Women and Migraine: the Role of Hormones

DOI: https://doi.org/10.1007/s11910- 018- 0845- 3

Abstract-Summary Migraine is a debilitating disease, that is encountered in countless medical offices every day and since it is highly prevalent in women, it is imperative to have a clear understanding of how to manage migraine.

There is a growing body of evidence regarding the patterns we see in women throughout their life cycle and how we approach migraine diagnosis and treatment at those times.

This article seeks to provide an overview of a woman’s migraine throughout her

lifetime, the impact of hormones and an approach to management.

Extended: Migraine is a lifelong disorder in women, often beginning just before

or around puberty and continuing through the post-menopausal years.

Introduction Migraine is an exceptionally common medical condition, recently ranked by the World Health Organization as the third most prevalent and if not managed well, it can be extremely disabling.

The effect of migraine on ability to function and the degree of disability it causes also varies, ranging from mild impairment to being unable to work or to enjoy social activities.

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In 2016, the World Health Organization ranked migraine as the second leading

cause of disability [437, 679].

Migraine Is More Common in Women As migraine is three times more common in women than in men, it behooves clini- cians to be well versed in effective diagnosis and treatment.

The American Migraine Prevalence and Prevention study notes a higher preva- lence of migraine in women as compared to men over the age of 12, which is also consistent across all ethnicities [680–682].

It is thought that migraine is more prevalent in women during reproductive years and it is well known that there is a strong relationship between headache and hor- mone homeostasis, particularly related to ovarian hormones [683].

Sex hormones can act as important modulators hence the different effects of

migraine in men and women [684].

Stroke and Migraine By Champaloux and from the European Headache Federation consensus statement, it is clear that hormonal contraceptive use in women with migraine carries an increased risk of stroke [685, 686].

For a woman with migraine without aura, using hormonal contraception, the risk of stroke is increased fourfold and were she to have aura, the risk is increased six- fold [685–687].

There are several hypotheses to support the relationship between migraine with

aura and ischemic stroke.

The concept of migrainous infarction is known; however, in these circumstances, to report the stroke as a migrainous infarction, the symptoms of stroke must exactly match the patient’s known previous aura symptoms.

Some believe that women with migraine with aura may have a high prevalence of other vasculopathies that include antiphospholipid syndrome and systemic lupus erythematosus, and/or have vascular risk factors, such as smoking and hyperten- sion, which place them at higher risk of stroke [687].

Menstruation and Migraine MRM occurs in 60% of women who have migraine attacks perimenstrually as well as at other times of the month [688].

Menstrual migraine typically occurs 2 days prior to or in the first 3 days of

the cycle.

In women who suffer from menstrual migraine, skipping the placebo week may reduce the number of menstrual cycles and therefore reduce the number of menstru- ally related migraine attacks [689, 690].

In women for whom estrogen-containing contraceptives are contraindicated, a progesterone-only pill can be considered; however, a meta-analysis by Warhurst and others concluded that while some observational studies found a benefit in migraine day reduction, there were no randomized trials and thus data is not definitive.

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2 Mechanisms

If migraines are occurring 3–4 times per month or the MM attack is not respon- sive to acute therapy, preventative options, including mini-prophylaxis, must be considered.

Pregnancy and Migraine A significant challenge in managing migraine during the childbearing years is the safe treatment of symptoms pre- and post conception and since up to 50% of preg- nancies are unplanned, care providers ought to discuss and document risks with patients and choose medications with no known risk of teratogenicity.

Several NSAIDs are generally considered safe in early pregnancy; however, they should be used with caution in the third trimester, as there is an increased risk of premature closure of the ductus arteriosus, impaired renal function, cerebral palsy, and neonatal intra-ventricular hemorrhage [691].

Codeine is sometimes used in pregnancy and a study looking at this found no increased risk of fetal malformations in pregnancy outcomes of codeine-exposed compared to non-codeine-exposed pregnancies; however, its use in the third trimes- ter should be cautioned as there was an increased risk of acute C-section delivery and postpartum hemorrhage [691, 692].

Breastfeeding and Migraine When choosing a medication, consider the drug as well as the protein binding capa- bilities of the drug, as these factors influence maternal plasma levels and, in the case of a highly protein bound drug, entry into breast milk may be impeded.

A review of the literature and safety profile of acute migraine drugs during lacta- tion found that low-dose aspirin, ibuprofen, acetaminophen, caffeine, metoclo- pramide, eletriptan and sumatriptan can be used safely [693, 694].

For many lactating mothers, pumping and dumping breast milk for 4–6 h after

taking a medication provides some additional reassurance.

Preventative medications that are contraindicated during lactation include among many, high-dose aspirin atenolol, nadolol, cinnarizine, flunarizine, ergotamine, methysergide, and pizotifen [693, 695].

Perimenopause, Menopause, and Migraine Migraine tends to improve with age, especially in women who have MM and while women expect that following menopause, a reduction in headache will occur, but this transition could take many years.

Perimenopause can be associated with fatigue, insomnia, irritability, night sweats, hot flashes, forgetfulness, drop in libido, and difficulty concentrating, which may contribute to migraine, especially when hormone replacement therapy (HRT) is deemed necessary [696, 697].

HRT is commonly provided to women during perimenopause and depending on the duration, type, dose, and route of administration of estrogen, migraine can be exacerbated, unchanged, or improved.

HRT is not prescribed for migraine alone, especially in a migraineur who has aura or other vascular risk factors, but rather when it is deemed necessary to control the symptoms of peri-or post-menopause.

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Conclusions Through standard migraine lifestyle recommendations, abortive and preventative therapies including hormonal options, the majority of women can experience improvement in their migraines and associated symptoms.

Clinicians need to be well versed in this extremely common and disabling condi- tion, including the implications of hormonal therapies on migraine, as well as the concerns regarding hormonal use in a woman who has migraine with aura or other vascular risk factors.

More definitive research on the use of current low-dose hormonal therapies in a

migraineur is needed to help guide treatment.

Acknowledgement A machine generated summary based on the work of Todd, Candice; Lagman- Bartolome, Ana Marissa; Lay, Christine. 2018  in Current Neurology and Neuroscience Reports.

Hormonal effect on the relationship between migraine and female sexual dysfunction