Are women on low dose estrogen OCPs with history of migraine at increased risk of CVA than those without migraine?

Appraiser: B.A Porter, MD
9 May 1997

Clinical Scenario:
A 25 year old woman with migraine headaches asks for contraceptive advice.

Clinical Bottom Lines
While there are statistically significant associations between OCP use and ischemic stroke in women with history of migraine headaches, more than 10,000 women with migraine history need to be exposed to OCPs before a CVA will be observed, i.e. a strong association exists but the risk remains low.
If desiring oral contraceptives, women with a history of migraine headaches should be advised to opt for the OCP with the lowest estrogen content

The Background:

1. In 1977, the Collaborative Group for the Study of Stroke in Young Women¹ demonstrated a significantly increased risk for thrombotic stroke both in women with a history of migraine headaches, and in women using contraceptives with a history of migraine headaches. The relative risk of stroke increased from 2.0 in the women with migraine headaches to 5.9 in the migraine sufferer on OCPs. This case-control study was performed when OCPs typically contained 80-100 ug of estrogen, and used a somewhat arbitrary definition for migraine headache.

2. A few studies have associated migraine headaches with risk of stroke in young people, particularly women under age 35. Recently, the Italian National Research Council Study Group on Stroke in the Young² demonstrated a significant association between history of migraine and cerebral ischemia in women under the age of 35 (OR=1I.9, p-0.02). This association was not seen in men, and was the only significant risk factor for ischemia (among HTN, smoking, hypercholesterolemia, DM, obesity, etOH, and OCP use) in this young age group.

3. Very recently, a case-control study conducted in the US³ demonstrated no apparent increase in the risk of stroke in women using low-estrogen (30-35ug estrogen) oral contraceptives. Interaction with migraine headache was not studied.

The Evidence⁴:

Comments:
I. This study used history of migraine headache as a risk factor, an important distinction as it eliminates headache with stroke, and headache after stroke. No migrainous infarcts were observed.
2. There was not an association between migraine headaches and OCP use in this study.
3. The risk of stroke was related to estrogen dose, but the numbers are too small to verify dose-response.
4. Like any case-control study, the results are subject to bias, particularly recall bias. There may be an increased likelihood of recalling a history of headache if you've suffered a necrologic event.
5. 1/3 of the controls used in this study were patients hospitalized for "traumatic orthopedic injury", raising the question of increased risk of thromboembolic event in the control population.

References:
^1. Collaborative Group for the Study of Stroke in Young Women. Oral contraceptives and stroke in young women: associated risk factors. JAMA 1975;231:718-22.
². Carolei A, Marini C, DeMatteis G. et al. History of migraine and risk of cerebral ischaemia in young adults. Lancet 1996; 347:1503-06.
³. Petitti DB, Sidney S. Bernstein A, et al. Stroke in users of low-dose oral contraceptives. N Engl J Med 1996;335 :8-15.
⁴. Tzourio C. Tehindrazanarivelo A, Iglesias S. et al. Case-control study of migraine and risk of ischaemic stroke in young women. BMJ 1995;310:830-5.