Home Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate
Article
Licensed
Unlicensed Requires Authentication

Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate

  • Karen O. Klein EMAIL logo , Sanja Dragnic , Ahmed M. Soliman and Peter Bacher
Published/Copyright: May 11, 2018
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 31 Issue 6

Abstract

Background:

Children with central precocious puberty (CPP) are treated with gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty. Optimizing treatment outcomes continues to be studied. The relationships between growth, rate of bone maturation (bone age/chronological age [ΔBA/ΔCA]), luteinizing hormone (LH), predicted adult stature (PAS), as well as variables influencing these outcomes, were studied in children treated with depot leuprolide (LA Depot)

Methods:

Subjects (64 girls, seven boys) with CPP received LA Depot every 3 months for up to 42 months. Multivariate regression analyses were conducted to examine the predictors affecting ΔBA/ΔCA, PAS and growth rate.

Results:

Ninety percent of subjects (18 of 20) were suppressed (LH levels <4 IU/L) at 42 months. Over 42 months, the mean growth rate declined 2 cm/year, the mean BA/CA ratio decreased 0.21 and PAS increased 8.90 cm for girls (n=64). PAS improved to mid-parental height (MPH) in 46.2% of children by 30 months of treatment. Regression analysis showed that only the Body Mass Index Standardized Score (BMI SDS) was significantly associated (β+0.378 and +0.367, p≤0.05) with growth rate. For PAS, significant correlations were with MPH (β+0.808 and +0.791, p<0.001) and ΔBA/ΔCA (β+0.808 and +0.791, p<0.001). For ΔBA/ΔCA, a significant association was found only with BA at onset of treatment (β−0.098 and −0.103, p≤0.05). Peak-stimulated or basal LH showed no significant influence on growth rate, ΔBA/ΔCA or PAS.

Conclusions:

Growth rate and bone maturation rate normalized on treatment with LA Depot. LH levels were not significantly correlated with growth rate, ΔBA/ΔCA or PAS, suggesting that suppression was adequate and variations in gonadotropin levels were below the threshold affecting outcomes.

Keywords: central precocious puberty; growth rate; LA Depot; luteinizing hormone levels; rate of bone maturation
Corresponding author: Karen O. Klein, MD, Clinical Professor of Pediatrics, Rady Children’s Hospital San Diego, 3020 Children’s Way, MC 5103, San Diego, CA 92123, USA, Phone: +(858) 966 4032

Acknowledgments

This work was funded by AbbVie Inc. AbbVie participated in the study design, research, data collection, analysis and interpretation of data, writing, reviewing and approving the publication. The authors would like to thank Aditya Lele, James W. Thomas, and Sun Li of AbbVie for assistance with the paper. Medical writing and editorial support was provided by Robin Smith, PhD, of The Curry Rockefeller Group, LLC, Tarrytown, NY. Funding for this support was provided by AbbVie.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was sponsored by AbbVie Inc. (North Chicago, IL, USA).

  3. Employment or leadership: Sanja Dragnic, Ahmed Soliman, and Peter Bacher are employees of AbbVie and may own AbbVie stock and/or stock options.

  4. Honorarium: None declared.

  5. Competing interests: AbbVie participated in the study design, research, data collection, analysis and interpretation of data, writing, reviewing and approving the publication. Sanja Dragnic, Ahmed Soliman and Peter Bacher are employees of AbbVie and may own AbbVie stock and/or stock options. Karen Klein is a consultant for AbbVie; has been paid for participating in speaker’s bureaus and educational presentations for AbbVie; and has had travel/accommodations paid for by AbbVie.

References

1. Carel JC, Lahlou N, Roger M, Chaussain JL. Precocious puberty and statural growth. Hum Reprod Update 2004;10:135–47.10.1093/humupd/dmh012Search in Google Scholar

2. Menon PS, Vijayakumar M. Precocious puberty-perspectives on diagnosis and management. Indian J Pediatr 2014;81:76–83.10.1007/s12098-013-1177-6Search in Google Scholar

3. Carel JC, Roger M, Ispas S, Tondu F, Lahlou N, et al. 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;84:1973–8.10.1210/jcem.84.6.5647Search in Google Scholar

4. Lebrethon MC, Bourguignon JP. Management of central isosexual precocity: diagnosis, treatment, outcome. Curr Opin Pediatr 2000;12:394–9.10.1097/00008480-200008000-00020Search in Google Scholar

