Migraine, Contraceptives, and Stroke: What's the Connection?
Migraine, Contraceptives, and Stroke: What’s the Connection?
Stroke and migraine are both high frequency conditions that have a large impact on public health. Migraine affects about 18% of women in the U.S. — about three times more than men — and is most prevalent during a woman's reproductive years.1 According to data from 2006-2010, about 62% of women of reproductive age are using contraception. The most widely used is oral contraception, which constitutes about 10.6 million women in the U.S.2 Therefore, there is likely a large overlap between women who have migraine and are using hormonal contraceptives.
The overlapping characteristics of those populations then raise the question: Is it safe for women with migraine to use hormonal contraceptives? The answer is hugely debated and difficult to sort out.
Understanding the Link Between Migraine and Stroke
Migraine affects more than 20% of women of childbearing age and is the fourth most disabling illness among women worldwide, and stroke is one of the top causes of death and disability in the U.S. Years of research has shown that migraine is an independent risk factor for stroke, in particular for women with migraine with aura.1,3 It is also believed that estrogen-containing contraceptives increase the risk of circulatory diseases, many venous clots as well as possibly stroke.4 It would follow, then, that women who have migraine and are using oral contraceptives would have an even greater increased risk of stroke.
The fact that the pathophysiology of migraine is still not completely understood only complicates matters.3 Genetic factors along with vascular mechanisms both play a role, as both migraine and stroke involve an intimate connection between neuronal activity and blood vessels, also known as “neurovascular coupling.”16 There is also thought to be an association between migraine and stroke through a fundamental mechanism that is common to both migraine and cardiovascular events, which may include endothelial dysfunction or an underlying hypercoagulability.12
Other theories include alterations in cerebral blood flow during aura, where constriction of cerebral arterioles occurs.13 There are also rare disorders which manifest both migraine with aura and ischemic stroke, including MELAS and CADASIL.14,15
Due to this information, many national organizations have guided against the use of hormonal contraceptives for women who have migraines. The World Health Organization (WHO) and American Congress of Obstetricians and Gynecologists (ACOG) regard migraine with aura to be an absolute contraindication to the use of exogenous hormones.5 However, for many women, hormonal contraceptives are a useful and practical method to not only prevent pregnancy, but also find relief from other medical conditions, including endometriosis or polycystic ovarian disease. These recommendations leave many women without options when it comes to treating these painful and debilitating diseases.
Inconsistencies in Data
However, not all data is clear. Some studies find that oral contraceptives can increase the risk of stroke, while a large case-control study showed that the risk is not present with low-dose estrogen contraceptives in patients without migraine.6,7 Some of the confusion arises from the fact that many of the previous findings about hormonal contraceptives were based off of heterogeneous studies with a number of confounding risk factors, including other cardiovascular risk factors like smoking and hypertension. Many of the individual studies were under-powered to adequately study the question of whether migraine or its subtypes are associated with increased stroke risk.8
A recent case control study found that adding on oral contraceptives (OCPs) did not increase the risk of stroke in women with migraine with aura.9 However, smoking in addition to taking OCPs did increase the risk significantly. Another case control study, which looked at women younger than 45 who had migraine with aura and were taking OCPs, showed that those women did have an increased risk of stroke compared to those who did not take an OCP.10
In a recent meta-analysis that examined the relationship between migraine and cardiovascular disease, the authors concluded that there was an increased risk of ischemic stroke in patients with migraine who also smoke and use OCPs. However, the studies in the meta-analysis were small in number and some used higher dosed OCPs that are no longer in use, and the distinction between high dose and low dose estrogen-containing contraceptives was not made.3,11 Additionally, some of the studies used are now nearly 20 years old, so they don't take into account the new innovations in the dosages and types of hormonal contraceptives available.
Despite the confusing data, what is important to understand is the risk and benefits of using a hormonal contraceptive. The overall absolute risk of developing a stroke in a young woman is extremely low, about 5-10 per 100,000 woman-years.6 This must be weighed against the risks of the disease that the woman is trying to avoid if she is using hormonal contraceptives for illnesses like polycystic ovarian disease or endometriosis. These are also diseases that carry some amount of morbidity.
There are also a number of organizations that are re-analyzing the previous data in order to determine if previous guidelines still hold true today. The American Headache Society, for instance, is developing a guideline committee to help guide neurologists in treating patients with migraine with aura who may be at risk for developing stroke and other cardiovascular diseases.
Huma U. Sheikh, MD, is a clinical instructor of neurology at Harvard Medical School and a board-certified neurologist with specialization in both vascular neurology and headache at Brigham & Women's Hospital in Boston. She is the co-chair of the Migraine and Vascular Disease special interest section at the American Headache Society (AHS) and on the AHS committee to develop “Guidelines for Vascular Issues and Headache.” She is currently investigating the role of low dose oral contraceptives in stroke for women with migraine. Follow her on Twitter @HumaSheikhMD
- Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-9.
- Jones J, Mosher W, Daniels K. Current contraceptive use in the United States, 2006–2010, and changes in patterns of use since 1995. National health statistics reports; no 60. Hyattsville, MD: National Center for Health Statistics. 2012.
- Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
- Chan WS, Ray J, Wai EK, et al. Risk of stroke in women exposed to low-dose oral contraceptives: a critical evaluation of the evidence. Arch Intern Med. 2004;164(7):741-7.
- Bousser MG, Conard J, Kittner S, et al. Recommendations on the risk of ischaemic stroke associated with use of combined oral contraceptives and hormone replacement therapy in women with migraine. The International Headache Society Task Force on Combined Oral Contraceptives & Hormone Replacement Therapy. Cephalalgia. 2000;20(3):155-6.
- Petitti DB, Sidney S, Bernstein A, Wolf S, Quesenberry C, Ziel HK. Stroke in users of low-dose oral contraceptives. N Engl J Med. 1996;335(1):8-15.
- Schwartz SM, Petitti DB, Siscovick DS, et al. Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies. Stroke. 1998;29(11):2277-84.
- Sacco S, Ricci S, Carolei A. Migraine and vascular diseases: a review of the evidence and potential implications for management. Cephalalgia. 2012;32(10):785-95.
- Macclellan LR, Giles W, Cole J, et al. Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study. Stroke. 2007;38(9):2438-45.
- Tzourio C, Tehindrazanarivelo A, Iglésias S, et al. Case-control study of migraine and risk of ischaemic stroke in young women. BMJ. 1995;310(6983):830-3.
- Macgregor EA. Migraine and use of combined hormonal contraceptives: a clinical review. J Fam Plann Reprod Health Care. 2007;33(3):159-69.
- Vanmolkot FH, Van bortel LM, De hoon JN. Altered arterial function in migraine of recent onset. Neurology. 2007;68(19):1563-70.
- Diener HC, Kurth T, Dodick D. Patent foramen ovale, stroke, and cardiovascular disease in migraine. Curr Opin Neurol. 2007;20(3):310-9.
- Pavlakis SG, Phillips PC, Dimauro S, De vivo DC, Rowland LP. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol. 1984;16(4):481-8.
- Tournier-lasserve E, Joutel A, Melki J, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nat Genet. 1993;3(3):256-9.
- Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA. Glial and neuronal control of brain blood flow. Nature. 2010;468(7321):232-43.