Migraine affects more than 1 in 6 US adults . This figure masks the fact that migraine is a predominantly female disorder; compared with men, 3-month migraine prevalence is more than 2-fold higher (21% vs. 10%) in women. Research by the World Health Organization has established migraine as second among the world’s causes of disability, and first among women of reproductive age .
Despite this burden of illness, migraine is often not diagnosed or treated effectively. General lifestyle advice such as maintaining a healthy weight, sleep hygiene, regular meals, regular exercise and hydration, and management of identified predisposing or triggering factors—together with optimization of symptomatic migraine treatment—can benefit all women with migraine. However, specific hormonal events such as menstruation, hormonal contraception, pregnancy, menopause, and hormone replacement therapy have variable, but often predictable, effects on the frequency and severity of migraine. At each of these life stages, there are specific opportunities to intervene and relieve migraine burden.
Menstrual migraine
Menstruation is one of the most significant risk factors for migraine, notably migraine without aura, with increased prevalence during a 5-day perimenstrual window that starts 2 days before the onset of menses and continues through the first 3 days of menstruation.
The International Headache Society (IHS) recognizes 2 types of menstrual migraine. There is menstrually related migraine, which is migraine without aura that regularly occurs on or between day −2 to +3 of menstruation (there is no day 0), with additional attacks of migraine with or without aura at other times of the cycle. There is also pure menstrual migraine, which is migraine without aura that occurs only on or between day −2 to +3, with no attacks at any other time of the cycle.
In women with menstrually related migraine, the diagnosis should only be made if the relationship between migraine and menstruation is greater than a chance association. To confirm this diagnosis, migraine attacks during the day −2 to +3 window must occur in at least 2 of 3 menstrual cycles . Relying on history to confirm the diagnosis can be misleading. Use of a 3-month diary can reveal the predictable patterns associated with menstrual migraine, aiding diagnosis and management.
Menstrual migraine affects 20% to 25% of women with migraine in the general population, and 22% to 70% of women seen in headache clinics. In women diagnosed with menstrual migraine, their perimenstrual attacks have distinctive clinical features which include more associated symptoms, longer duration, greater severity, greater susceptibility to relapse, greater resistance to treatment, and greater disability than migraines occurring at other times during the menstrual cycle.
Symptomatic treatment of perimenstrual attacks of migraine is the same as for treatment of non-menstrual attacks, but due to the longer duration of perimenstrual attacks, treatment usually needs to be repeated on several consecutive days . With respect to prevention, specific consideration should be given to the presence of menstrual disorders, contraceptive requirements, pregnancy wishes, and symptoms of perimenopause.
The 2 established triggers for perimenstrual migraine attacks are prostaglandin release, which also results in dysmenorrhea, and late luteal phase estrogen "withdrawal" . There are no investigations to identify the relevant mechanism(s). However, a history of dysmenorrhea is suggestive of a prostaglandin trigger and both migraine and dysmenorrhea can benefit from treatment with prostaglandin inhibitors.
Contraceptive methods can effectively manage both perimenstrual triggers. The European Headache Federation and the European Society of Contraception and Reproductive Health recommend combined hormonal contraception (CHC) in women with menstrual migraine who require contraception or who have additional menstrual disorders that use of CHC would benefit. The desogestrel progestogen-only pill is an alternative option , particularly for women with aura, but bleeding side effects are a common reason for discontinuation.
The principal barriers to effective management of menstrual migraine are lack of awareness and under-diagnosis. Although the IHS criteria facilitate research diagnosis, there continues to be important unmet needs in the clinical management of women with menstrual migraine. Improved awareness by healthcare professionals is critical; women visiting their primary care physician or who are referred to a gynecologist seldom mention migraine unless specifically asked.
Contraception
Most women use contraception at some stage in their lives. Hormonal contraception, particularly CHC, is popular and effective, with additional non-contraceptive benefits.
As with the natural menstrual cycle, estrogen “withdrawal” (in this case the consequence of stopping contraceptive hormones during the hormone-free interval) can trigger migraine without aura . Eliminating the hormone-free interval by taking CHCs continuously, without a break, eliminates the risk of estrogen withdrawal migraine. Further, continuous use of CHC increases contraceptive efficacy and there are no differential safety concerns.
Contraceptive use of CHC is contraindicated in women with migraine aura, since migraine aura and use of ethinylestradiol are independent risk factors for ischemic stroke. Effective contraception need not be compromised since progestogen-only and non-hormonal methods—
several of which are more effective than CHC—are not associated with increased risk.
