THE METABOLISM OF ETHINYL ESTRADIOL IN MAN*

Abstract

IN REVIEWING the literature on ethinyl estradiol, Thompson has pointed out that despite the increasing clinical use of this orally potent estrogen, there is a relative paucity of information on the more subtle details of its fate in the various parts of the body, such as its site of inactivation, degradation products, path of excretion, and effect on the pituitary (1). As part of a study on the metabolism of therapeutic doses of the natural estrogens in man we reported that we were unable to detect colorimetrically, measurable amounts of estradiol, estrone, and estriol in the urine following oral treatment with 1.0 mg. of ethinyl estradiol, where as a somewhat similar dose (2.0 mg.) of α-estradiol yielded measurable amounts of all three of these estrogens in the urine (2, 3). Apparently no other studies of the urinary estrogen excretion products of ethinyl estradiol have been reported. In view of the important implications of such a study with regard not only to the intermediary metabolism of this derivative of α-estradiol, but to the mode of action of the natural estrogens as well, it seemed of interest to reinvestigate at higher dosage levels and with a more rigorous fractionation procedure (4), the metabolism of ethinyl estradiol in man. The results of 4 of these studies form the subject matter of this report.