Efficacy of Leuprolide Acetate 1-Month Depot for Central Precocious Puberty (CPP): Growth Outcomes During a Prospective, Longitudinal Study

Peter A Lee, E Kirk Neely, John Fuqua, Di Yang, Lois M Larsen, Cynthia Mattia-Goldberg, Kristof Chwalisz, Peter A Lee, E Kirk Neely, John Fuqua, Di Yang, Lois M Larsen, Cynthia Mattia-Goldberg, Kristof Chwalisz

Abstract

Introduction: Gonadotropin-releasing hormone analogs (GnRHa) are the treatment of choice for CPP. We investigated growth in GnRHa-naïve subjects, treated with leuprolide acetate 1-month depot for CPP.

Methods: This prospective, open-label study had a long-term, observational, follow-up period. Forty-nine females and 6 males were enrolled. Leuprolide acetate depot was administered intramuscularly every 28 days. Height and growth rate during and after treatment until adulthood were measured.

Results: Among 30 of 49 females having an adult height (AH) measurement, 29 had target heights available (mean = 163.8 cm) and 27 had pretreatment predicted adult heights (PAHs; mean = 157.4 cm). After treatment, the mean AH at mean age 21.8 years [range 13.7-26.7 years] was 162.5 cm, a mean height gain over baseline PAH of 4.0 cm. The mean height standard deviation score was -0.1 at AH.

Conclusions: Treatment of CPP with leuprolide acetate 1-month depot had beneficial effects on growth rate and preservation of AH.

Trial registration: ClinicalTrials.gov: NCT00660010.

Figures

Figure 1
Figure 1
Patient disposition. Flow of female patients through the trial. Patients may have had more than one reason for treatment discontinuation.
Figure 2
Figure 2
Mean ± SE growth rates for females. Incremental growth rates were calculated every 6 months. The baseline growth rate was defined as the growth rate for 1 year prior to the start of study drug. Numbers reflect available results.
Figure 3
Figure 3
Change in bone age to change in chronological age during each year of treatment for females. The ratio of the change in BA from the previous visit to the change in CA from the previous visit was calculated at approximately one year intervals. Numbers reflect available results.
Figure 4
Figure 4
Height outcomes for females during the study. Adult height includes data from patients whose height was collected at adulthood after age 18. For patients who were missing adulthood height data, adult height was established when their growth velocity was <1 cm/year or bone age was ≥14 years during the follow-up period.
Figure 5
Figure 5
Height standardized scores for females during the study. The pretreatment baseline is the mean standardized height score of patients before initiation of leuprolide acetate therapy. The height at the end of treatment refers to the mean standardized height score for patients at the end of the treatment period. Adult height includes standardized scores for those patients whose height was collected at adulthood after age 18. For those without adult height available, adult height was established when their growth velocity was <1 cm/year or bone age was ≥14 years during the follow-up period.

