Submitted on July 26, 2006
Accepted on November 19, 2006
Progesterone acutely increases LH pulse amplitude but does not acutely influence nocturnal LH pulse frequency slowing during the late follicular phase in women
Christopher R McCartney1*, Susan K Blank1, and John C. Marshall1
1 Center for Research in Reproduction, University of Virginia Health System, PO Box 800391, Charlottesville, Virginia, 22908, United States; Division of Endocrinology, Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia, United States
* To whom correspondence should be addressed. E-mail: cm2hq{at}virginia.edu.
Progesterone (P) is the primary effector of LH (and by inference gonadotropin-releasing hormone) pulse frequency slowing in cycling women, but the time course of this action is unclear. We hypothesized that P administration to estradiol (E2)-pretreated women would slow LH pulse frequency within 12 hours. We studied eight normally cycling women in two separate cycles (follicular phase, cycle days 7-11). After 3 days of E2 pretreatment (0.2 mg/day via transdermal patches), a 25-hour blood sampling protocol (starting at 0800 h) was performed to define LH pulsatility. Oral micronized P (100 mg) or placebo (PBO) was administered at 1800 h in a randomized, double-blind fashion, with treatment crossover occurring during a subsequent cycle. The 10-hour mean P concentration increased from 0.6 ± 0.1 ng/ml before P (0800-1800 h) to 3.9 ± 0.3 ng/ml after P administration (2200-0800 h; P < 0.01). Ten-hour mean LH interpulse interval increased significantly after both P and PBO administration, with no significant difference between P and PBO. In contrast, mean LH, LH amplitude, and mean FSH increased significantly within 4 hours of P administration, but not after PBO. We conclude that in E2-pretreated women in the late follicular phase, (1) nocturnal LH pulse frequency is not acutely (within 12 hours) influenced by P administration; (2) an acute increase in P causes pronounced augmentation of gonadotropin pulse amplitude within 4 hours; and (3) LH pulse frequency slows overnight during the second half of the follicular phase.