5. Lee PA. Central precocious puberty. An overview of diagnosis, treatment, and outcome. Endocrinol Metab Clin North Am 1999;28:901–18, xi.10.1016/S0889-8529(05)70108-0Search in Google Scholar

6. Mul D, Hughes IA. The use of GnRH agonists in precocious puberty. Eur J Endocrinol 2008;159(Suppl 1):S3–8.10.1530/EJE-08-0814Search in Google Scholar PubMed

7. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009;123:e752–62.10.1542/peds.2008-1783Search in Google Scholar PubMed

8. Lee PA, Klein K, Mauras N, Neely EK, Bloch CA, et al. Efficacy and safety of leuprolide acetate 3-month depot 11.25 milligrams or 30 milligrams for the treatment of central precocious puberty. J Clin Endocrinol Metab 2012;97:1572–80.10.1210/jc.2011-2704Search in Google Scholar PubMed

9. AbbVie Inc. Lupron-Depot-PED® (leuprolide acetate for depot suspension): Prescribing Information. North Chicago, IL: AbbVie, Inc., 2013.Search in Google Scholar

10. Lee PA, Klein K, Mauras N, Lev-Vaisler T, Bacher P. 36-month treatment experience of two doses of leuprolide acetate 3-month depot for children with central precocious puberty. J Clin Endocrinol Metab 2014;99:3153–9.10.1210/jc.2013-4471Search in Google Scholar PubMed

11. Lee PA, Luce M, Bacher P. Monitoring treatment of central precocious puberty using basal luteinizing hormone levels and practical considerations for dosing with a 3-month leuprolide acetate formulation. J Pediatr Endocrinol Metab 2016;29: 1249–57.10.1515/jpem-2016-0026Search in Google Scholar PubMed

12. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. J Pediatr 1952;40:423–41.10.1016/S0022-3476(52)80205-7Search in Google Scholar

13. Carel JC, Blumberg J, Seymour C, Adamsbaum C, Lahlou N. Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty. Eur J Endocrinol 2006;154:119–24.10.1530/eje.1.02056Search in Google Scholar

14. Eugster EA, Clarke W, Kletter GB, Lee PA, Neely EK, et al. Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial. J Clin Endocrinol Metab 2007;92:1697–704.10.1210/jc.2006-2479Search in Google Scholar

15. Brito VN, Spinola-Castro AM, Kochi C, Kopacek C, Silva PC, et al. Central precocious puberty: revisiting the diagnosis and therapeutic management. Arch Endocrinol Metab 2016;60:163–72.10.1590/2359-3997000000144Search in Google Scholar

16. Tanaka T, Niimi H, Matsuo N, Fujieda K, Tachibana K, et al. Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate: evaluation of effectiveness of treatment and recovery of gonadal function. The TAP-144-SR Japanese Study Group on Central Precocious Puberty. J Clin Endocrinol Metab 2005;90:1371–6.10.1210/jc.2004-1863Search in Google Scholar

17. Parker KL, Lee PA. Depot leuprolide acetate for treatment of precocious puberty. J Clin Endocrinol Metab 1989;69:689–91.10.1210/jcem-69-3-689Search in Google Scholar

18. Neely EK, Lee PA, Bloch CA, Larsen L, Yang D, et al. Leuprolide acetate 1-month depot for central precocious puberty: hormonal suppression and recovery. Int J Pediatr Endocrinol 2010;2010:398639.10.1186/1687-9856-2010-398639Search in Google Scholar

19. Neely EK, Hintz RL, Wilson DM, Lee PA, Gautier T, et al. Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr 1995;127:40–6.10.1016/S0022-3476(95)70254-7Search in Google Scholar

20. Neely EK, Wilson DM, Lee PA, Stene M, Hintz RL. Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. J Pediatr 1995;127:47–52.10.1016/S0022-3476(95)70255-5Search in Google Scholar

21. Brito VN, Batista MC, Borges MF, Latronico AC, Kohek MB, et al. Diagnostic value of fluorometric assays in the evaluation of precocious puberty. J Clin Endocrinol Metab 1999;84:3539–44.Search in Google Scholar

22. Houk CP, Kunselman AR, Lee PA. Adequacy of a single unstimulated luteinizing hormone level to diagnose central precocious puberty in girls. Pediatrics 2009;123:e1059–63.10.1542/peds.2008-1180Search in Google Scholar PubMed

