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Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke
Open accessAbstract
BACKGROUND: Combined oral contraceptives (COCs) have been associated with an increased risk of arterial thrombosis, i.e. myocardial infarction or ischemic stroke. However, as these diseases are rare in young women and as many types of combined oral contraception exist, the magnitude of the risk and the effect of different hormonal contents of COC preparations remain unclear. OBJECTIVES: To estimate the risk of myocardial infarction or ischemic stroke in users compared with non-users of different types, doses and generations of combined oral contraception. SEARCH METHODS: We searched electronic databases (MEDLINE (1966 to July 08, 2015), EMBASE (1980 to July 08, 2015), Popline (1970 to July 08, 2015) and LILACS (1985 to July 08, 2015) for eligible studies, without language restrictions. SELECTION CRITERIA: We included observational studies that recruited women in the reproductive age group (18 to 50 years) and compared the risk of myocardial infarction or ischemic stroke between users and non-users of COCs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected relevant studies and extracted data. We pooled relative risks ()(combined odds ratios and one incidence rate ratio) and 95% confidence intervals (CIs) for myocardial infarction or ischemic stroke in users versus non-users of COCs.We combined the outcomes of myocardial infarction and ischemic stroke and also analysed these outcomes separately. Analyses were stratified according to estrogen dose and progestagen type. MAIN RESULTS: In total, we identified 1298 publications through the search strategy. We included 28 publications reporting on 24 studies. COC users were at increased risk of myocardial infarction or ischemic stroke compared with non-users: relative risk (RR) 1.6 (95% CI 1.3-1.9).These RRs were similar for myocardial infarction (1.6, 95% CI 1.2 to 2.1) and ischemic stroke (1.7, 95% CI 1.5 to 1.9). The risks did not vary clearly according to the generation of progestagen or according to progestagen type. When we stratified preparations according to estrogen dose, the risk of myocardial infarction or ischemic stroke seemed to increase with higher doses of estrogen. AUTHORS' CONCLUSIONS: This meta-analysis showed that the risk of myocardial infarction or ischemic stroke was 1.6-fold increased in women using COCs . The risk was highest for pills with > 50 microgram estrogen. When combined with the results of studies on the risk of venous thrombosis in COC users, it seems that the COC pill containing levonorgestrel and 30 μg of estrogen is the safest oral form of hormonal contraception.
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“Oral contraceptives and non-oral forms of combined hormonal contraceptives were associated with an increased risk of arteriothrombotic events (table 1).55 67 79”
From Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review (2020) · cites this paper as [55]
In the citing paper
“Current users of combined oral contraceptives had a greater risk of developing myocardial infarction and stroke than non-current users of combined oral contraceptives.55”
From Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review (2020) · cites this paper as [55]
In the citing paper
“The same review55 showed that the risk was increased in women on higher doses of oestrogen but was not related to the dose, generation, or type of progesterone (supplementary table 3).”
From Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review (2020) · cites this paper as [55]
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Metadata
- Authors
- Roach, R. E. J., Helmerhorst, F. M., Lijfering, W. M., Stijnen, T., Algra, A., & Dekkers, O. M.
- Affiliations
- Leiden University Medical Center (NL)
- University Medical Center Utrecht (NL)
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2015-08-27
- Volume
- 2018
- Issue
- 3
- Pages
- CD011054-CD011054
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- PMC
- PMC6494192
- OpenAlex
- W2160662478
- Cited by
- 299
- References
- 186
- Citations by year
- 2026: 10 · 2025: 31 · 2024: 34 · 2023: 20 · 2022: 50 · 2021: 33 · 2020: 36 · 2019: 25 · 2018: 27 · 2017: 16 · 2016: 14 · 2015: 2
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- combined oral contraceptives, myocardial infarction, ischemic stroke, arterial thrombosis, estrogen dose, progestogens, hormonal contraception, cardiovascular risk, young women, relative risk, estrogen-progestin combination, thrombosis risk stratification
- MeSH terms
- Contraceptives, Oral, Combined, Estrogens, Female, Humans, Myocardial Infarction, Progestins, Cohort Studies, Case-Control Studies, Risk Assessment, Stroke, Observational Studies as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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