Demonstration of an early abortifacient effect of norethisterone (NET) in the primate (baboon).
A long-acting injectable contraceptive which provides continuous controlled release of norethisterone (NET) for three months following a single intramuscular injection was tested for antifertility effects in baboons using a low dose of microcapsules (total NET dose 2.5 mg; daily dose approximately 0.03 mg/day) which has no effect on ovarian function or ovulation. The continuous administration of NET during the cycle of conception had no effect on ovulation, fertilization or implantation as evidenced by the occurrence of nine pregnancies following 23 test matings. Pregnancy was diagnosed by the measurement of baboon chorionic gonadotropin hormone and the maintenance of elevated serum progesterone levels past the normal time of menstruation. Six of the nine pregnancies, however, ended in abortion between days 27 and 35 of pregnancy. The remaining three pregnancies continued to term and normal, healthy babies were delivered. Five control baboons included in this study became pregnant and all delivered normal, healthy infants. The results of this study demonstrate that early abortion should be considered as a mechanism of antifertility action of NET when administered continuously in low doses. These findings are contrary to the generally accepted explanation that low-dose synthetic progestins exert their contraceptive effect by inhibiting sperm transport and/or preventing implantation.
D000022:Abortion, Spontaneous / Q000139:chemically induced*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000097:blood; D003692:Delayed-Action Preparations; D005260:Female; D008183:Luteal Phase; D008863:Microspheres; D009640:Norethindrone / Q000097:blood / Q000494:pharmacology*; D010060:Ovulation / Q000187:drug effects; D010215:Papio; D011247:Pregnancy; D011374:Progesterone / Q000097:blood
D006063:Chorionic Gonadotropin; D003692:Delayed-Action Preparations; D011374:Progesterone; D009640:Norethindrone