By Dara Jamieson, MD

Associate Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Jamieson reports she is a consultant for Bayer and Boehringer-Ingelheim.

SYNOPSIS: Hormonal and genetic differences factor into a greater prevalence and disability burden of migraine in teenaged girls and women; however, migraine is underdiagnosed and inadequately treated in boys and men.

SOURCE: Vetvik KG, MacGregor EA. Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol 2017;16:76-87.

Migraine is more prevalent in women, who are more likely to seek medical help for their headaches and to participate in clinical trials, as compared to similarly affected men. However, men with migraine may be underdiagnosed or misdiagnosed and, therefore, inappropriately treated. This review outlined the sex differences in epidemiology, clinical features, and pathophysiology in this female-predominant, but male-afflicting, primary headache disorder. Although data from the Global Burden of Disease Study 2015 found that migraine is two to three times more prevalent in adult women than in men, migraine is equally likely to occur in both sexes prior to puberty. Age-specific prevalence of migraine, both without and with aura, peaks at a younger age in boys than in girls. Then, girls in their teens develop migraines more frequently than do teenaged boys. Migraine incidence peaks in the late teens in boys at 6.2 cases per 1,000 human-years and in their early 20s in women at 18.2 cases per 1,000 human-years. The rate of increase in migraine prevalence is dramatically higher in women in their late teens and young adulthood than it is in similarly aged men, who are more likely to have longer-lasting periods of migraine remission after childhood.

Clinical features of migraine appear to be relatively similar in men and women, although women report longer duration of attacks. Migraine with aura, in about 8% of women and 4% of men, occurs in the same ratio in both sexes as does the twice-as-prevalent migraine without aura. Disability associated with migraine is greater in women (fourth leading cause of years lived with disability, according to the Global Burden of Disease Study 2015) than in men (eighth leading cause), possibly related to longer duration of attacks and higher relapse rates, in combination with multiple household, childcare, and employment responsibilities for women. Despite migraine’s comorbidity with medical and psychiatric disorders, there is no consistent sex difference in comorbid conditions. The known data on the link between migraine with aura and stroke are based on observational studies with female predominance, thus limiting the analysis of sex differences.

The treatment difference found between men and women, with women more likely to use prescription acute pain and preventive medications, likely reflects their greater likelihood to seek professional consultation for their migraine disorder. Men and women appear to have similar responses to triptans and to medications used preventively.

Migraine is a polygenetic disorder with variable transmission and a strong influence from environmental and hormonal factors. Clinical features of migraine in women emphasize the role of female sex hormones in migraine triggering. Migraine without aura is associated with estrogen withdrawal leading to menstrual migraine, which are symptomatically more disabling than non-menstrual migraine. Later stages of pregnancy are often a time of relief from migraine without aura. However, high estrogen states, including with exogenous estrogen, may be associated with an increase in migraine with aura. Perimenopausal and menopausal fluctuations in estrogen levels caused increased migraine, until postmenopausal hormone stabilization leads to migraine improvement. The prevalence of migraine in male to female transgender people is similar to the prevalence in genetic females. Little is known about the role of testosterone in migraine, although the hormone may have anti-nociceptive and anti-inflammatory properties.

COMMENTARY

The most important theme from this comprehensive and well-written review of sex differences in migraine is that boys and men deserve attention. About 43% of women have a migraine in their lifetime and the majority of their headaches are appropriately diagnosed and treated. About 18% of men have a migraine in their lifetime and the majority of their headaches are misdiagnosed and undertreated. The authors emphasized that, “[t]he under-diagnosis of migraine in men is likely to result in suboptimal management and less participation in clinical trials.” Males, from boyhood to adulthood with migraine, are not going to get relief from migraine pain and the associated symptoms until they seek help from knowledgeable physicians who recognize the variability in the presentation of migraine, make the correct diagnosis, and offer appropriate and effective advice for lifestyle management and use of prescription medication. There may be stigma associated with “a women’s disorder” so that the misdiagnoses of “chronic sinus,” “recurrent sinus infections,” or “tension headache” may be made in boys and men with migraine, if headaches as a medical complaint are even addressed at all. Sinus surgery, antibiotics, opiates, barbiturates, and the frequent use of over-the-counter medications are not appropriate treatments for migraine in males or females. Discussions of trigger recognition and preventive lifestyle modification are not initiated if male migraine is not recognized. Triptans, which are of life-changing benefit to millions of migraine sufferers, should be prescribed for boys and men with migraine. Given the significant effect of frequent migraine on quality of life, prescription preventive treatments should be discussed with every male migraine sufferer. Boys and men with migraine deserve to be treated with the same care and respect that are accorded to girls and women.