Progesterone Antagonists On The Horizon

The pharmacology and potential uses of RU-486, the only anti- progesterone to reach clinical trials, including luteolytic, abortifacient, menstrual regulator, postcoital contraceptive, oral contraceptive and other uses, are reviewed. RU-486 acts on the progesterone receptors in the endometrium, specifically the decidua, with a half life of 24 hours. Although it has anti-glucocorticoid activity enough to reverse the clinical and biochemical effects of Cushings disease, it has not anti-glucocorticoid activity at doses used for early abortion. It blocks progesterone and thereby reduces beta-hCG levels in women who will successfully abort, and also increases prostaglandin (PG) secretion and cervical maturation. If hCG remains the same or rises, pregnancy has not been terminated. RU-486 is more effective and also causes less bleeding in pregnancies of less than 6 weeks. PGs and the Chinese "vacation pill" enhance the action of RU- 486. So far the drug has not been 100% effective as a once-a-month pill, nor has it been completely studied for post-coital contraception. RU-486 has potential as an oral contraceptive, since it both inhibits gonadotropin secretion and ovulation. It is effective in cervical ripening and dilatation, and could be used for evacuation in case of fetal death, to aid in difficult delivery and to avoid cesarean section, and to treat progesterone-sensitive tumors.