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Precocious puberty

Precocious puberty
Classification and external resources
Specialty Gynecology
ICD-10 E30.1, E22.8
ICD-9-CM 259.1
OMIM 176400
DiseasesDB 10519
MedlinePlus 001168
eMedicine ped/1882
MeSH D011629

In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every respect except the unusually early age, and simply represents a variation of normal development. In a minority of children, the early development is triggered by a disease such as a tumor or injury of the brain.[1] Even when there is no disease, unusually early puberty can have adverse effects on social behavior and psychological development, can reduce adult height potential, and may shift some lifelong health risks. Central precocious puberty can be treated by suppressing the pituitary hormones that induce sex steroid production.

The term is used with several slightly different meanings that are usually apparent from the context. In its broadest sense, and often simplified as early puberty, "precocious puberty" sometimes refers to any physical sex hormone effect, due to any cause, occurring earlier than the usual age, especially when it is being considered as a medical problem. Stricter definitions of "precocity" may refer only to central puberty starting before a statistically specified age based on percentile in the population (e.g., 2.5 standard deviations below the population mean),[2] on expert recommendations of ages at which there is more than a negligible chance of discovering an abnormal cause, or based on opinion as to the age at which early puberty may have adverse effects. A common definition for medical purposes is onset before 8 years in girls or 9 years in boys.[3]


  • Causes 1
    • Central 1.1
    • Peripheral 1.2
    • Isosexual and heterosexual 1.3
    • Research 1.4
  • Diagnosis 2
  • Treatment 3
  • See also 4
  • References 5
  • External links 6


Pubertas praecox is the Latin term used by physicians in the 19th century. Early pubic hair, breast, or genital development may result from natural early maturation or from several other conditions.


If the cause can be traced to the hypothalamus or pituitary, the cause is considered central. Other names for this type are complete or true precocious puberty.[4]

Causes of central precocious puberty can include:

Central precocious puberty can be caused by intracranial neoplasm, infection (most commonly central nervous system tuberculosis especially in developing countries), trauma, hydrocephalus, and Angelman syndrome.[5] Precocious puberty is associated with advancement in bone age, which leads to early fusion of epiphyses, thus resulting in reduced final height and short stature.[6]

Precocious puberty can make a child fertile when very young, with the youngest mother on record being Lina Medina, who gave birth at the age of 5 years, 7 months and 21 days.[7][8]

"Central precocious puberty (CPP) was reported in some patients with suprasellar arachnoid cysts (SAC), and SCFE (slipped capital femoral epiphysis) occurs in patients with CPP because of rapid growth and changes of growth hormone secretion."[9]

If no cause can be identified, it is considered idiopathic or constitutional.


Secondary sexual development induced by sex steroids from other abnormal sources is referred to as peripheral precocious puberty or precocious pseudopuberty. It typically presents as a severe form of disease with children. Symptoms are usually as a sequelae from adrenal insufficiency (because of 21-hydroxylase deficiency or 11-beta hydroxylase deficiency, the former being more common), which includes but is not limited to hypertension, hypotension, electrolyte abnormalities, ambiguous genitalia in females, signs of virilization in females. Blood tests will typically reveal high level of androgens with low levels of cortisol.

Causes can include:

Isosexual and heterosexual

Generally, patients with precocious puberty develop phenotypically appropriate secondary sexual characteristics. This is called isosexual precocity.

Sometimes a patient may develop in the opposite direction. For example, a male may develop breasts and other feminine characteristics, while a female may develop a deepened voice and facial hair. This is called heterosexual precocity. It is very rare in comparison to isosexual precocity and is usually the result of only unusual circumstances. As an example, children with a very rare genetic condition called familial hyperestrogenism in which exceptionally high circulating levels of estrogen are present usually develop precocious puberty. Males and females are hyperfeminized by the syndrome.


