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Case-control study of oral contraceptives and risk of thromboembolic stroke: results from international study on oral contraceptives and health of young women

^a ZEG-Centre for Epidemiology and Health Research Berlin, D-16341 Zepernick, Germany, ^b EPES Epidemiology Pharmaco-epidemiology and Systems Research, D-12165 Berlin, Germany, ^c Health Promotion Sciences Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, ^d Department of Epidemiology and Biostatistics, McGill University Montreal, QC, Canada H3A 1A2, ^e Institute of Medical Statistics, Epidemiology and Informatics, Free University Berlin, D-12200 Berlin, Germany, ^f University Basle, CH-4310 Rheinfelden, Switzerland,

Correspondence to: Professor Heinemann

Objective: To determine the influence of oral contraceptives (particularly those containing modern progestins) on the risk for ischaemic stroke in women aged 16-44 years.
Design: Matched case-control study.
Setting: 16 centres in the United Kingdom, Germany, France, Switzerland, and Austria.
Subjects: Cases were 220 women aged 16-44 who had an incident ischaemic stroke. Controls were 775 women ( at least one hospital and one community control per case) unaffected by stroke who were matched with the corresponding case for 5 year age band and for hospital or community setting. Information on exposure and confounding variables were collected in a face to face interview.
Main outcome measures: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding.
Results: Adjusted odds ratios (95% confidence intervals) for ischaemic stroke (unmatched analysis) were 4.4 (2.0 to 9.9), 3.4 ( 2.1 to 5.5), and 3.9 (2.3 to 6.6) for current use of first, second, and third generation oral contraceptives, respectively. The risk ratio for third versus second generation was 1.1 (0.7 to 2.0) and was similar in the United Kingdom and other European countries. The risk estimates were lower if blood pressure was checked before prescription.
Conclusion: Although there is a small relative risk of occlusive stroke for women of reproductive age who currently use oral contraceptives, the attributable risk is very small because the incidence in this age range is very low. There is no difference between the risk of oral contraceptives of the third and second generation; only first generation oral contraceptives seem to be associated with a higher risk. This small increase in risk may be further reduced by efforts to control cardiovascular risk factors, particularly high blood pressure.

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