Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC)

DOI: https://doi.org/10.1186/s10194- 017- 0815- 1

Abstract-Summary Of concern is whether the risk of ischemic stroke in migraineurs is magnified by the use of hormonal contraceptives.

In this document, we systematically reviewed data about the association between

migraine, ischemic stroke and hormonal contraceptive use.

Quality of current evidence regarding the risk of ischemic stroke in migraineurs

associated with the use of hormonal contraceptives is low.

Available data suggest that combined hormonal contraceptive may further increase the risk of ischemic stroke in those who have migraine, specifically migraine with aura.

As the quality of available data is poor further research is needed on this topic to

increase safe use of hormonal contraceptives in women with migraine.

Methods Two core panelists (SS, PM) developed a draft document containing the list of items to be included in the statements based on available literature and on clinical grounds. Panelists were asked to provide free-text responses for each of the open ques-

tions and to suggest additional items of relevance as warranted.

In round 2, the draft of the statements was sent by e-mail to all panelists.

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Panelists selected “partly agree” or “disagree” for a statement, they were asked

to provide a free-text explanation for their selection.

Panelists were also given the opportunity to provide comments and sugges- tions and to identify further additional items not included in the initial list of statements.

In round 3, a revised draft was developed and emailed to all panelists and the panelists were asked again to vote their agreement, as in round 2, but with the knowledge of the group scores and comments.

In round 4, a final draft of the statements was e-mailed to all panelists.

Results One population-based, case-control study reported separate results for women with migraine with and without aura, and for HC users and non-users; in that study, the combination of HC use and migraine with aura was associated with an OR of 6.1 (95% CI 3.1–12.1) for ischemic stroke in women aged 15–49 years and the combi- nation of HC use and migraine without aura was associated with an OR of 1.8 (95% CI 1.1–2.9) in the same risk [663].

One recent study indicated an increased risk of ischemic stroke in women with

migraine without aura using HCs (OR 1.8; 95% CI 1.1–2.9) [663].

Comment: As combined HCs may have also non-contraceptive benefits the Panel supports their possible use in women with migraine without aura in the absence of any other factor which could potentially increase the risk of ischemic stroke.

Discussion Despite those limitations, available data pointed toward an increased risk of isch- emic stroke associated with the use of HCs in women with migraine.

The Consensus Group considers that it is necessary to conduct further research to identify safe HC methods for women with migraine (i.e. evaluation of the differ- ent doses of ethinylestradiol, of the risk associated with natural estrogens, and the risk associated with the different progestogen formulations), to clarify mechanisms linking HCs to increased stroke risk in women with migraine, and to identify sub- groups of migraineurs with high risk of stroke.

Future studies should assess the risk of ischemic stroke in women with migraine according to migraine subtype (i.e. with or without aura) using combined HCs (including dose and type of hormones) or progestogen-only contraceptives versus those women with migraine not using combined HCs or progestogen-only contraceptives.

Basic research studies should try to understand why combined HCs increase the risk of ischemic stroke and the specific mechanisms leading to the vascular events in women with migraine.

[Section 4] Most of the evidence supports an increased risk of ischemic stroke associated with migraine with aura [404, 663–673].

For migraine without aura, the interpretation of available data is more complex as some studies reported that migraine without aura is also associated with an

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increased risk of ischemic stroke [663, 673, 674] whereas in others the association was not confirmed [404, 664, 667, 671].

Two meta-analyses did not demonstrate an association between migraine with-

out aura and ischemic stroke [675, 676].

Acknowledgement A machine generated summary based on the work of Sacco, Simona; Merki-Feld, Gabriele S.; Ægidius, Karen Lehrmann; Bitzer, Johannes; Canonico, Marianne; Kurth, Tobias; Lampl, Christian; Lidegaard, Øjvind; Anne MacGregor, E.; MaassenVanDenBrink, Antoinette; Mitsikostas, Dimos-Dimitrios; Nappi, Rossella Elena; Ntaios, George; Sandset, Per Morten; Martelletti, Paolo; on behalf of the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC). 2017 in The Journal of Headache and Pain.

Male and female sex hormones in primary headaches