FIGURE B1.1 Mifepristone (RU 486).

limit the population explosion. During those decades, ideas for new methods of contraception emerged as biology became focused more on the cellular and molecular elements of regulation of the reproductive system. The hormone-responsive proteins of target cells in the reproductive tract (termed receptors) were discovered, while progesterone (P), designated as the hormone of gestation (pro gestare) by Corner (in 1932) (Corner, 1963), was now easy to quantitate by radioimmunoassays (Lieberman et al., 1959). The uterine progesterone receptor (PR) (Milgrom et al., 1970) and the synthesis and action of prostaglandins (PG) (Bergström et al., 1972) were described, while the role of progesterone in the establishment and maintenance of pregnancy in women was demonstrated (Csapo and Pulkkinen, 1977). As it became clear that progesterone is involved at all steps of the reproductive processes, antagonists of progesterone were actively sought. As early as 1975, the concept of a "midcycle" contraceptive, a method based on progesterone receptor down-regulation with an "antiprogesterone" ligand, was proposed (Baulieu, 1975). Now, in 1993, we have a number of efficient antiprogestins. Although induction of abortion has been the most immediate application of such compounds, other potential applications include delivery, contraception, and treatment of several hormone-dependent diseases.

When developing a procedure for the termination of pregnancy in women, it is important to be aware of both moral and physiological ideals, as well as psychological concerns. For centuries, abortion has been not only a morally difficult event for women, but also a physically painful and often dangerous procedure. A medical means for pregnancy termination should diminish this threat to women's health and, in turn, allow them to maintain their dignity. Furthermore, the distinction between abortion and contraception has lessened because the beginning of pregnancy is now understood, in physiological terms, to be a progression of steps. Hence, the term "contragestion" was proposed (Baulieu, 1985, 1989a, b) to clearly designate a method that can provoke pregnancy interruption (contra gestation) and operates as soon as possible after fertilization might have occurred, before the word abortion is appropriate (is an IUD considered an abortifacient?, see later discussion). This change in concept may be one of the most important outcomes of RU 486 development and usage.



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