Estradiol and progesterone-induced slowing of gonadotropin-releasing hormone pulse frequency is not reversed by subsequent administration of mifepristone
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...
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Published in | Endocrine Vol. 36; no. 2; pp. 239 - 245 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Boston
Springer US
01.10.2009
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Subjects | |
Online Access | Get full text |
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Summary: | 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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ISSN: | 1355-008X 1559-0100 |
DOI: | 10.1007/s12020-009-9215-x |