Keenan, L., Kerr, T., Duane, M., & Van Gundy, K. (2018). Systematic Review of Hormonal Contraception and Risk of Venous Thrombosis. The Linacre Quarterly, 85(4), 470-477. https://doi.org/10.1177/0024363918816683
Keenan L, Kerr T, Duane M, Van Gundy K. Systematic Review of Hormonal Contraception and Risk of Venous Thrombosis. Linacre Q. 2018;85(4):470-477. doi:10.1177/0024363918816683
Keenan, Lynn, et al. "Systematic Review of Hormonal Contraception and Risk of Venous Thrombosis." The Linacre Quarterly, vol. 85, no. 4, 2018, pp. 470-477.
Most hormonal contraception linked to 3 to 9 times the clot risk
A 2018 review of 15 observational studies in healthy women found hormonal contraception, a suppressive medication, was linked to three to nine times the risk of blood clots in veins. The levonorgestrel IUD did not raise risk.
Study at a glance, observational studies of 15 observational studies: Hormonal contraception was linked to higher clot risk in a 2018 review. Source: Keenan L et al., 2018, PMID 32431379.
Key Findings
Of 1,962 publications retrieved, 15 met the criteria: twelve case control studies and three cohort studies, published between 1995 and 2017.
Second-generation oral contraceptives carried odds ratios of 2.79–4.07. Third-generation pills ranged from 4.0 to 48.6, with most studies falling between 4 and 9.
Vaginal rings carried a relative risk of 6.5 (4.7–8.9), patches 7.9 (3.5–17.7), and depot-medroxyprogesterone injections 3.6 (1.8–7.1).
Etonogestrel implants showed a nonsignificant increase at 1.4. One cohort study of the levonorgestrel intrauterine device found a relative risk of 0.6 (0.4–0.8).
A Swedish death registry study found a relative risk of 18.8 for fatal venous thrombosis among women aged fifteen to twenty-four using oral contraceptives.
Interpretation
This review analyzed 15 observational studies of hormonal contraception and venous thromboembolism risk, published between 1995 and 2017. Using the minimum threefold risk increase and about 13 million users, the authors calculate an estimated 300 to 400 deaths a year among healthy women in the United States from contraceptive-associated blood clots. The authors note that randomized trials of hormonal contraception lasting beyond a few months have not been conducted. The findings support larger studies of long-term clotting risk in women using these methods.
RRM Context
Restorative reproductive medicine treats the ovulatory cycle as a vital sign and works with it. Hormonal contraception suppresses that cycle. The authors advise that women learn these risks and be offered fertility awareness-based methods. They state that several such methods have no medical side effects and work about as well as typical pill use, citing a 2013 review.
Our editorial summary of this paper, not the article's abstract.
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.