23. 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;159:982–7 e1.10.1016/j.jpeds.2011.05.036Search in Google Scholar PubMed

24. Neely EK, Silverman LA, Geffner ME, Danoff TM, Gould E, et al. Random unstimulated pediatric luteinizing hormone levels are not reliable in the assessment of pubertal suppression during histrelin implant therapy. Int J Pediatr Endocrinol 2013;2013:20.10.1186/1687-9856-2013-20Search in Google Scholar PubMed PubMed Central

25. Kunz GJ, Sherman TI, Klein KO. Luteinizing hormone (LH) and estradiol suppression and growth in girls with central precocious puberty: is more suppression better? Are pre-injection LH levels useful in monitoring treatment? J Pediatr Endocrinol Metab 2007;20:1189–98.10.1515/JPEM.2007.20.11.1189Search in Google Scholar PubMed

26. Clemons RD, Kappy MS, Stuart TE, Perelman AH, Hoekstra FT. Long-term effectiveness of depot gonadotropin-releasing hormone analogue in the treatment of children with central precocious puberty. Am J Dis Child 1993;147:653–7.10.1001/archpedi.1993.02160300059023Search in Google Scholar PubMed

27. Mul D, Oostdijk W, Waelkens JJ, Drop SL. Final height after treatment of early puberty in short adopted girls with gonadotrophin releasing hormone agonist with or without growth hormone. Clin Endocrinol (Oxf) 2005;63:185–90.10.1111/j.1365-2265.2005.02323.xSearch in Google Scholar PubMed

28. Pucarelli I, Segni M, Ortore M, Arcadi E, Pasquino AM. Effects of combined gonadotropin-releasing hormone agonist and growth hormone therapy on adult height in precocious puberty: a further contribution. J Pediatr Endocrinol Metab 2003;16:1005–10.10.1515/JPEM.2003.16.7.1005Search in Google Scholar PubMed

29. Tuvemo T, Jonsson B, Gustafsson J, Albertsson-Wikland K, Aronson AS, et al. Final height after combined growth hormone and GnRH analogue treatment in adopted girls with early puberty. Acta Paediatr 2004;93:1456–62.10.1111/j.1651-2227.2004.tb02629.xSearch in Google Scholar

30. Faienza MF, Brunetti G, Acquafredda A, Delvecchio M, Lonero A, et al. Metabolic outcomes, bone health, and risk of polycystic ovary syndrome in girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogues. Horm Res Paediatr 2017;87:162–9.10.1159/000456546Search in Google Scholar PubMed

31. Guaraldi F, Beccuti G, Gori D, Ghizzoni L. Management of endocrine disease: long-term outcomes of the treatment of central precocious puberty. Eur J Endocrinol 2016;174:R79–87.10.1530/EJE-15-0590Search in Google Scholar PubMed

32. Fennoy I. Effect of obesity on linear growth. Curr Opin Endocrinol Diabetes Obes 2013;20:44–9.10.1097/MED.0b013e32835b7f15Search in Google Scholar PubMed

33. Marcovecchio ML, Chiarelli F. Obesity and growth during childhood and puberty. World Rev Nutr Diet 2013;106:135–41.10.1159/000342545Search in Google Scholar PubMed

34. Mul D, Oostdijk W, Otten BJ, Rouwe C, Jansen M, et al. Final height after gonadotrophin releasing hormone agonist treatment for central precocious puberty: the Dutch experience. J Pediatr Endocrinol Metab 2000;13(Suppl 1):765–72.10.1515/JPEM.2000.13.S1.765Search in Google Scholar

35. Silverman LA, Neely EK, Kletter GB, Lewis K, Chitra S, et al. Long-term continuous suppression with once-yearly histrelin subcutaneous implants for the treatment of central precocious puberty: a final report of a phase 3 multicenter Trial. J Clin Endocrinol Metab 2015;100:2354–63.10.1210/jc.2014-3031Search in Google Scholar PubMed PubMed Central

36. Rahhal S, Clarke WL, Kletter GB, Lee PA, Neely EK, et al. Results of a second year of therapy with the 12-month histrelin implant for the treatment of central precocious puberty. Int J Pediatr Endocrinol 2009;2009:812517.10.1186/1687-9856-2009-812517Search in Google Scholar

