Migraine is a common neurologic disorder that occurs in approximately 3 times as many females as males in the United States. Among 30,000 respondents, the American Migraine Study II found that the prevalence of migraine was 18.2% among females and 6.5% among males, and was much higher in females from age 12 across the lifespan.1 In comparison, for tension-type headache the female to male ratio of occurrence is 5:4, occurring only slightly more in females.2 The reasons for this disparity in migraine prevalence are not well understood. The disproportionate number of women of reproductive age with migraine suggests that hormonal factors may play a role, but the complex pathophysiology of migraine indicates additional factors are involved.3
Recent research on menstrual-related migraine and two significant comorbidities of migraine—obesity and posttraumatic stress disorder (PTSD)—shed new light on the differences in how men and women present with and experience this often disabling disorder.
Epidemiologic differences
The incidence of migraine, defined here as age of first onset, is different in boys and girls. For migraine without aura, age of first onset is approximately 10 to 11 years in boys versus 14 to 17 years in girls. For migraine with aura, age of first onset is approximately 5 years in boys and 12 to 13 years in girls.4
The picture of migraine differs by sex before and after puberty. Before age 12, boys have a higher incidence and prevalence of migraine. After age 12, prevalence increases for both sexes, peaking between age 35 to 45, with an increase in the female-to-male ratio from 2:1 at age 20 to 3.3:1 at age 40.5,6
Disparities in migraine symptoms
Common symptoms associated with severe or unilateral migraine pain include photophobia, phonophobia, and nausea. In the American Migraine Study II, the most frequently reported symptoms were pulsatile pain (85%of migraineurs), light sensitivity (80%), sound sensitivity (76%), nausea (73%), unilateral pain (59%), blurred vision (44%), aura (36%), and vomiting (29%).1 Females were more likely than males to report light sensitivity, sound sensitivity, and nausea. More females experienced 1 to 2 days of migraine-associated activity restriction than males (30.5% vs 22.9%).1 Separate studies have shown neck pain to be second after menstruation in its predictive value for onset of migraine, and to be more prevalent than nausea at the time of treatment.7,8
Migraine comorbidities
Migraine is known to be comorbid with a variety of disorders including psychiatric conditions such as depression and anxiety,9,10 and medical comorbidities such as stroke, epilepsy, and hypothyroidism.11-13 In women, migraine is also comorbid with endometriosis.14
Hormonal factors: Menstrual-related migraine
With migraine disproportionately affecting women of reproductive age, as many as 70% of female migraineurs are aware of a menstrual association with their headaches.15 A menstrual migraine is defined as migraine without aura that occurs during the 5-day window that begins 2 days before the onset of bleeding and extends through the third day of active bleeding—and that occurs in at least two-thirds of menstrual cycles.16 Approximately 14% of women experience what is termed pure menstrual migraine, meaning the only time they experience migraine is during menstruation. For women who also have migraines triggered by other mechanisms, the menstrual migraine is typically their most severe migraine of the month.
For many women, menstrual migraines are more painful, longer lasting, and more resistant to acute therapy than migraines occurring at other times.17,18 It is specifically the reduction in estradiol in the late luteal phase that appears to be the greatest trigger for menstrual migraine.
About two-thirds of women with migraine improve in menopause, particularly those for whom migraine attacks were associated with menstruation.19,20 As disabling as menstrual related migraine can be, clinically it is often found to coexist with chronic migraine and medication overuse headache.21
In a study that looked at the impact of eliminating menstrual migraine, investigators treated women with hormonal preventives based on the hypothesis that, because these agents confer no known benefit for migraines that are not hormonally triggered, use of these agents might allow them to separate out menstrual-related migraine and its effect on the overall clinical picture.21 Among 229 consecutive women seen in follow-up, 81% of those patients who were taking the hormonal preventive as prescribed had a complete resolution of menstrual-related migraine. Among those in whom menstrual migraine was eliminated, 58.9% reverted back to episodic migraine, compared with only 11% of patients whose menstrual-migraine was not eliminated.21 Resolution of menstrual-related migraine also was associated with resolution of medication overuse. Patients in whom menstrual-related migraine resolved were >2 times as likely to stop medication overuse as those in whom the migraines were not eliminated. The results offer preliminary evidence that hormonal regimens may be of benefit in preventing menstrual-related migraine.