pregnenolone, which in turn is converted into progesterone by the Δ5-3β-hydroxysteroid dehydrogenase enzyme complex (3β-HSD) (Dorfman, 1973). Several synthetic progestogens have been shown to be capable of inhibiting ovarian 3β-HSD activity (Shinada et al., 1978), but clinical exploitation of this "antiprogestational" effect has been prevented by the intrinsic progestational activity of these compounds. Of more clinical interest is the series of steroidal 3β-HSD inhibitors that includes azastene, trilostane, and epostane. Cyanoketone also belongs to this series, but this compound is unsuitable for fertility regulation because it causes irreversible inhibition of 3β-HSD (Goldman, 1967).

Although azastene, trilostane, and epostane are competitive inhibitors of 3β-HSD, the compounds differ with regard to their relative potency in vivo as inhibitors of adrenal or ovarian/placental steroidogenesis. Azastene and epostane appear to be preferential inhibitors of ovarian and placental steroidogenesis rather than of adrenal hormone production, at least in primates (Schane et al., 1978; Creange et al., 1981). Epostane is the more potent of these two compounds; hence virtually all of the studies in primates, including the human, have been done with this inhibitor. A detailed review of these studies has been published (Van Look and Bygdeman, 1989).

As one might expect, the clinical effects of epostane administration are not unlike those resulting from treatment with a progesterone-receptor blocker such as mifepristone. Repeated dosing during the midluteal phase of the cycle causes premature menstruation in the majority of subjects, whereas daily treatment from the beginning of the cycle has been shown to modulate or inhibit follicular development and ovulation, depending on the dose used (Rannevik et al., 1988).

When given to pregnant women over a period of several days, the drug induces uterine contractions and increased myometrial reactivity to prostaglandins. In the two largest efficacy trials conducted (Birgerson et al., 1987; Crooij et al., 1988), a seven-day course with epostane (four times 200 mg/day) resulted in 89 (84 percent) complete abortions among 106 women with amenorrhea of less than 56 days. The limited experience that is available suggests that, as with mifepristone, the complete abortion rate can be increased significantly by complementing the epostane treatment with a prostaglandin analogue in a sequential regimen (Webster et al., 1985). Like mifepristone, administration of epostane during the second trimester of pregnancy augments uterine sensitivity to exogenous prostaglandins and significantly shortens the time needed to induce abortion with extra-amniotically administered prostaglandin E2 (Selinger et al., 1987).

Epostane and related molecules were synthesized by the pharmaceutical company Sterling-Winthrop. When this firm was taken over by the Eastman-Kodak company, epostane was no longer made available to



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