Cardiovascular risk associated with the use of an etonogestrel-containing vaginal ring

Obstet Gynecol. 2013 Oct;122(4):800-808. doi: 10.1097/AOG.0b013e3182a5ec6b.


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.

Level of evidence: : II.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Contraceptives, Oral, Combined / adverse effects*
  • Desogestrel / adverse effects
  • Desogestrel / analogs & derivatives*
  • Drug Combinations
  • Ethinyl Estradiol / adverse effects*
  • Female
  • Humans
  • Product Surveillance, Postmarketing
  • Prospective Studies
  • Risk Assessment
  • Venous Thromboembolism / etiology*
  • Young Adult


  • Contraceptives, Oral, Combined
  • Drug Combinations
  • NuvaRing
  • Ethinyl Estradiol
  • Desogestrel