Effect of oral contraceptives on endogenous estradiol metabolism

Effect of oral contraceptives on endogenous estradiol metabolism

A.O. Mueck, H. Seeger

University Women’s Hospital, Section of Endocrinology and Menopause,

Tuebingen, Germany

Introduction: Recent clinical studies indicate that an increase of

D-ring estradiol metabolites over A-ring metabolites may be a risk factor for

breast cancer. The present work was aimed to investigate the effect of oral

contraceptives (OC) on the endogenous estradiol metabolism in premenopausal


Aims and Methods: Two studies were conducted, firstly comparing two

different progestins i.e norethisterone and dienogest each in combination with a

constant ethinylestradiol dosage (study A) and secondly comparing a single

progestin, i.e. levonorgestrel in two ethinylestradiol/progestin dosage

combinations (study B). The main A- and D-ring metabolites, i.e. 2-OHE1 and

16-OHE1, were measured by enzyme immunoassay in 8h night-urine collected before

and after 3 cycles’ OC administration.

Results: In study A, i.e. ethinylestradiol plus dienogest or

norethisterone acetate, the ratios of 16-OHE1 to 2-OHE1 before administration

were 0.62 and 0.68, and after 3 months 0.31 and 0.54 respectively. The ratio

after ethinylestradiol and dienogest was significantly lower after treatment. In

study B, i.e. ethinylestradiol plus levonorgestrel (0.03 mg/0.15 mg and 0.02 mg/

0.1mg), the ratios before treatment were 0.71 and 0.75 for the higher and the

lower dosages, respectively, which changed not significantly to 0.73 and 0.71

after 3 cycles.

Conclusion: OCs containing norethisterone acetate, dienogest or

levonorgestrel did not have a negative effect on estradiol metabolism, i.e. they

did not elicit a higher D-ring metabolism, which is believed to increase breast

cancer risk.

Scroll to Top