Background: Gonadotropin-releasing hormone agonists (GnRHa) represent the gold-standard treatment for central precocious puberty (CPP). In CPP children, GnRHa treatment slows bone age progression and preserves adult height (Ht) by suppressing sexual steroid secretion. In some patients, however, GnRHa induce an inappropriate growth deceleration impairing Ht outcome. Furthermore, slowly progressive CPP (spCPP) forms were reported which do not need GnRHa treatment. Methods: We evaluated the growth outcome of 26 spCPP girls treated with triptorelin (TR) and 21 with leuprorelin acetate (LA) for 36.5 ± 0.7 months. Results: GnRHa treatment induced a progressive growth deceleration in both spCPP groups. No difference in bone maturation was detected (p > 0.05; TR vs. LA group), however compared to LA, TR treatment resulted in significantly higher Ht after 24 months (p < 0.05; LA vs. TR group). Although target height (TH) standard deviation score (SDS) and predicted adult height (PAH)-SDS at diagnosis were similar in both spCPP groups (p > 0.05; LA vs. TR group), final height (FH-SDS) was lower in LA-treated subjects (p < 0.05; LA vs. TR group). In both spCPP groups, FH-SDS was significantly lower than TH-SDS (p < 0.001) but not lower than PAH-SDS at diagnosis (p > 0.05). Ht-SDS correlated with 17β-estradiol (E2) blood levels in both spCPP groups (p < 0.0001) throughout GnRHa treatment, and E2 values were higher in the TR- than in the LA-treated patients during the 12 months after GnRHa administration (p < 0.05; LA vs. TR group). GnRHa-induced E2 secretion and Ht-SDS at GnRHa withdrawal correlated positively with FH (p < 0.01 and p < 0.001, respectively). Conclusions: The effectiveness of GnRHa treatment in improving FH in spCPP girls was doubtful.

Keywords:
Central precocious puberty, Growth outcome, Final height, Gonadotropin-releasing hormone agonists, Leuprorelin acetate, Slowly progressive central precocious puberty, Triptorelin
1.
Lebrethon MC, Bourguignon JP: Management of central isosexual precocity: diagnosis, treatment, outcome. Curr Opin Pediatr 2000;12:394–399.
2.
Partsch CJ, Sippell WG: Treatment of central precocious puberty. Best Pract Res Clin Endocrinol Metab 2002;16:165–189.
3.
Fontoura M, Brauner R, Prevot C, Rappaport R: Precocious puberty in girls: early diagnosis of a slowly progressing variant. Arch Dis Child 1989;64:1170–1176.
4.
Kreiter M, Burstein S, Rosenfield RL, Moll GW Jr, Cara JF, Yousefzadeh DK, Cuttler L, Levitsky LL: Preserving adult height potential in girls with idiopathic true precocious puberty. J Pediatr 1990;117:364–370.
5.
Bassi F, Bartolini O, Neri AS, Gheri RG, Bucciantini S, Cheli D, Bruni V: Precocious puberty: auxological criteria discriminating different forms. J Endocrinol Invest 1994;17:793–797.
6.
Leger J, Reynaud R, Czernichow P: Do all girls with apparent idiopathic precocious puberty require gonadotropin-releasing hormone agonist treatment? J Pediatr 2000;137:819–825.
7.
Palmert MR, Malin HV, Boepple PA: Unsustained or slowly progressive puberty in young girls: initial presentation and long-term follow-up of 20 untreated patients. J Clin Endocrinol Metab 1999;84:415–423.
8.
Brauner R, Adan L, Malandry F, Zantleifer D: Adult height in girls with idiopathic true precocious puberty. J Clin Endocrinol Metab 1994;79:415–420.
9.
Ghirri P, Bottone U, Gasperi M, Bernardini M, Coccoli L, Giovanelli R, Boldrini A: Final height in girls with slowly progressive untreated central precocious puberty. Gynecol Endocrinol 1997;11:301–305.
10.
Adan L, Chemaitilly W, Trivin C, Brauner R: Factors predicting adult height in girls with idiopathic central precocious puberty: implications for treatment. Clin Endocrinol 2002;56:297–302.
11.
Lazar L, Pertzelan A, Weintrob N, Phillip M, Kauli R: Sexual precocity in boys: accelerated versus slowly progressive puberty gonadotropin-suppressive therapy and final height. J Clin Endocrinol Metab 2001;86:4127–4132.
12.
Lahlou N, Carel JC, Chaussain JL, Roger M: Pharmacokinetics and pharmacodynamics of GnRH agonists: clinical implications in pediatrics. J Pediatr Endocrinol Metab 2000;13:S723–S737.
13.
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. J Clin Endocrinol Metab 1999;84:1973–1978.
14.
Kauli R, Galatzer A, Kornreich L, Lazar L, Pertzelan A, Laron Z: Final height of girls with central precocious puberty, untreated versus treated with cyproterone acetate or GnRH analogue. A comparative study with re-evaluation of predictions by the Bayley-Pinneau method. Horm Res 1997;47:54–61.
15.
