Progesterone has rapid positive feedback actions on LH release but fails to reduce LH pulse frequency within 12 h in estradiol-pretreated women

Abstract

In women, progesterone suppresses luteinizing hormone (LH) (gonadotropin‐releasing hormone) pulse frequency, but how rapidly this occurs is unknown. In estradiol‐pretreated women in the late follicular phase, progesterone administration at 1800 did not slow sleep‐associated LH pulse frequency. However, mechanisms controlling LH pulse frequency may differ according to sleep status; and we thus hypothesized that progesterone acutely suppresses waking LH pulse frequency. This was a randomized, double‐blind, crossover study of LH secretory responses to progesterone versus placebo administered at 0600. We studied 12 normal women in the late follicular phase (cycle days 7–11), pretreated with 3 days of transdermal estradiol (0.2 mg/day). Subjects underwent a 24‐h blood sampling protocol (starting at 2000) and received either 100 mg oral micronized progesterone or placebo at 0600. In a subsequent menstrual cycle, subjects underwent an identical protocol except that oral progesterone was exchanged for placebo or vice versa. Changes in 10‐h LH pulse frequency were similar between progesterone and placebo. However, mean LH, LH pulse amplitude, and mean follicle‐stimulating hormone exhibited significantly greater increases with progesterone. Compared to our previous study (progesterone administered at 1800), progesterone administration at 0600 was associated with a similar increase in mean LH, but a less pronounced increase in LH pulse amplitude. We conclude that, in estradiol‐pretreated women in the late follicular phase, a single dose of progesterone does not suppress waking LH pulse frequency within 12 h, but it acutely amplifies mean LH and LH pulse amplitude – an effect that may be influenced by sleep status and/or time of day.

Influence of Sleep Stage on LH Pulse Initiation in the Normal Late Follicular Phase and in Polycystic Ovary Syndrome

“…In this study, overnight sampling and PSG occurred before progesterone or placebo administration (at 06: 00), but transdermal estradiol was continued throughout admissions. Primary analyses regarding normal women were recently reported [10]. For the current analysis, we only included admissions for which PSG data were available: 12 admissions of 8 normal women and 5 admissions of 4 women with PCOS.…”

“…1). For each LH concentration time series, we employed a computerized data reduction protocol (StdCurve) to establish statistically accurate estimates for experimental LH measurement error, and pulsatile LH secretion was characterized using deconvolution (AutoDecon) [10, 18]. The temporal location of LH pulse initiation was assigned as 2 secretory standard deviations (SD) before the time of peak LH secretion rate (Fig.…”

“…Normally cycling women also demonstrate decreases in LH pulse frequency during sleep, most prominently in the early follicular phase [1-6], but also in the mid- to late follicular phase [7-10]. In contrast, early neuroendocrine puberty is characterized by increases in LH pulse frequency during sleep [11, 12].…”

Progesterone administration does not acutely alter LH pulse secretion in the mid-follicular phase in women

“…; Hutchens et al. ). In these studies, a single 100 mg oral dose of progesterone was administered at either 1800 h (McCartney et al.…”

“…) or 0600 h (Hutchens et al. ). In both studies, LH pulse frequency was not suppressed within 12 h, but mean LH and LH pulse amplitude increased markedly.…”