Abstract
In this study, results are presented on the long-term contraceptive effectiveness in the rats and rabbits of silastic implants containing either norethindrone acetate (ENTA) or norgestrel. A comparison of the relative biological potencies of ENTA administered by silastic capsule and by gavage, using inhibition of compensatory ovarian hypertrophy (COH) as the end point, showed that 25 times less norethindrone acetate was needed when administered by subcutaneous silastic implants than when administered orally. A single implant of ENTA releasing approximately 125 μg of ENTA/24 hr was found to be highly effective in preventing pregnancy in the rats and rabbits up to 4 months. Ovulation, in both species, was not suppressed. The major mode of action of ENTA so administered appeared to be mediated via the inhibition of implantation in the two species. Following removal of implant at the end of the treatment period, the fertility was restored within 1 to 1 1 2 months in rats. The antifertility effects and the mode of action of norethindrone acetate released from subdermal silastic implants are discussed.
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