Dataset Information

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

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.

SUBMITTER: Lee PA

PROVIDER: S-EPMC3159140 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

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

Lee Peter A PA Neely E Kirk EK Fuqua John J Yang Di D Larsen Lois M LM Mattia-Goldberg Cynthia C Chwalisz Kristof K

International journal of pediatric endocrinology 20110712 1

<h4>Introduction</h4>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.<h4>Methods</h4>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 me ...[more]

PMID: 21860633

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Project description:BackgroundRecent studies demonstrated that changes in DNA methylation (DNAm) and inactivation of two imprinted genes (MKRN3 and DLK1) alter the onset of female puberty. We aimed to investigate the association of DNAm profiling with the timing of human puberty analyzing the genome-wide DNAm patterns of peripheral blood leukocytes from ten female patients with central precocious puberty (CPP) and 33 healthy girls (15 pre- and 18 post-pubertal). For this purpose, we performed comparisons between the groups: pre- versus post-pubertal, CPP versus pre-pubertal, and CPP versus post-pubertal.ResultsAnalyzing the methylome changes associated with normal puberty, we identified 120 differentially methylated regions (DMRs) when comparing pre- and post-pubertal healthy girls. Most of these DMRs were hypermethylated in the pubertal group (99%) and located on the X chromosome (74%). Only one genomic region, containing the promoter of ZFP57, was hypomethylated in the pubertal group. ZFP57 is a transcriptional repressor required for both methylation and imprinting of multiple genomic loci. ZFP57 expression in the hypothalamus of female rhesus monkeys increased during peripubertal development, suggesting enhanced repression of downstream ZFP57 target genes. Fourteen other zinc finger (ZNF) genes were related to the hypermethylated DMRs at normal puberty. Analyzing the methylome changes associated with CPP, we demonstrated that the patients with CPP exhibited more hypermethylated CpG sites compared to both pre-pubertal (81%) and pubertal (89%) controls. Forty-eight ZNF genes were identified as having hypermethylated CpG sites in CPP.ConclusionMethylome profiling of girls at normal and precocious puberty revealed a widespread pattern of DNA hypermethylation, indicating that the pubertal process in humans is associated with specific changes in epigenetically driven regulatory control. Moreover, changes in methylation of several ZNF genes appear to be a distinct epigenetic modification underlying the initiation of human puberty.

Dataset Information

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

Publications

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

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