Endogenous estradiol metabolism during treatment with oral contraceptives.

Objective: Recent clinical studies indicate that an increase in 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. Methods: Two studies were conducted firstly comparing 2 different progestins i.e. norethisterone and dienogest each in combination with a constant ethinyl estradiol dosage (study A) and secondly comparing a single progestin i.e. levonorgestrel in 2 ethinyl estradiol/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 8-h night-urine collected before and after 3 cycles of OC administration. Results: In study A i.e. ethinyl estradiol 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 ethinyl estradiol and dienogest was significantly lower after treatment. In study B i.e. ethinyl estradiol plus levonorgestrel (0.03 mg/0.15 mg and 0.02 mg/0.1 mg) 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. Conclusions: 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 considered to increase breast cancer risk. (authors)