Use of combined hormonal contraceptives among women with migraines and risk of ischemic stroke

Background: Migraine with aura and combined hormonal contraceptives are independently associated with an increased risk of ischemic stroke. However, little is known about whether there are any joint effects of migraine and hormonal contraceptives on risk of stroke.

Objective: We sought to estimate the incidence of stroke in women of reproductive age and examine the association among combined hormonal contraceptive use, migraine type (with or without aura), and ischemic stroke.

Study design: This study used a nationwide health care claims database and employed a nested case-control study design. Females ages 15-49 years with first-ever stroke during 2006 through 2012 were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification inpatient services diagnosis codes. Four controls were matched to each case based on age. Migraine headache with and without aura was identified using inpatient or outpatient diagnosis codes. Current combined hormonal contraceptive use was identified using the National Drug Code from the pharmacy database. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals of ischemic stroke by migraine type and combined hormonal contraceptive use.

Results: From 2006 through 2012, there were 25,887 ischemic strokes among females ages 15-49 years, for a cumulative incidence of 11 strokes/100,000 females. Compared to those with neither migraine nor combined hormonal contraceptive use, the odds ratio of ischemic stroke was highest among those with migraine with aura using combined hormonal contraceptives (odds ratio, 6.1; 95% confidence interval, 3.1-12.1); odds ratios were also elevated for migraine with aura without combined hormonal contraceptive use (odds ratio, 2.7; 95% confidence interval, 1.9-3.7), migraine without aura and combined hormonal contraceptive use (odds ratio, 1.8; 95% confidence interval, 1.1-2.9), and migraine without aura without combined hormonal contraceptive use (odds ratio, 2.2; 95% confidence interval, 1.9-2.7).

Conclusion: The joint effect of combined hormonal contraceptives and migraine with aura was associated with a 6-fold increased risk of ischemic stroke compared with neither risk factor. Use of combined hormonal contraceptives did not substantially further increase risk of ischemic stroke among women with migraine without aura. Determining migraine type is critical in assessing safety of combined hormonal contraceptives among women with migraine.