Progesterone-Mediated Inhibition of the GnRH Pulse Generator: Differential Sensitivity as a Function of Sleep Status.

Progesterone-Mediated Inhibition of the GnRH Pulse Generator: Differential Sensitivity as a Function of Sleep Status.

J Clin Endocrinol Metab. 2017 Dec 28;:

Authors: Kim SH, Lundgren JA, Bhabhra R, Collins JS, Patrie JT, Burt Solorzano CM, Marshall JC, McCartney CR

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: 11 normal post-menarcheal girls, ages 12-15 years.
Intervention: Subjects completed two 18-hour admissions in separate menstrual cycles (cycle day 6-11). Frequent blood sampling for LH assessment was performed 1800-1200 h; sleep was encouraged 2300-0700 h. Either oral micronized progesterone (0.8 mg/kg per dose) or placebo was given at 0700, 1500, 2300, and 0700 h before and during the first admission. A second admission, performed at least two months later, was identical to the first except that placebo was exchanged for progesterone or vice versa (treatment crossover).
Main Outcome Measure: 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.

PMID: 29300925 [PubMed - as supplied by publisher]

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