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

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.