Systematic Review of Hormonal Contraception and Risk of Venous Thrombosis

Abstract

Background: Hormonal contraception (HC) is widely used throughout the world and has been associated with venous thrombosis (VT) such as deep vein thrombosis, pulmonary emboli, and cerebral VT. Objectives: To provide a current comprehensive overview of the risk of objectively confirmed VT with HC in healthy women compared to nonusers. Search methods: PubMed was searched from inception to April 2018 for eligible studies in the English language, with hand searching from past systematic reviews. Selection criteria: We selected original research evaluating risk of objectively confirmed VT in healthy women taking oral or nonoral HC compared with nonusers. Data collection: The primary outcome of interest was a fatal or nonfatal VT in users of HC compared to nonusers or past users. Studies with at least twenty events were eligible. Adjusted relative risks with 95 percent confidence intervals were reported. Three independent reviewers extracted data from selected studies. Results: 1,962 publications were retrieved through the search strategy, with 15 publications included. Users of oral contraception with levonorgesterol had increased risk of VT by a range of 2.79–4.07, while other oral hormonal preparations increased risk by 4.0–48.6. Levonorgestrel intrauterine devices did not increase risk. Etonogestrel/ethinyl estradiol vaginal rings increased the risk of VT by 6.5. Norelgestromin/ethinyl estradiol patches increased risk of VT by 7.9. Etonogestrel subcutaneous implants by 1.4 and depot-medroxyprogesterone by 3.6. The risk of fatal VT was increased in women aged fifteen to twenty-four by 18.8-fold. Conclusion: Users of HC have a significant increased risk of VT compared to nonusers. Current risks would project at least 300–400 healthy young women dying yearly in the United States due to HC. Women should be informed of these risks and offered education in fertility-awareness-based methods with comparable efficacy for family planning. Summary: HC is widely used throughout the world and has been associated with blood clots in the legs and lungs. We searched the literature and found the risks of currently used forms of birth control increased between three- and ninefold for blood clots for healthy women. The risks found would project 300–400 women dying from using HC each year in the United States.