Progesterone-Mediated Inhibition of the GnRH Pulse Generator: Differential Sensitivity as a Function of Sleep Status
Su Hee Kim, Jessica A Lundgren, Ruchi Bhabhra, Jessicah S Collins, James T Patrie, Christine M Burt Solorzano, John C Marshall, Christopher R McCartney, Su Hee Kim, Jessica A Lundgren, Ruchi Bhabhra, Jessicah S Collins, James T Patrie, Christine M Burt Solorzano, John C Marshall, Christopher R McCartney
Abstract
Context: During normal, early puberty, luteinizing hormone (LH) pulse frequency is low while awake but increases during sleep. Mechanisms underlying such changes are unclear, but a small study in early pubertal girls suggested that differential wake-sleep sensitivity to progesterone negative feedback plays a role.
Objective: To test the hypothesis that progesterone acutely reduces waking LH pulse frequency more than sleep-associated pulse frequency in late pubertal girls.
Design: Randomized, placebo-controlled, double-blinded crossover study.
Setting: Academic clinical research unit.
Participants: Eleven normal, postmenarcheal girls, ages 12 to 15 years.
Intervention: Subjects completed two 18-hour admissions in separate menstrual cycles (cycle days 6 to 11). Frequent blood sampling for LH assessment was performed at 1800 to 1200 hours; sleep was encouraged at 2300 to 0700 hours. Either oral micronized progesterone (0.8 mg/kg/dose) or placebo was given at 0700, 1500, 2300, and 0700 hours, before and during the first admission. A second admission, performed at least 2 months later, was identical to the first except that placebo was exchanged for progesterone or vice versa (treatment crossover).
Main outcome measures: LH pulse frequency during waking and sleeping hours.
Results: Progesterone reduced waking LH pulse frequency by 26% (P = 0.019), with no change observed during sleep (P = 0.314). The interaction between treatment condition (progesterone vs placebo) and sleep status (wake vs sleep) was highly significant (P = 0.007).
Conclusions: In late pubertal girls, progesterone acutely reduced waking LH pulse frequency more than sleep-associated pulse frequency. Differential wake-sleep sensitivity to progesterone negative feedback may direct sleep-wake LH pulse frequency changes across puberty.
Trial registration: ClinicalTrials.gov NCT00929006.
Figures
Source: PubMed