Many causes of early puberty are somewhat unclear, though girls who have a high-fat diet and are not physically active or are [15][16] "Factors other than obesity, however, perhaps genetic and/or environmental ones, are needed to explain the higher prevalence of early puberty in black versus white girls."[13] While more girls are increasingly entering puberty at younger ages, new research indicates that some boys are actually starting later (delayed puberty).[17][18] "Increasing rates of obese and overweight children in the United States may be contributing to a later onset of puberty in boys, say researchers at the University of Michigan Health System."[18]

High levels of beta-hCG in serum and cerebrospinal fluid observed in a 9-year-old boy suggest a pineal gland tumor. The tumor is called a chorionic gonadotropin secreting pineal tumor. Radiotherapy and chemotherapy reduced tumor and beta-hCG levels normalized.[19]

In a study using neonatal melatonin on rats, results suggest that elevated melatonin could be responsible for some cases of early puberty.[20]

Familial cases of idiopathic central precocious puberty (ICPP) have been reported, leading researchers to believe there are specific genetic modulators of ICPP. Mutations in genes such as LIN28,[21][22] and LEP and LEPR, which encode leptin and the leptin receptor,[23] have been associated with precocious puberty. The association between LIN28 and puberty timing was validated experimentally in vivo, when it was found that mice with ectopic overexpression of LIN28 show an extended period of pre-pubertal growth and a significant delay in puberty onset.[24]

Mutations in the kisspeptin (KISS1) and its receptor, KISS1R (also known as GPR54), involved in GnRH secretion and puberty onset, are also thought to be the cause for ICPP [25][26] However, this is still a controversial area of research, and some investigators found no association of mutations in the LIN28 and KISS1/KISS1R genes to be the common cause underlying ICPP.[27]


Studies indicate that breast development in girls and the appearance of pubic hair in girls and boys are starting earlier than in previous generations.[13][28][29] As a result, "early puberty" in children, particularly girls, as young as 9 and 10 is no longer considered abnormal, although it may be upsetting to parents[17][30] and can be harmful to children who mature physically at a time when they are immature mentally.[31]

No age reliably separates normal from abnormal processes in children, but the following age thresholds for evaluation are thought to minimize the risk of missing a significant medical problem:

Medical evaluation is sometimes necessary to recognize the few children with serious conditions from the majority who have entered puberty early but are still medically normal. Early sexual development warrants evaluation because it may:

  • induce early bone maturation and reduce eventual adult height,
  • indicate the presence of a tumor or other serious problem,
  • cause the child, particularly a girl, to become an object of adult sexual interest.[14][32][33]

Early puberty is believed to put girls at higher risk of sexual abuse,[14][33] unrelated to pedophilia because the child has developed secondary sex characteristics; however, a causal relationship is, as yet, inconclusive.[33] Early puberty also puts girls at a higher risk for teasing or bullying, mental health disorders and short stature as adults.[14][32][34] Helping children control their weight is suggested to help delay puberty. Early puberty additionally puts girls at a "far greater" risk for breast cancer later in life. Girls as young as 8 are increasingly starting to menstruate, develop breasts and grow pubic and underarm hair; these "biological milestones" typically occurred only at 13 or older in decades past. Females of African ancestry are especially prone to early puberty.[13] There are theories debating the trend of early puberty, but the exact causes are not known.

Though boys face fewer problems upon early puberty than girls, early puberty is not always positive for boys; early sexual maturation in boys can be accompanied by increased aggressiveness due to the surge of hormones that affect them.[35] Because they appear older than their peers, pubescent boys may face increased social pressure to conform to adult norms; society may view them as more emotionally advanced, despite the fact that their cognitive and social development may lag behind their appearance.[35] Studies have shown that early maturing boys are more likely to be sexually active and are more likely to participate in risky behaviors.[36]


One possible treatment is with anastrozole. Histrelin acetate (Supprelin LA), triptorelin or leuprolide, any GnRH agonists, may be used. Non-continuous usage of GnRH agonists stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH).[37] However, when used regularly, GnRH agonists cause a decreased release of FSH and LH. Prolonged use has a risk of causing osteoporosis. After stopping GnRH agonists, pubertal changes resume within 3 to 12 months.

