Suppression of corpus luteum function by the gonadotropin-releasing hormone antagonist Nal-Glu: effect of the dose and timing of human chorionic gonadotropin administration.
OBJECTIVE
To assess the effect of gonadotropin-releasing hormone antagonist Nal-Glu administration in the luteal phase and the potential rescue by exogenous human chorionic gonadotropin (hCG) of corpus luteum (CL) after antagonist treatment.


METHODS
We studied the dose of Nal-Glu required for luteolysis and subsequently we coadministered low doses of hCG for 3 consecutive days either simultaneously to Nal-Glu administration (n = 5), or 48 (n = 5), or 72 hours (n = 5) later. Six additional participants received pharmacological doses of hCG 48 hours after the luteolytic dose of Nal-Glu.


METHODS
Participants were studied in Clinique Endocrinologique, Nantes, and in Service d'Endocrinologie, Hôpital Bicêtre, Le Kremlin Bicetre, France.


METHODS
Twenty-nine normal young women (ages 20 to 35) were studied.


METHODS
None.


METHODS
Measurements of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, Progesterone (P) levels were performed by radioimmunoassay before, during, and after the various treatment regimens.


RESULTS
Complete luteolysis occurred in women who received 10 mg of Nal-Glu daily on days 4 and 5 after the LH surge. The coadministration of Nal-Glu and hCG overrode the effect of the antagonist (P = 48.8 +/- 22.5 versus 60.8 +/- 3.1 nmol/L in controls treated with hCG alone [NS]). When hCG treatment was started 48 hours after Nal-Glu, a partial luteolysis occurred (P = 33.8 +/- 10.9 versus 117 +/- 12.9 nmol/L, P less than 0.01). When hCG was started 72 hours after Nal-Glu, a complete luteolysis occurred (P = 5.8 +/- 2.05 versus 36.2 +/- 0.6 nmol/L, P less than 0.01). Higher doses of hCG (1,500 or 5,000 IU) administered 72 hours after Nal-Glu resulted in a significant rescue of CL function (P = 37.7 +/- 4.8 and P = 43.8 +/- 22.2 versus 74.5 +/- 19.8 and 130.2 +/- 14.3 nmol/L, P less than 0.05), respectively.


CONCLUSIONS
These results confirm the LH dependence of CL function. The suppression of CL LH support for 72 hours induced a compromise of the CL nonreversible by low doses of hCG mimicking early pregnancy but reversible with pharmacological doses.
Dubourdieu
S
S
Clinique Endocrinologique, Hôtel-Dieu, Nantes, France.
Charbonnel
B
B
Massai
M R
MR
Marraoui
J
J
Spitz
I
I
Bouchard
P
P
D000328:Adult; D006063:Chorionic Gonadotropin / Q000008:administration & dosage* / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans
D006063:Chorionic Gonadotropin; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D007987:Gonadotropin-Releasing Hormone