1, about children tiny puberty At birth, the hypothalamic-pituitary-gonadal (testes or ovaries) axis, as one of the important endocrine regulatory systems in the body, is not yet as stable as in adults, but the establishment has been basically completed. Before birth, this system is temporarily put on hold in the mother’s body due to the large amount of estrogen produced by the placenta. After birth, as the umbilical cord is cut and the fetus loses its connection to the mother, the fetal endocrine system must begin to learn to carry the load on its own. Soon after leaving the mother’s body, the future manhood, in particular, begins to commission the operational functions of its reproductive endocrine system within minutes, secreting levels of androgens up to the low end of normal adult male levels. At this time, the testicles are mildly enlarged, there is an erection, and may even be a transient manifestation of a little acne on the face, which lasts until about half a year of age; compared with male infants, female infants are a little slower to respond, but they also begin to debug their own reproductive endocrine system within a few hours. At this time, this system is not yet very stable and may secrete estrogen intermittently. During this period, estradiol levels can fluctuate between 0 and 50 pg/ml (the lower limit of estrogen levels in normal adult women). Some estrogen-sensitive female infants may develop more pronounced breast development. Due to fluctuating estrogen levels, a few girls may even experience light bleeding similar to adolescent menstruation. These manifestations are usually short-lived and not very noticeable, but can occur before the age of 2 years. This manifestation in infancy and early childhood is extremely similar to the process of true puberty. For this reason, the medical term “minipuberty” has been coined. Minipuberty can be viewed as a small preview of the real “big” puberty that will occur a few years later. At present, the actual meaning of minipuberty is not well understood, and its manifestations vary from person to person. It is often overlooked, but it is indeed a physiological phenomenon that exists early in our lives. 2, about children’s precocious puberty Precocious puberty is a relative time concept, refers to the age of the appearance of secondary sexual characteristics than the same generation, the same race, the same sex of the normal population earlier. The age of puberty in the normal population varies with the times, and there is a tendency to advance continuously. For present purposes, the appearance of visible secondary sexual characteristics and/or the onset of menstruation before the age of 8 years in girls, and the appearance of secondary sexual characteristics and/or testicular volume ≥4 ml on one side before the age of 9 years in boys, is considered to be precocious puberty. It suggests that necessary medical investigations should be carried out to exclude the presence of health-affecting diseases in the body.3. Types of precocious puberty in children 3. Precocious puberty has been categorized in various ways. In order to guide the etiological diagnosis and treatment, clinically it is mainly classified according to its different pathogenesis: central (true) precocious puberty and peripheral (pseudo) precocious puberty. Central precocious puberty is identical to the real pubertal development process, which has the participation of hypothalamus-pituitary-gonad (testis or ovary) axis, can produce germ cells, and can have the ability to bear children; peripheral precocious puberty only has the development of secondary sexual characteristics caused by the action of sex hormones, and does not have the participation of hypothalamus-pituitary-gonad axis, so it is not necessary to have the participation of hypothalamus-pituitary-gonad. Peripheral precocious puberty only has the development of secondary sexual characteristics due to the action of sex hormones, without the participation of the hypothalamic-pituitary-gonadal axis, and is unable to produce sperm or eggs, and thus does not have the ability to reproduce. The cause of true precocious puberty is complex, either due to intracranial infections, trauma or tumors and other organic diseases that trigger the “switch” of puberty, or the so-called idiopathic central precocious puberty for which no cause can be found; peripheral precocious puberty leads to the development of the secondary sexual characteristics of the hormones can come from inside or outside the body. In vivo, they can come from various tumors that secrete sex hormones, and in vitro they can come from food or drugs. According to the degree of the development of secondary sexual characteristics are divided into: complete (true) precocious puberty, partial (pseudo) precocious puberty, simple breast development, simple pubic hair precocious puberty and so on. According to whether the hypothalamic-pituitary-gonadal axis is truly activated or not, there are two categories: gonadotropin-dependent (true) and gonadotropin-independent (pseudo) precocious puberty. Treatment with long-acting gonadotropin-releasing hormone analogs (GnRH-a) is effective in the former but not in the latter. In short, the various classifications may overlap with each other. 