Comparison of Detection of Normal Puberty in Girls by a Hormonal Sleep Test and a Gonadotropin-Releasing Hormone Agonist Test

Abstract

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.

Pubertal Onset in Girls is Strongly Influenced by Genetic Variation Affecting FSH Action

“…FSH is essential for female reproductive maturation28, and our findings are therefore supported by a plausible biological mechanism. Female FSHB and FSHR knock-out mice and women with loss-of-function mutations in these specific genes present with primary amenorrhea and sterility due to disrupted follicle maturation29303132.…”

High-Sensitivity Micro LC-MS/MS Assay for Serum Estradiol without Derivatization

“…In consultation with our endocrinologists, we determined that both assays are analytically and clinically equivalent, and the existing reference intervals established by the classic RIA method developed in our institution and published by our endocrinologists in the literature (34)(35)(36)(37)(38) are transferrable to the LC-MS/MS assay. The bias of this assay at the LOQ level was also not assessed, since there are currently no low E 2 reference materials available, and bias study by spiking standards and serially diluting up to 200-fold could result in large variation at the low end.…”

The Effect of the Testis on the Ovary: Structure-Function Relationships in a Neonate with a Unilateral Ovotestis (Ovotesticular Disorder of Sex Development)

“…Girls’ gonadal function is relatively less robust than that of boys: whereas boys’ serum testosterone levels rise into the midpubertal-adult range during months 2–3 of life [23], girls’ serum estradiol levels hover around the early pubertal range [24, 25]. The meager available data suggest that during early infancy, girls’ hormonal responses to GnRHag are comparable to those of pubertal girls [26, 27] and thus may be better than baseline levels in distinguishing prepubertal from pubertal pituitary-gonadal function, which is intermediate between prepubertal and adult function [9, 11, 28, 29]. By 6 months of age, boys’ testosterone typically falls to levels compatible with adrenal fetal zone origin [30], but in girls, pubertal hormone values may persist for 2–3 years [7, 24].…”

“…Chromosomal analysis was done by analyzing 50 metaphase cells from each different tissue sample, using florescence in situ hybridization (FISH) to distinguish sex chromosomes using probes specific for SRY on the short arm of the Y chromosome and a probe for the chromosome X centromere (Abbott Molecular, Des Plaines, IL, USA). Leuprolide acetate (GnRHag) 10 μg/kg was administered subcutaneously after obtaining a baseline blood sample: sampling was performed to respectively test gonadotropin (4 h) and gonadal steroid (21 h) peak responses [8, 9]. Dexamethasone 1.0 mg/m 2 daily was co-administered during two of the GnRHag tests to blunt coincidental adrenal contributions to 17OHP and sex steroid levels [11].…”

“…Plasma testosterone remained high (113 ng/dL) after dexamethasone suppression of adrenal function that lowered DHEAS to <15 and cortisol to <0.3 μg/dL. Gonadotropin-releasing hormone agonist (GnRHag) testing on DOL 12 revealed adult male range serum luteinizing and follicle-stimulating hormone (LH, FSH), and testosterone before and after stimulation, yet prepubertal estradiol baseline and response levels (Table 1) [8, 9]. Serum AMH was 28 ng/mL, which is very elevated for a female and approximates the lower end of the normal male range for age [10].…”