Migraine attacks are no ordinary headache. They can cause intense pain and sickness, lasting hours or even days, making it impossible to do anything but rest in a dark, quiet room. And for millions of women, these debilitating attacks aren’t just an occasional experience but a recurring ordeal.
Women suffer from migraines three times as often as men, with episodes that are more prolonged and intense. “It’s far more common than most people realize,” says Anne MacGregor, a specialist in headache and women’s health. Despite various treatment options, migraines remain the leading cause of disability-adjusted life years (DALYs)—a measure of disease burden that accounts for time lost to ill health—for women between the ages of 15 and 49. While there’s still some mystery around how migraines work, one reason for this sex difference is hormones.
During early childhood, boys are slightly more prone to migraines than girls, but puberty tips the balance dramatically. At this time, sex hormones begin to fluctuate and trigger physical changes including the onset of menstruation. This is often when girls experience their first migraine. From puberty onwards, girls experience migraines at a higher rate than boys, with this disparity growing more pronounced as people reach their mid-thirties and persisting into late life. “It’s chaotic at the two ends of a woman’s reproductive years,” MacGregor says.
In adulthood, many women who suffer from migraines report experiencing attacks associated with their menstrual cycle. A sudden drop in estradiol—a potent form of estrogen—is thought to play a key role. A few days before menstruation, known as the late luteal phase, estradiol levels plummet. Women who are susceptible to migraines tend to experience a faster rate of estradiol decline around the time of their period compared to women who don’t. While estrogen drops around ovulation, too, the decline is not as rapid, which might explain why migraines aren’t as common at this time. The role of estrogen has also been observed in transgender women on hormone therapy, who show similar migraine frequency to cisgender women.
Periods of fluctuating estrogen are also tied to migraines in women. As women hit perimenopause, the transitional period leading up to menopause, hormones become especially erratic. “Those women who didn’t particularly have menstrual migraine beforehand become more likely to experience it during perimenopause,” MacGregor says. After menopause, some experience relief. “But it’s important to say that patterns are variable—not everyone gets better,” says Richard Lipton, a neurologist and epidemiologist at the Albert Einstein College of Medicine in New York.
Estrogen’s link to migraine is well documented, but researchers don’t yet fully understand how it contributes to the onset and progression of migraine. Lipton explains that migraine is a disorder characterized by a sensitive brain. “When I say sensitive, I mean vulnerable to exogenous factors that make migraine more likely,” he says. Something like a change in hormones can trigger a reaction.
But estrogen doesn’t act alone. Changing estrogen levels also influence other hormones such as serotonin, which typically protects against migraine by lowering pain sensitivity. When estrogen levels drop, so do serotonin levels, increasing the likelihood of migraine. Triggers also act in tandem. When enough factors align—such as the drop in estrogen, combined with a lack of sleep, irregular meals, dehydration, or stress— an attack can ensue.
Estrogen’s interaction with calcitonin gene-related peptide (CGRP) also complicates the picture. CGRP is a chemical that nerve cells use to talk to each other, explains Lipton. It dilates blood vessels and increases blood flow—which has been implicated in the onset and pain of migraine. “We know that during migraine attacks, if you draw blood from people with migraine, CGRP levels are high,” Lipton says. Women have higher levels of CGRP than men, and changes in estrogen levels influence CGRP in the brain’s pain pathways. Research in mice has also shown that females respond more intensely to CGRP.
Emerging research suggests progesterone, another sex hormone, could also play a role in migraines. Recent findings suggest the activation of progesterone receptors in the brain could increase susceptibility to pain. A team at the University of Virginia treated mice with nitroglycerin, a vasodilator that simulates migraine. When they then gave the mice progesterone, they found that it made them more susceptible to pain—exhibited through their avoidance of light and reaction to a pinprick sensation.
Suchitra Joshi, lead author of the study, says the role of progesterone in migraine has been ignored for years, and that the findings “could provide a potential target for treatment.”
New research is also mapping possible genetic components to migraines in women, and other sex-specific investigations are gaining momentum, helping to move migraine science beyond outdated myths about “hysterical” or “sensitive” women. Even today, an element of sexism persists in migraine treatment, with women less likely to be prescribed medication than men. “Characterizing it as a women’s disease is sometimes a means of dismissing it,” Lipton says. Even though women are more likely to see a doctor for their migraine, and more likely to be diagnosed with migraine, “men diagnosed with migraine are more likely than women with migraine to be treated.”
