Clinical use of mifepristone (RU 486)

Because progesterone is essential for the establishment and maintenance of pregnancy, it has long been recognized that a substance which antagonized the action of progesterone would have potential as an antifertility agent. Within 2 years of the synthesis of the progesterone antagonist RU 486 (mifepristone) it was demonstrated that bleeding and uterine contractions occurred following its administration in non-pregnant and pregnant women. Extensive trials over the last 10 years have established that a single dose of mifepristone followed 36-48 hours later by a prostaglandin, is an effective, safe alternative to vacuum aspiration for the termination of early pregnancy. Although this combination is licensed in France, China and the United Kingdom for induction of abortion, research is continuing to determine the minimum effective dose of mifepristone and type of prostaglandin which is associated with minimum side effects without loss of efficacy. In addition, studies to determine the acceptability of this type of medical abortion to women in different cultures and societies are required. The facilities necessary for medical termination differ from those for surgical abortion, although the requirements for access to emergency resuscitation and treatment of (rare) complications are similar for the two methods. Mifepristone is very effective in the management of prostaglandin-induced midtrimester abortion. By sensitizing the uterus to prostaglandin, the dose of prostaglandin can be reduced with a shortened prostaglandin-abortion interval. Administration of mifepristone in the early luteal phase of the cycle delays the development of a secretory endometrium. Preliminary studies suggest that it may be highly effective when given at this time as a post-coital contraceptive or 'once a month' pill. Although antigestagens offer great promise as agents to help regulate human fertility, their widespread use may be constrained more by religious and political factors, rather than by demonstration of clinical efficacy.