Abstract
Several nonsteroidal estrogens, such as ORF 3858 and F6103, which inhibit pregnancy in experimental animals when given postcoitally, have been previously described. ORF 8511 (1-diphenylmethylenyl-2-methyl-3-ethyl-4-acetoxycyclohexane) which is structurally similar to these compounds was studied for its postcoital antifertility activity and estrogenicity in rats, hamsters, mice and rabbits. Results of these studies suggest a relationship between these two biological endpoints. ORF 8511 produced uterotropic stimulation in the rat at microgram doses and totally inhibited implantation at 250 μg/kg/day administered on days 1–6 of pregnancy. However, the other species were considerably less sensitive to the compound with respect to both parameters. The compound stimulated tubal transport in rats at its minimum effective dose for antifertility activity as did diethylstilbestrol, a known estrogen. In the hamster, a species relatively insensitive to the antifertility effect of ORF 8511, endogenous estrogen titres during early pregnancy were higher than those in the rat. These data suggest that ORF 8511 and similar nonsteroidal compounds may owe their postcoital antifertility activity to their estrogenicity and that estrogens may act as pharmacological agents only in species with low normal endogenous estrogen titres.
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