Central Versus Endometrial Effects of Antiprogestins: Is Endometrial Selectivity Possible?

Progesterone is a key hormone in the regulation of many reproductive processes, including the establishment and maintenance of pregnancy. During the luteal phase, progesterone stimulates the development and maturation of the endometrium. It has long been recognized that compounds which interfere with synthesis of progesterone or block its action may offer a significant advantage in fertility control (Baulieu 1975), since exact synchrony between embryonic development and the state of the endometrium seems to be essential for successful implantation (Navot et al. 1991). Several antiprogestins which bind to the progesterone receptor, thereby preventing progesterone from expressing its biological effect, have been developed. Among these are mifepristone (Roussel Uclaf, Paris, France) and onapristone and lilopristone (Schering AG, Berlin, Germany). The effect of these two compounds has mainly been tested in various animal species, including nonhuman primates. Mifepristone in humans and onapristone in bonnet monkeys have both been shown to prevent pregnancy by affecting endometrial development (Glasier et al. 1992; Gemzell-Danielsson et al. 1993; Katkam et al. 1995).