Luteal phase contraception with mifepristone (RU 486) in the rhesus monkey

Abstract

Mifepristone (RU 486), an antiprogesterone, is a promising luteal phase contraceptive agent for human use. However, at present its use is limited by the practical constraint of determining the day of ovulation for an LH + 2 day administration of the drug as indicated from experimental and clinical studies. The aim of the present study was to identify the effective period of luteal phase (luteal phase window) when a single administration of mifepristone would induce antinidatory activity without disturbing menstrual cyclicity and ovulatory pattern in the rhesus monkey. RU 486 (2 mg/kg body weight in benzyl benzoate/olive oil, 1:3) was given to mated monkeys (n = 9) on cycle day 16 in the first treatment cycle (treatment group T1, n = 9), and in the following cycle on cycle day 20 (treatment group T2, n = 8). A single s.c. injection of this antiprogestin during early to midluteal phase (days 1-10 after ovulation, as determined from retrospective analysis of serum concentrations of estrogen and progesterone) provided a one hundred per cent protection against pregnancy, with no apparent side effects. There were no changes in cycle lengths (F = 3.5; P < 0.3), day of ovulation (F = 1.8; P < 0.7) and duration of menses (F = 3.5; P < 0.3) compared with the pre-treatment and post-treatment cycles. Pooled analyses of serum concentrations of estrogen and progesterone during luteal phases of T1 and T2 cycles also showed no variations with those in pre- and post-treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)