Migraine, low-dose combined hormonal contraceptives, and ischemic stroke in young women: a systematic review and suggestions for future research

ABSTRACT

Introduction: Migraine and combined hormonal contraceptives (CHCs) increase the risk of ischemic stroke in young women; however, the contribution of low-dose (<50 μg ethinylestradiol) CHCs to the risk of ischemic stroke in young women with migraine is not well defined.

Areas covered: The authors performed a systematic review of observational studies indexed in PubMed and Scopus from inception to 22 May 2019, reporting the effect sizes of ischemic stroke in women with migraine using low-dose CHCs compared with those without migraine not using CHCs. All the four included case-control studies, including a total of 12,256 women, reported increased odds of ischemic stroke in women with migraine and low-dose CHC use compared with those without migraine not using CHCs. A meta-analysis was not feasible due to significant heterogeneity.

Expert opinion: Strong data on the joint effect of migraine and CHC use on risk of ischemic stroke are lacking especially referring to the role of aura and headache frequency. Evidence suggests that the association with ischemic stroke is driven by migraine with aura. More robust data are needed to assess whether CHCs remain viable for women with migraine without aura, and whether their use could extend to some women with migraine with aura.

KEYWORDS:

• Migraine
• contraception
• ischemic stroke
• systematic review
• stroke in the young

Article highlights

• The available data on the joint effect of low-estrogen combined hormonal contraceptives and migraine on the risk of ischemic stroke in young women are scant and mostly outdated; besides, their heterogeneity prohibits the feasibility of a meta-analysis.

• The available literature data do not adequately consider the contribution of several migraine characteristics, including aura and frequency, and of the most recent formulations of combined hormonal contraceptives with natural estrogens or very low estrogen doses.

• Our systematic review stresses the need for larger studies with better definition of populations and outcomes; further data are also needed to disentangle the contribution of combined hormonal contraception from that of migraine in determining the risk of ischemic stroke in young women.

Declaration of interest

R Ornello has received sponsorship to attend meetings from Novartis and Teva. G Merki-Feld had financial relationship (lecturer, member of advisory boards and/or consultant) with Bayer-Schering Pharma and MSD. T Kurth reports having contributed to an advisory board of CoLucid and a research project funded by Amgen, for which the Charité – Universitätsmedizin Berlin received an unrestricted compensation, having received honoraria from Lilly, Newsenselab, and Total for providing methodological advice, from Novartis and from Daiichi Sankyo for providing a lecture on neuroepidemiology and research methods, and from the British Medical Journal for editorial services. EA MacGregor has worked as a paid adviser for Asarina Pharma, Eli Lilly and Novartis and has received sponsorship to attend meeting from Theramex. C Lampl received honoraria for planning and conducting clinical trials, participating in AD-board meetings and speaking for Allergan, Jansen-Cilag, Lilly, MSD, Novartis, Pfizer, Sanofi-Aventis and Teva. RE Nappi had a financial relationship (lecturer, member of advisory boards and/or consultant) with Bayer HealthCare, Endoceutics, Exceltis, Gedeon Richter, MSD, Novo Nordisk, Palatin, Pfizer, Shionogi, Teva, Theramex. P Martelletti received travel grants, consulting fees and speaking fees from Allergan, Amgen, Eli Lilly, Novartis, and Teva. S Sacco had a financial relationship (lecturer or member of advisory board) with Abbott, Allergan, Novartis, Teva, and Eli Lilly, Medscape. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.