See also


  1. ^ "Precocious Puberty". KidsHealth. Retrieved 2013-09-09. 
  2. ^ precocious puberty at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. ^ "precocious puberty" at Dorland's Medical Dictionary
  4. ^ David Gardner, Dolores Shoback. Basic And Clinical Endocrinology. McGraw-Hill Medical; 2011. 9th Edition. Pg. 550
  5. ^ Dickerman, R. D.; Stevens, Q. E.; Steide, J. A.; Schneider, S. J. (2004). "Precocious puberty associated with a pineal cyst: is it disinhibition of the hypothalamic-pituitary axis?". Neuro endocrinology letters 25 (3): 173–175.  
  6. ^ Kumar, Manoj; Mukhopadhyay, Satinath; Dutta, Deep (2015-01-15). "Challenges and controversies in diagnosis and management of gonadotropin dependent precocious puberty: An Indian perspective". Indian Journal of Endocrinology and Metabolism 19 (2): 228–235.  
  7. ^ "Little Mother".  
  8. ^  
  9. ^ Yamato, Fumiko; Takaya, Junji; Higashino, Hirohiko; Yamanouchi, Yasuo; Suehara, Hiroshi; Kobayashi, Yohnosuke (March 2005). "Slipped capital femoral epiphysis during the treatment of precocious puberty with a gonadotropin-releasing hormone-agonist: aetiological considerations". European Journal of Pediatrics 164 (3): 173–174.  
  10. ^ Masse, R. J.; Shaw, P. J.; Burgess, M. (2008). "Intracranial choriocarcinoma causing precocious puberty and cured with combined modality therapy". Journal of Paediatrics and Child Health 29 (6): 464–467.  
  11. ^ Antoniazzi, F.; Zamboni, G. (2004). "Central precocious puberty: current treatment options". Paediatric drugs 6 (4): 211–231.  )
  12. ^ (Tanner, 1990).
  13. ^ a b c d Kaplowitz, P. B.; Slora, E. J.; Wasserman, R. C.; Pedlow, S. E.; Herman-Giddens, M. E. (2001). "Earlier onset of puberty in girls: relation to increased body mass index and race". Pediatrics 108 (2): 347–353.  
  14. ^ a b c d e McKenna, Phil (2007-03-05). "Childhood obesity brings early puberty for girls".  
  15. ^ Jane Houlihan, Sonya Lunder, Anila Jacob. "Timeline: BPA from Invention to Phase-Out".  
  16. ^ Libertun, C.; Lux-Lantos, V.; Bianchi, M.; Fernández, M. (2009). "Neonatal Exposure to Bisphenol a Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats". Environmental Health Perspectives.  
  17. ^ a b Cooney, Elizabeth (2010-02-11). "Puberty gap: Obesity splits boys, girls. Adolescent males at top of the BMI chart may be delayed".  
  18. ^ a b "Childhood Obesity May Contribute to Later Onset of Puberty for Boys".  
  19. ^ Kuo, H. C.; Sheen, J. M.; Wu, K. S.; Wei, H. H.; Hsiao, C. C. (2006). "Precocious puberty due to human chorionic gonadotropin-secreting pineal tumor". Chang Gung medical journal 29 (2): 198–202.  
  20. ^ Esouifino, A. I.; Villanúa, M. A.; Agrasal, C. (1987). "Effect of neonatal melatonin administration on sexual development in the rat". Journal of Steroid Biochemistry 27 (4–6): 1089–1093.  
  21. ^ Park, Sung Won; Lee, Seung-Tae; Sohn, Young Bae; Cho, Sung Yoon; Kim, Se-Hwa; Kim, Su Jin; Kim, Chi Hwa; Ko, Ah-Ra; Paik, Kyung-Hoon; Kim, Jong-Won; Jin, Dong-Kyu (1 January 2012). "polymorphisms are associated with central precocious puberty and early puberty in girls". Korean Journal of Pediatrics 55 (10): 388–92.  
