Norethisterone, a Major Ingredient of Contraceptive Pills, Is a Suicide Inhibitor of Estrogen Biosynthesis

Abstract
Norethisterone (17 alpha-ethynyl-19-nortestosterone) is an effective irreversible inhibitor of estrogen synthetase (aromatase), the enzyme responsible for the conversion of androgens to estrogens, even at a 2 X 10(-6) molar concentration. This irreversible inactivation, which is directed toward the active site of aromatase and requires the cofactor-reduced nicotinamide adenine dinucleotide phosphate, is both time- and concentration-dependent. Ethisterone (17 alpha-ethynyltestosterone), in contrast, is not a suicide inhibitor of aromatase even at concentrations of 10(-4) molar.