The ability to block steroidogenesis with 4,4,17-[alpha] -trimethylandrost- 5-eno[2,3,-d]isoxazol-17-ol (azastene) was studied in 3 different models. Oral administration of 500 mg to rhesus monkeys on different days of their luteal phase induced marked depression of circulating progesterone concentrations, and in some cases early onset of menses. Simultaneous administration of human chorionic gonadotropin (hCG) during the midluteal phase did not overcome the luteolytic effect of azastene. Concentrations of 50 [mu] g/ml of azastene inhibited testosterone secretion by decapsulated mice testes in vitro in response to hCG [controls, 1165 +/- 196 ng/ml, azastene, 306 +/- 40 ng/ml (P<.01)]. Production of progesterone by dispersed luteal cells from rhesus monkey corpora lutea was markedly inhibited by the presence of 25 and 50 /ug/ml azastene in the incubation media (P<.05 and<.01, respectively). The availability of a compound that blocks in vivo and in vitro gonadal steroidogenesis opens a new approach to postcoital contraception in primates because of its luteolytic and interceptive activity. The possible mechanisms of action of azastene are discussed.
(C) 1982 The American College of Obstetricians and Gynecologists