Abstract

PIP: At present, RU-486 is best known for its ability to terminate unwanted pregnancies of up to 49 days' duration, and this chemical approach is being selected over surgery by 25-33% of women who interrupt an early pregnancy. The development of this noninvasive and potentially safer means of abortion was inadvertent. RU-486 emerged from experiments conducted in the mid-1970s at the University of Chicago aimed at synthesizing versions of steroids that do not exist in nature. RU-486 was 1 or 3 molecules synthesized that bound strongly to the glucocorticoid receptor and interfered with certain activities of glucocorticoids in cell cultures. This compound was not only best able to block the actions of dexamethasone, but also bound very strongly to the progesterone receptor. Animal studies soon indicated that RU-486 was a progesterone antagonist and testing for fertility control potential was initiated. Initially, RU-486 led to successful pregnancy termination in 80% of cases through a process that included erosion of the endometrium, atrophy of the corpus luteum, enhanced uterine contractibility, cervical softening and dilatation, and eventual expulsion of the embryo and endometrium. The additional administration of a small dose of prostaglandin 36-48 hours afterwards increased the effectiveness rate of RU-486 to 96%. There are many additional used for RU-486, including postcoital contraception, induction of term labor, and increases in human milk volume. Other applications under investigation are RU-486 as a glucocorticoid antagonist and a treatment of certain cancers.