Effect of exogenous estrogens and progestogens on the course of migraine during reproductive age: a consensus statement by the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESCRH)

DOI: https://doi.org/10.1186/s10194- 018- 0896- 5

Abstract-Summary We systematically reviewed data about the effect of exogenous estrogens and pro- gestogens on the course of migraine during reproductive age.

A consensus procedure among international experts was undertaken to develop statements to support clinical decision making, in terms of possible effects on migraine course of exogenous estrogens and progestogens and on possible treat- ment of headache associated with the use or with the withdrawal of hormones.

As the quality of available data is poor, further research is needed on this topic to improve the knowledge about the use of estrogens and progestogens in women with migraine.

Introduction Exogenous hormones may change the course of migraine by inducing de novo migraine, inducing de novo aura, worsening previous migraine but also improving migraine particularly those attacks related to menstruation [655, 656].

The authors recognized that in some women, migraine without aura (MO) may be almost exclusively linked with menstruation, so called menstrual migraine (MM), and indicated that it seemed reasonable to require that 90% attacks should occur between two days before menses and the last day of menses.

2.5 Hormones

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Two entities were recognised: pure menstrual migraine (PMM) where attacks are exclusively related to menstruation; menstrually related migraine (MRM) where attacks occur additionally at other times of the cycle.

As in users of combined hormonal contraceptives (CHC) migraine attacks mostly occur during the hormone free interval, studies also evaluated how different estro- gen or progestogen regimens impact on the course of migraine [657–660].

Methods We included studies that were (1) observational (retrospective and prospective) or interventional and in which an estrogen and/or a progestogen drug was assessed as possible treatment strategy for migraine; (2) were published in English or in other languages if a reliable translation could be obtained; (3) using reliable criteria to diagnose migraine; (4) assessing treatment with any form of estrogen or progesto- gen; (5) reporting any outcome referring to migraine frequency, severity, duration, disability, or use of drugs to treat the acute attacks before and after treatment or in treated and untreated women.

In round 1, the draft containing the statements was sent by e-mail to all panelists accompanied by a clear explanation of the objectives of the study and specific instructions.

Panelists were also given the opportunity to identify further additional items not

included in the initial list of statements.

Results Current evidence on the use of extended oral CHCs regimens in women with migraine is limited as it comes from observational studies performed in the gyneco- logical setting [658–660].

One observational study assessed the role of CHC with oral estrogen supplemen- tation during the pill-free interval in women with MO associated with menstruation and women with migraine associated with CHC withdrawal bleeding [661].

Evidence on the use of oral CHCs with oral estrogen supplementation during the

pill-free interval in women with migraine is limited to a single unreliable study.

One interventional study assessed the possible benefits of transdermal estradiol supplementation with patch in women with migraine during the pill-free interval of combined oral contraceptives [662].

The study was performed in the setting of reproductive clinics in women who were prescribed with the study treatments and not specifically for headache management.

Discussion Our systematic review revealed that available evidence referring to the use of estro- gens and progestogens in women of reproductive age and their effect on migraine is limited.

It has been addressed only in women who required it for contraception or medi- cal reasons and no studies specifically aimed to evaluate this drug as a specific therapeutic option for women with migraine is available.

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2 Mechanisms

The extended regimen of CHC either oral or with the patch is a further strategy

to consider in women with migraine.

Although no studies addressed specifically the issue, Panelists suggested trying this option for women with estrogen withdrawal headache, particularly those women already experiencing headache or migraine during the pill-free interval.

The available evidence is weak and further research in needed to clarify which

are the best estrogens and progestogens options in women with migraine.

Acknowledgement A machine generated summary based on the work of Sacco, Simona; Merki-Feld, Gabriele S.; Ægidius, Karen Lehrmann; Bitzer, Johannes; Canonico, Marianne; Gantenbein, Andreas R.; Kurth, Tobias; Lampl, Christian; Lidegaard, Øjvind; Anne MacGregor, E.; MaassenVanDenBrink, Antoinette; Mitsikostas, Dimos-Dimitrios; Nappi, Rossella Elena; Ntaios, George; Paemeleire, Koen; Sandset, Per Morten; Terwindt, Gisela Marie; Vetvik, Kjersti Grøtta; Martelletti, Paolo; 2018  in The Journal of Headache and Pain.

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)