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

Physiol Rep. 2016 Aug;4(16):e12891. doi: 10.14814/phy2.12891.

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.

Keywords: Circadian rhythm; estradiol; gonadotropin surge; gonadotropin‐releasing hormone; luteinizing hormone; luteinizing hormone surge; progesterone.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Cutaneous
  • Adolescent
  • Circadian Rhythm / physiology
  • Cross-Over Studies
  • Double-Blind Method
  • Estradiol / administration & dosage
  • Estradiol / adverse effects
  • Estradiol / blood
  • Estradiol / pharmacology*
  • Feedback, Physiological / physiology*
  • Female
  • Follicle Stimulating Hormone / blood
  • Follicular Phase / drug effects
  • Gonadotropin-Releasing Hormone / blood
  • Gonadotropin-Releasing Hormone / metabolism
  • Humans
  • Luteinizing Hormone / blood
  • Luteinizing Hormone / metabolism*
  • Progesterone / administration & dosage
  • Progesterone / blood
  • Progesterone / pharmacology*
  • Pulsatile Flow / drug effects
  • Pulsatile Flow / physiology*
  • Young Adult

Substances

  • Gonadotropin-Releasing Hormone
  • Progesterone
  • Estradiol
  • Luteinizing Hormone
  • Follicle Stimulating Hormone