• Posted February 27, 2023

Unraveling the Link Between Menstrual Cycles and Migraine

Many women experience blinding migraine headaches around their monthly period, and now researchers have a clue about why.

Levels of the female hormone estrogen fluctuate during menstruation, which may lead to increases in calcitonin gene-related peptide (CGRP). This protein widens blood vessels in the brain, which is part of the cascade of events that cause migraines.

"Women with migraine had higher CGRP levels in the blood and tear fluid during menstruation than women without migraine,"said study leader Dr. Bianca Raffaelli, a neurology resident at Charité--University Medicine Berlin in Germany. She is also a fellow with the Clinician Scientist Program jointly operated by Charité and the Berlin Institute of Health at Charité.

More research is needed before drawing any firm conclusion about the role that CGRP plays in menstrual migraines, Raffaelli said.

"Once the exact processes are understood, appropriate treatment strategies can be developed,"she said. "In recent years, new migraine drugs have been developed that target CGRP, [and] it would be exciting to investigate whether these drugs act differently depending on the hormonal state."

The good news for women with menstrual migraines is that symptoms improve during pregnancy, and their frequency tends to decline after menopause, Raffaelli said.

For the study, the researchers measured CGRP levels in blood and tears of 180 women with a history of migraine, including those with a regular menstrual cycle, those taking oral contraceptives, and women who had gone through menopause.

They measured CGRP during menstruation and ovulation in women with a regular menstrual cycle. CGRP was measured during the hormone-free and hormone-intake time among women taking birth control pills, and randomly among those who had gone through menopause. CGRP levels were compared to those of another group of women who do not get migraines.

The study found that women with migraine and a regular menstrual cycle had higher CGRP concentrations during their periods than those without migraine.

Specifically, CGRP blood levels were 5.95 picograms per milliliter (pg/ml) compared to 4.61 pg/ml for those without migraine. When researchers looked at CGRP in tear fluid, they found levels of 1.20 nanograms per milliliter (ng/ml) in women with migraine and 0.4 ng/ml in those without migraine.

By contrast, women taking oral contraceptives and those who have gone through menopause had similar CGRP levels in both the migraine and non-migraine groups.

The study was published online Feb. 22 in Neurology.

Outside experts on migraine said the findings help unravel the role that hormones may play in migraine headaches.

"This is a very interesting study that provides the first evidence of an association between CGRP and different sex hormone profiles in humans,"said Dr. Brian Grosberg, director of the Hartford HealthCare Headache Center in Hartford, Conn. "The findings could help to explain a higher susceptibility for migraine around and during menstruation."

Dr. Teshamae Monteith is the chief of the headache division and an associate professor of clinical neurology at University of Miami Health Systems.

"While the study results should be confirmed, it is clear that clinical trials are needed to investigate the role of CGRP ... for the acute and preventive treatment of menstrual migraine," Monteith said.

Menstrual migraine requires specific strategies that may include preventive therapy in addition to in-the-moment treatment, she said.

"If menstrual migraine is a source of disability, make an appointment to see a neurologist or headache specialist,"Monteith advised.

More information

The American Migraine Foundation has more about menstrual migraines.

SOURCES: Bianca Raffaelli, MD, neurology resident, Charité--University Medicine Berlin, fellow, Clinician Scientist Program, Charité--University Medicine Berlin, Berlin Institute of Health, Germany; Brian Grosberg, MD, director, Hartford HealthCare Headache Center, Hartford, Conn.; Teshamae Monteith, MD, chief, Headache Division, associate professor, clinical neurology, University of Miami Health Systems, Miami, Fla.; Neurology, Feb. 23, 2023, online