Inherent Estrogenicity of Norethindrone and Norethynodrel: Comparison with Other Synthetic Progestins and Progesterone1

Abstract

A series of progestins was tested in men and women for estrogenicity as judged by clinical results and biological estrogen assay of the urine. A sharp division was found between norethynodrel and norethindrone, on the one hand, and ethisterone, progesterone, 17α-hydroxyprogesterone caproate, 17α-vinyl-19-nortestosterone and norethandrolone, on the other. The former were both converted to estrogen and contained estrogen (3-MEE) as a contaminant, whereas the latter progestins were totally nonestrogenic. This estrogenic property of norethynodrel and norethindrone appears to account for their greater progestational potency (synergism with estrogen) as well as for their somewhat different therapeutic response and side-reactions. It is postulated that the absence of the methyl group at the 19 position and the presence of the ethynyl side chain at the 17 position are important in modifying their biologic actions.