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Long-term outcomes after gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty.

ABSTRACT: Objective: Gonadotropin-releasing hormone agonist (GnRHa) treatment improves the potential for gaining height in patients with central precocious puberty (CPP). However, most studies have focused on girls because CPP in boys is relatively rare. Therefore, we aimed to determine the effect of GnRHa treatment on auxological outcomes in boys with CPP.

Methods: Eighty-five boys with CPP were treated with leuprolide or triptorelin acetate 3.75 mg over 2 years. Anthropometry, bone age, sexual maturity rating, and predicted adult height (PAH) were assessed every 6 months. Furthermore, 20 boys were followed up after treatment discontinuation until achievement of the final adult height (FAH).

Results: The mean chronological age (CA) and bone age (BA) of the patients with CPP at treatment initiation were 9.5 ± 0.5 years and 11.7 ± 0.9 years, respectively. The mean duration of treatment was 2.87 ± 0.63 years. The PAH at treatment initiation was 172.1 cm (-0.23 ± 1.05 PAH standard deviation score). The PAH at treatment discontinuation (176.2 ± 6.6 cm) was significantly higher than the pretreatment PAH. In addition, the mean final adult height in the 20 boys who were followed up after discontinuation of treatment was 173.4 ± 5.8 cm, which was significantly higher than the initial PAH (170.1 ± 4.5 cm; p = 0.006). In multivariate analysis, the height gain (the difference between the FAH and PAH at treatment initiation) significantly correlated with the target height.

Conclusion: Long-term GnRHa treatment significantly improved the growth potential and FAH in boys with CPP.

SUBMITTER: Shim YS

PROVIDER: S-EPMC7728242 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long-term outcomes after gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty.

Shim Young Suk YS Lim Kyung In KI Lee Hae Sang HS Hwang Jin Soon JS

PloS one 20201210 12

<h4>Objective</h4>Gonadotropin-releasing hormone agonist (GnRHa) treatment improves the potential for gaining height in patients with central precocious puberty (CPP). However, most studies have focused on girls because CPP in boys is relatively rare. Therefore, we aimed to determine the effect of GnRHa treatment on auxological outcomes in boys with CPP.<h4>Methods</h4>Eighty-five boys with CPP were treated with leuprolide or triptorelin acetate 3.75 mg over 2 years. Anthropometry, bone age, sex ...[more]

PMID: 33301485

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Project description:Background Traditional Chinese medicine (TCM) believes that central precocious puberty (CPP) is affected by the imbalance of kidney Yin and Yang. Dabuyin pill is a recipe for nourishing Yin and lowering fire. The network pharmacology method was used to analyze the active components, action targets, and molecular pathways of Dabuyin pill in the treatment of CPP. Methods The main chemical components of Dabuyin pill were obtained from the Integrative database of Traditional Chinese Medicine enhanced by Symptom Mapping (SymMap) database and Traditional Chinese Medicine Systems Pharmacology (TCMSP), and compound targets were retrieved from SymMap and the Encyclopedia of Traditional Chinese Medicine (ETCM). Disease targets were retrieved from the DisGeNET and Gene Expression Omnibus (GEO) databases, and the intersection of compound targets and disease targets was performed to obtain the prediction targets of Dabuyin pill acting on CPP. The key targets enriched by Database for Annotation, Visualization, and Integrated Discovery (DAVID) were then used for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results GO analysis showed that the biological functions of Dabuyin pill in the treatment of key targets of CPP mainly involved apoptosis, nitric oxide synthesis, estradiol response, angiogenesis, inflammation, and so on. KEGG pathway analysis was mainly enriched in the tumor necrosis factor (TNF) signaling pathway, phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, and apoptosis. Among them, the regulation effect of Dabuyin pill prescription on apoptosis may both act on TP53 and different signaling pathways of apoptosis, thus playing a synergistic role. Conclusions Dabuyin pill combined with GnRHa for the prevention and treatment of CPP in girls can effectively intervene CPP, and the effect of Dabuyin pill on sex hormones is one of its protective mechanisms against CPP.