Despite there being little concern regarding use of CHCs in women with migraine without aura, clinical experience suggests that many women with migraine are denied CHCs. In some cases, this stems from misdiagnosing premonitory migraine symptoms as aura. In other cases, even a clear diagnosis of menstrual migraine without aura can result in CHCs being withheld due to the misconception of risk. To ensure that women receive optimum contraceptive options, contraceptive providers need a better understanding of the Medical Eligibility Criteria for Contraceptive Use as well as simple tools to aid migraine diagnosis.
Pregnancy and breastfeeding
Around 60-70% of pregnant women with migraine experience fewer attacks compared to pre-pregnancy, with improvement more likely in women with a history of menstrual migraine. In contrast, migraine with aura tends to continue to occur throughout pregnancy and postpartum and may start for the first time during this period. Women can be reassured that migraine, both with or without aura, does not have any adverse effect on the outcome of pregnancy. However, women with aura should be monitored during pregnancy since there is an increased risk of comorbid conditions, such as arterial and venous thrombosis, pre-eclampsia, and gestational hypertension.
Healthcare professionals need to be aware of their female patients with migraine who may be planning to conceive so that strategies for treating migraine can be discussed. Most drugs and other teratogens exert their greatest effects on the fetus in the first trimester , often before pregnancy is confirmed. Symptomatic treatment with acetaminophen and metoclopramide is safe. If this is ineffective, sumatriptan is an option. Ergot derivatives are contraindicated. If prophylaxis is considered necessary, propranolol is the safest and most effective option. Valproate is contraindicated for migraine prophylaxis in women of reproductive capacity who are not using adequate contraception due to the increased risk of neural tube defects, cardiac defects, and other developmental effects associated with use of this medication.
Fertility treatment is frequently associated with increased headache and migraine. It is also important to consider that headache can be symptomatic of emotional stress, which would benefit from supportive management.
Breastfeeding generally maintains the benefits of pregnancy on migraine and should be encouraged, where possible. Recent studies suggest that the number of women choosing to breastfeed is rising, but there is also evidence that women with migraine do not initiate breastfeeding or discontinue because of their concerns about taking medication .
Unfortunately, many women and healthcare professionals rely on information in the package inserts, which may not tell the full story. Milk supply can reduce within 48 hours without full and repeated emptying of the breast, so advising a woman to interrupt breastfeeding for even a few days while treating a migraine attack can destroy her milk production. Hence, maintaining breastfeeding during drug treatment is increasingly recommended. Healthcare professionals should be informed about which treatments can safely be used at this time. For acute treatment, acetaminophen and NSAIDS are first-line options and can be combined with metoclopramide. Sumatriptan is a second-line option that allows breastfeeding to continue without the need to ‘pump and dump’.
Menopause and hormone replacement therapy
Despite increased prevalence of menstrual migraine during perimenopause, headache and migraine are under-reported by women with perimenopausal migraine . Management should be directed to treating the menopausal symptoms, which may include hormone replacement therapy (HRT). Studies suggest a significant association between migraine and current use of HRT .
Understanding the effects of different types of HRT is important, as some studies suggest that a history of worsening migraine at menopause is a factor in predicting worsening migraine with HRT. However, the regimen of HRT, route of estrogen, and type of progestogen all have differing effects on migraine. Non -oral routes of continuous estrogen/progestogen are less likely to have a negative effect on migraine than oral formulations, and continuous estrogen/progestogen appears to be better tolerated than cyclical combined HRT. Oral micronized progesterone may directly benefit migraine due to GABAergic effects. Disturbed sleep is both a common migraine trigger and the action of progesterone to restore normal sleep will also benefit migraine.
In contrast to CHCs, physiologic doses of transdermal estradiol and progesterone used in HRT are not associated with increased risk of ischemic stroke and can be used by women with migraine aura.
Conclusion
Many questions related to these topics don't have ready answers—questions like increased prevalence of hormone-related migraine, age of onset of menstrual migraines, and multispecialty treatment of these patients. Research is either limited or yet to be done, and we may not get the answers until healthcare professionals and women are more aware of the hormonal effects of migraine.
The effects of hormonal changes on migraine provide physicians with specific opportunities to identify and manage migraine in women. Under-treatment – in addition to causing unnecessary disability and suffering – is not economically cost-effective in terms of time lost from work and burden placed on the families of these patients. More effective health care would alleviate much of the suffering and therefore reduce both the personal and financial costs of migraine. Ineffective management of migraine in women has significant implications for women, their families, and their employers.