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.