References

    1. Brauner R. Central precocious puberty in girls: prediction of the aetiology. J Pediatr Endocrinol Metab. 2005;18(9):845–7. doi: 10.1515/JPEM.2005.18.9.845.
    1. Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR, Antoniazzi F. et al.Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009;123(4):e752–62. doi: 10.1542/peds.2008-1783.
    1. Parker KL, Lee PA. Depot leuprolide acetate for treatment of precocious puberty. The Journal of clinical endocrinology and metabolism. 1989;69(3):689–91. doi: 10.1210/jcem-69-3-689.
    1. Arrigo T, Cisternino M, Galluzzi F, Bertelloni S, Pasquino AM, Antoniazzi F. et al.Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty. European journal of endocrinology/European Federation of Endocrine Societies. 1999;141(2):140–4.
    1. Brauner R, Adan L, Malandry F, Zantleifer D. Adult height in girls with idiopathic true precocious puberty. The Journal of clinical endocrinology and metabolism. 1994;79(2):415–20. doi: 10.1210/jc.79.2.415.
    1. Carel JC, Roger M, Ispas S, Tondu F, Lahlou N, Blumberg J. 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. The Journal of clinical endocrinology and metabolism. 1999;84(6):1973–8. doi: 10.1210/jc.84.6.1973.
    1. 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. Hormone research. 1997;47(2):54–61. doi: 10.1159/000185432.
    1. Kaye D, Frankl W, Arditi LI. Probable postcardiotomy syndrome following implantation of a transvenous pacemaker: report of the first case. American heart journal. 1975;90(5):627–30. doi: 10.1016/0002-8703(75)90227-6.
    1. Kreiter M, Burstein S, Rosenfield RL, Moll GW Jr, Cara JF, Yousefzadeh DK. et al.Preserving adult height potential in girls with idiopathic true precocious puberty. The Journal of pediatrics. 1990;117(3):364–70. doi: 10.1016/S0022-3476(05)81074-1.
    1. 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(5):759–66. doi: 10.1515/JPEM.2004.17.5.759.
    1. Leger J, Reynaud R, Czernichow P. Do all girls with apparent idiopathic precocious puberty require gonadotropin-releasing hormone agonist treatment? The Journal of pediatrics. 2000;137(6):819–25. doi: 10.1067/mpd.2000.109201.
    1. Mul D, Oostdijk W, Otten BJ, Rouwe C, Jansen M, Delemarre-van de Waal HA. 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.
    1. 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. The Journal of clinical endocrinology and metabolism. 1999;84(2):449–52. doi: 10.1210/jc.84.2.449.
    1. 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. American journal of diseases of children (1960) 1993;147(6):653–7.
    1. Neely EK, Hintz RL, Parker B, Bachrach LK, Cohen P, Olney R. et al.Two-year results of treatment with depot leuprolide acetate for central precocious puberty. The Journal of pediatrics. 1992;121(4):634–40. doi: 10.1016/S0022-3476(05)81162-X.
    1. Tanaka T, Niimi H, Matsuo N, Fujieda K, Tachibana K, Ohyama 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. The Journal of clinical endocrinology and metabolism. 2005;90(3):1371–6.
    1. Neely EK, Lee PA, Bloch CA, Larsen L, Yang D, Mattia-Goldberg C. et al.Leuprolide acetate 1-month depot for central precocious puberty: hormonal suppression and recovery. Int J Pediatr Endocrinol. 2010;2010:398639.
    1. Roche AF, Chumlea WC, Thissen D. Assessing the skeletal maturity of the hand wrist: FELS method. Springfield, IL: Charles C. Thomas; 1988.
    1. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. The Journal of pediatrics. 1952;40(4):423–41. doi: 10.1016/S0022-3476(52)80205-7.
    1. Brito VN, Latronico AC, Cukier P, Teles MG, Silveira LF, Arnhold IJ. et al.Factors determining normal adult height in girls with gonadotropin-dependent precocious puberty treated with depot gonadotropin-releasing hormone analogs. The Journal of clinical endocrinology and metabolism. 2008;93(7):2662–9. doi: 10.1210/jc.2007-2183.
    1. Badaru A, Wilson DM, Bachrach LK, Fechner P, Gandrud LM, Durham E. et al.Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty. The Journal of clinical endocrinology and metabolism. 2006;91(5):1862–7. doi: 10.1210/jc.2005-1500.
    1. Carel JC, Lahlou N, Jaramillo O, Montauban V, Teinturier C, Colle M. et al.Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg) The Journal of clinical endocrinology and metabolism. 2002;87(9):4111–6. doi: 10.1210/jc.2001-020243.
    1. Eugster EA, Clarke W, Kletter GB, Lee PA, Neely EK, Reiter EO. et al.Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial. The Journal of clinical endocrinology and metabolism. 2007;92(5):1697–704. doi: 10.1210/jc.2006-2479.
    1. 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. The Journal of clinical endocrinology and metabolism. 2008;93(1):190–5.
    1. Lazar L, Padoa A, Phillip M. Growth pattern and final height after cessation of gonadotropin-suppressive therapy in girls with central sexual precocity. The Journal of clinical endocrinology and metabolism. 2007;92(9):3483–9. doi: 10.1210/jc.2007-0321.
    1. Magiakou MA, Manousaki D, Papadaki M, Hadjidakis D, Levidou G, Vakaki M. et al.The efficacy and safety of gonadotropin-releasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study. The Journal of clinical endocrinology and metabolism. 2010;95(1):109–17. doi: 10.1210/jc.2009-0793.
    1. 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. The Journal of pediatrics. 1995;126(6):955–8. doi: 10.1016/S0022-3476(95)70221-0.

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