Pituitary sensitizing effect of GnRH antagonists: a mechanism explaining LH escape during IVF?
BACKGROUND
GnRH antagonists have been introduced to induce persistent LH suppression. Many studies show a gradual increase of LH levels after several days of GnRH antagonist administration, the so-called escape or rebound effect. We hypothesize that, under chronic GnRH antagonist administration, a higher pituitary response to GnRH could be an underlying mechanism explaining the escape phenomenon.


METHODS
In a prospective study, pituitary response to a supramaximal test dose of GnRH was tested in 12 post-menopausal women before and 8 days after daily treatment with 0.5 mg GnRH antagonist (ganirelix). The same strategy was applied, after a wash-out period, in 11 of the same women using daily 0.5 mg GnRH antagonist in combination with daily estradiol (E(2), 50 microg) administration. The main outcome measure was the LH response 30 min after GnRH administration (Delta LH 30) after the various GnRH tests.


RESULTS
The Delta LH 30 increased significantly after antagonist administration [Median (range): from 65.5 (32-85) to 77.5 (47-122) IU/l; P = 0.002]. During E(2) administration, the LH response to the GnRH test did not change significantly.


CONCLUSIONS
Pituitary response increases after 8 days of GnRH antagonist administration. An escape/rebound phenomenon may result from increased pituitary response to endogenous GnRH.
Banga
F R
FR
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, VU University Medical Centre (VUmc), PO Box 7075, 1007 MB Amsterdam, The Netherlands. fr.banga@vumc.nl
Huirne
J A
JA
Korsen
T
T
Homburg
R
R
Hompes
P G A
PG
Lambalk
C B
CB
D000368:Aged; D004334:Drug Administration Schedule; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015200:Fluoroimmunoassay; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood*; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects*; D017698:Postmenopause; D011446:Prospective Studies
D004967:Estrogens; D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; C061018:ganirelix