Formation of ethinyl estradiol in women during treatment with norethindrone acetate

J Clin Endocrinol Metab. 2007 Jun;92(6):2205-7. doi: 10.1210/jc.2007-0044. Epub 2007 Mar 6.


Context: The significance of the conversion of norethindrone acetate (NET-A), a commonly prescribed, synthetic, oral progestogen, to ethinyl estradiol (EE(2)) is controversial.

Objective: 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.

Results: 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.

Conclusions: 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).

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Area Under Curve
  • Contraceptives, Oral, Synthetic / administration & dosage
  • Contraceptives, Oral, Synthetic / pharmacokinetics*
  • Ethinyl Estradiol / blood*
  • Female
  • Humans
  • Norethindrone / administration & dosage
  • Norethindrone / analogs & derivatives*
  • Norethindrone / pharmacokinetics
  • Norethindrone Acetate
  • Premenopause


  • Contraceptives, Oral, Synthetic
  • Ethinyl Estradiol
  • Norethindrone Acetate
  • Norethindrone