increased. E3 is an irreversible metabolite from E2, and the activity of E3 is only equivalent to 10% of E2, which has little effect on the endometrium and mainly acts on the cervix and vagina. E3 is significantly increased during pregnancy and is a monitoring E4 is a steroid hormone produced by the fetal liver and has a weak estrogenic effect. Exogenous estrogens include non-steroidal synthetic estrogens (ethylene estradiol), steroidal synthetic estrogens (ethinyl estradiol, nil estrol), natural estrogens (conjugated estrogens, estradiol valerate), hormones that act selectively on hormones (tibolone), selective estrogen receptor modulators (tamoxifen citrate, raloxifene) and phytoestrogens. Understand the causes and mechanisms of estrogen abnormalities to determine the need for estrogen use. Estrogen abnormalities include abnormalities in quantity and abnormalities in timing of secretion. Volume abnormalities are dominated by absolute or relative decreases in estrogen, but it is necessary to understand the normal changes in estrogen to determine whether there is a real decrease. In a normally ovulating woman, her estrogen levels change cyclically. E2 in the blood circulation is 147 pmol/L in the early proliferative phase and reaches its peak level of about 1100 to 1470 pmol/L by the time of ovulation, increasing to 920 pmol/L in the middle of the menstrual cycle and 730 to 1100 pmol/L in the middle of secretion, which varies greatly. Doctors should understand the pattern of fluctuations in estrogen levels, and when evaluating whether estrogen levels are normal, they should know at what period of the menstrual cycle estrogen was measured, and should combine this with the manifestations of the disease (e.g., amenorrhea, decreased menstrual flow, failure to develop or atrophy of secondary sexual characteristics, hot flashes, sweating, sleep disturbances, vaginal dryness, etc.) and the diagnosis of the disease (gonadal dysgenesis, hypothalamic pituitary amenorrhea, premature ovarian failure, etc.). Repeat measurements of estrogen are performed if necessary. Most of them are due to non-ovulation or poor ovulation, so they do not need estrogen supplementation and can be treated with progesterone withdrawal or ovulation promotion regularly as needed. Most patients with polycystic ovary syndrome do not lack estrogen either, and it is common to see many physicians casually treating patients with polycystic ovary syndrome with estrogen plus progestin artificial cycles in clinical practice. Abnormal timing of estrogen secretion includes secretion when it should not be secreted (e.g. precocious puberty, post-menopause) and not secreted when it should be secreted (e.g. delayed puberty, premature ovarian failure). Therefore, the evaluation of whether estrogen is abnormal and whether estrogen needs to be added depends on the patient’s age, the physiological period she is in, and the state of the disease. 3 . Issues to be noted in clinical application of estrogens (1) In the process of clinical application of estrogens, different types and doses of estrogens should be selected according to different therapeutic purposes. a. Physiological regulation To maintain and promote female reproductive function, development of sexual characteristics and normal function of related organs and tissues throughout the body, it is best to use natural estrogens to simulate normal physiological changes. For example, for hypothalamic-pituitary amenorrhea and abnormal gonadal development, small doses of natural estrogen alone can be used at the beginning, and when there is vaginal bleeding, natural progestin can be added to achieve better results and reduce the adverse effects of progestin without increasing the risk of endometrial hyperplasia. Studies have shown that small doses of estrogen can induce hypothalamic-pituitary function, while large doses of estrogen can inhibit hypothalamic-pituitary function, so for patients with hypogonadotropic hypogonadism leading to amenorrhea, small doses of estrogen induction therapy can be used to achieve restoration of menstruation and ovulation; to regulate height growth, it should mimic To regulate height growth, small doses of estrogen should be used at an early stage to avoid premature healing of the epiphysis, and then gradually increase the dose of estrogen as age increases. In order to suppress excessive height growth, high doses of estrogen should be used in the short term to promote accelerated healing of the epiphysis. For long-term supplemental treatment with estrogen, the lowest effective dose of natural estrogen should be used. Because any drug has adverse effects, and the adverse effects of drugs are proportional to the dose, and the dose is also positively correlated with the economic cost. Therefore, for long-term use of hormones, it is not necessary to use large doses if small doses can be used to solve problems. b. Therapeutic control To achieve specific therapeutic purposes, different estrogens and different doses of estrogen are needed. For women who need contraception, higher doses of estrogen and progestin contraceptives are needed to suppress hypothalamic-pituitary function and thus ovulation. The estrogens used in contraceptives are now mostly synthetic, highly effective and bioavailable estrogens, ethinyl estradiol, in small amounts (20-35 μg) but with strong effects. In functional uterine bleeding with severe anemia