Context: The magnitude of sleep-related gonadotropin rise required to activate pubertal feminization is not established.
Objective: 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.
Design/setting: This was a prospective study in a General Clinical Research Center.
Participants: Sixty-two healthy 6- to 13-year-old volunteer girls participated in the study.
Interventions: Interventions included overnight blood sampling followed by GnRHag (leuprolide acetate) injection.
Primary outcome variables: The primary outcome variables included LH, FSH, and estradiol.
Results: 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.
Conclusions: 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.