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

ACCESS DATA

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:BackgroundThis study aimed to explore the effects of triptorelin and leuprolide on serum hormone levels and the clinical efficacy of girls with idiopathic central precocious puberty (ICPP).MethodsRetrospective analysis was performed on 128 girls with ICPP who were diagnosed and treated in our hospital from January 2017 to January 2020, including 71 girls in the leuprolide group and 57 girls in the triptorelin group. The differences of serum sex hormone level, ovarian volume, uterine volume, follicle diameter, bone age, growth rate (height change within half a year), maturity (bone age/living age), and other aspects between the two groups of girls were compared.ResultsBefore treatment, there was no significant difference in the baseline levels of sex hormones [estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH)] between the triptorelin group and the leuprorelin group (P>0.05). After 1 year of treatment, serum levels of E2 and FSH in the triptorelin group were lower than those in the leuprolide group (P<0.05). There was no significant difference in LH levels between the two groups after 1 year of treatment (P>0.05). At baseline, there was no significant difference in the ovarian volume, follicle diameter, and uterine volume between the triptorelin group and the leuprolide group (P>0.05). After 1 year of treatment, the ovarian volume, follicle diameter, and uterine volume of the girls in the triptorelin group were all lower than those in the leuprolide group (P<0.05). Before treatment, there was no statistical difference in bone age, growth rate, and maturity between the triptorelin group and the leuprolide group (P>0.05). After 1 year of treatment, the growth rate and maturity of participants in the triptorelin group were lower than those in the leuprolide group (P<0.05). There was no significant difference in bone age between the two groups after 1 year of treatment (P>0.05).ConclusionsFor girls with ICPP, triptorelin is superior to leuprolide in reducing sex hormone level, reducing uterine volume, follicle diameter, ovarian volume, slowing down the growth rate, and decreasing maturity. Triptorelin should be selected as a priority for the treatment of girls with ICPP.

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.

Project description:BackgroundGenetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls.ResultsAnalysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin).ConclusionsThe different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.

Dataset Information

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

Introduction

Methods

Results

Conclusions

Trial registration

Publications

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

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