Biological spectrum of two spirolactone derivatives with some observations on anti-fertility activity

Bioassays were conducted to determine various endocrinological properties of two spirolactone derivatives, 4',5'-dihydrospiro-[estr-4-ene-17,2'(3'H)-furan]-3-one (Compound I) and dispiro[cyclopropane-1,6'-estr-4'-ene-17',2"(3"h)-furan]-3'-one (Compound II). They proved to be very potent estrogen antagonists in immature mice and castrate ewes and neither exhibited inherent estrogenicity. They were moderately active as progestins and gonadotropin inhibitors. Compound II possessed slight androgenic activity and was more active orally than I. Compound I underwent a limited amount of testing in normally cycling rhesus monkeys. It was found to increase viscosity of the cervical mucus and, in oral doses of 0.5 or 2.0 mg/day, prevented pregnancy. One animal given 0.5 mg/day did become pregnant in her first treatment cycle, probably before a drug effect had been established. The results obtained indicate both compounds have potential utility as low-dose oral contraceptives.