Every month, millions of women worldwide experience at least one PMS-related symptom during their menstrual cycle, including cramps, acne, bloating, and tender breasts. Some women, however, tend to struggle with frequent migraines at this time. But why does this happen? 

Fortunately, scientists in Berlin may have just discovered a possible explanation as to why this occurs. According to their study published in the journal Neurology, women who suffer migraines have higher levels of CGRP during menstruation than those who don’t experience migraines.

Calcitonin Gene-Related Peptide or CGRP for short plays a key role in migraine onset. Studies have shown that migraine is three times more prevalent in women than in men. Usually, the attacks come more frequently around the time of menstruation, including the period around menopause. 

When someone is experiencing a migraine, CGRP is released and elicits an inflammatory response. Researchers suggest this could be the reason why females of childbearing age suffer migraines the most. 

Lead study author Dr. Bianca Raffaelli and her colleagues analyzed over 180 women to explore the link between female sex hormones and the release of CGRP. They included three groups of participants suffering from migraine: those with a regular cycle, those taking contraceptives, and those who had entered menopause.

Participants with migraine made two scheduled visits to measure their CGRP levels. The first was on the second day of menstruation, and the second was around ovulation. The team picked these time intervals because estrogen levels are at their lowest during menstruation and at their highest when ovulating. 

They then compared women who experienced migraines with those who did not.

In the end, they observed that CGRP levels rose significantly among those with migraine compared to those who didn’t suffer migraine during menstruation. They noted that it appeared to only hold when the estrogen levels drop from an initial high point.

“This means that when estrogen levels drop immediately before the start of a menstrual period, migraine patients release more CGRP,” explains Raffaelli.

They further explain that this increase in CGRP following a shift in hormone levels could help explain why these women are more vulnerable to migraine attacks before and during their monthly cycle.

On the other hand, the researchers did not detect such fluctuations in estrogen levels among those who took oral contraceptives or among postmenopausal women. Thus, the levels of CGRP were relatively low, similar to those of women who did not suffer from migraine at all. 

Prior in vitro and animal studies on the influence of estrogen on CGRP release have also suggested that a shortage of female sex hormones—particularly estrogen—raises CGRP concentrations in various brain regions.

While they still see the need for further studies on a larger population, overall, their findings support a hormone-dependent change in the levels of CGRP in women suffering constant migraines. 

“Taking birth control pills and the end of menopause do in fact bring relief for some female migraine patients,” Rafaelli says. “But as our study also shows, there are women who suffer from migraine even without any hormonal fluctuations. We suspect that other processes in the body play a role in triggering attacks in those patients.”

“After all, CGRP isn’t the only inflammatory peptide that can cause a migraine attack,” she concludes. 

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