Migraines are one of medicine's most frustrating mysteries, both causes and treatments. Now researchers believe they've solved one part of the puzzle: a protein affected by fluctuating estrogen levels may explain why more women suffer from migraines than men.

Migraines are the third most common illness in the world, affecting more than 1 in 10 people. Some 75 percent of sufferers are women, who also experience them more frequently and more intensely, and don't respond as well to drug treatments as men do.

At this year's Experimental Biology meeting in San Diego, researcher Emily Galloway presented new findings on the connection between the protein NHE1 and the development of migraine headaches. NHE1 regulates the transfer of protons and sodium ions across cell membranes, including the membranes that separate incoming blood flow from the brain.

When NHE1 levels are low or the molecule isn't working as it's supposed to, migraine-level head pain can ensue. And because irregular NHE1 disrupts the flow of protons and sodium ions to the brain, medications like pain killers have trouble crossing the blood-brain barrier as well. This may explain why the condition is so hard to treat.

When the researchers analyzed NHE1 levels in the brains of male and female lab rats, the researchers found them to be four times higher in the males than in the females. Additionally, when estrogen levels were highest in the female specimens, NHE1 levels in the blood vessels of their brains were at their lowest.

Previous research had implicated fluctuating estrogen levels in migraines, but the mechanism behind it has remained elusive. The new finding could change the way migraines are studied and treated in the future, which is especially important considering that most migraine studies have focused on male animal subjects.

"Conducting research on the molecular mechanisms behind migraine is the first step in creating more targeted drugs to treat this condition, for men and women," Galloway said in a press statement. "Knowledge gained from this work could lead to relief for millions of those who suffer from migraines and identify individuals who may have better responses to specific therapies."

The new research is part of a broader effort to build a molecular map of the relationship between sex hormones and NHE1 expression. The next step is testing drugs that regulate these hormones to see how they affect NHE1 levels in the brain.