Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter February 17, 2016

Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty

  • Karen Klein EMAIL logo , Joshua Yang , Javier Aisenberg , Nancy Wright , Paul Kaplowitz , Najiba Lahlou , Jeannete Linares , Eija Lundström , Daniela Purcea and Fernando Cassorla



Triptorelin is an established treatment for central precocious puberty (CPP) as 1- and 3-month formulations. The current triptorelin 22.5 mg 6-month formulation is approved for prostate cancer therapy. This is the first study in patients with CPP.


The efficacy and safety of the triptorelin 6-month formulation in CPP were investigated. The primary objective was to evaluate the efficacy in achieving luteinizing hormone (LH) suppression to pre-pubertal levels at month 6. This was an international, non-comparative phase III study over 48 weeks. Eighteen medical centers in the US, Chile and Mexico participated. Forty-four treatment naïve patients (39 girls and five boys) aged at treatment start 2–8 years for girls and 2–9 years for boys with an advancement of bone age over chronological age ≥1 year were to be included. Triptorelin was administered im twice at an interval of 24 weeks. LH, follicle stimulating hormone (FSH) (basal and stimulated), estradiol (girls), testosterone (boys), auxological parameters, clinical signs of puberty and safety were assessed.


Forty-one patients (93.2%) showed pre-pubertal LH levels (stimulated LH ≤5 IU/L) at month 6 and maintained LH suppression through month 12. The percentage of patients with LH suppression exceeded 93% at each time point and reached 97.7% at month 12. No unexpected drug-related adverse events were reported.


The triptorelin 6-month formulation was safe and effective in suppressing the pituitary-gonadal axis in children with CPP. The extended injection interval may improve compliance and increase comfort in the management of CPP.

Corresponding author: Karen Klein, MD, University of California and Rady Children’s Hospital, 3020 Children’s Way, MC 5103 San Diego, CA 92123, USA, Phone: +858-966-4032


The authors thank the children and their families for participation in the study and the study coordinators for the conduct of the study. The authors also thank the following investigators for their participation: Tala Dajani, MD, Oskar Flores-Caloca, MD, Gad Kletter, MD, Susan Rose, MD, Kathleen Bethin, MD, David Domek, MD, Diane Merritt, MD, Quentin Van Meter, MD, Heidi Shea, MD, Lawrence Silverman, MD, Opada Alzohaili, MD, and Ricardo Gomez, MD.

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

  2. Research funding: Clinical Trial Registration Number: NCT01467882.

  3. Employment or leadership: JL, FC, NW, PK have nothing to declare. KK is a consultant for and serves on the speaker bureau for Abbvie Pharmaceuticals. JA serves on a speaker bureau for Abbvie, and Novo Nordisk. EL and DP are employees of Debiopharm International S.A.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played a role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


1. 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

2. Phillip M, Lazar I. Precocious puberty: growth and genetics. Horm Res 2005;64(Suppl 2):56–61.10.1159/000087760Search in Google Scholar

3. Antoniazzi F, Zamboni G. Central precocious puberty: current treatment options. Paediatr Drugs 2004;6:211–31.10.2165/00148581-200406040-00002Search in Google Scholar

4. Comite F, Cutler GB Jr, Rivier J, Vale WW, Loriaux DL, et al. Short-term treatment of idiopathic precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. A preliminary report. N Engl J Med 1981;305:1546–50.10.1016/S0022-5347(17)52860-8Search in Google Scholar

5. Kappy M, Stuart T, Perelman A, Clemons R. Suppression of gonadotropin secretion by a long-acting gonadotropin-releasing hormone analog (leuprolide acetate, Lupron Depot) in children with precocious puberty. J Clin Endocrinol Metab 1989;69:1087–9.10.1210/jcem-69-5-1087Search in Google Scholar PubMed

6. Brauner R, Rappaport R. Treatment of central precocious puberty with an LHRH analog. Effect on growth and bone maturation after 2 years of treatment. Arch Fr Pediatr 1987;44:271–6.Search in Google Scholar

7. Pescovitz OH, Barnes KM, Cutler GB Jr. Effect of deslorelin dose in the treatment of central precocious puberty. J Clin Endocrinol Metab 1991;72:60–4.10.1210/jcem-72-1-60Search in Google Scholar PubMed

8. Cisternino M, Arrigo T, Pasquino AM, Tinelli C, Antoniazzi F, et al. Etiology and age incidence of precocious puberty in girls: a multicentric study. J Pediatr Endocrinol Metab 2000; 13(Suppl 1):695–701.10.1515/JPEM.2000.13.S1.695Search in Google Scholar PubMed

9. Lahlou N, Carel JC, Chaussain JL, Roger M. Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in pediatrics. J Pediatr Endocrinol Metab 2000; 13(Suppl 1):723–37.10.1515/JPEM.2000.13.S1.723Search in Google Scholar PubMed

