Formation of ethinyl estradiol in women during treatment with norethindrone acetate.
BACKGROUND
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).
Chu
Micheline C
MC
Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Zhang
Xiaohua
X
Gentzschein
Elisabet
E
Stanczyk
Frank Z
FZ
Lobo
Rogerio A
RA
D000328:Adult; D019540:Area Under Curve; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004997:Ethinyl Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077563:Norethindrone Acetate; D017697:Premenopause
D003280:Contraceptives, Oral, Synthetic; D004997:Ethinyl Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone