Combined Hormonal Contraceptives

Is It Time to Reassess Their Role in Migraine?

Anne Calhoun, MD


Headache. 2012;52(4):648-660. 

In This Article

Abstract and Introduction


Objective.— This paper will review the extensive array of hormonal contraceptives. It will examine the benefits and risks associated with them – particularly with regard to stroke risk – and shed light on divergent findings in the literature.
Background.— Menstrual-related migraine is a particularly disabling presentation of migraine often deserving of specific prevention. There is accumulating evidence that hormonal preventives may offer such protection. Although a legacy of research shows an increased risk of stroke with high-dose oral contraceptives (OCs) (those containing 50–150 μg of estrogen), there is evidence to suggest that this does not apply to ultralow-dose OCs – those containing <25 μg ethinyl estradiol – when used in appropriate populations (ie, normotensive non-smokers). Migraine with aura (MwA) increases stroke risk, and that risk is directly correlated to the frequency of aura, a factor that can be modified – either upward or downward – by combined hormonal contraceptives (CHCs). The argument against using CHCs in MwA is based on the concerns that (1) OCs increase stroke risk, (2) MwA increases stroke risk, and (3) combining these risk factors might produce additive or synergistic risk. Evidence does not support concerns (1) and (3), and suggests otherwise.
Summary.— The risk/benefit analysis of CHCs is shifting. There is growing evidence for a potential role for CHCs in the prevention of menstrual-related migraine. At the same time, the risk of these products is declining, as newer and lower dose formulations replace their historical predecessors. And although migraine aura is a risk factor for stroke, there is not convincing evidence to suggest that the addition of a low-dose CHC alters that risk in non-smoking, normotensive users. Selected hormonal preventives could potentially decrease stroke risk in MwA via reduction in aura frequency achieved by reducing peak estrogen exposure. With this shift in risk/benefit analysis, it is time to reconsider the role of CHCs in migraine – both with and without aura.


For many headache specialists, "oral contraceptives" (OCs) are fighting words. On one side are specialists whose position is that combined hormonal contraceptives (CHCs) worsen migraine and increase stroke risk. On the other side are headache specialists who routinely prescribe selected or modified CHCs to stabilize estrogen and prevent menstrual-related migraine (MRM). The goal of this paper is to explain and reconcile these 2 conflicting views of CHCs.

(Note: MRM will refer to migraine attacks that occur consequent to a decline in estrogen concentration, encompassing pure menstrual migraine, MRM and estrogen withdrawal migraines that accompany withdrawal bleeds on CHCs.[1])

Wherever generalizations are applied to widely diverse members, disagreement abounds. Such is the case with CHCs. This diverse category includes a spectrum of delivery systems from pills and patches through chewing gums and vaginal rings. Even recent reviews may be inadvertently misleading when they reference studies that reflect historical doses long since replaced with formulations a mere fraction of their potency.


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