Project description:BackgroundIdiopathic central precocious puberty (ICPP) is supposed to be non-existent in a context of testicular destruction that is typically present in Klinefelter syndrome (KS). Herein, we describe a rare case of ICPP in a Klinefelter patient (47,XXY) with 2 maternal X chromosomes. Moreover, we highlight the differences in gonadotropin levels in comparison to males with ICPP and a normal karyotype.Case presentationAn 8 years old boy with a history of cryptorchidism was evaluated for precocious puberty (Tanner staging: P2/G3). Both testes measured 25x35mm. His hormonal profile confirmed a central origin of precocious puberty with high serum testosterone (4.3 ng/ml), luteinizing hormone [LH (3.5 UI/l)] and follicle stimulating hormone [FSH (7.7 UI/l)] levels. Luteinizing hormone-releasing hormone (LHRH) test amplified LH and FSH secretion to 24 and 14 UI/l respectively. Brain magnetic resonance imaging (MRI) was normal. No MKRN3 mutation was detected. He was treated for ICPP for two years. During puberty, he suffered from hypergonadotropic hypogonadism leading to the diagnosis of KS (47,XXY karyotype). Chromosomal analysis by fluorescent multiplex polymerase chain reaction (PCR) using X chromosome microsatellite markers identified 2 maternal X chromosomes. Analysing 8 cases of KS developing ICPP (our reported case and 7 other published cases) revealed that these KS patients with ICPP have higher LH and FSH levels during ICPP episode than in ICPP patients with a normal karyotype (ICPP with KS vs ICPP with a normal karyotype: LH levels 9.4 ± 12 vs 1.1 ± 0.6 UI/l; FSH levels 23.1 ± 38.5 vs 2.7 ± 1.5 UI/l). Furthermore, their response to gonadotropin-releasing hormone (GnRH) stimulation is characterized by excessive LH and FSH secretion (LH levels post-GnRH: 58 ± 48 vs 15.5 ± 0.8 UI/l; FSH levels post-GnRH: 49.1 ± 62.1 vs 5.7 ± 3.9 UI/l).ConclusionsICPP in boys is extremely rare. The pathophysiology of ICPP in KS is unknown. However, maternal X supplementary chromosome and early testicular destruction may play a significant role in the initiation of ICPP, in part explaining the relative "overrepresentation of ICPP in KS. Thus, karyotype analysis could be considered for boys suffering from ICPP, especially if testicular size is smaller or gonadotropins are significantly elevated.

Project description:BackgroundThe main objective of the present work was to compare the effects of the gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant) on the gene expression profiles of oocytes obtained from Iranian infertile couples undergoing in vitro fertilization (IVF).MethodsFifty infertile couples who underwent IVF between June 2012 and November 2013 at the Infertility Center of Tehran Women General Hospital, Tehran University of Medical Sciences, were included in this study. We included women that had undergone IVF treatment because of male factor, tubal factor, or unexplained infertility. The women randomly underwent controlled ovarian stimulation (COS) with either the GnRH-a (n = 26) or the GnRH-ant (n = 24). We obtained 50 germinal vesicle (GV) oocytes donated by women in each group. After the sampling, pool of 50 GV oocytes for each group was separately analyzed by quantitative polymerase chain reaction (qPCR).ResultThe expression levels of Adenosine triphosphatase 6 (ATPase 6), Bone morphogenetic protein 15 (BMP15), and Neuronal apoptosis inhibitory protein (NAIP) genes were significantly upregulated in the GnRH-ant group compared to the GnRH-a group, with the fold change of 3.990 (SD ± 1.325), 6.274 (SD ± 1.542), and 2.156 (SD ± 1.443), respectively, (P < 0.001). Growth differentiation factor 9 (GDF9) mRNA did not have any expression in the GnRH-a group; however, GDF9 mRNA was expressed in the GnRH-ant group. Finally, it was found that the genes involved in the DNA repairing and cell cycle checkpoint did not have any expression in either group.ConclusionThe present study showed, for the first time, the expression levels of genes involved in the cytoplasmic maturity (BMP15, GDF9), adenosine triphosphate production (ATPase 6), and antiapoptotic process (NAIP), in human GV oocytes were significantly higher in the GnRH-anta group than in the GnRH-a group in COS. Higher expression level of these genes when GnRH-ant protocol is applied, this protocol seems to be a more appropriate choice for women with poly cystic ovarian syndrome, because it can probably improve the expression of the aforementioned genes.Trial registrationCurrent Controlled Trials: IRCT 2014031112307 N3.

Dataset Information

Long-term outcomes after gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty.

Publications

Long-term outcomes after gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty.

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