Pituitary sensitizing effect of GnRH antagonists: A mechanism explaining LH escape during IVF?

Abstract

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 (E2, 50 g) administration. The main outcome measure was the LH response 30 min after GnRH administration (ΔLH 30) after the various GnRH tests. Result SThe ΔLH 30 increased significantly after antagonist administration [Median (range): from 65.5 (32-85) to 77.5 (47-122) IU/l; P = 0.002]. During E2 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. © The Author 2010.