Formation of Ethinyl Estradiol in Women during Treatment with Norethindrone Acetate

• Published in: The journal of clinical endocrinology and metabolism Vol. 92; no. 6; pp. 2205 - 2207
• Main Authors: Chu, Micheline C., Zhang, Xiaohua, Gentzschein, Elisabet, Stanczyk, Frank Z., Lobo, Rogerio A.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.06.2007; Endocrine Society
• Subjects: 17β-Estradiol; Acetic acid; Adult; Area Under Curve; Biological and medical sciences; Contraceptives, Oral, Synthetic - administration & dosage; Contraceptives, Oral, Synthetic - pharmacokinetics; Ethinyl Estradiol - blood; Ethinylestradiol; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Norethindrone - administration & dosage; Norethindrone - analogs & derivatives; Norethindrone - pharmacokinetics; Premenopause; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Ethinylestradiol; Human; Nutrition; Estrogen; Metabolic diseases; Acetate; Ovarian hormone; Progestagen; Treatment; Adult; Female; Contraceptive; Norethisterone; Sex steroid hormone; Woman; Formation; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2007-0044

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 before drug 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.