title: The antiprogestin RU486 delays the midcycle gonadotropin surge and ovulation in gonadotropin-releasing hormone-induced cycles.
abstract: OBJECTIVE
  To investigate whether the antiprogestin RU486 acts primarily on the hypothalamus to delay the midcycle gonadotropin surge and thus gain insight into the site(s) of action of P in the control of ovulation.
  
  
  METHODS
  Prospective, crossover, single-blinded clinical study.
  
  
  METHODS
  Outpatient clinic in an academic research environment.
  
  
  METHODS
  Women with hypothalamic amenorrhea.
  
  
  METHODS
  RU486 or a placebo was given orally at a low dose of 1 mg/d for 5 days, starting when the dominant follicle reached 14 to 16 mm, to women with hypothalamic amenorrhea undergoing ovulation induction with GnRH pulses of unvarying frequency and dose. Blood samples and ovarian ultrasounds were obtained daily in the late follicular phase and every 3 to 4 days in the remainder of the cycle.
  
  
  METHODS
  Follicular diameter and plasma levels of LH, FSH, E2, and P.
  
  
  RESULTS
  RU486 consistently delayed the timing of the midcycle gonadotropin surge and ovulation. Gonadotropin and steroid levels were suppressed during RU486 treatment, but follicular growth progressed normally in most patients.
  
  
  CONCLUSIONS
  RU486 does not act primarily on the hypothalamus to delay ovulation. Rather, this compound appears to antagonize P at the pituitary level to suppress gonadotropin and steroid hormone secretion. P may thus act on the pituitary, independent of any hypothalamic effects, to regulate the timing of the midcycle gonadotropin surge and ovulation.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: M C
authors.initials: MC
authors.lastname: Batista
authors.forename: T P
authors.initials: TP
authors.lastname: Cartledge
authors.forename: A W
authors.initials: AW
authors.lastname: Zellmer
authors.forename: L K
authors.initials: LK
authors.lastname: Nieman
authors.forename: D L
authors.initials: DL
authors.lastname: Loriaux
authors.forename: G R
authors.initials: GR
authors.lastname: Merriam
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects; D008597:Menstrual Cycle / Q000187:drug effects*; D015735:Mifepristone / Q000494:pharmacology*; D006080:Ovarian Follicle / Q000187:drug effects; D010060:Ovulation / Q000187:drug effects*; D010919:Placebos; D011372:Progestins / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D012739:Gonadal Steroid Hormones; D010919:Placebos; D011372:Progestins; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone