Abstract
Background: Oral contraceptive (OCP) use might increase the risk of stroke in women. We examined a possible dose–response relation between OCP use and the risk of stroke in young and middle-aged women.Methods: A retrieval of PubMed and EMBASE databases was performed. We selected observational studies that reported odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of stroke in OCP users. A two-stage dose–response analysis was conducted using the random-effects model and the restricted spline model.Results: A total of 6 cohort studies and 12 case–control studies were included, which involved 2,143,174 participants and 11,661 cases of stroke including ischemic stroke (IS), hemorrhagic stroke (HS), and stroke of unknown origin. The pooled ORs of total stroke were 1.19 (95% CI, 1.16–1.23) for every 10-μg increment in estrogen dosage, 1.20 (95% CI, 1.05–1.37) for every 5-years increment in duration of OCP use, and 0.82 (95% CI, 0.68–0.98) for every 5-years increment in duration of OCP cessation. The ORs of IS were 1.20 (95% CI, 1.17–1.22) in estrogen dosage, 1.24 (95% CI, 1.04–1.49) in duration of OCP use, and 0.78 (95% CI, 0.67–0.92) in duration of OCP cessation. The ORs of HS were 1.10 (95% CI, 1.04–1.16) in estrogen dosage, 1.13 (95% CI, 0.93–1.36) in duration of OCPs, and 0.71 (95% CI, 0.55–0.92) in duration of OCP cessation. The pooled ORs of total stroke from prospective studies (1.12; 95% CI, 1.01–1.24) were lower than those from retrospective studies (1.30; 95% CI, 1.01–1.67).Conclusions: The higher estrogen dosage significantly increased the risks of total stroke, IS, and HS, respectively. The longer duration of OCP use significantly increased the risks of total stroke and IS, but its effects on HS risk were marginal. The longer duration of OCP cessation significantly decreased the risks of total stroke, IS, and HS, respectively. These findings affirm the contribution of estrogen dose and duration of OCP use to the increased risk of stroke, which may be critical for the instruction of OCP use and the prevention and management of cerebrovascular diseases.
Highlights
Stroke is a cerebrovascular disease with high mortality and morbidity [1]
During full-article screening, the primary cause of study ineligibility was the lack of quantitative data of oral contraceptives (OCPs) use, and more detailed reasons of exclusion in full-article view are shown in Supplemental Table 1
Our findings indicated that [1] the increased estrogen dosage and duration of OCP use were associated with the increased risk of stroke in women, and the longer duration of OCP cessation was related to less risk of stroke; [2] there was only a marginal significance between duration of OCP use and increased hemorrhagic stroke (HS) risk; [3] there was an approximate linear association of estrogen dosage or OCP cessation but a non-linear association of duration of OCP use with the risk of stroke
Summary
Stroke is a cerebrovascular disease with high mortality and morbidity [1]. According to the heart disease and stroke statistics update 2018 from the American Heart Association (AHA), females had higher lifetime incidence and mortality of stroke than males in the United States [2]. Numerous observational studies have been conducted to assess the association between OCP use and stroke incidence. To date, it remains controversial whether women who are taking OCPs are at an increased risk of stroke [4,5,6,7,8,9,10]. A recent meta-analysis indicated that the risk of first-ever ischemic stroke (IS) was increased significantly in females currently taking OCPs [11]. Another meta-analysis study showed that current OCP use led to a small increase in hemorrhagic stroke (HS) incidence [12]. We examined a possible dose–response relation between OCP use and the risk of stroke in young and middle-aged women
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