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. Design: Prospective, crossover, single-blinded clinical study. Setting: Outpatient clinic in an academic research environment. Patients: Women with hypothalamic amenorrhea. Interventions: 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. Main Outcome Measures: Follicular diameter and plasma level 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, independent of any hypothalamic effects, to regulate the timing of the midcycle gonadotropin surge and ovulation.
- gonadotropin-releasing hormone
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology