Precocious Puberty Questions & Answers

1. Kaplowitz P, Bloch C, Section on Endocrinology, American Academy of Pediatrics. Evaluation and Referral of Children With Signs of Early Puberty. Pediatrics. 2016 Jan. 137 (1):[QxMD MEDLINE Link]. [Full Text].

2. Pedicelli S, Alessio P, Scire G, Cappa M, Cianfarani S. Routine screening by brain magnetic resonance imaging is not indicated in every girl with onset of puberty between the ages of 6 and 8 years. J Clin Endocrinol Metab. 2014 Dec. 99 (12):4455-61. [QxMD MEDLINE Link]. [Full Text].

3. Teilmann G, Pedersen CB, Jensen TK, Skakkebaek NE, Juul A. Prevalence and incidence of precocious pubertal development in Denmark: an epidemiologic study based on national registries. Pediatrics. 2005 Dec. 116 (6):1323-8. [QxMD MEDLINE Link].

4. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969 Jun. 44(235):291-303. [QxMD MEDLINE Link].

5. Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics. 1997 Apr. 99(4):505-12. [QxMD MEDLINE Link]. [Full Text].

6. [Guideline] 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 Wilkins Pediatric Endocrine Society. Pediatrics. 1999 Oct. 104(4 Pt 1):936-41. [QxMD MEDLINE Link]. [Full Text].

7. Biro FM, Galvez MP, Greenspan LC, Succop PA, Vangeepuram N, Pinney SM. Pubertal assessment method and baseline characteristics in a mixed longitudinal study of girls. Pediatrics. 2010 Sep. 126(3):e583-90. [QxMD MEDLINE Link].

8. Sorensen K, Aksglaede L, Petersen JH, Juul A. Recent changes in pubertal timing in healthy Danish boys: associations with body mass index. J Clin Endocrinol Metab. 2010 Jan. 95(1):263-70. [QxMD MEDLINE Link].

9. Parent AS, Teilmann G, Juul A, et al. The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr Rev. 2003 Oct. 24(5):668-93. [QxMD MEDLINE Link]. [Full Text].

10. Aksglaede L, Sorensen K, Petersen JH, et al. Recent decline in age at breast development: the Copenhagen Puberty Study. Pediatrics. 2009 May. 123(5):e932-9. [QxMD MEDLINE Link].

11. Ma HM, Du ML, Luo XP, et al. Onset of breast and pubic hair development and menses in urban Chinese girls. Pediatrics. 2009 Aug. 124(2):e269-77. [QxMD MEDLINE Link].

12. Eckert-Lind C, Busch AS, Petersen JH, Biro FM, Butler G, Brauner EV, et al. Worldwide Secular Trends in Age at Pubertal Onset Assessed by Breast Development Among Girls: A Systematic Review and Meta-analysis. JAMA Pediatr. 2020 Feb 10. e195881. [QxMD MEDLINE Link].

13. Teilmann G, Petersen JH, Gormsen M, Damgaard K, Skakkebaek NE, Jensen TK. Early puberty in internationally adopted girls: hormonal and clinical markers of puberty in 276 girls examined biannually over two years. Horm Res. 2009. 72(4):236-46. [QxMD MEDLINE Link].

14. Hayes P. International adoption, "early" puberty, and underrecorded age. Pediatrics. 2013 Jun. 131 (6):1029-31. [QxMD MEDLINE Link].

15. Bodicoat DH, Schoemaker MJ, Jones ME, et al. Timing of pubertal stages and breast cancer risk: the Breakthrough Generations Study. Breast Cancer Res. 2014 Feb 4. 16 (1):R18. [QxMD MEDLINE Link]. [Full Text].

16. Wu T, Mendola P, Buck GM. Ethnic differences in the presence of secondary sex characteristics and menarche among US girls: the Third National Health and Nutrition Examination Survey, 1988-1994. Pediatrics. 2002 Oct. 110(4):752-7. [QxMD MEDLINE Link]. [Full Text].

17. Biro FM, Greenspan LC, Galvez MP, et al. Onset of breast development in a longitudinal cohort. Pediatrics. 2013 Dec. 132 (6):1019-27. [QxMD MEDLINE Link]. [Full Text].

18. Bridges NA, Christopher JA, Hindmarsh PC, Brook CG. Sexual precocity: sex incidence and aetiology. Arch Dis Child. 1994 Feb. 70(2):116-8. [QxMD MEDLINE Link].

19. Bar A, Linder B, Sobel EH, Saenger P, DiMartino-Nardi J. Bayley-Pinneau method of height prediction in girls with central precocious puberty: correlation with adult height. J Pediatr. 1995 Jun. 126 (6):955-8. [QxMD MEDLINE Link].

20. Jaruratanasirikul S, Thongkum K, Krisaneepaiboon S, Sriplung H. Girls with early puberty attain a near-final height similar to their target height. J Pediatr Endocrinol Metab. 2011. 24 (5-6):339-45. [QxMD MEDLINE Link].

21. Walvoord EC, Mazur T. Behavioral problems and idiopathic central precocious puberty: Fact or fiction?. Pediatr Endocrinol Rev. June 2007. 4 (suppl 3):306-12.

22. Schoelwer MJ, Donahue KL, Didrick P, Eugster EA. One-Year Follow-Up of Girls with Precocious Puberty and Their Mothers: Do Psychological Assessments Change over Time or with Treatment?. Horm Res Paediatr. 2017. 88 (5):347-53. [QxMD MEDLINE Link]. [Full Text].

23. [Guideline] Carel JC, Eugster EA, Rogol A, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009 Apr. 123(4):e752-62. [QxMD MEDLINE Link].

24. Lazar L, Padoa A, Phillip M. Growth pattern and final height after cessation of gonadotropin-suppressive therapy in girls with central sexual precocity. J Clin Endocrinol Metab. 2007 Sep. 92(9):3483-9. [QxMD MEDLINE Link].

25. Bertelloni S, Massart F, Miccoli M, Baroncelli GI. Adult height after spontaneous pubertal growth or GnRH analog treatment in girls with early puberty: a meta-analysis. Eur J Pediatr. 2017 Jun. 176 (6):697-704. [QxMD MEDLINE Link].

26. Bereket A. A Critical Appraisal of the Effect of Gonadotropin-Releasing Hormon Analog Treatment on Adult Height of Girls with Central Precocious Puberty. J Clin Res Pediatr Endocrinol. 2017 Dec 30. 9 (Suppl 2):33-48. [QxMD MEDLINE Link]. [Full Text].

27. [Guideline] American Academy of Pediatrics. Sexuality education for children and adolescents: Committee on Psychosocial Aspects of Child and Family Health and Committee on Adolescence. Pediatrics. 2001 Aug. 108(2):498-502.

28. de Vries L, Kauschansky A, Shohat M, Phillip M. Familial central precocious puberty suggests autosomal dominant inheritance. J Clin Endocrinol Metab. 2004 Apr. 89(4):1794-800. [QxMD MEDLINE Link]. [Full Text].

29. Mamun AA, Hayatbakhsh MR, O'Callaghan M, Williams G, Najman J. Early overweight and pubertal maturation--pathways of association with young adults' overweight: a longitudinal study. Int J Obes (Lond). 2009 Jan. 33(1):14-20. [QxMD MEDLINE Link].

30. Lee JM, Appugliese D, Kaciroti N, et al. Weight status in young girls and the onset of puberty. Pediatrics. 2007 Mar. 119(3):e624-30. [QxMD MEDLINE Link].

31. Currie C, Ahluwalia N, Godeau E, Nic Gabhainn S, Due P, Currie DB. Is Obesity at Individual and National Level Associated With Lower Age at Menarche? Evidence From 34 Countries in the Health Behaviour in School-aged Children Study. J Adolesc Health. 2012 Jun. 50(6):621-6. [QxMD MEDLINE Link].

