Comparison of the long-term endometrial effects of synthetic progestins used in fertility control

Abstract

With the widespread use of progestational hormones as oral contraceptives the impact of these agents on the endometrium led to an evaluation of 2 representative preparations norethindrone (a 19-nor steroid) and chlormadinone (a 17-acetoxyprogesterone derivative) in order to study the changes resulting from the long-term cyclic use of these compounds. One group of women received a combination of 60 mcg mestranol and 10 mg norethindrone and the other group received a combination of 80 mcg mestranol and 2 mg chlormadinone. Almost 1100 endometrial biopsies were made. The endometria of the norethindrone subjects were completely different from those of the normal cycle the postmenopausal period and those produced during the first cycle of oral progestin treatment. The morphological picture was one of inhibition of endometrial growth and especially of glandular development reaching a stable degree of involution soon after the third cycle of treatment. Stromal edema and minor degrees of predecidual change continued to develop to about the same extent even after 36 months of cyclic treatment. The endometria of the chlormadinone subjects were markedly underdeveloped with transitory minimal and irregular secretory changes. By Day 19 or later the tissue was similar to an atrophic postmenopausal endometrium except that the stroma instead of having a fibrous appearance showed edema and cells with pyknotic nuclei. These endometria showed the same general differences in comparison to norethindrone as were observed during the initial cycle of treatment i.e. earlier and more marked glandular involution less secretion slightly more intense edema and less frequent predecidual reaction.