1.About the tiny puberty in children
At birth, the hypothalamic-pituitary-gonadal (testicular or ovarian) axis, as one of the important endocrine regulatory systems in the body, is not yet as stable as that of adults, but has basically completed its establishment. 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, the fetus loses its connection to the mother and the fetal endocrine system must begin to learn to carry the burden alone. Soon after leaving the mother’s body, future men in particular begin to commission the operational functions of their reproductive endocrine system within minutes, secreting androgen levels up to the low end of normal adult male levels.
At this time, the testicles are mildly enlarged, there is penile erection, and even a transient manifestation of a little facial acne, which can last until about half a year of age; compared to baby boys, baby girls respond a little slower, but also begin to debug their reproductive endocrine system within a few hours. At this time, this system is not yet very stable and can produce estrogen intermittently. During this time, estradiol levels can fluctuate between 0 and 50 pg/ml (equivalent to the lower limit of estrogen levels in normal adult women). Some female infants who are sensitive to estrogen may show more pronounced breast development.
Due to fluctuations in estrogen levels, a very few infants may even experience a little bleeding similar to menstruation in adolescent girls. These manifestations are usually short-lived and not very pronounced, but can occur before the age of 2 years. This manifestation in infancy is extremely similar to the process of true puberty. Therefore, the medical term for it is “minipuberty”. Minipuberty can be thought of as a mini-rehearsal for the real “big” puberty a few years later. 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 precocious puberty in children
Precocious puberty is a relative concept of time, which refers to the appearance of secondary sexual characteristics at an earlier age than the normal population of the same generation, race and gender. The age of puberty of the normal population varies with the times and there is a tendency to advance constantly. For present purposes, the appearance of visible secondary sexual characteristics and/or the onset of menstruation before the age of 8 years for girls and the appearance of secondary sexual characteristics and/or a testicular volume ≥ 4 ml on one side before the age of 9 years for boys are considered precocious. It is suggested that necessary medical tests should be performed to exclude the presence of diseases affecting health in the body.3. Types of precocious puberty in children
3. There are various ways to classify precocious puberty. 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 (pseudoprecocious) precocious puberty. Central precocious puberty is exactly the same as the real puberty development process, it has the participation of hypothalamus-pituitary-gonadal (testes or ovaries) axis, which can produce germ cells and can have the ability to have children; peripheral precocious puberty only has the development of secondary sexual characteristics caused by the action of sex hormones, without the participation of hypothalamus-pituitary-gonadal axis. In peripheral precocious puberty, there is only the development of secondary sexual characteristics caused by the action of sex hormones, without the participation of hypothalamus-pituitary axis system, which cannot produce sperm or eggs, and therefore does not have the ability to have children. The causes of true precocious puberty are complex and can be caused by organic diseases such as intracranial infections, trauma or tumors that trigger the “switch” of puberty development, or by so-called idiopathic central precocious puberty for which no cause can be found; the sex hormones that cause the development of secondary sexual characteristics in peripheral precocious puberty can come from in vivo or in vitro. In vivo, it can come from various tumors that secrete sex hormones, and in vitro, it can come from food or drugs.
According to the degree of development of secondary sexual characteristics, there are: complete (true) precocious puberty, partial (pseudo) precocious puberty, simple breast development, simple precocious pubic hair, etc.
According to whether the hypothalamic-pituitary-gonadal axis is actually activated or not, there are two categories: gonadotropin-dependent (true) and gonadotropin-non-dependent (pseudoprecocious) precocious puberty. Treatment with a long-acting gonadotropin-releasing hormone analogue (GnRH-a) is effective in the former but not in the latter. In short, the various classification methods may overlap with each other.
4.About the early development of simple breast and the infant will occur simple breast development
Premature breast development alone refers to a girl who only has early breast development without the appearance of other sexual characteristics (e.g. pubic hair, axillary hair) and without the advancement of bone age and growth acceleration. The majority of cases occur in infants and toddlers between 6 months and 2 years of age and are often the result of micro-pubescence.
Premature 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 and childhood. In addition to the instability of the hypothalamic-pituitary-gonadal axis, the occurrence of premature simple breast development in childhood may be related to the following factors: a long-term high-protein diet, the influence of estrogen-like pollutants in the environment, the intake of foods containing sex hormones, and frequent exposure to sex-related media. What is clear is that the hypothalamic-pituitary-gonadal axis is not yet fully activated in cases of premature development of simple breasts.
5. About pseudo-precocious puberty in children
Peripheral precocious puberty, also known as pseudoprecocious puberty or gonadotropin non-dependent precocious puberty, refers to children who only have early development of secondary sexual characteristics, but no maturation of gonadal function (ovulation or sperm production), no real activation of hypothalamic-pituitary-gonadal axis, but is related to elevated levels of endogenous or exogenous sex hormones unrelated to hypothalamic GnRH. The symptoms of precocious puberty are often one of the clinical manifestations of an underlying disease and are not an independent disease. Therefore, treatment of patients with pseudoprecocious puberty should cut off the source of sex hormone production, and treatment with the drug used to treat central precocious puberty, the long-acting gonadotropin-releasing hormone analogue (GnRH-a), is ineffective.
