Estradiol and progesterone-induced slowing of gonadotropin-releasing hormone pulse frequency is not reversed by subsequent administration of mifepristone

• Published in: Endocrine Vol. 36; no. 2; pp. 239 - 245
• Main Authors: McCartney, Christopher R., Blank, Susan K., Marshall, John C.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2009
• Subjects: Adult; Circadian Rhythm - physiology; Diabetes; Drug Administration Routes; Drug Administration Schedule; Endocrinology; Estradiol - administration & dosage; Estradiol - adverse effects; Estradiol - pharmacology; Female; Follicle Stimulating Hormone - blood; Gonadotropin-Releasing Hormone - blood; Gonadotropin-Releasing Hormone - metabolism; Hormone Antagonists - administration & dosage; Hormone Antagonists - adverse effects; Hormone Antagonists - pharmacology; Humanities and Social Sciences; Humans; Internal Medicine; Luteinizing Hormone - blood; Medicine; Medicine & Public Health; Mifepristone - administration & dosage; Mifepristone - adverse effects; Mifepristone - pharmacology; multidisciplinary; Original Paper; Progesterone - administration & dosage; Progesterone - adverse effects; Progesterone - pharmacology; Pulsatile Flow - drug effects; Science; Young Adult; Luteinizing hormone; Luteal-follicular transition; Mifepristone; Gonadotropin-releasing hormone; Progesterone; Estradiol
• DOI: 10.1007/s12020-009-9215-x
• ISSN: 1355-008X

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.