Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins

doi:10.1016/0010-7824(90)90039-X

Contraception

Volume 41, Issue 4, April 1990, Pages 399-410

https://doi.org/10.1016/0010-7824(90)90039-X Get rights and content

Abstract

The progestational and androgenic in vitro receptor binding affinity and the in vivo activity of norgestimate was compared with that of its metabolites and other progestins. The relative binding affinities (RBAs) of norgestimate and its 17-deacetylated metabolite for rabbit uterine progestin receptors were similar to that of progesterone (P); those of 3-keto norgestimate and levonorgestrel were about five times that of P; those of gestodene and 3-keto desogestrel were about nine times that of P. The RBAs of norgestimate, P, and 3-keto norgestimate for rat prostatic androgen receptors were from 0.003 to 0.025 times that of dihydrotestosterone (DHT); those of 3-keto desogestrel, gestodene, and levonorgestrel were from 0.118 to 0.220 times that of DHT. The order of receptor level selectivity represented by the ratio of androgen:progestin IC₅₀ values (with a greater ratio value reflecting a better selectivity) was norgestimate>P = 3-keto norgestimate>17-deacetylated norgestimate>3-keto desogestrel>gestodene>levonorgestrel. In vivo studies demonstrated similar profiles for norgestimate and its 17-deacetylated metabolite. These latter two steroids were equally potent as progestins in stimulating rabbit endometrium, and compared with the other progestins, both steroids exhibited minimal androgenicity as measured by the stimulation of rat prostate growth. In conclusion, these studies, as well as previous preclinical and clinical studies, provide evidence of the selectivity of norgestimate based on minimal androgenicity, indicating an improvement over other progestins used in oral contraceptives.

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Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins

Abstract

Am J Med

Contraception

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J Steroid Biochem

Contraception

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Effect of oral contraceptives on serum lipid and cardiovascular disease

Br J Family Planning