Effect of long-term treatment of norethisterone on the ovary of the cycling albino rat.

The effects of long-term administration of norethisterone, a progestogen-only contraceptive, at a dose of 0.5 mg/rat daily for 75 days, were evaluated in the ovary of cycling rats using histomorphic and karyokinetic (by colchicine technique) techniques. Norethisterone induced follicular atresia, decreased the number of normal follicular population and altered the appearance of the interstitial gland. Atresia was markedly noticed particularly in the follicles less than 200 micron in diameter. In addition, fresh or old corpora lutea were not found in the ovary. Simultaneously the progestin also stimulated the mitotic activity in the granulosa and theca of the normal follicles, especially of 201-300 micron in diameter. The findings suggest that norethisterone causes antifertility mainly by preventing follicular development and inducing atresia, thereby inhibiting perhaps ovulation.