4, about the simple early breast development and infants will occur simple early breast development simple early breast development refers to the girl only breast development advancement, not accompanied by other sexual characteristics (such as pubic hair, armpit hair) appear, and there is no advancement of bone age and growth acceleration. The majority of cases occur in infants and young children between the ages of 6 months and 2 years, and are often the result of micropuberty. Early breast development alone can also occur in childhood (2 to 8 years of age), and the mechanism of occurrence is not identical to that of infancy. In addition to instability of the hypothalamic-pituitary-gonadal axis, the occurrence of premature simple breast development in childhood may be associated with a prolonged high-protein diet, the influence of environmental estrogenic pollutants, the intake of sex hormone-containing foods, and exposure to sexually oriented media. It is clear that the hypothalamic-pituitary-gonadal axis is not yet fully activated in cases of precocious development of simple breasts. Pseudo-precocious puberty in children Peripheral precocious puberty, also known as pseudo-precocious puberty or gonadotropin-independent precocious puberty, refers to the children who only have the development of secondary sexual characteristics ahead of schedule, without the maturation of gonadal function (ovulation or spermatogenesis), without the real activation of the hypothalamic-pituitary-gonadal axis, but rather, it is related to the elevation of the level of endogenous or exogenous sex hormones unrelated to the GnRH in the hypothalamus. The symptoms of precocious puberty are often part of the clinical manifestations of an underlying disease and are not an independent disorder. Therefore, the treatment of patients with pseudoprecocious puberty should cut off the source of sex hormone production, and treatment with long-acting gonadotropin-releasing hormone analogs (GnRH-a), a drug used to treat central precocious puberty, is ineffective. Pseudo-precocious puberty has many causes, regardless of whether it is a boy or a girl, the most common causes of pseudo-precocious puberty are tumors of the gonadal glands that secrete sex hormones, adrenal hyperplasia or tumors, and the ingestion of, or repeated large amounts of exposure to, exogenous sex hormones. 6, about the girl breast development law The girl is born to youth development and maturity, physiological situation, there are three ages can be seen in the breast development of sexual enlargement. The first is the newborn 1 week after birth, visible breast enlargement, touch the texture is slightly hard, even a small amount of milk overflow; this state is the mother’s estrogen through the placenta into the child’s body due to the birth of the mother’s estrogen from the child’s own metabolism soon after the removal, so there is no need to deal with. 2 weeks after the enlarged breasts naturally subside, the folk believe that to squeeze out the milk to make the treatment of its subside is wrong. The second age at which breasts enlarge naturally is infancy. The ovaries of female infants are already capable of producing estrogen at birth, but estrogen secretion has to receive instructions from the brain, and this control system is called the hypothalamic-pituitary-gonadal axis, which is regulated by the fetus at the end of 3 months of age. In the early postnatal period, the hypothalamic-pituitary-gonadal axis is in a relatively physiologically active state. The hypothalamus-pituitary gland actively releases signals to cause the ovaries to secrete estrogen, which results in the development of enlarged breasts for some female infants in the absence of any external factors. This state is called “micro-puberty”, but at this time the diameter of the breasts is generally not more than 2-3 centimeters, and will not be progressively enlarged, do not need any treatment, and after a few months of self-subsidence. 1 year of age, this active state of gradual suppression (so that the enlarged breasts gradually disappear by themselves), and until the child’s age its function is basically quiescent. After that, the breasts develop again and puberty begins. Chinese Medical Association Pediatrics Branch, Pediatric Endocrinology Genetic Metabolism Group in 2005 organized a survey of puberty development in nine major cities across the country, the results show that the average age of pubertal breast development of girls in urban areas of China is 9.2 years old (7.7-10.95 years old), which is in line with the trend of the international trend of the age of puberty development in the years ahead of the age of puberty. 