Formation of ethinyl estradiol in women during treatment with norethindrone acetate

Context: The significance of the conversion of norethindrone acetate (NET-A), a commonly prescribed, synthetic, oral progestogen, to ethinyl estradiol (EE2) is controversial. Objective: We sought to determine accurately the extent to which NET-A may be converted to EE2 and if so, whether circulating levels of EE2 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 EE2 levels beforedrug intake; at 1, 2, 4, 8, and 24 h after the first dose; and 2 h after the seventh dose. Results: The mean EE2 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 EE2 ranged from 0.20 to 0.33% for the different doses. Conclusions: NET-A is converted to EE2 and although the conversion rate is relatively small, higher doses of NET-A, as used clinically, give rise to substantial levels of EE2.