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  • Title: Estradiol and progesterone-induced slowing of gonadotropin-releasing hormone pulse frequency is not reversed by subsequent administration of mifepristone.
    Author: McCartney CR, Blank SK, Marshall JC.
    Journal: Endocrine; 2009 Oct; 36(2):239-45. PubMed ID: 19609733.
    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.
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