Endogenous estradiol metabolism during treatment with oral contraceptives
Mueck, A.O.; Seeger, H.; Wallwiener, D.
International Journal of Clinical Pharmacology and Therapeutics 42(3): 160-164
2004
ISSN/ISBN: 0946-1965 PMID: 15049436 Document Number: 577194
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. 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 considered to increase breast cancer risk.