title: Estradiol and progesterone-induced slowing of gonadotropin-releasing hormone pulse frequency is not reversed by subsequent administration of mifepristone.
abstract: Subsequent to suppression of LH (GnRH) pulse frequency by progesterone (P) and estradiol (E(2)), LH pulse frequency remains slow for 7 days after P withdrawal if mid-luteal E(2) concentrations are maintained. This may reflect an ability of E(2) to potentiate the suppressive effects of low P levels. We explored this notion in a similar experimental paradigm by administering a P-receptor antagonist (mifepristone) after P withdrawal while continuing E(2). Studies were performed in seven ovulatory, non-obese women. Transdermal E(2) (0.2 mg/day) and oral micronized P (100 mg every 8 h) were started within 24 h of the LH surge and continued for 10 days. Subjects then underwent a 13-h blood sampling protocol for determination of LH pulse characteristics and various hormone concentrations. Oral P was then discontinued, and oral mifepristone (50, 100, or 200 mg daily) and transdermal E(2) (0.2 mg/day) were administered for 7 days, after which the above sampling protocol was repeated. Results with all mifepristone doses were similar and therefore pooled. Mean LH, LH amplitude, and mean FSH markedly decreased after 7 days of mifepristone, but LH pulse frequency did not change (3.3 +/- 1.5 vs. 2.4 +/- 1.5 pulses/13 h). Prolactin and androstenedione increased between the first and second admissions, with no changes in E(2), cortisol, testosterone, or DHEAS. In conclusion, blockade of P action by mifepristone does not reverse a suppressed LH pulse frequency within 7 days when E(2) concentrations are maintained, suggesting that P withdrawal alone may not explain the luteal-follicular increase of GnRH pulse frequency.
authors.affiliation: Center for Research in Reproduction, University of Virginia Health System, Box 800391, Charlottesville, VA, 22908, USA. cm2hq@virginia.edu
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McCartney
authors.forename: Susan K
authors.initials: SK
authors.lastname: Blank
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
mesh_terms: D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000097:blood* / Q000378:metabolism; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D015735:Mifepristone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011374:Progesterone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011673:Pulsatile Flow / Q000187:drug effects; D055815:Young Adult
chemical_list: D006727:Hormone Antagonists; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone