Migraine can afflict men, women and children. But it is not an equal opportunity disorder.

Of those who suffer chronic crippling migraine attacks, the vast majority are women. They are as many as 85 percent, according to the Migraine Research Foundation.

"A researcher once said that 'the femaleness of migraine is inescapable,' " says Elizabeth Loder, associate professor of neurology at Harvard Medical School and chief of the division of headache and pain at Brigham and Women's Hospital.

"It's true. Migraine disproportionately affects women."

A migraine is much more than just a terrible headache. To be sure, migraine typically involves a painful throbbing headache, most times on one side of the head, sometimes both.

But it also is an incapacitating neurological disease with a wide range of symptoms, including visual disturbances, nausea and vomiting, dizziness, sensitivity to lights, noises, and scents, and - for some - temporary weakness on one side. Episodes can last for hours, sometimes even days.

About 25 percent of victims also experience "aura," a collection of sensory disruptions, such as flashes of light, blind spots, or tingling and numbness in the hands and face. Moreover, migraine with aura in women under age 50 increases their risk of ischemic stroke, especially if they also smoke and use oral contraceptives.

Migraine affects 1 in every 7 adults globally, according to the World Health Organization. In the United States, nearly 40 million Americans suffer from them, including 28 million women and girls, according to the research foundation.

Migraines costs the nation an estimated US$78 billion per year, with women accounting for about 80 percent of direct medical and lost labor costs, according to a recent report from the Society for Women's Health Research.

"We don't have the answer for why migraines are more common in women than in men, but women are more susceptible to every pain condition than men," says Janine Clayton, who directs the Office of Research on Women's Health at the National Institutes of Health (NIH).

"Also, women in pain are not always taken seriously. Women are perceived as excessively seeking help."

Cindy McCain, widow of Senator John McCain, has spoken out about her experiences with migraine, and the frustration of getting doctors to take her debilitating headaches seriously.

"I saw many doctors who wrote me off as just being 'overstressed,' " she said in one interview.

"Their advice was to go home, relax and have a glass of wine."

Since migraines affect young women and get better with age, they are most prevalent during a time when women are expected to be most productive at home and work.

Because the pain is often worse with routine activity, "people tend to remain still, which has obvious detriments towards productivity," says Mark W. Green, professor of neurology and anesthesiology and director of the Center of Headache and Pain Medicine at Mount Sinai's Icahn School of Medicine.

"They also get light and sound sensitivity, and it is difficult to work, or even function, under those conditions."

Boys experience more migraine than girls before puberty, then the equation changes, with girls and women bearing the brunt of migraine until after menopause. The disorder then eases for most women.

For this reason, most experts believe that women's fluctuating hormones are a major influence, especially when estrogen falls around the time a women has her menstrual period. Most attacks occur several days before or after menstruation.

Green thinks estrogen withdrawal is a major trigger.

"Around period and ovulation, and just after a delivery, levels drop precipitously, which can be a problem," he says.

"After menopause, when the levels of estrogen remain low - they don't fall - most women improve. Estrogen falls increase the excitability of the brain cortex. Migraine is a condition where the cerebral cortex is more 'excitable,' often genetically, so that is one reason why."

One recent small study suggested that elevated estrogen may be related to migraines in men, although the scientists said additional research was needed.

A migraine can be set off by other triggers, including stress, changes in sleep patterns, loud noises, bright lights, strong smells, and various foods and beverages - wine and chocolate, among them.

McCain would have been ill-served by the early medical advice she was given, as wine is one of her triggers.

"Think of migraine as a problem where the threshold for an attack is low," Green says.

"Triggers that might be irrelevant to someone else can become a big migraine trigger. Anyone might get a headache after drinking a quart of red wine, but it takes very little to trigger it in someone with migraine."

Loder agrees. "In my clinical experience, I hear a lot about strong scents, women who don't want to walk into a department store and be sprayed by someone trying to sell them perfume," she says.

Moreover, "women face challenges different from men in the workplace and their personal lives, and we know that stress can have a negative impact on the course of this disorder."

Most experts agree that migraine probably results from the brain's reaction to a complex interaction among hormones, genetics and environmental factors.

"Migraine is not a hormonal disorder," says Michael Oshinsky, program director of pain and migraine at the National Institute of Neurological Disorders and Stroke at NIH.

"That's a mistake. Think of it as a very diverse disorder. Each patient has to be diagnosed with her own criteria."

While he agrees with other experts that hormones often play a pivotal role, "There are likely many different pathways not working properly in the brain that lead to an attack," he says.

"It's a disorder of the nerves and the brain."

Loder points out that many people with regular hormonal cycles do not get migraines, "so it's probably modulated by many other things in the internal and external environment," she says.

"Hormonal influences probably can affect whether certain neurons in the brain will be activated or not. It's a neurological problem."

Inna Belfer, a neurologist and scientist in NIH's National Center for Complementary and Integrative Health, agrees.

"Migraine is an intriguing condition, when you think about it," she says. "You have a group of neurons in the brain that for some reasons starts firing, then for another reason stops firing - and that is an episode."

She knows about migraine firsthand, having suffered from the disorder starting at age 12. "I would have about four or five a month," she says. "Some lasted five hours, other times, as long as three days."

Now that she is past 50, the number of episodes has decreased to one or two a month.

"The severity of the pain is nothing like it was," she says. "I can function. I can work. However, the aura is still there. The nausea is still there. I am still light sensitive."

Also, she still always smells chlorine - not from a swimming pool, but from tap water - before an onset. That's how she knows an attack is coming.

Research shows that migraines tend to run in families. Studies of twins, for example, show "that if one has migraines, it's more likely for the other twin to have them," Oshinsky says.

Also, research suggests that mutations in certain genes can cause familial hemiplegic migraine, a type of migraine that also causes weakness or numbness on one side of the body.

A substantial body of research has found women feel greater pain and show more sensitivity to experimentally induced pain (controlled pain tests on subjects in a laboratory) when compared to men, a possible reason they are more vulnerable to migraine.

"We don't know exactly how the migraine brain is different from the non-migraine brain, but I do think that sex specific differences make the female brain more prone to pain than men, and to experience it differently," Belfer says.

Although there is no cure, prescription and over-the-counter medications and complementary approaches, such as certain dietary supplements, massage, relaxation techniques and biofeedback, can treat or prevent symptoms.

Clinicians also recommend keeping a migraine diary to figure out one's triggers - then avoid them, if possible.

Recent research also has found that light-sensitive migraine sufferers might benefit from exposure to green light, which seems to lessen the severity of headaches compared with being in regular light.

"A hot water bottle on my head, neck or shoulders is always a rescue for me, while a friend of mine needs ice," Belfer says. "I told my husband if we ever get a new house, I want a green light room."

For most women, relief usually comes with aging. Unfortunately, the worst migraines "hit when women are trying to balance and juggle a career with family responsibilities," Loder says.

"Migraines improve for most women over time, but you never get back those lost work or school years, or that lost time with your family."

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