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Comparison of detection of normal puberty in girls by a hormonal sleep test and a gonadotropin-releasing hormone agonist test.

ABSTRACT: The magnitude of sleep-related gonadotropin rise required to activate pubertal feminization is not established.The objective of the study was to determine the normal relationship of pubertal hormone responses to sleep and to GnRH agonist (GnRHag) challenge across the female pubertal transition.This was a prospective study in a General Clinical Research Center.Sixty-two healthy 6- to 13-year-old volunteer girls participated in the study.Interventions included overnight blood sampling followed by GnRHag (leuprolide acetate) injection.The primary outcome variables included LH, FSH, and estradiol.LH levels rose steadily during sleep and after GnRHag throughout the prepubertal years. The LH response to sleep and GnRHag correlated well across groups (eg, r = 0.807, peak vs 4 h post-GnRHag value); however, this correlation was less robust than in boys (r = 0.964, P < .01). Sleep peak LH of 1.3 U/L or greater had 85% sensitivity and 2.1 U/L or greater 96% specificity for detecting puberty (thelarche). The LH 1-hour post-GnRHag value of 3.2 U/L or greater had 95% sensitivity and 5.5 U/L or greater 96% specificity for detecting puberty. Girls entered puberty at lower LH levels than boys. FSH levels rose day and night during the prepubertal years to reach 1.0 U/L or greater during puberty but discriminated puberty poorly. Estradiol of 34 pg/mL or greater at 20-24 hours after GnRHag was 95% sensitive and 60 pg/mL or greater was 95% specific for puberty. Thirty-six percent of overweight early pubertal girls had meager hormonal evidence of puberty.These data suggest that sleep-related pubertal hormone levels critical for puberty are normally reflected in the responses to GnRHag testing across the normal female pubertal transition. Inconsistencies between clinical and hormonal staging may arise from peripubertal cyclicity of neuroendocrine function and from excess adiposity.

SUBMITTER: Rosenfield RL

PROVIDER: S-EPMC3615202 | biostudies-other | 2013 Apr

REPOSITORIES: biostudies-other

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Comparison of detection of normal puberty in girls by a hormonal sleep test and a gonadotropin-releasing hormone agonist test.

Rosenfield Robert L RL Bordini Brian B Yu Christine C

The Journal of clinical endocrinology and metabolism 20130301 4

<h4>Context</h4>The magnitude of sleep-related gonadotropin rise required to activate pubertal feminization is not established.<h4>Objective</h4>The objective of the study was to determine the normal relationship of pubertal hormone responses to sleep and to GnRH agonist (GnRHag) challenge across the female pubertal transition.<h4>Design/setting</h4>This was a prospective study in a General Clinical Research Center.<h4>Participants</h4>Sixty-two healthy 6- to 13-year-old volunteer girls particip ...[more]

PMID: 23457407

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Project description:To assess whether add-back therapy with norethindrone acetate or norethindrone acetate plus conjugated equine estrogens is superior to maintain bone health in adolescents and young women using gonadotropin-releasing hormone agonists for endometriosis. Gonadotropin-releasing hormone agonists are associated with deleterious effects on bone. Hormonal add-back may mitigate these effects.Adolescents and young women (n=51) received a random, double-blind assignment to add-back with norethindrone acetate (5 mg/day) plus conjugated equine estrogens (0.625 mg/day) or norethindrone acetate plus placebo for 12 months. Body composition, bone mineral content, and bone mineral density (BMD) were obtained by dual-energy X-ray absorptiometry every 6 months. Quality-of-life measures were collected every 3 months. Intention-to-treat comparison of outcomes was conducted by repeated-measures analysis of variance.Thirty-four adolescents and young women completed the trial; dropouts did not differ from those who completed the trial. Bone mineral density was normal at baseline. At 12 months, total body bone mineral content and BMD had increased in the norethindrone acetate plus conjugated equine estrogens group (bone mineral content +37 g, P<.001 and BMD +0.012 g/cm, P=.05), but not in those receiving norethindrone acetate plus placebo (bone mineral content P=.19 and BMD P=.95). Lean mass increased only in those receiving conjugated equine estrogens (+1.4 kg, P=.001). Improvements in physical functioning domains of quality-of-life assessments were greater with norethindrone acetate plus conjugated equine estrogens (P=.005). No differences were seen at the hip or lumbar spine by dual-energy X-ray absorptiometry. No significant adverse events occurred.Hormonal add-back successfully preserved bone health and improved quality of life for adolescents and young women with endometriosis during 12 months of gonadotropin-releasing hormone agonist therapy. Combination norethindrone acetate plus conjugated equine estrogens add-back appears to be more effective for increasing total body bone mineral content, areal BMD, and lean mass than norethindrone acetate monotherapy.ClinicalTrials.gov; www.clinicaltrials.gov, NCT00474851.I.

Project description:BACKGROUND:The 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). METHODS:Fifty 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). RESULT:The 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. CONCLUSION:The 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 REGISTRATION:Current Controlled Trials: IRCT 2014031112307 N3.

Dataset Information

Comparison of detection of normal puberty in girls by a hormonal sleep test and a gonadotropin-releasing hormone agonist test.

Publications

Comparison of detection of normal puberty in girls by a hormonal sleep test and a gonadotropin-releasing hormone agonist test.

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