Assessing and Treating Migraine in Women and Men

As a stigmatized, painful disease that disproportionately affects women, migraine has significant negative consequences for individuals, their families, and society as a whole. Migraine is three times more common in women, reaching peak prevalence between 30 and 39 years of age, at a time when many women are rapidly growing in their career and balancing work, family, and social obligations. As a result, women account for a large majority of the estimated $78 billion in migraine-associated economic costs in the United States,¹ representing about 80% of both direct medical costs and lost labor costs.²

Migraine affects women differently than men both physiologically and socially. The biological differences between women and men, as well as sociocultural norms, are key variables in the etiology, diagnosis, and management of migraine. In addition, because of the high preponderance in women, the disease has become feminized, furthering the differences between women and men in seeking and receiving care.^3-5

The Society for Women’s Health Research recently published a report⁶ that assesses the state of the science of sex differences in migraine and calls for more research on, and attention to, these differences in order to improve care for both women and men. It is important to apply what we know to both scientific research and clinical practice, including migraine detection, treatment, care, and education. As such, this article provides a review of what is known about sex differences in migraine and its relevance to clinical care.

Pain is reported more frequently by women than men, and specific pain conditions, such as migraine, are considerably more common in women than in men. (Source: 123RF)

Differences in Risk Factors

Determining the differences between women and men in migraine risk factors, such as those outlined below, may aid clinicians in diagnosis and management, leading toward a more personalized care approach.

Female sex hormones are thought to be a major risk factor in migraine, which may explain, in part, the differences in prevalence and presentation between women and men. Changes in migraine prevalence in women correlate with periods of large hormonal shifts (eg, puberty, pregnancy, menopause).⁷ One longitudinal study found that earlier age of a woman's first menstrual cycle increased risk for migraine.⁸

Sociocultural factors may play a role in the observed differences in migraine between women in men as well. For example, victims of intimate partner violence and adverse childhood experiences are associated with an increased risk for migraine, and rates of sexual harassment and assault are higher in women.^9-11

Some studies show being female itself is a risk factor for transformed migraine (ie, the transition from episodic to chronic migraine)^12,13 although results on this are mixed.¹⁴ The risk factors for both women and men for transformed migraine include depression, anxiety, and headache-related nausea, all of which are more commonly reported in women than men.^15-17 These data suggest that women with episodic migraine could be at a higher risk for transitioning to chronic migraine than men.

Differences in Presentation

Migraine may present differently in women and men, and understanding the differences for each subtype and their associated comorbidities may help clinicians improve diagnosis and treatment. Women are more likely to experience longer and more intense migraine attacks, report more migraine-associated symptoms – including nausea, visual aura, blurred vision, photophobia, and phonophobia – and have higher levels of migraine-related disability (eg, requiring bed rest with attacks, reduced productivity at school or work).^3,18 On the other hand, men experience less headache-related disability and are more likely to report being able to work/function normally during a migraine attack.³

Comorbidities are very common in migraine patients, with nearly 90% of all individuals with chronic migraine having at least one comorbid condition.¹⁹ On average, women with migraine have 11 comorbid conditions, while men have five.¹⁸ The types of comorbid conditions can differ between women and men as well. Some evidence suggests women with migraine are more likely to have anxiety, depression, fibromyalgia, endometriosis, and restless legs syndrome, whereas men with migraine are more likely to have obesity, coronary thrombosis, diabetes, epilepsy, and kidney stones, although other data show conflicting results.^3,20-22

As noted, hormonal fluctuations are a common trigger for many women with migraine,²³ with up to 50% of women with migraine experiencing attacks that co-occur with menstruation.^24,25 Menstrual migraine, which is defined as migraine attacks occurring in at least two of three menstrual cycles, extending from two days prior to onset of menses through three days after onset, is a female-specific migraine subtype.²⁶ Menstrual migraine attacks can be more disabling (leading to a larger loss of productivity), more severe and longer lasting, and more resistant to treatment than non-menstrual migraine.^27,28

There are also extra barriers to receiving a menstrual migraine diagnosis, including the need for diary documentation for at least three menstrual cycles and the fact the menstrual migraine does not appear in the main text of the International Classification of Headache Disorders (ICHD), but is only found in the appendix.²⁶ The lack of codification implies that menstrual migraine has been deemed less important in the healthcare community and further enhances the general lack of awareness about this migraine subtype, which places a disproportionate burden on women with the disease. In addition, treatment strategies for menstrual migraine may differ from those for non-menstrual migraine. For example, treatment options for menstrual migraine tend to include mini prophylaxis or estrogen supplementation around the time of the menstrual period.^29-31

Differences in Seeking and Receiving Care

Migraine is heavily stigmatized, leading many individuals with the disorder, regardless of gender, to go undiagnosed or to underreport symptoms.⁵ This norm may exist, in large part, because migraine, like many chronic pain conditions, is an “invisible” disease. In addition, despite the millions of men with migraine, the disease is still thought of as a “woman’s disease” and therefore often delegitimized by the public, providers, and employers.⁴ Healthcare providers have the opportunity to drive discussion around migraine in ways that address this stigma and ask more detailed questions to identify those with suspected migraine.

Women with migraine are more likely than men to consult a healthcare provider about their symptoms, which may be because women on average have more severe and disabling attacks than men.^3,32 Men may be more hesitant to consult a healthcare provider to report symptoms because of the feminization of migraine. Women are also more likely to have received a diagnosis of migraine, tension headache, or sinus headache from a healthcare provider.^3,33 They are less likely to be diagnosed with cluster headache,³ which is more prevalent in men.³⁴ Women are also more likely than men to have sought care for their headaches in the emergency department or in urgent care.^3,33 It is important to recognize these gender differences to help overcome patient and provider bias in the diagnosis and treatment of migraine.

Differences in Treatment Response and Use

When considering treatment options for their patients, it is important for clinicians to understand the observed differences in migraine treatment use and response between women and men. Women with migraine are more likely than men to take prescription medicine (acute and prophylaxis) or a combination of prescription and over-the-counter medications to treat their attacks, while men are more likely to take over-the-counter medications or no medications at all.^3,33,35 Women are also more likely than men to use complementary and alternative medicine approaches, and in particular, acupuncture, homeopathy, massage, and yoga.36 Interestingly, use of complementary and alternative medicine is associated with decreased odds of moderate mental distress among women, but not men.³⁶ More research is needed to better understand why.

Few studies have looked at or reported sex differences in efficacy of migraine therapies. Of the studies that have, the focus has been on triptans. Some studies have found that women had higher headache recurrence rates post-triptan use,^37-39 while one large pooled analysis did not find this difference.⁴⁰

There have been no clinical trials on the use of migraine therapies during pregnancy or breastfeeding.^29,31 Some migraine therapies are contraindicated for pregnancy, although others—including acetaminophen and sumatriptan—are shown to be relatively safe.^31,41-44 Healthy lifestyles, trigger avoidance, and biobehavioral treatments are also important management tools during pregnancy and breastfeeding.^31,42

Conclusion

Since sex and gender play a crucial role in the risk, pathophysiology, and management of migraine, it is important that clinicians take differences between women and men into account when diagnosing and treating the disease. However, more research is needed to truly understand these differences and optimize care for both women and men. As noted, there are currently no sex-specific guidelines for acute treatment of migraine, aside from menstrual migraines. Researching and developing sex-specific guidelines may be an important aspect for the field to consider to improve migraine treatment for the entire adult population.