32. Shim YS, Lee HS, Hwang JS. Genetic Factors in Precocious Puberty. Clin Exp Pediatr. 2021 Oct 18. [QxMD MEDLINE Link].

33. Fanis P, Skordis N, Toumba M, et al. Central Precocious Puberty Caused by Novel Mutations in the Promoter and 5'-UTR Region of the Imprinted MKRN3 Gene. Front Endocrinol (Lausanne). 2019. 10:677. [QxMD MEDLINE Link]. [Full Text].

34. Williams RM, Ward CE, Hughes IA. Premature adrenarche. Arch Dis Chil. 2012. 97:250-254.

35. DeSalvo DJ, Mehra R, Vaidyanathan P, Kaplowitz PB. In children with premature adrenarche, bone age advancement by 2 or more years is common and generally benign. J Pediatr Endocrinol Metab. 2013. 26 (3-4):215-21. [QxMD MEDLINE Link].

36. Khokhar A, Mojica A. Premature Thelarche. Pediatr Ann. 2018 Jan 1. 47 (1):e12-5. [QxMD MEDLINE Link].

37. Ramsey JT, Li Y, Arao Y, et al. Lavender Products Associated With Premature Thelarche and Prepubertal Gynecomastia: Case Reports and Endocrine-Disrupting Chemical Activities. J Clin Endocrinol Metab. 2019 Nov 1. 104 (11):5393-405. [QxMD MEDLINE Link]. [Full Text].

38. Nella AA, Kaplowitz PB, Ramnitz MS, Nandagopal R. Benign vaginal bleeding in 24 prepubertal patients: clinical, biochemical and imaging features. J Pediatr Endocrinol Metab. 2014 Sep. 27 (9-10):821-5. [QxMD MEDLINE Link].

39. Stephen MD, Jehaimi CT, Brosnan PG, Yafi M. Sexual precocity in a 2-year-old boy caused by indirect exposure to testosterone cream. Endocr Pract. 2008 Nov. 14(8):1027-30. [QxMD MEDLINE Link].

40. Armengaud JB, Charkaluk ML, Trivin C, Tardy V, Bréart G, Brauner R. Precocious pubarche: distinguishing late-onset congenital adrenal hyperplasia from premature adrenarche. J Clin Endocrinol Metab. 2009 Aug. 94(8):2835-40. [QxMD MEDLINE Link].

41. Resende EA, Lara BH, Reis JD, Ferreira BP, Pereira GA, Borges MF. Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. J Clin Endocrinol Metab. 2007 Apr. 92(4):1424-9. [QxMD MEDLINE Link].

42. Houk CP, Kunselman AR, Lee PA. Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls. Pediatrics. 2009 Jun. 123(6):e1059-63. [QxMD MEDLINE Link].

43. Sathasivam A, Garibaldi L, Shapiro S, Godbold J, Rapaport R. Leuprolide Stimulation Testing for the Evaluation of Early Female Sexual Maturation. Clin Endocrinol (Oxf). 2010 Feb 23. [QxMD MEDLINE Link].

44. Chen T, Wu H, Xie R, et al. Serum anti-Müllerian hormone and inhibin B as potential markers for progressive central precocious puberty in girls. J Pediatr Adolesc Gynecol. 2017 Feb 1. [QxMD MEDLINE Link].

45. Ng SM, Kumar Y, Cody D, et al. Cranial MRI scans are indicated in all girls with central precocious puberty. Arch Dis Child. 2003 May. 88(5):414-8; discussion 414-8. [QxMD MEDLINE Link]. [Full Text].

46. Kaplowitz PB. Do 6-8 year old girls with central precocious puberty need routine brain imaging?. Int J Pediatr Endocrinol. 2016. 2016:9. [QxMD MEDLINE Link]. [Full Text].

47. Wang M, Zhang Y, Lan D, Hill JW. The Efficacy of GnRHa Alone or in Combination with rhGH for the Treatment of Chinese Children with Central Precocious Puberty. Sci Rep. 2016 Apr 13. 6:24259. [QxMD MEDLINE Link]. [Full Text].

