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Am J Physiol Heart Circ Physiol (February 2, 2007). doi:10.1152/ajpheart.00762.2006
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Submitted on July 14, 2006
Accepted on January 30, 2007

ENDOTHELIAL FUNCTION ACROSS AN ORAL CONTRACEPTIVE CYCLE IN WOMEN USING LEVONORGESTREL AND ETHINYL ESTRADIOL

Britta N Torgrimson1, Jessica R Meendering1, Paul F Kaplan2, and Christopher T. Minson3*

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

* To whom correspondence should be addressed. E-mail: minson{at}uoregon.edu.

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 to 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 oral contraceptive pill use in women.




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