I. About the tiny puberty in children
At birth, the hypothalamic-pituitary-gonadal (testicular or ovarian) axis, one of the important endocrine regulatory systems in the body, is not yet as stable as in adults, but has largely 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 an age; compared to male infants, female infants 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 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.
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 normal people of the same generation, race and gender. The age of puberty of normal people 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 first 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. This suggests that the necessary medical tests should be performed to exclude the presence of health-impairing diseases in the body.
Types of precocious puberty in children
There are various ways to classify precocious puberty. In order to guide the etiological diagnosis and treatment, it is clinically divided into: central (true) precocious puberty and peripheral (pseudoprecocious) precocious puberty mainly according to its different pathogenesis. Central precocious puberty is identical to the true puberty development process. It has the participation of hypothalamic-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 hypothalamic-pituitary-gonadal axis, 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 secondary sex characteristics development, it is classified into: complete (true) precocious puberty, partial (pseudo) precocious puberty, simple breast development, and simple precocious pubic hair development.
According to whether the hypothalamic-pituitary-gonadal axis is actually activated or not, there are two categories: gonadotropin-dependent (true) and gonadotropin-independent (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.
Premature breast development alone and infants with premature breast development alone
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-puberty.
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 associated with 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.
V. 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 without maturation of gonadal function (ovulation or sperm production) and without real activation of hypothalamic-pituitary-gonadal axis, but with 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 pseudoprecocious 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 pseudoprecocious puberty.
Sixth, about the law 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 one week after birth, the newborn’s breasts are swollen, slightly hard to the touch, and even a small amount of milk overflow; this state is caused by the mother’s estrogen entering the child’s body through the placenta, and after birth the estrogen from the mother is quickly removed by the child’s own metabolism, so there is no need to deal with it. 2 weeks later, the swollen breasts naturally subside, and folk believe that the treatment of squeezing out the milk to make it subside 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 breast does not exceed 2-3 cm and does not increase progressively, so it does not require any treatment and will subside after a few months. The function of the breasts is essentially static until 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 (7.7-10.95 years), which is in line with the international trend of early pubertal development.
VII. 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 naturally subside and will not adversely affect the growth and development of children, so no treatment is needed. However, it is necessary to avoid stimulation by harmful factors and to intensify 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 the uterus and ovaries, and performing LHRH stimulation test if necessary, in order to detect true precocious puberty and treat potential diseases in a timely manner.
VIII. Estrogen and its types
Estrogen is an important messenger substance that regulates the physiological functions of the body. Estrogens in the body mainly include estrone (E1), estradiol (E2), and estriol (E3), with E2 being the main estrogen in women. Estrogen promotes 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.
IX. What are the sources of estrogen?
Estrogen is a steroidal hormone naturally produced by the human or animal body and can be absorbed through the digestive tract by oral intake, as well as through the skin or mucous membranes.
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.
XI. About the source of milk powder samples tested
The samples of Shengyuan milk powder came from the remaining milk powder in the homes of children in Hubei Province, as well as the samples of Youbo and Youcong sold in Wuhan and Beijing markets in Hubei Province, totaling 42 samples. Other 14 companies at home and abroad also took 20 brands of products, a total of 31 samples.
XII. On the stability of hormone detection methods for food of animal origin
Isotope dilution of liquid chromatography – tandem mass spectrometry is a common detection method for the confirmation and quantitative determination of hormone residues in food of animal origin at home and abroad. China used the detection method for hormone detection of Olympic foods in the 2008 Beijing Olympic Games, which is applicable to the determination of androgens, estrogens, progesterone and glucocortisol hormones in foods of animal origin, such as milk and beef, etc. The detected components include endogenous sex hormones and exogenous synthetic hormones in the organism.
XIII. The detection method is consistent with the internationally accepted methods
The detection of liquid chromatography-tandem mass spectrometry is a sensitive and reliable, specific and confirmatory detection technology for the detection of multi-component target compounds in food, is a commonly used and recommended method for the detection of hormones and other residual compounds, with international advanced.
XIV. About the test results of Shengyuan milk powder
In the 42 servings of Shengyuan Yubo milk powder, no exogenous hexestrol and methyl progesterone acetate were detected, and only low levels of endogenous estrogen and progesterone were detected. The total amount of estrogen detected was 0.2-2.3 μg/kg and the total amount of progesterone was 13-72 μg/kg. 0.5 μg/kg and 33 μg/kg of estrogen and progesterone were detected in the samples left at the children’s homes respectively.
XV. Measurement results of other brands of milk powder
In order to scientifically evaluate the test results, foreign brands and other domestic brands of milk powder were also sampled, and a total of 31 samples from 14 companies and 20 brands were taken from Hubei Province and Beijing, and endogenous estrogen and progesterone were detected, and the contents were within the range reported in the literature.
XVI. About the endogenous estrogen content in milk in the range reported in the literature
Literature data show that the estrogen content in raw milk and commercially available cow’s milk in the United States, Korea and the Netherlands ranges from 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).
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; day 7 colostrum has about 5 times the estrogen content of milk powder.
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 hormone content in milk is affected by the mother’s breed, different physiological stages, the number of conceptions and the nutrition of the feed. 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 estrogens can be combined with proteins in milk, so the hormone content of dairy products will be increased.
XVIII. 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.
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, about 0.05/10,000 when they are 2-4 years old, and about 8/10,000 when they are 5-9 years old.