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 women.

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.