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Cardiovascular Risk Associated With the Use of an Etonogestrel-Containing Vaginal Ring

Dinger, Jürgen MD, PhD; Möhner, Sabine PhD; Heinemann, Klaas MD, PhD

doi: 10.1097/AOG.0b013e3182a5ec6b
Original Research

OBJECTIVE: To compare the risks of short-term and long-term use of an etonogestrel-containing and ethinylestradiol-containing vaginal ring and combined oral contraceptive pills (OCPs) in a routine clinical study population.

METHODS: This was a prospective, controlled, noninterventional cohort study performed in the United States and five European countries with the following two cohorts: new users of the vaginal ring and new users of combined OCPs (starters, switchers, or restarters). The study population included 33,295 users of the vaginal ring or combined OCPs recruited by 1,661 study centers. Follow-up of study participants occurred for 2 to 4 years. Main clinical outcomes of interest were cardiovascular outcomes, particularly venous and arterial thromboembolism. These outcomes were validated by attending physicians and further adjudicated by an independent board. Comprehensive follow-up ensured low loss to follow-up. Statistical analyses were based on Cox regression models. Primary statistical variable was the venous thromboembolic hazard ratio (HR) for the vaginal ring compared with combined OCPs.

RESULTS: Study participants were followed-up for 66,489 woman-years. Loss to follow-up was 2.9%. The venous thromboembolism incidence rates for the vaginal ring users and combined OCPs users were 8.3 and 9.2 per 10,000 woman-years, respectively. Cox regression analysis yielded crude and adjusted HRs for the vaginal ring users compared with combined OCPs users of 0.9 and 0.8 for venous thromboembolism (95% confidence intervals [CIs] 0.5–1.6 and 0.5–1.5) and 0.8 and 0.7 (95% CIs 0.2–2.5 and 0.2–2.3) for arterial thromboembolism, respectively.

CONCLUSION: Vaginal ring use and combined OCP use were associated with a similar venous and arterial thromboembolic risk during routine clinical use.


The contraceptive vaginal ring, which contains etonogestrel and ethinylestradiol, has a similar risk for venous and arterial thromboembolism as combined oral contraceptive pills.

ZEG-Berlin Center for Epidemiology and Health Research, Berlin, Germany.

Corresponding author: Jürgen Dinger, MD, PhD, Bundesratufer 9A, 10555 Berlin, Germany; e-mail:

Funding provided by Organon NV, the Netherlands (now Merck & Co). The study was supervised by an independent Safety Monitoring and Advisory Council that had full authority over the study (including study protocol, protocol amendments, data analysis, and stopping the study). The funder had no access to the source data and did not participate in designing or analyzing the study.

Presented at the 2012 annual meeting of the American College of Obstetricians and Gynecologists, May 5–9, 2012, San Diego, California. Interim results were presented at the 2011 annual meeting of the American Society for Reproductive Medicine, October 15–19, 2011, Orlando, Florida.

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2013 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.