7, simple early breast development will not affect the growth and development of children For early breast development, the most important thing is to exclude true (central) and pseudo (peripheral) precocious puberty. Generally speaking, simple precocious breast development will subside naturally and will not adversely affect a child’s growth and development, so no treatment is needed. However, avoidance of harmful stimuli and intensive follow-up are necessary. Parents must be aware that some children initially diagnosed as having simple precocious breast development may also have an underlying cause, and if this cause is not removed in time and persists over a long period of time, and the breasts do not subside or continue to enlarge, true precocious puberty may occur. If true precocious puberty occurs, it may affect the child’s lifelong height and mental health. Therefore, regular follow-up should be emphasized, with X-rays to review bone age, ultrasound of the uterus and ovaries, and LHRH provocation test if necessary, to detect true precocious puberty in time and treat the underlying disease. 8. About estrogen and its types Estrogen is an important messenger substance to regulate the physiological functions of the body. There are three main types of estrogen in the body, namely estrone (E1), estradiol (E2) and estriol (E3), and E2 is the main estrogen in women’s body. Estrogen can promote the development of female secondary sexual characteristics, such as breast development, endometrial thickening, menstrual cycle formation, etc. At the same time, estrogen also plays an important role in the male reproductive system, such as sperm development, and is also necessary to maintain male bone health. 9.What are the sources of estrogen? Estrogen is a steroidal steroid hormone produced naturally by human or animal body, and it can also be absorbed through the digestive tract via oral intake, as well as through the skin or mucous membranes. 10. Studies on the estrogen content of domestic milk There are reports showing that the estradiol hormone content of commercially available boxed liquid milk in China is 117-199.3±42.5ng/l, and the progesterone content is 0.49-2.81±0.4ug/l. (Note: 1g=106ug, 1g=108ng) 11, On the endogenous estrogen content of milk in the range reported in the literature Literature data show that the estrogen content of raw milk and commercially available cow’s milk in the United States, South Korea, and the Netherlands is in the range of 0.16- 4.4 μg/kg, and the highest value of progesterone is 98.0 μg/kg (converting liquid milk to milk powder at 8:1). Generally, colostrum has higher estrogen levels. 0-2 days of colostrum estrogen content is more than 10 times that of normal milk powder; the 7th day of colostrum estrogen content is about 5 times that of milk powder. 12, on the milk estrogen content factors affecting dairy cows in the regulation of milk secretion process, in addition to the role of prolactin in the body, there are estrogen, progesterone, growth hormone, thyroxine, adrenocorticotropic hormone, insulin and other hormones jointly involved in the completion of lactation this process. The hormone content in milk is affected by the breed of the mother, different physiological stages, the number of times of conception, feed nutrition and so on. Generally speaking, the range of estrogen and progesterone content in both raw and commercially available milk varies greatly. Also dairy products with high fat and protein content will have relatively high hormone levels. This is because estrogen and progesterone are fat-soluble, and some of the estrogen can bind to proteins in milk, thus increasing the hormone content of dairy products. 13, about the estrogen content in human breast milk There are literature reports that the range of estrogen in human breast milk is 7.9-18.5ug/L, and progesterone is 10-40 ug/L. 14, about the incidence of precocious puberty in children both at home and abroad According to the foreign literature, the incidence rate of precocious puberty in children is 1/10,000 to 2/10,000 per 100,000 population. Children with disorders or lesions of the central nervous system have a higher incidence than normal children. Specifically, for girls, the incidence rate is about 0.5 per 10,000 at less than 2 years of age, 0.05 per 10,000 at 2-4 years of age, and 8 per 10,000 at 5-9 years of age; for boys, the incidence rate is <1 per 10,000 at less than 8 years of age and 1 per 10,000 at 8-10 years of age. The prevalence of precocious puberty has also been reported to be 2-2.3 per 100,000 for girls and <0.5 per 100,000 for boys.