Prostaglandins and antigestagens for the interruption of early pregnancy

Abstract

During pregnancy the uterus is maintained in a quiescent state by the secretion of progesterone. Antigestagens antagonize the biological action of progesterone by binding to the nuclear receptor in the target organs. Administration of the antigestagen mifepristone to women induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. In addition, the sensitivity of the myometrium to exogenous prostaglandins is markedly increased. Although mifepristone will induce bleeding in the majority of women in early pregnancy, the incidence of incomplete abortion or ongoing pregnancies increases with increasing gestational age and is too high to be clinically useful as an agent for therapeutic abortion. However, a single dose of mifepristone (400-600 mg) followed by a vaginal pessary of a prostaglandin analogue (0.5-1.0 mg), gemeprost, induced complete abortion in 95 of 100 women of gestational age less than 42 days (less than or equal to 56 days amenorrhoea). The incidence of diarrhoea (15%) and abdominal pain requiring opiate analgesia (10%) was much lower than when abortion was induced with prostaglandin alone. Vaginal bleeding continued for 13.8 +/- 0.8 days after administration of the prostaglandin. A combination of an antigestagen with a small dose of a prostaglandin analogue is an effective alternative to vacuum aspiration for the therapeutic termination of early pregnancy.