title: The gonadotropin-releasing hormone antagonist (Nal-Glu) acutely blocks the luteinizing hormone surge but allows for resumption of folliculogenesis in normal women.
abstract: The gonadotropin-releasing hormone antagonist offers several advantages over the use of the agonist and allows several physiologic questions to be addressed. In this study, we evaluated the ability of Nal-Glu to acutely inhibit the luteinizing hormone surge and prevent ovulation. We also assessed whether recovery of the follicle would be possible after several days of gonadotropin deprivation and estradiol decrement. Eight normal ovulatory women were randomized to control or Nal-Glu-treated cycles (50 micrograms/kg intramuscularly) for 3 to 4 days. Monitoring was carried out with daily vaginal ultrasonographic scans and serum estradiol levels and twice-daily serum luteinizing and follicle-stimulating hormone levels. Nal-Glu acutely inhibited the luteinizing hormone surge and ovulation, even when administered as late as the onset of the luteinizing hormone surge. Evidence was provided that spontaneous follicular rescue recurred in eight of 10 cycles after 3 to 4 days of Nal-Glu administration. Although an estradiol to follicular size dissociation occurred with Nal-Glu, subsequent ovulation occurred in 5.1 +/- 0.6 days after the last Nal-Glu dose. The decrement in estradiol after Nal-Glu administration correlated negatively with the days required for subsequent ovulation to occur (r = 0.77, p less than 0.05). The subsequent luteal phase also was normal in terms of length and progesterone levels. These data confirm the potency and efficacy of Nal-Glu in acutely inhibiting gonadotropins and extends our knowledge on the physiologic characteristics of the dominant follicle.
authors.affiliation: Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles.
authors.forename: E C
authors.initials: EC
authors.lastname: Ditkoff
authors.forename: D L
authors.initials: DL
authors.lastname: Cassidenti
authors.forename: R J
authors.initials: RJ
authors.lastname: Paulson
authors.forename: M V
authors.initials: MV
authors.lastname: Sauer
authors.forename: W L
authors.initials: WL
authors.lastname: Paul
authors.forename: J
authors.initials: J
authors.lastname: Rivier
authors.forename: S S
authors.initials: SS
authors.lastname: Yen
authors.forename: R A
authors.initials: RA
authors.lastname: Lobo
mesh_terms: D000328:Adult; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D006080:Ovarian Follicle / Q000502:physiology*; D010060:Ovulation / Q000187:drug effects*
chemical_list: C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone