A single injection of a gonadotropin-releasing hormone (GnRH) antagonist (Cetrorelix) postpones the luteinizing hormone (LH) surge: further evidence for the role of GnRH during the LH surge.
OBJECTIVE
To assess the ability of a new third-generation GnRH antagonist, Cetrorelix (Asta Medica AG, Frankfurt am Main, Germany), to postpone the LH surge after a single injection during the late follicular phase.


METHODS
A single 5-mg (group 1, n = 7) or 3-mg (group 2, n = 3) dose SC of Cetrorelix was administered during the late follicular phase, on the day of the cycle when plasma E2 exceeded 150 pg/mL (550 pmol/L). Estradiol, LH, FSH, and P levels were measured daily from day 5 of the cycle until day 10 after antagonist administration. Transvaginal ultrasonographies were performed on the day of injection and after antagonist treatment.


METHODS
Ten normal women with regular ovulatory menstrual cycles.


RESULTS
In group 1, Cetrorelix was administered on day 14.6 +/- 5 (mean +/- SD) of the cycle, when the mean plasma E2 level was 181 +/- 32 pg/mL (664 +/- 117 pmol/L) (mean +/- SD). Plasma LH and FSH decreased by 56% +/- 19% and 29.5% +/- 16% (mean +/- SD), respectively, reaching the nadir 24 hours after Cetrorelix administration. Estradiol decreased by 85% +/- 17%, reaching the nadir 48 hours after antagonist injection. In group 2, Cetrorelix was administered on day 14.3 +/- 1.2 of the cycle when the mean plasma E2 level was 169 +/- 21 pg/mL (618 +/- 77 pmol/L). Plasma LH and FSH decreased by 66% +/- 18% and 32% +/- 6%, respectively, reaching a nadir 24 hours after Cetrorelix administration. Estradiol decreased by 81% +/- 9%, reaching the nadir 24 to 48 hours after antagonist administration. The LH surge was interrupted in every case. In six of seven subjects from group 1, the LH surge was delayed, occurring 6 to 17 days after the antagonist injection. In the remaining woman, Cetrorelix was administered at the beginning of the LH surge (LH = 13 IU/L): the LH level fell immediately by 54%, and the surge was postponed by 3 days. In group 2, in three of three subjects, the LH surge was delayed, occurring 6 to 9 days after the antagonist injection. No adverse effects were observed, except for very slight and transient erythema and pruritus at the injection site.


CONCLUSIONS
Cetrorelix is a very potent new GnRH antagonist. A single injection during the late follicular phase delays the LH surge, even if the latter has already begun. In addition, this new-generation GnRH antagonist is very well tolerated and simple to use. Our data reinforce the role of GnRH during the LH surge and point to a role for new GnRH antagonists in controlled ovarian hyperstimulation to avoid premature LH surges and subsequent luteinization.
Leroy
I
I
Service d'Endocrinologie et des Maladies de la Reproduction, Hôpital Bicêtre, France.
d'Acremont
M
M
Brailly-Tabard
S
S
Frydman
R
R
de Mouzon
J
J
Bouchard
P
P
D000328:Adult; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005498:Follicular Phase; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D008183:Luteal Phase; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors* / Q000097:blood*; D006080:Ovarian Follicle / Q000000981:diagnostic imaging; D013997:Time Factors; D014463:Ultrasonography
D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C062876:cetrorelix