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Hormonal responses to GnRH agonist indicative of puberty in girls
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Pubertal hormone responses to a gonadotropin-releasing hormone agonist accurately represent sleep-related increases in gonadotropin levels associated with puberty in girls, according to new data.
Research suggests a link between greater nocturnal gonadotropin increases in pubertal vs. prepubertal girls, but the scale of the increase necessary to adequately activate ovarian function to initiate feminization has not been studied, researchers wrote in the Journal of Clinical Endocrinology & Metabolism.
“The hormonal responses to [gonadotropin-releasing hormone] and a [gonadotropin-releasing hormone agonist] challenge are known to increase with pubertal maturation,” they wrote. “It seems likely that the degree of responsiveness of the pituitary-ovarian axis to the [gonadotropin-releasing hormone agonist challenge] reflects the degree of antecedent activation of the neuroendocrine axis.”
To further investigate this concept, the researchers evaluated 62 girls aged 6 to 13 years at the University of Chicago General Clinical Research Center. They administered a hormonal sleep test using overnight blood sampling followed by a gonadotropin-releasing hormone (GnRH) agonist test using a leuprolide acetate injection.
Results revealed a steady increase in luteinizing hormone (LH) levels during sleep and after GnRH agonist administration throughout prepuberty. The responses to both sleep and GnRH agonist correlated well across groups (r=0.807, peak vs. 4 hour post-GnRH agonist test value), but the association was less strong than in boys (r=0.807; P<.01). Data showed that sleep peaks in LH of 1.3 U/L or greater had 85% sensitivity and 2.1 U/L or greater had 96% specificity for detecting puberty. Similarly, at 1 hour after GnRH agonist administration, an LH of 3.2 U/L or greater had 95% sensitivity and 5.5 U/L or greater had 96% specificity for detecting puberty. LH levels also appeared lower for girls entering puberty vs. boys.
The researchers also identified estradiol and follicle-stimulating hormone (FSH) as endpoints. They found that at 20 to 24 hours after GnRH agonist administration, estradiol levels of 34 pg/mL or greater had 95% sensitivity and 60 pg/mL or greater had 95% specificity for detecting puberty. FSH values, however, had poor discriminatory value for detecting puberty.
Analysis of overweight vs. normal weight girls showed that 36% of overweight girls in early puberty had little hormonal evidence of puberty, which may be related to obesity accelerating gonadotropin clearance, the researchers said.
“This study demonstrates that girls’ pubertal hormone responses to [GnRH agonist] testing indicate the degree to which their pituitary-gonadal axis has been activated during sleep and provides normative data on the maturation of girls’ pituitary-gonadal axis and its response to [GnRH agonist],” the researchers wrote.
Disclosure: The researchers report no relevant financial disclosures.
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