Impact of combined oral contraceptives containing ethinylestradiol on the liver microsomal metabolism

Abstract

Objectives To check whether currently used combined oral contraceptives (COCs) containing ethinylestradiol (EE) affect the liver microsomal metabolism. Methods 13C-methacetin breath test (13C-MBT) – a sensitive non-invasive probe of cytochrome P-450 1A2 activity – was performed in 15 women on day 14, 15, 16, 17 or 18 of intake of their COC (containing EE), and between day 1 and 5 during the withdrawal bleeding, as well as in nine women not using hormonal contraception during the luteal phase of their cycle (between the 17th and the 23rd day), and between day 1 and 5 during menstruation. Results The maximum breath 13C elimination was significantly lower during the phase of intake of contraceptive pills than during withdrawal bleeding: 31.5 ± 2.2 %/h vs. 38.2 ± 1.9 %/h (p = 0.0045), whereas the time to reach it was similar on the two study days: 21.2 ± 1.2 min vs. 21.0 ± 1.1 min. Between the 27th and the 180th min of observation the cumulative breath 13C elimination was statistically significantly lower during intake of the pill than during withdrawal bleeding. No significant menstrual cycle phase-dependent fluctuations in the results of the 13C- methacetin breath test were observed in the control group. Conclusion COCs containing EE markedly inhibit hepatic microsomal function. This phenomenon must be taken into consideration when interpreting results of 13C-MBT.