37. Oerter KE, Manasco PK, Barnes KM, Jones J, Hill S, et al. Effects of luteinizing hormone-releasing hormone agonists on final height in luteinizing hormone-releasing hormone-dependent precocious puberty. Acta Paediatr Suppl 1993;388:62–8; discussion 9.10.1111/j.1651-2227.1993.tb12846.xSearch in Google Scholar PubMed

38. 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;86:4711–6.10.1210/jcem.86.10.7915Search in Google Scholar PubMed

39. Partsch CJ, Heger S, Sippell WG. Treatment of central precocious puberty: lessons from a 15 years prospective trial. German Decapeptyl Study Group. J Pediatr Endocrinol Metab 2000;13(Suppl 1):747–58.10.1515/JPEM.2000.13.S1.747Search in Google Scholar PubMed

40. Micillo M, Salerno M, Officioso A, Perna E, Gasparini N, et al. Near final height after GnRH agonist treatment in central precocious puberty. J Pediatr Endocrinol Metab 2000;13(Suppl 1): 787–90.10.1515/JPEM.2000.13.S1.787Search in Google Scholar PubMed

Received: 2017-12-11
Accepted: 2018-4-16
Published Online: 2018-5-11
Published in Print: 2018-6-27

©2018 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Congenital hypothyroidism
  4. Original Articles
  5. Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?
  6. Incidence of congenital hypothyroidism in China: data from the national newborn screening program, 2013–2015
  7. The etiologies and incidences of congenital hypothyroidism before and after neonatal TSH screening program implementation: a study in southern Thailand
  8. Current status of the congenital hypothyroidism neonatal screening program in Adana Province, Turkey
  9. Risk of hypoglycemia in youth with type 2 diabetes on insulin
  10. Metabolic risk factors in adolescent girls with type 1 diabetes
  11. Definition of reference ranges for β-isomerized carboxy-terminal telopeptide collagen type I for children and adolescents
  12. Brown adipose tissue in young adults who were born preterm or small for gestational age
  13. Circulating soluble RAGE and cell surface RAGE on peripheral blood mononuclear cells in healthy children
  14. Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate
  15. Trends in the use of puberty blockers among transgender children in the United States
  16. Initial presentations and associated clinical findings in patients with classical congenital adrenal hyperplasia
  17. Cardiac examination in children with Laron syndrome undergoing mecasermin therapy
  18. Five novel ALMS1 gene mutations in six patients with Alström syndrome
  19. Case Reports
  20. Cutaneous mucormycosis as a presenting feature of type 1 diabetes in a boy – case report and review of the literature
  21. Severe lactic acidosis in an extremely low birth weight infant due to thiamine deficiency
  22. Exertional rhabdomyolysis in carbonic anhydrase 12 deficiency
https://doi.org/10.1515/jpem-2017-0523
Keywords for this article
central precocious puberty; growth rate; LA Depot; luteinizing hormone levels; rate of bone maturation

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Congenital hypothyroidism
  4. Original Articles
  5. Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?
  6. Incidence of congenital hypothyroidism in China: data from the national newborn screening program, 2013–2015
  7. The etiologies and incidences of congenital hypothyroidism before and after neonatal TSH screening program implementation: a study in southern Thailand
  8. Current status of the congenital hypothyroidism neonatal screening program in Adana Province, Turkey
  9. Risk of hypoglycemia in youth with type 2 diabetes on insulin
  10. Metabolic risk factors in adolescent girls with type 1 diabetes
  11. Definition of reference ranges for β-isomerized carboxy-terminal telopeptide collagen type I for children and adolescents
  12. Brown adipose tissue in young adults who were born preterm or small for gestational age
  13. Circulating soluble RAGE and cell surface RAGE on peripheral blood mononuclear cells in healthy children
  14. Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate
  15. Trends in the use of puberty blockers among transgender children in the United States
  16. Initial presentations and associated clinical findings in patients with classical congenital adrenal hyperplasia
  17. Cardiac examination in children with Laron syndrome undergoing mecasermin therapy
  18. Five novel ALMS1 gene mutations in six patients with Alström syndrome
  19. Case Reports
  20. Cutaneous mucormycosis as a presenting feature of type 1 diabetes in a boy – case report and review of the literature
  21. Severe lactic acidosis in an extremely low birth weight infant due to thiamine deficiency
  22. Exertional rhabdomyolysis in carbonic anhydrase 12 deficiency
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 17.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2017-0523/html
Scroll to top button