Current use of oral contraceptives and the risk of first-ever ischemic stroke: A meta-analysis of observational studies.
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.
Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Zhenlin
Z
Xu
Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: liying2008@qq.com.
Ying
Y
Li
Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Shaowen
S
Tang
Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Xiaoping
X
Huang
Ningbo Municipal Center for Disease Control and Prevention, Ningbo, China.
Tong
T
Chen
D002545:Brain Ischemia / Q000139:chemically induced*; D003276:Contraceptives, Oral / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects; D005260:Female; D006801:Humans; D064887:Observational Studies as Topic; D016017:Odds Ratio; D011372:Progestins / Q000009:adverse effects; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced*
D003276:Contraceptives, Oral; D004967:Estrogens; D011372:Progestins
ischemic stroke; meta-analysis; oral contraceptive pills; pharmacoepidemiology