PROGESTATIONAL ACTIVITY OF CERTAIN 19-NOR STEROIDS AND PROGRESTERONE DERIVATIVES1

Abstract

Seven 19-norsteroids, 17[alpha]-ethinyl-19-nortestosterone (I), 17[alpha]-ethinyl-5(10)-estraenolone (II), 17[alpha]-ethyl-19-nortestosterone (III), 17[alpha]-methyl-19-nortestosterone (IV), 17[alpha]-propyl-19-nortestosterone (V), 17[alpha]-butenyl-19-nortestosterone (VI), and 17[alpha]-allyl-19-nortestosterone (VII), and two progesterone derivatives[long dash]17[alpha]-hydroxyprogesterone-17-acetate (VIII) and 17[alpha]-hydroxy-6[alpha]-methyl-progesterone acetate (IX) have been administered subcuta-neously or orally into Clauberg rabbits to demonstrate their progestational activity by estimation of endometrial carbonic anhydrase content and measurement of the uterine G/M ratio. The increase of endometrial carbonic anhydrase content induced by treatment with each compound correlates well with that of the G/M ratio which measures uterine proliferation. Similarly, the relative potencies by the enzyme test correspond to those obtained by the G/M assay either in subcutaneous treatment or in oral administration. The relationship between the progestational activity and the length of 17-side-chain in the 17-substituted-19-nor-testosterones found by Saunders et al. (3) seems to be applicable to the potencies obtained by subcutaneous injection but not to those found on oral administration. Among the 17-substituted-19-nortestosterones, the allyl-compound is the most active in the subcutaneous assay, but the most active by oral route is the ethyl-compound. Three 19-norsteroids, I, II and IV are much more active by the oral route than by the subcutaneous route, while the others are quite opposite. The progestational activity of progesterone administered either parenterally or orally is increased by 17[alpha]-acetoxylation, and further increase is obtained by 6[alpha]-methylatisn of this acetate ester.