PROSTAGLANDINS AND ANTIPROGESTINS

There is considerable interest in the development of a non-surgical method to terminate early pregnancy. During the three weeks immediately following the first missed menstrual period, several prostaglandin (PG) analogs such as sulprostone, gemeprost and 9-methylene PGE2 have been used to terminate the pregnancy. Prostaglandins, however, at the doses required to induce disruption of the conceptus cause gastrointestinal side effects and uterine pain which are more severe than those subsequent to vacuum aspiration. Treatment with the antiprogestin, mifepristone counteracts the effects of progesterone in pregnancy and thus prevents maintenance of the pregnancy. Mifepristone administered alone causes termination of the pregnancy in most, but not all, cases. In addition to removing the influence of progesterone, mifepristrone also induces regular uterine contractions and significantly increased the sensitivity of the uterus to PG analogs. Mifepristone (50 mg/day) followed by an intramuscular injection of a low dose, (0.25 mg), of sulprostone (approximately 1/6 of the dose of prostaglandin necessary to induce abortion if used alone) was highly effective in terminating early pregnancy, causing complete abortion in 94% of cases. Gastrointestinal side effects were rare and uterine pain significantly less common than if PG analogs were used alone. Subsequently the combination of mifepristone and vaginal administration of gemeprost (0.5–1.0 mg) has been shown to be equally effective (1). Ideally, the PG analog would be administered orally rather than by injection or vaginal administration. Preliminary data indicate that 9-methylene PGE2 but not PGE2 may be suitable for this purpose in combination with mifepristone. In a naturally occurring spontaneous abortions a decreased influence of progesterone and increased local production of PGF2α are thought to result in uterine contractions and hence termination of pregnancy. Thus sequential therapy with antiprogestin and a PG analog may mimic the physiological events of a spontaneous abortion.