There are many causes of pseudogenital precocious puberty. Regardless of boys or girls, tumors of gonadal glands that secrete sex hormones, adrenal cortical hyperplasia or tumors and intake or repeated exposure to large amounts of exogenous sex hormones are the most common causes of pseudogenital precocious puberty.
6.Regulation of breast development in girls
From birth to puberty, there are three physiological age groups in which breast development can increase. The first is within 1 week after the birth of a newborn, the breast is swollen, slightly hard to the touch, and even a small amount of milk overflow; this state is the result of the mother’s estrogen through the placenta into the child’s body, after birth from the mother’s estrogen is quickly removed by the child’s own metabolism, so there is no need to deal with. 2 weeks after the swollen breast naturally recede, folk believe that the treatment to squeeze out the milk to make it recede is wrong. The second age at which the breast will naturally enlarge is during infancy. The female infant’s ovaries are already capable of producing estrogen at birth, but estrogen production is subject to instructions from the brain, a control system called the hypothalamic-pituitary-gonadal axis, which is already regulated by the end of the third month of life. In the early postnatal period, the hypothalamic-pituitary-gonadal axis is relatively physiologically active, and the hypothalamus-pituitary gland actively releases signals to the ovaries to secrete estrogen, causing some female infants to develop larger breasts without any external interference. This state is called “micro-puberty”, but the diameter of the breasts does not exceed 2-3 cm and does not increase progressively, so it does not require any treatment and will subside on its own after a few months; after the age of one, this active state is gradually suppressed (so that the enlarged breasts gradually subside on their own), and its function basically ceases in childhood. Thereafter, the breasts develop again at the onset of true puberty. In 2005, the Pediatric Endocrine Genetic Metabolism Group of the Pediatric Branch of the Chinese Medical Association organized a survey on pubertal development in nine major cities across China. The results showed that the average age of onset of pubertal breast development in Chinese urban girls was 9.2 years old (7.7-10.95 years old), which is consistent with the international trend of an earlier chronological age of pubertal development.
7. Simple early breast development does 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 premature breast development will subside naturally and will not adversely affect the growth and development of children, so no treatment is needed. However, it is necessary to avoid the stimulation of harmful factors and to intensify the follow-up. Parents must be aware that some children who are initially diagnosed with simple premature breast development may also have underlying causes, and if such causes are not removed in a timely manner and persist for a long time, the breasts may not subside or continue to increase in size, and true precocious puberty may develop. If true precocious puberty occurs, it can affect the child’s lifelong height and mental health. Therefore, we should emphasize regular follow-up examinations, taking X-rays to review bone age, performing ultrasound of uterus and ovaries, and performing LHRH stimulation test if necessary, in order to detect true precocious puberty and treat potential diseases in time.
8. About estrogen and its types
Estrogen is an important messenger substance that regulates the physiological functions of the body. The three main types of estrogen in the body are estrone (E1), estradiol (E2) and estriol (E3), and E2 is the main estrogen in women. Estrogen can promote the development of female secondary sex characteristics, such as breast development, endometrial thickening and menstrual cycle formation, etc. Estrogen also plays an important role in the male reproductive system, such as sperm development, and is necessary for maintaining male bone health.
9.What are the sources of estrogen?
Estrogen is a steroidal hormone naturally produced by the human or animal body, and can also be absorbed through the digestive tract by oral intake, as well as through the skin or mucous membranes.
10.Research on the estrogen content of domestic milk
Some reports show that the content of estradiol hormone in liquid milk in boxes sold in China is 117-199.3±42.5ng/l, and the content of progesterone is 0.49-2.81±0.4ug/l. (Note: 1g=106ug, 1g=108ng)
11. Regarding the endogenous estrogen content in 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, Korea and the Netherlands ranges from 0.16- 4.4μg/kg, and the highest value of progesterone is 98.0μg/kg (converting liquid milk to milk powder content at 8:1).
In general, the estrogen level of colostrum is higher: day 0-2 colostrum has more than 10 times the estrogen content of normal milk powder, while day 7 colostrum has about 5 times the estrogen content of milk powder.
12. Factors affecting estrogen content in milk
During the regulation of milk secretion in dairy cows, in addition to the role of prolactin in the body, there are estrogen, progesterone, growth hormone, thyroid hormone, adrenocorticotropic hormone, insulin and other hormones that participate together to complete the process of lactation. The content of hormones in milk is affected by maternal breed, different physiological stages, number of conceptions, feed nutrition and so on. In general, the range of estrogen and progesterone content in both raw milk and commercially available milk varies widely.
Also dairy products with high fat and protein content will have relatively high hormone levels. This is because both estrogen and progesterone are fat-soluble and some of the estrogens can be combined with the proteins in milk, so the hormone content of dairy products will be increased.
13. About the estrogen content in human breast milk
It has been reported in the literature 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 at home and abroad
According to foreign literature, the incidence of precocious puberty in children is 1/10,000 to 2/10,000. The incidence of children with central nervous system disorders or lesions is higher than that of normal children. Specifically, for girls, the prevalence is about 0.5/10,000 when they are younger than 2 years old; 0.05/10,000 when they are 2-4 years old and 8/10,000 when they are 5-9 years old; for boys, the prevalence is <1/10,000 when they are younger than 8 years old and 1/10,000 when they are 8-10 years old.
The prevalence of precocious puberty has also been reported to be 2-2.3 per 10,000 for girls and <0.5 per 10,000 for boys.