  22. ^ Ong, Ken K; Elks, Cathy E; Li, Shengxu; Zhao, Jing Hua; Luan, Jian'an; Andersen, Lars B; Bingham, Sheila A; Brage, Soren; Smith, George Davey; Ekelund, Ulf; Gillson, Christopher J; Glaser, Beate; Golding, Jean; Hardy, Rebecca; Khaw, Kay-Tee; Kuh, Diana; Luben, Robert; Marcus, Michele; McGeehin, Michael A; Ness, Andrew R; Northstone, Kate; Ring, Susan M; Rubin, Carol; Sims, Matthew A; Song, Kijoung; Strachan, David P; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Wong, Andrew; Deloukas, Panagiotis; Barroso, Inês; Mooser, Vincent; Loos, Ruth J; Wareham, Nicholas J (16 May 2009). "Genetic variation in LIN28B is associated with the timing of puberty". Nature Genetics 41 (6): 729–733.  
  23. ^ Su, Pen-Hua; Yang, Shun-Fa; Yu, Ju-Shan; Chen, Suh-Jen; Chen, Jia-Yuh (15 February 2012). "Study of leptin levels and gene polymorphisms in patients with central precocious puberty". Pediatric Research 71 (4–1): 361–367.  
  24. ^ Zhu H, Shah S, Shyh-Chang N, Shinoda G, Einhorn WS, Viswanathan SR, Takeuchi A, Grasemann C, Rinn JL, Lopez MF, Hirschhorn JN, Palmert MR, Daley GQ. (July 2010). "Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies". Nat Genet 42 (7): 626–30.  
  25. ^ Teles, Milena Gurgel; Silveira, Leticia Ferreira Gontijo; Tusset, Cintia; Latronico, Ana Claudia (1 October 2011). "New genetic factors implicated in human GnRH-dependent precocious puberty: The role of kisspeptin system". Molecular and Cellular Endocrinology 346 (1–2): 84–90.  
  26. ^ Silveira, LG; Noel, SD; Silveira-Neto, AP; Abreu, AP; Brito, VN; Santos, MG; Bianco, SD; Kuohung, W; Xu, S; Gryngarten, M; Escobar, ME; Arnhold, IJ; Mendonca, BB; Kaiser, UB; Latronico, AC (May 2010). "Mutations of the KISS1 gene in disorders of puberty". The Journal of Clinical Endocrinology and Metabolism 95 (5): 2276–80.  
  27. ^ Tommiska, Johanna; Sørensen, Kaspar; Aksglaede, Lise; Koivu, Rosanna; Puhakka, Lea; Juul, Anders; Raivio, Taneli (1 January 2011). "LIN28B, LIN28A, KISS1, and KISS1R in idiopathic central precocious puberty". BMC Research Notes 4 (1): 363.  
  28. ^ Zukauskaite, S.; Lasiene, D.; Lasas, L.; Urbonaite, B.; Hindmarsh, P. (2005). "Onset of breast and pubic hair development in 1231 preadolescent Lithuanian schoolgirls". Archives of Disease in Childhood 90 (9): 932–936.  
  29. ^ Roberts, Michelle (2005-05-15). "Why puberty now begins at seven". BBC News. Retrieved 2010-05-22. 
  30. ^ Ritter, Jim (2000-08-02). "Parents worried by girls' earlier start of puberty".  
  31. ^ Diana Zuckerman Ph.D. (2001). "Early Puberty in Girls". The Ribbon. Cornell University Program on Breast Cancer and Environmental Risk Factors. Retrieved 14 January 2010. 
  32. ^ a b (Stattin & Magnussion, 1990).
  33. ^ a b c Mendle J, Leve L, Van Ryzin M, Natsuaki M. (August 2013). "Linking Childhood Maltreatment With Girls' Internalizing Symptoms: Early Puberty as a Tipping Point". Journal of Research on Adolescence 24 (3): 626–30.  
  34. ^ (Caspi et al.1993: Lanza and Collins, 2002)
  35. ^ a b Garn, SM. Physical growth and development. In: Friedman SB, Fisher M, Schonberg SK. , editors. Comprehensive Adolescent Health Care. St Louis: Quality Medical Publishing; 1992. Retrieved on 2009-02-20
  36. ^ Susman, EJ; Dorn, LD; Schiefelbein, VL. Puberty, sexuality, and health. In: Lerner MA, Easterbrooks MA, Mistry J. , editors. Comprehensive Handbook of Psychology. New York: Wiley; 2003. Retrieved on 2009-02-20
  37. ^  

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