Oerter KE, Manasco PK, Barnes KM, Jones J, Hill S, Cutler GB Jr: Effects of luteinizing hormone-releasing hormone agonists on final height in luteinizing hormone-releasing hormone-dependent precocious puberty. Acta Paediatr Suppl 1993;388:62–69.
16.
Pasquino AM, Municchi G, Pucarelli I, Segni M, Mancini MA, Troiani S: Combined treatment with gonadotropin-releasing hormone analog and growth hormone in central precocious puberty. J Clin Endocrinol Metab 1996;81:948–951.
17.
Cheung TK, Lo KW, Lam CW, Lau W, Lam PK: A crossover study of triptorelin and leuprorelin acetate. Fertil Steril 2000;74:299–305.
18.
Matteo M, Caroppo E, Gliozheni O, Carone D, Schonauer LM, Vizziello G, Greco P, D’Amato G: Pituitary desensitization for eight weeks after the administration of two distinct gonadotrophin-releasing hormone agonists. Eur J Obstet Gynecol Reprod Biol 2006;126:77–80.
19.
Lanes R, Soros A, Jakubowicz S: Accelerated versus slowly progressive forms of puberty in girls with precocious and early puberty. Gonadotropin-suppressive effect and final height obtained with two different analogs. J Pediatr Endocrinol Metab 2004;17:759–766.
20.
Massart F, Harrell JC, Federico G, Saggese G: Thyroid outcome during long-term gonadotropin-releasing hormone agonist treatments for idiopathic precocious puberty. J Adolesc Health 2007;40:252–257.
21.
Massart F, Parrino R, Placidi G, Massai G, Federico G, Saggese G: Prolactin secretion before, during, and after chronic gonadotropin-releasing hormone agonist treatments in children. Fertil Steril 2005;84:719–724.
22.
Iughetti L, Predieri B, Ferrari M, Gallo C, Livio L, Milioli S, Forese S, Bernasconi S: Diagnosis of central precocious puberty: endocrine assessment. J Pediatr Endocrinol Metab 2000;13:709–715.
23.
Tanner JM, Goldstein H, Whitehouse RH: Standards for children’s height at ages 2–9 years allowing for heights of parents. Arch Dis Child 1970;45:755–762.
24.
Arrigo T, Cisternino M, Galluzzi F, Bertelloni S, Pasquino AM, Antoniazzi F, Borrelli P, Crisafulli G, Wasniewska M, De Luca F: Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty. Eur J Endocrinol 1999;141:140–144.
25.
Micillo M, Salerno M, Officioso A, Perna E, Gasparini N, Pisaturo L, Di Maio S: Near final height after GnRH agonist treatment in central precocious puberty. J Pediatr Endocrinol Metab 2000;13(suppl 1):S787–S790.
26.
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):S747–S758.
27.
Arrigo T, De Luca F, Antoniazzi F, Galluzzi F, Segni M, Rosano M, Messina MF, Lombardo F: Reduction of baseline body mass index under gonadotropin-suppressive therapy in girls with idiopathic precocious puberty. Eur J Endocrinol 2004;150:533–537.
28.
Lazar L, Kauli R, Pertzelan A, Phillip M: Gonadotropin-suppressive therapy in girls with early and fast puberty affects the pace of puberty but not total pubertal growth or final height. J Clin Endocrinol Metab 2002;87:2090–2094.
29.
Partsch CJ, Sippell WG: Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens. Hum Reprod Update 2001;7:292–302.
30.
Filicori M, Flamigni C, Cognigni G, Dellai P, Arnone R, Falbo A, Capelli M: Comparison of the suppressive capacity of different depot gonadotropin-releasing hormone analogs in women. J Clin Endocrinol Metab 1993;77:130–133.
31.
Cutler GB Jr: The role of estrogen in bone growth and maturation during childhood and adolescence. J Steroid Biochem Mol Biol 1997;61:141–144.
32.
Caruso-Nicoletti M, Cassorla F, Skerda M, Ross JL, Loriaux DL, Cutler GB Jr: Short-term, low-dose estradiol accelerates ulnar growth in boys. J Clin Endocrinol Metab 1985;61:896–898.
33.
Klein KO, Baron J, Colli MJ, McDonnell DP, Cutler GB Jr: Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay. J Clin Invest 1994;94:2475–2480.
34.
Lampit M, Golander A, Guttmann H, Hochberg Z: Estrogen mini-dose replacement during GnRH agonist therapy in central precocious puberty: a pilot study. J Clin Endocrinol Metab 2002;87:687–690.
35.
Bhatia S, Neely EK, Wilson DM: Serum luteinizing hormone rises within minutes after depot leuprolide injection: implications for monitoring therapy. Pediatrics 2002;109:E30.
36.
Wilson DM: Regular monitoring of bone age is not useful in children treated with growth hormone. Pediatrics 1999;104:1036–1039.
37.
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.
38.
Klein KO, Baron J, Barnes KM, Pescovitz OH, Cutler GB Jr: Use of an ultrasensitive recombinant cell bioassay to determine estrogen levels in girls with precocious puberty treated with a luteinizing hormone-releasing hormone agonist. J Clin Endocrinol Metab 1998;83:2387–2389.
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.