Steroid antagonists and receptor-associated proteins

: In research to control human reproduction, after the discovery of the progesterone receptor, an idea emerged about a molecule that could compete with progesterone for its binding site on the receptor, and at the same time block the receptor in a non-functional conformation to prevent or even terminate pregnancy. Among new progesterone antagonists tested, Roussel-UCLAF's RU-486 or mifepristone was the most fascinating. Currently in France (in 1993), a woman pays 4 visits over a 3-week period in a licensed hospital to terminate an unwanted pregnancy. She is given 3 x 200 mg pills of RU-486. 48 hours later, she receives the oral prostaglandin Misoprostol (2 x 200 mcg). She remains for 4 hours at the center, during which time 70% of the women abort. If expulsion does not occur, a third Misoprostol 200 mcg tablet is given. A fourth control visit takes place 10-15 days later. This protocol achieved 98% efficacy in pregnancies of 49 days of amenorrhea, but it is currently not applicable to heavy smokers or women over 35 years old. Other uses for RU-486: 1) Cervical ripening in second or third trimester abortions with a dose of 200-600 mg RU-486. 2) Initiation of labor in women for medical indications. 3) Contraception: a) late luteal postcoital administration of 400 or 600 mg RU-486 once or twice for 2 days before menses, b) monthly late luteal phase, premenstrual administration of a low-dose of RU-486 plus Misoprostol 2 days before menses, c) emergency postcoital contraception in a single 600 mg dose after unprotected intercourse within 72 hours, d) once a month anti-implantation with 200 mg of RU-486 given 2 days after unprotected intercourse, e) suppression of ovulation, f) endometrial contraception. After more than 10 years of administration to more than 150,000 women, RU-486, particularly in association with Misoprostol, is an excellent and safe agent for termination of pregnancy under the mandatory supervision of a physician.