10. 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 PubMed

11. 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 PubMed

12. 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;92:3483–9.10.1210/jc.2007-0321Search in Google Scholar PubMed

13. Martinez-Aguayo A, Hernandez MI, Beaz F, Iniguez G, Avila A, et al. Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation. J Pediatr Endocrinol Metab 2006;19:963–70.10.1515/JPEM.2006.19.8.963Search in Google Scholar PubMed

14. Lundstrom E, Rencken RK, van Wyk JH, Coetzee LJ, Bahlmann JC, et al. Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: an open-label, non-comparative, multicentre, phase III study. Clin Drug Investig 2009;29:757–65.10.2165/11319690-000000000-00000Search in Google Scholar PubMed

15. Lee PA, Klein K, Mauras N, Neely EK, Bloch CA, et al. Efficacy and safety of leuprolide acetate 2-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

16. 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 PubMed

17. Tanner JM. Growth at adolescence. Oxford: Blackwell Scientific Publications, 1962.Search in Google Scholar

18. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. Stanford, California: Stanford University Press. Second edition, 1959.10.1097/00000441-195909000-00030Search in Google Scholar

19. Kuczmarski RJ, Ogden CL, Guo SS. 2000 CDC growth charts for the United States: Methods and development. National Center for Health Statistics. Vital Health Stat 2002;246:1–203.Search in Google Scholar

20. Roger M, Lahlou N, Chaussain JL. Gonadotropin-releasing hormone testing in paediatrics. In: Ranke MB, editor. Diagnostics of endocrine function in children and adolescents (2nd revised and expanded edition). Heidelberg – Leipzig: Johann Ambrosius Barth Verlag, 1997:1322–86.Search in Google Scholar

21. Ibanez L, Potau N, Zampolli M, Virdis R, Gussinye A, et al. Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: comparison with the gonadotropin-releasing hormone test. J Clin Endocrinol Metab 1994;78:30–5.10.1210/jc.78.1.30Search in Google Scholar

22. Houk CP, Kunselman AR, Lee PA. The diagnostic value of a brief GnRH analogue stimulation test in girls with central precocious puberty: a single 30-min post-stimulation LH sample is adequate. J Pediatr Endocrinol Metab 2008;21:1113–8.10.1515/JPEM.2008.21.12.1113Search in Google Scholar PubMed

23. Garibaldi LR, Aceto T Jr, Weber C, Pang S. The relationship between luteinizing hormone and estradiol secretion in female precocious puberty: evaluation by sensitive gonadotropin assays and the leuprolide stimulation test. J Clin Endocrinol Metab 1993;76:851–6.Search in Google Scholar

24. Bertelloni S, Cassio A, Arrigo T, Wasniewska M, Galluzzi F, et al. Central precocious puberty: short-term comparative data of treatment with monthly or long-acting three months depot triptorelin. J Pediatr Endocrinol Metab 2007;20:297–305.Search in Google Scholar

25. Sathasivam A, Garibaldi L, Shapiro S, Wang H, Rapaport R. Leuprolide stimulation testing for the evaluation of early female sexual maturation. Clin Endocrinol (Oxf) 2010;73:375–81.10.1111/j.1365-2265.2010.03796.xSearch in Google Scholar PubMed

26. Zec I, Kučak I, Begčević I, Simundić AM, Tišlarić-Medenjak D, et al. Reference intervals for reproductive hormones in prepubertal children on the automated Roche cobas e 411 analyzer. Clin Biochem 2012;45:1206–12.10.1016/j.clinbiochem.2012.05.019Search in Google Scholar PubMed

27. Lahlou N. An open-label, non-comparative, multicenter study on the efficacy, safety, and pharmacokinetics of triptorelin pamoate (embonate) 22.5 mg 6-month formulation in patients suffering from central (gonadotropin-dependent) precocious puberty. Determination of follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone concentrations in serum samples collected during the study. Debiopharm study Debio 8206-CPP-301. IREM study MarPol-1203, 2014.Search in Google Scholar

28. Kelly A, Winer KK, Kalkwarf H, Oberfield SE, Lappe J, et al. Age-based reference ranges for annual height velocity in US children. J Clin Endocrin Metab 2014;99:2104–12.10.1210/jc.2013-4455Search in Google Scholar PubMed PubMed Central

29. Jwa HJ, Yang SI, Lim HH. The difference in serum alkaline phosphatase levels between girls with precocious puberty and those with normal puberty. Ann Pediatr Endocrinol Metab 2013;18:191–5.10.6065/apem.2013.18.4.191Search in Google Scholar PubMed PubMed Central

Received: 2015-9-16
Accepted: 2015-12-14
Published Online: 2016-2-17
Published in Print: 2016-11-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 7.2.2023 from
Scroll Up Arrow