Combined Hormonal Contraceptives: Is It Time to Reassess Their Role in Migraine?


  • Anne Calhoun MD

    Corresponding author
    1. From the Carolina Headache Institute, Chapel Hill, NC, USA, and Departments of Anesthesiology and Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
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  • Conflict of Interest: None

A. Calhoun, Carolina Headache Institute, 103 Market Street, Chapel Hill, NC 27516, USA, email:


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.