Endothelial Function, Endothelin-1, and Fibrinogen in Young Women Using the Vaginal Contraceptive Ring

Abstract

Objective-To assess the effects of the vaginal contraceptive ring cycle on indices of cardiovascular health and risk by studying healthy women during the active hormone phase compared with the ring-free phase of a standard 21/7-day cycle.Design-Observational prospective cohort; 4 weeks' duration. Setting-Department of Human Physiology, University of Oregon. Patient(s)-Twenty healthy women.Intervention(s)-Endothelial function testing using standard flow-mediated vasodilation of the brachial artery and sublingual nitroglycerin administration. All participants underwent venous blood collection.Main Outcome Measure(s)-Endothelium-dependent and endothelium-independent vasodilation of the brachial artery using Doppler ultrasound imaging. Baseline levels of highdensity lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, endothelin-1, and fibrinogen. Result(s)-The active hormone phase of thevaginal ringcycle showed significantly higher vasodilation compared with the ring-free phase. The active hormone phase also showed increased fibrinogen levels compared with the ring-free phase. Low-density lipoprotein lipid levels also fluctuated and were significantly higher during the ring-free phase. Conclusion(s)-Preliminarystudy observations of improved endothelial function and lowered low-density lipoprotein levels during the active hormone phase versus the ring-free phase suggest that the vaginal contraceptive ring has beneficial effects on vascular health in women. KeywordsEstradiol; etonorgestrel; hormone delivery; vascular health; hormonal contraception; flowmediated dilation; progestin; estrogen Reprint requests to: Christopher T. Minson, Human Physiology, University of Oregon, 122 C Esslinger Hall, Eugene, OR 97403 (FAX: 541-346-7841; minson@uoregon.edu). B.T. has nothing to disclose. J.M. has nothing to disclose. N.M. has nothing to disclose. P.K. has nothing to disclose. C.M. has nothing to disclose.Presented at the 56th Annual Meeting, Pacific Coast Reproductive Society, Rancho Las Palmas Resort and Spa, Palm Springs, Florida, April 9-13, 2008. NIH Public Access Although decades of research have consistently shown that oral contraceptives increase the relative risk for vascular thromboembolic events (1-3), we know much less about nonoral hormonal contraceptives and cardiovascular risk. Historically, vascular thrombosis risk in oral contraceptive pills users has been associated with high oral estrogen dosing (3) and the subsequent effects of oral estrogen on coagulation pathways in the vasculature (4-8). To date, there are few data on coagulation factors and vascular function in women using nonoral hormonal contraceptives.The combination ethinyl estradiol/etonorgestrel monthly vaginal contraceptive ring is considered to be an advantageous route for hormone delivery compared with oral contraceptive pills (OCPs), because it avoids first-pass hepatic metabolism, allows for lower hormone doses, provides steady serum hormone levels, and requires less frequent administration. Compared with oral...

A combined oral contraceptive containing 30 mcg ethinyl estradiol and 3.0 mg drospirenone does not impair endothelium-dependent vasodilation

“…Consistent with these findings, a recent study demonstrated that endothelial function was less in women using a levonorgestrel combined OCP compared to non-users [4]. Additionally, our laboratory has also shown that women using the combined monophasic ethinyl estradiol and etonorgestrel progestin vaginal ring exhibited greater endothelial function when the ring was in place compared to when the ring was absent [2]. …”

Short-term oral progesterone administration antagonizes the effect of transdermal estradiol on endothelium-dependent vasodilation in young healthy women

“…Data were collected and analyzed for 9-min postadministration. The administration of nitroglycerine elicits maximum dilation of the conduit arteries (25,26,47,48). EIVD is calculated as the percent change between baseline diameter and peak dilation post-nitroglycerine administration:…”

“…Lizarelli et al (22) also discovered similar responses in FMD in young women, showing that levonorgestrel (when combined with ethinyl estradiol) and depot MPA decrease FMD, compared with that in age-matched controls. Alternatively, our laboratory found an increase in FMD upon the administration of transvaginal etonorgestrel (48) and oral drospirenone when combined with ethinyl estradiol (24), compared with that of their respective placebo weeks. We suspect the specific form of progestogen may cause the varying effects on the cardiovascular system (38) and may be related to variable effects of hormones on NO production and possibly endothelin-1 (25).…”

“…Our laboratory has previously shown that levonorgestrel, desogestrel, and medroxyprogesterone acetate (MPA) all antagonized the effects of ethinyl estradiol on FMD (25,26,47). Conversely, etonorgestrel (via a vaginal ring) and drospirenone did not (24,48). Whereas various progestins produce different effects on the vasculature, it is unknown what effect progesterone itself might have on endothelial function.…”

Is the Vagina an Adequate Route for the Administration of Hormonal Contraceptives?

“…Obviously, the vaginal ring is contraindicated in women predisposed to this condition. Even so, there have been very few cases observed to date in such patients treated with this device, probably due to the low doses of EE employed [46,49,84].…”