J Korean Med Assoc.  2015 Dec;58(12):1138-1144. 10.5124/jkma.2015.58.12.1138.

Overview and treatment of precocious puberty

• Rhie YJ
• Lee KH

• KMID: 2195142
• DOI: http://doi.org/10.5124/jkma.2015.58.12.1138

Abstract

Puberty is a complex and coordinated biologic process of sexual development that leads to complete gonadal maturation and function, and attainment of reproductive capacity. The pubertal activation of pulsatile gonadotropin-releasing hormone (GnRH) secretion requires coordinated changes in excitatory and inhibitory neurotransmitters, growth factors, and a group of transcriptional regulators. Kisspeptin and its putative receptor, G protein-54 signaling complex, have recently emerged as essential gatekeepers of GnRH activation. Precocious puberty is defined as the onset of secondary sexual characteristics before the age of 8 years for girls and 9 years for boys. The prevalence of precocious puberty is rapidly increasing in Korea. Factors affecting early puberty include genetic traits, nutrition, and exposure to endocrine disrupting chemicals. Precocious puberty may cause psychosocial problems with inappropriate early biological maturation and significant impairment of final height due to accelerated bone maturation. In rapidly progressing central precocious puberty, GnRH agonists appear to increase final height without significant side effects, if administered in the early stages. Further large-scale randomized controlled studies of the long-term safety and efficacy of GnRH agonist treatment are needed.

Keyword

Puberty; Gonadotropin-releasing hormone; Endocrine disruptors; Precocious puberty; Gonadotropin-releasing hormone agonist

MeSH Terms

Adolescent
Endocrine Disruptors
Female
Gonadotropin-Releasing Hormone
Gonads
Humans
Intercellular Signaling Peptides and Proteins
Korea
Neurotransmitter Agents
Prevalence
Puberty
Puberty, Precocious*
Sexual Development
Endocrine Disruptors
Gonadotropin-Releasing Hormone
Intercellular Signaling Peptides and Proteins
Neurotransmitter Agents

Reference

1. Grumbach MM, Styne DM. Puberty: ontogeny, neuroendocrinology, physiology, and disorders. In : Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, editors. Williams textbook of endocrinology. 12th ed. Philadelphia: Saunders;2011. p. 1054–1108.

2. Semple RK, Achermann JC, Ellery J, Farooqi IS, Karet FE, Stanhope RG, O'rahilly S, Aparicio SA. Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2005; 90:1849–1855.

3. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O'Rahilly S, Carlton MB, Crowley WF Jr, Aparicio SA, Colledge WH. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003; 349:1614–1627.

4. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A. 2005; 102:2129–2134.

5. Tena-Sempere M. Keeping puberty on time: novel signals and mechanisms involved. Curr Top Dev Biol. 2013; 105:299–329.

6. Korean Society of Pediatric Endocrinology. Pediatric endocrinology. 3rd ed. Seoul: Koonja;2014.

7. Ahn JH, Lim SW, Song BS, Seo J, Lee JA, Kim DH, Lim JS. Age at menarche in the Korean female: secular trends and relationship to adulthood body mass index. Ann Pediatr Endocrinol Metab. 2013; 18:60–64.

8. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001; 108:347–353.

9. Rhie YJ, Nam HK, Oh YJ, Kim HS, Lee KH. Influence of bottle-feeding on serum bisphenol a levels in infants. J Korean Med Sci. 2014; 29:261–264.

10. Kaplowitz PB, Oberfield SE. Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment: Drug and Therapeutics and Executive Committees of the Lawson Wil-kins Pediatric Endocrine Society. Pediatrics. 1999; 104(4 Pt 1):936–941.

11. Rosenfield RL, Cooke DW, Radovick S. Puberty and its disorderin the female. In : Sperling MA, editor. Pediatric endocrinology. 4th ed. Philadelphia: Saunders;2014. p. 569–663.

12. Johansson T, Ritzen EM. Very long-term follow-up of girls with early and late menarche. Endocr Dev. 2005; 8:126–136.

13. Lakshman R, Forouhi NG, Sharp SJ, Luben R, Bingham SA, Khaw KT, Wareham NJ, Ong KK. Early age at menarche associated with cardiovascular disease and mortality. J Clin Endocrinol Metab. 2009; 94:4953–4960.

