The antiprogestins: a recent advance in fertility regulation.
RU 468 (mifepristone) is the first antiprogestin available for clinical purposes. Its pharmacological properties are presented. It possesses antiprogestin and antiglucocorticoid activities. It is now in phase II-III clinical studies as a fertility control agent. The drug appears useful per se in four circumstances: (1) for early pregnancy (amenorrhea of less than 5 weeks' duration). Complete interruption is obtained in approximately 90% of women with a single dose of 600 mg. For this stage of pregnancy, RU 486 appears to be an interesting alternative to vacuum aspiration; (2) for late occasional luteal contraception when given as a single dose on the date of the expected period in women at risk of pregnancy; (3) for dead fetus expulsion in the 2nd or 3rd trimester of pregnancy, and (4) for cervical ripening before obstetrical procedures in pregnant women, such as D and C or vacuum aspiration. The antiglucocorticoid activity of the molecule can be demonstrated in humans by a rise in plasma cortisol, ACTH and LPH after RU 486 intake, and by blockade of some peripheral effects of cortisol. Results obtained in more than 1000 women undergoing short-term treatment with RU 486 (600 or 800 mg once) clearly indicate that the antiglucocorticoid activity of the molecule has no clinical relevance at the doses used for fertility control purposes. In conclusion, RU 486 appears to be a promising new tool for fertility control, but large-scale trials are necessary to confirm its safety and to define its optimal mode of utilization for each indication.
Ulmann
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Institut Roussel Uclaf, Romainville, France.
D000021:Abortifacient Agents, Steroidal; D000818:Animals; D003267:Contraception; D003280:Contraceptives, Oral, Synthetic; D004963:Estrenes / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors; D006801:Humans; D015735:Mifepristone; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology; D011372:Progestins / Q000037:antagonists & inhibitors*; D011987:Receptors, Steroid / Q000378:metabolism
D000021:Abortifacient Agents, Steroidal; D003280:Contraceptives, Oral, Synthetic; D004963:Estrenes; D005938:Glucocorticoids; D011372:Progestins; D011987:Receptors, Steroid; D015735:Mifepristone; D011374:Progesterone