Contragestion by antiprogestin: a new approach to human fertility control.

Abstract

The steroidal derivative RU 486 (17 beta-hydroxy-11 beta-(4-dimethylaminophenyl 1)-17 alpha (prop-1-ynyl)-estra-4,9-dien-3-one) is the first potent antiprogestin. Acting reversibly at the molecular level of receptor binding, it interrupts progesterone action definitively if the target cell dynamics are irreversibly disrupted. Its preferred target cells are those of the uterine decidualized mucosa and uterine cervix, and increased myometrial contractility facilitates the termination of pregnancy. Luteolysis is secondary to the decrease in chorionic gonadotropin, itself brought about by secondary alteration or detachment of the trophoblast. Clinical results so far indicate that RU 486 can be a very efficient and safe contragestive agent, especially for the medical termination of early pregnancy or as a postcoital menses inducer or menstrual regulator. Incomplete expulsion is sometimes noted at present when RU 486 is given alone but this may not happen when efficient form(s) of administration are used and/or when uterotonics are added. When a small amount of prostaglandin (which by itself would be inefficient) is given at the end of treatment with RU 486, the results are highly satisfactory. The antiprogestin RU 486 does not expose women to hormones continuously. Based on a dual concept, physiological and molecular, it may be typical of the second generation of agents required to achieve safe and effective control of human fertility.