14. van Lenthe FJ, Kemper CG, van Mechelen W. Rapid maturation in adolescence results in greater obesity in adulthood: the Amsterdam Growth and Health Study. Am J Clin Nutr. 1996; 64:18–24.

15. Lakshman R, Forouhi N, Luben R, Bingham S, Khaw K, Wareham N, Ong KK. Association between age at menarche and risk of diabetes in adults: results from the EPIC-Norfolk cohort study. Diabetologia. 2008; 51:781–786.

16. Shin A, Song YM, Yoo KY, Sung J. Menstrual factors and cancer risk among Korean women. Int J Epidemiol. 2011; 40:1261–1268.

17. Lebrethon MC, Bourguignon JP. Management of central isosexual precocity: diagnosis, treatment, outcome. Curr Opin Pediatr. 2000; 12:394–399.

18. Crowley WF Jr, Comite F, Vale W, Rivier J, Loriaux DL, Cutler GB Jr. Therapeutic use of pituitary desensitization with a long-acting lhrh agonist: a potential new treatment for idiopathic precocious puberty. J Clin Endocrinol Metab. 1981; 52:370–372.

19. Carel JC, Lahlou N, Jaramillo O, Montauban V, Teinturier C, Colle M, Lucas C, Chaussain JL. Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg). J Clin Endocrinol Metab. 2002; 87:4111–4116.

20. Eugster EA, Clarke W, Kletter GB, Lee PA, Neely EK, Reiter EO, Saenger P, Shulman D, Silverman L, Flood L, Gray W, Tierney D. Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial. J Clin Endocrinol Metab. 2007; 92:1697–1704.

21. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR, Antoniazzi F, Berenbaum S, Bourguignon JP, Chrousos GP, Coste J, Deal S, de Vries L, Foster C, Heger S, Holland J, Jahnukainen K, Juul A, Kaplowitz P, Lahlou N, Lee MM, Lee P, Merke DP, Neely EK, Oostdijk W, Phillip M, Rosenfield RL, Shulman D, Styne D, Tauber M, Wit JM. ESPE-LWPES GnRH Analogs Consensus Conference Group. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009; 123:e752–e762.

22. Pasquino AM, Pucarelli I, Segni M, Matrunola M, Cerroni F. Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone analogues and growth hormone. J Clin Endocrinol Metab. 1999; 84:449–452.

23. Klein KO, Barnes KM, Jones JV, Feuillan PP, Cutler GB Jr. Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience. J Clin Endocrinol Metab. 2001; 86:4711–4716.

24. Kim EY. Long-term effects of gonadotropin-releasing hormone analogs in girls with central precocious puberty. Korean J Pediatr. 2015; 58:1–7.

25. Carel JC, Roger M, Ispas S, Tondu F, Lahlou N, Blumberg J, Chaussain JL. Final height after long-term treatment with triptorelin slow release for central precocious puberty: importance of statural growth after interruption of treatment. French study group of Decapeptyl in Precocious Puberty. J Clin Endocrinol Metab. 1999; 84:1973–1978.

26. Pasquino AM, Pucarelli I, Accardo F, Demiraj V, Segni M, Di Nardo R. Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogs: impact on adult height, body mass index, bone mineral content, and reproductive function. J Clin Endocrinol Metab. 2008; 93:190–195.

27. Magiakou MA, Manousaki D, Papadaki M, Hadjidakis D, Levidou G, Vakaki M, papaefstathiou A, Lalioti N, Kanaka-Gantenbein C, Piaditis G, Chrousos GP, Dacou-Voutetakis C. The efficacy and safety of gona-dotropinreleasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study. J Clin Endocrinol Metab. 2010; 95:109–117.

28. Baek JW, Nam HK, Jin D, Oh YJ, Rhie YJ, Lee KH. Age of menarche and near adult height after long-term gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty. Ann Pediatr Endocrinol Metab. 2014; 19:27–31.

29. Lazar L, Meyerovitch J, de Vries L, Phillip M, Lebenthal Y. Treated and untreated women with idiopathic precocious puberty: long-term follow-up and reproductive outcome between the third and fifth decades. Clin Endocrinol (Oxf). 2014; 80:570–576.