Combined oral contraceptives affect liver mitochondrial activity.

Objectives: To examine liver mitochondrial function in women using combined oral contraceptives (COCs) containing ethinylestradiol.

Methods: A breath test after oral administration of 1 mg/kg (13)C-alpha-ketoisocaproic acid ((13)C-KICA) and 20 mg/kg L-leucine was performed twice: (i) in 15 women on day 14, 15, 16, 17 or 18 of COC intake, and between day 1 and 5 of the withdrawal bleeding; and (ii) in 15 regularly menstruating females not taking hormonal contraceptives: during the luteal phase, between the 18th and the 22nd day of the cycle, and again between day 1 and 5 of the menstruation.

Results: In women on COCs the maximum (13)C elimination in breath air (Dmax) was higher (26.8 ± 1.6%/h) than during withdrawal bleeding (23.5 ± 1.2%/h; p = 0.012). The time to reach the Dmax was similar on the two study days: 33.3 ± 2.4 min during the phase of pill intake vs. 37.0 ± 2.5 min during the pill-free interval. The one-hour cumulative breath (13)C elimination was greater after two weeks of COC intake than during the withdrawal bleeding: 17.49 ± 1.03% vs. 15.32 ± 0.85% (p = 0.024). In the control group no menstrual cycle phase-dependent fluctuations in the results of the (13)C-KICA breath test were observed.

Conclusion: The metabolism of (13)C-alpha-ketoisocaproic acid augments during the intake of COCs containing ethinylestradiol, reflecting enhanced liver mitochondrial metabolic activity.