The antiprogestin RU486 delays the midcycle gonadotropin surge and ovulation in gonadotropin-releasing hormone-induced cycles.
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.
Batista
M C
MC
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Cartledge
T P
TP
Zellmer
A W
AW
Nieman
L K
LK
Loriaux
D L
DL
Merriam
G R
GR
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
D012739:Gonadal Steroid Hormones; D010919:Placebos; D011372:Progestins; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone