Current use of oral contraceptives and the risk of first-ever ischemic stroke: A meta-analysis of observational studies
Abstract
Objective To evaluate the risk of first-ever ischemic stroke associated with current use of oral contraceptive pills (OCPs), and to describe how the risk was influenced by estrogen dose, progestin type, and study characteristics.Methods We obtained relevant articles published between 1970 and March 2014 by conducting a search of Pubmed, Embase and the Cochrane Library. Two investigators independently identified eligible studies based on selection criteria in a two-step method. The quality of studies was assessed with the Newcastle-Ottawa scale. Pooled odds ratios were calculated with a random-effects meta-analysis model.Results A total of 18 independent studies (3 cohort studies and 15 case-control studies) were identified. The overall summary odds ratio for first-ever ischemic stroke risk associated with current OCP use compared with noncurrent OCP use was 2.47 [95% confidence interval (CI), 2.04-2.99]. The risk of ischemic stroke among current OCP users decreased significantly with decreasing estrogen dose: OCPs of ≥50μg ethinyl estradiol (EE), 30-40 ug EE, 20 ug EE and progestin only pills implied odds ratios of 3.28 (95%CI, 2.49-4.32), 1.75 (95%CI, 1.61-1.89), 1.56 (95%CI, 1.36-1.79), and 0.99 (95%CI, 0.71-1.37), respectively. All four generations of progestin were associated with an elevated risk of ischemic stroke, and the risk of ischemic stroke among users of the fourth-generation progestins seemed to be slightly lower than those of other generations of progestins.Conclusions Data from observational studies suggest that current use of modern OCPs is associated with an increased risk of first-ever ischemic stroke. OCPs containing lower estrogen doses incline to contribute to a smaller elevated risk of ischemic stroke.
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Oral contraceptives and non-oral forms of combined hormonal contraceptives are associated with an increased risk of arteriothrombotic events.
“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 [67]
Current users of any oral contraceptive have an increased risk of stroke compared with non-current users.
“Current users of any oral contraceptive (combined oral contraceptives containing a combination of oestrogen and progesterone, or progesterone only pill) had an increased risk of stroke compared with non-current users.67 71”
From Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review (2020) · cites this paper as [67]
The increase in stroke risk for current users of any oral contraceptive is greater for ischaemic stroke than for haemorrhagic stroke.
“The increase in risk was greater for ischaemic stroke67 than haemorrhagic stroke.71”
From Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review (2020) · cites this paper as [67]
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Self-citation
- Authors
- Xu, Z., Li, Y., Tang, S., Huang, X., & Chen, T.
- Affiliations
- Nanjing Medical University (CN)
- Ningbo Center for Disease Control and Prevention (CN)
- Corresponding author
- Li, Ying
- Venue
- Thrombosis Research
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 136
- Issue
- 1
- Pages
- 52-60
- ISSN
- 0049-3848 (ISSN-L)
- OpenAlex
- W1991633668
- Cited by
- 80
- References
- 50
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 10 · 2023: 6 · 2022: 9 · 2021: 5 · 2020: 9 · 2019: 4 · 2018: 3 · 2017: 9 · 2016: 7 · 2015: 1
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thrombosis Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30972542, BM2012062)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- oral contraceptives, ischemic stroke, estrogen dose, ethinyl estradiol, progestins, stroke risk, hormone replacement therapy
- MeSH terms
- Brain Ischemia, Contraceptives, Oral, Estrogens, Female, Humans, Progestins, Risk Factors, Odds Ratio, Stroke, Observational Studies as Topic
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