ANTIPROGESTINS - MECHANISM OF ACTION AND CONTRACEPTIVE POTENTIAL

Antiprogestins are characterized by substitutions at the 11 beta and 1 7 alpha positions of the steroid ring system and bind strongly to both progesterone and glucocorticoid receptors. Although they function pre dominantly as antiprogestins and antiglucocorticoids, on occasion they display progestin agonistic and even antiestrogenic properties. The m ost common clinical use of the antiprogestin mifepristone is to induce a medical abortion in the early stages of pregnancy. Progesterone mai ntains the endometrium, transforming it from a proliferative to a secr etory state. It also facilitates the luteinizing hormone surge, which initiates ovulation. As a consequence, antiprogestins may also have co ntraceptive potential. Although antiprogestins do delay ovulation, thi s effect is inconsistent unless high doses are given, and under these circumstances, the antiprogestin effect is associated with unopposed e strogen action on the endometrium. Very low doses of antiprogestins do not affect hormonal secretion or ovulation or alter bleeding patterns , but they do have contraceptive potential by inducing profound altera tions in endometrial morphology. Mifepristone is also a very effective and safe postcoital agent This new class of pharmacological agents ha s numerous other gynecological and obstetrical indications, such as en dometriosis, uterine myoma, and expulsion of the fetus in the case of fetal death in utero. Antiprogestins may also be used in the treatment of steroid-dependent tumors. There are also therapeutic implications consequent to their antiglucocorticoid properties.