Formation of ethinyl estradiol in women during treatment with norethindrone acetate.

Abstract

The significance of the conversion of norethindrone acetate (NET-A), a commonly prescribed, synthetic, oral progestogen, to ethinyl estradiol (EE(2)) is controversial. We sought to determine accurately the extent to which NET-A may be converted to EE(2), and if so, whether circulating levels of EE(2) would be of clinical significance. DESIGN, SUBJECTS, AND INTERVENTIONS: We administered NET-A 10, 20, or 40 mg once daily for 7 d to 20 regularly menstruating premenopausal women and measured NET-A and EE(2) levels before drug intake; at 1, 2, 4, 8, and 24 h after the first dose; and 2 h after the seventh dose. The mean EE(2) maximum serum concentration obtained from the 10-, 20-, and 40-mg doses of NET-A in this study is 58, 178, and 231 pg/ml, respectively. The conversion ratio of NET-A to EE(2) ranged from 0.20 to 0.33% for the different doses. NET-A is converted to EE(2), and although the conversion rate is relatively small, higher doses of NET-A, as used clinically, give rise to substantial levels of EE(2).