We know that women are around three times more likely to get migraines than men, and yet we’ve never really understood why. Now, new research might be able to shed some light on why this is the case.

The latest study, the results of which are being presented at the American Society for Biochemistry and Molecular Biology meeting in San Diego this week, has found that a particular protein in the brain known as NHE1 might be involved. The research suggests that fluctuating levels of estrogen might be inhibiting the expression of this protein, and therefore increasing the rate of migraines in women.

It is thought that out of some 38 million Americans who get migraines, around 28 million of these are women. In fact, as many as 18 percent of women suffer from the often debilitating condition, according to a survey conducted in both Europe and North America. Not only that, but women also experience more severe and more frequent headaches, and many don’t respond to the standard medication given to help douse the migraines.

While women are more likely to be affected by the condition, figuring out why this is has been a little trickier. One of the obstacles, according to Emily Galloway who worked on the research, could be down to the simple fact that many lab-based experiments on migraines have been done on male animal models.

By studying both male and female rats, this latest research was able to show some fundamental differences between the sexes. One of the most significant finds showed that the expression of NHE1 in the brains of male rats was four times that seen in the brains of female rats. What is more, they found that the female rats with the highest levels of estrogen also had the lowest amount of NHE1 expression.

“Based on our findings, we think that women are more susceptible to a migraine because the larger magnitude sex hormone fluctuations lead to changes in NHE1 expression, which may leave the brain vulnerable to ion dysregulation and pain activation,” explains Galloway.

The protein is known as a sodium-proton exchanger and regulates the transport of both sodium and protons across cell membranes in the brain, including the blood-brain barrier. It is thought that when there are fewer NHE1 exchangers present, it can lead to increased pain signaling and precipitate a migraine. This could be why some drugs are less effective on women, as the ability of the medication to cross the blood-brain barrier is inhibited.

This work could help researchers better target ways to treat migraines in both women and men, helping tens of millions of people in the process.