A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception
Open accessAbstract
BACKGROUND: Combined oral contraceptives (COCs) containing various progestogens could be associated with differential risks for venous thromboembolism (VTE). OBJECTIVE: To evaluate the comparative risks of VTE associated with the use of low-dose (less than 50 μg ethinyl estradiol) COCs containing different progestogens. SEARCH STRATEGY: PubMed and the Cochrane Library were searched from database inception through September 15, 2016, by combining search terms for oral contraception and venous thrombosis. SELECTION CRITERIA: Studies reporting VTE risk estimates among healthy users of progestogen-containing low-dose COCs were included. DATA COLLECTION AND ANALYSIS: A random-effects model was used to generate pooled adjusted risk ratios and 95% confidence intervals; subgroup and sensitivity analyses assessed the impact of monophasic-COC use and study-level characteristics. MAIN RESULTS: There were 22 articles included in the analysis. The use of COCs containing cyproterone acetate, desogestrel, drospirenone, or gestodene was associated with a significantly increased risk of VTE compared with the use of levonorgestrel-containing COCs (pooled risk ratios 1.5-2.0). The analysis restricted to monophasic COC formulations with 30 μg of ethinyl estradiol yielded similar findings. After adjustment for study characteristics, the risk estimates were slightly attenuated. CONCLUSIONS: Compared with the use of levonorgestrel-containing COCs, the use of COCs containing other progestogens could be associated with a small increase in risk for VTE.
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In the general population, CPA increases the risk of venous thromboembolism compared with other COCP.
“General population studies have shown that CPA increases the risk of venous thromboembolism compared with other COCP (71, 72); hence, COCPs containing CPA are currently not recommended as first-line treatments for PCOS (20).”
From Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis (2024) · cites this paper as [71]
The Results report that cyproterone acetate (CPA)-containing combined oral contraceptives were associated with increased VTE risk compared with levonorgestrel-containing contraceptives. The claim broadens that specific comparator to “other COCP” generally and states the association as a causal increase. Page numbers are unavailable in our copy. (LLM, conf=0.87)
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- Authors
- Dragoman, M. V., Tepper, N. K., Fu, R., Curtis, K. M., Chou, R., & Gaffield, M. E.
- Affiliations
- World Health Organization (CH)
- Centers for Disease Control and Prevention (US)
- Oregon Health & Science University (US)
- Corresponding author
- Tepper, Naomi K.
- Venue
- International Journal of Gynecology & Obstetrics
- Publisher
- Wiley
- Published
- 2018-02-22
- Volume
- 141
- Issue
- 3
- Pages
- 287-294
- ISSN
- 0020-6695 (ISSN-L)
- 0020-7292
- 1879-3479
- PMC
- PMC5969307
- OpenAlex
- W2790432733
- Cited by
- 253
- References
- 53
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 34 · 2023: 45 · 2022: 30 · 2021: 39 · 2020: 32 · 2019: 18 · 2018: 10
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- International Journal of Gynecology & Obstetrics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- World Health Organization
- National Institute of Child Health and Human Development
- United States Agency for International Development
- Topics
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- venous thromboembolism, combined oral contraceptives, progestogens, levonorgestrel, cyproterone acetate, desogestrel, drospirenone, gestodene, monophasic oral contraceptives, thrombosis risk
- MeSH terms
- Contraceptives, Oral, Combined, Ethinyl Estradiol, Female, Humans, Progestins, Risk, Odds Ratio, Venous Thrombosis, Venous Thromboembolism
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