48. Kaplowitz PB, Backeljauw PF, Allen DB. Toward More Targeted and Cost-Effective Gonadotropin-Releasing Hormone Analog Treatment in Girls with Central Precocious Puberty. Horm Res Paediatr. 2018. 90 (1):1-7. [QxMD MEDLINE Link]. [Full Text].

49. Bangalore Krishna K, Fuqua JS, Rogol AD, et al. Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium. Horm Res Paediatr. 2019. 91 (6):357-72. [QxMD MEDLINE Link]. [Full Text].

50. Fuld K, Chi C, Neely EK. A randomized trial of 1- and 3-month depot leuprolide doses in the treatment of central precocious puberty. J Pediatr. 2011 Dec. 159(6):982-7.e1. [QxMD MEDLINE Link].

51. Chalumeau M, Chemaitilly W, Trivin C, et al. Central precocious puberty in girls: an evidence-based diagnosis tree to predict central nervous system abnormalities. Pediatrics. 2002 Jan. 109(1):61-7. [QxMD MEDLINE Link]. [Full Text].

52. Leschek EW, Flor AC, Bryant JC, Jones JV, Barnes KM, Cutler GB Jr. Effect of Antiandrogen, Aromatase Inhibitor, and Gonadotropin-releasing Hormone Analog on Adult Height in Familial Male Precocious Puberty. J Pediatr. 2017 Nov. 190:229-35. [QxMD MEDLINE Link].

53. Frisch RE, McArthur JW. Menstrual cycles: fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science. 1974 Sep 13. 185(4155):949-51. [QxMD MEDLINE Link].

54. Liu S, Liu Q, Cheng X, Luo Y, Wen Y. Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis. J Endocrinol Invest. 2016 May 25. [QxMD MEDLINE Link].

55. Kim HR, Nam HK, Rhie YJ, Lee KH. Treatment outcomes of gonadotropin-releasing hormone agonist in obese girls with central precocious puberty. Ann Pediatr Endocrinol Metab. 2017 Dec. 22 (4):259-65. [QxMD MEDLINE Link]. [Full Text].

56. Yoo JW, Song CW, Lim HH. Leptin and adiponectin levels in girls with central precocious puberty before and during GnRH agonist treatment. Ann Pediatr Endocrinol Metab. 2016 Dec. 21 (4):199-205. [QxMD MEDLINE Link]. [Full Text].

57. Williams RM, Ward CE, Hughes IA. Premature adrenarche. Arch Dis Child. 2012 Mar. 97 (3):250-4. [QxMD MEDLINE Link].

58. Klein K, Yang J, Aisenberg J, et al. Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty. J Pediatr Endocrinol Metab. 2016 Nov 1. 29 (11):1241-8. [QxMD MEDLINE Link].

59. Eugster EA, Clarke W, Kletter GB, et al. Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial. J Clin Endocrinol Metab. 2007 May. 92 (5):1697-704. [QxMD MEDLINE Link]. [Full Text].

60. Lewis KA, Goldyn AK, West KW, Eugster EA. A single histrelin implant is effective for 2 years for treatment of central precocious puberty. J Pediatr. 2013 Oct. 163 (4):1214-6. [QxMD MEDLINE Link]. [Full Text].

Paul B Kaplowitz, MD, PhD Professor Emeritus of Pediatrics, Division of Endocrinology, Children's National Medical Center

Paul B Kaplowitz, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Robert P Hoffman, MD Professor and Program Director, Department of Pediatrics, Ohio State University College of Medicine; Pediatric Endocrinologist, Division of Pediatric, Endocrinology, Diabetes, and Metabolism, Nationwide Children's Hospital

Robert P Hoffman, MD is a member of the following medical societies: American College of Pediatricians, American Diabetes Association, American Pediatric Society, Christian Medical and Dental Associations, Endocrine Society, Midwest Society for Pediatric Research, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

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