Anti-nidatory effect of a single, early post-ovulatory administration of mifepristone (RU 486) in the rhesus monkey.
The hypothesis that post-coital administration of mifepristone (RU 486) as a single dose in the early luteal phase can be an effective anti-nidatory strategy was tested using the rhesus monkey as the experimental model. Incidence of pregnancy, vaginal bleeding patterns, profiles of menstrual cyclicity and of serum levels of progesterone and oestrogen were examined following administration of RU 486 as a single dose of 10 mg/kg and 2 mg/kg body weight on the second day after ovulation. In control monkeys (group 1; n = 5) receiving the vehicle alone (benzyl benzoate:olive oil, 1:4, v/v) there was a 60% pregnancy rate. Following s.c. administration of RU 486 at both doses, no pregnancy was recorded in a total of 33 treatment cycles in 12 monkeys. Five monkeys received RU 486 at 10 mg/kg s.c. (group 2) in three consecutive cycles. All animals had complete inhibition of implantation; in addition, the treatment cycle length was prolonged (P < 0.001) due to an extension of the luteal phase. The subsequent follicular phase was unaffected. Mild, premature vaginal bleeding during the luteal phase was recorded in five treatment cycles, 3-5 days after drug application. Though the serum profiles of progesterone and oestrogen in these monkeys showed marked individual variations, there was a characteristic progesterone rebound about 18-20 days after drug administration. Monkeys in group 3 were given RU 486 at 2 mg/kg, s.c. either for three consecutive cycles (group 3a; n = 4) or for two consecutive cycles (group 3b; n = 3). Premature luteal phase vaginal bleeding occurred only in four treatment cycles, within 2-6 days post-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, All India Institute of Medical Sciences, New Delhi.
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D
Ghosh
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Sengupta
D000818:Animals; D004353:Drug Evaluation, Preclinical; D010064:Embryo Implantation / Q000187:drug effects*; D004967:Estrogens / Q000097:blood; D005260:Female; D008183:Luteal Phase; D008253:Macaca mulatta; D008597:Menstrual Cycle / Q000187:drug effects*; D015735:Mifepristone / Q000008:administration & dosage*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011374:Progesterone / Q000097:blood
D004967:Estrogens; D015735:Mifepristone; D011374:Progesterone