Contraceptive potential of RU 486 by ovulation inhibition: III. Preliminary observations on once weekly oral administration.
Acute administration of the potent progesterone antagonist RU 486 during the luteal/secretory phase of the menstrual cycle induces premature menses in women and monkeys. Using a variety of regimens, administration of RU 486 during the follicular/proliferative phase causes anovulation and amenorrhea. Single treatment in the late follicular phase blocks the preovulatory LH surge and ovulation; mid-luteal phase administration of RU 486 can cause premature luteolysis. The objective of the present study was to evaluate the contraceptive potential of the antiprogesterone RU 486 during once weekly oral administration in normally cycling cynomolgus monkeys. Oral administration of 25 mg of RU 486 on cycle days 3, 10, 17 and 24 blocked the expected midcycle LH/FSH surges. Interestingly, whereas progesterone remained undetectable throughout the treatment cycle, estradiol levels began to increase during the last two weeks of treatment. In contrast, halving the dose to 12.5 mg did not inhibit apparent ovulation or luteal function, as judged by serum LH, estradiol and progesterone levels. We conclude that at adequate doses, RU 486 effectively blocks ovulation when administered orally in a once weekly regimen. Further studies are warranted to evaluate RU 486 and other progesterone antagonists as potential contraceptive agents.
Danforth
D R
DR
Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk 23510.
Dubois
C
C
Ulmann
A
A
Baulieu
E E
EE
Hodgen
G D
GD
D000818:Animals; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D004963:Estrenes / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008252:Macaca fascicularis; D008597:Menstrual Cycle / Q000187:drug effects; D015735:Mifepristone; D010060:Ovulation / Q000187:drug effects*; D011374:Progesterone / Q000097:blood
D003280:Contraceptives, Oral, Synthetic; D004963:Estrenes; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone