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Endothelial function across an oral contraceptive cycle in women using levonorgestrel and ethinyl estradiol

¹Department of Human Physiology, University of Oregon, Eugene, Oregon; and ²Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Oregon Health and Sciences University, Portland, Oregon

Submitted 14 July 2006 ; accepted in final form 30 January 2007

Oral contraceptive pills (OCPs) are a popular contraception method. Currently, lower-dose ethinyl estradiol formulations are most commonly prescribed, although they have been linked to increased arterial vascular risk. The aim of this study was to investigate endothelial function in healthy young women using lower-dose ethinyl estradiol OCPs. We examined flow-mediated, endothelium-dependent and nitroglycerin-mediated, endothelium-independent vasodilation of the brachial artery, comparing two doses of ethinyl estradiol/levonorgestrel OCPs in 15 healthy young women on two study days: once during the active phase and once during the placebo phase of an OCP cycle. Group low dose (LD) (n = 7) active pills contained 150 µg levonorgestrel/30 µg ethinyl estradiol versus Group very low dose (VLD) (n = 8) with 100 µg levonorgestrel/20 µg ethinyl estradiol. Endothelium-dependent vasodilation was lower during the active phase in Group VLD (5.33 ± 1.77% vs. 7.23 ± 2.60%; P = 0.024). This phase difference was not observed in Group LD (8.00 ± 0.970% vs. 7.61 ± 1.07%; P = 0.647). Endothelium-independent vasodilation did not differ between phases in either group. Finally, we measured endothelium-dependent vasodilation in two additional women who received 10 µg of unopposed ethinyl estradiol. Endothelium-dependent vasodilation was increased by unopposed ethinyl estradiol compared with the placebo phase (10.88 ± 2.34% vs. 6.97 ± 1.83%). These results suggest that levonorgestrel may antagonize the activity of ethinyl estradiol. Thus both the progestin type and estradiol dose need to be considered when assessing arterial vascular risk of OCP use in women.

progestin; estrogen; hormonal contraception; flow-mediated dilation; birth control pills

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