Accelerated dissolution of luteal-endometrial integrity by the administration of antagonists of gonadotropin-releasing hormone and progesterone to late-luteal phase women.
Sequential blockade of gonadotropin-releasing hormone (GnRH) and progesterone (P) receptors by potent antagonists (Nal-Glu GnRH antagonist and RU486) was conducted in late-luteal phase women to develop a once-a-month birth control method by timed advancement of ongoing luteolysis and endometriolysis. Hormonal dynamics and timing of uterine bleeding during the antagonists' imposed luteal-follicular transition were compared with spontaneous (1st to 2nd) and recovery (2nd to 3rd) cycles in 10 normally cycling women. Serum luteinizing hormone (LH) and follicle-stimulating hormone levels declined (47 +/- 4.3% and 24 +/- 3.0%, respectively) by 24 hours after Nal-Glu injection, which accelerated the ongoing luteolytic process, as evidenced by more rapid declines of serum concentrations of estradiol, P, and ir-inhibin, as compared with the corresponding control cycle. This was accompanied by the prompt (16 +/- 3.2 hours after RU486) onset of a single episode of uterine bleeding, which was advanced by 2 days. Whereas the luteal phase length was foreshortened by 2 days, the subsequent follicular phase duration was prolonged by 2 days with a normal sequence of follicular maturation, LH surge, and luteal function during the recovery cycle. We conclude that the late-luteal sequential administration of antagonists of GnRH and P resulted in acceleration of the ongoing luteolytic and endometriolytic processes without functional alterations of the subsequent cycle.
Roseff
S J
SJ
Department of Reproductive Medicine, School of Medicine, University of California, San Diego.
Kettel
L M
LM
Rivier
J
J
Burger
H G
HG
Baulieu
E
E
Yen
S S
SS
D000328:Adult; D003338:Corpus Luteum / Q000187:drug effects* / Q000502:physiology; D004717:Endometrium / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D007265:Inhibins / Q000097:blood; D008183:Luteal Phase / Q000187:drug effects* / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood; D003341:Luteolysis / Q000187:drug effects / Q000502:physiology; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology*; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000097:blood
C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone