For many migraine sufferers, the severe headaches occur shortly before or during the menstrual period. A study now offers a possible explanation for this. Accordingly, the inflammatory messenger CGRP is increasingly released in the brain of the affected women during menstruation. This has previously been associated with migraine attacks. In contrast, the research team found no fluctuations in CGRP levels in women who take the pill or are going through the menopause.
Women are three times more likely to suffer from migraines than men. Fluctuations in sex hormones, estrogen in particular, play an important role in this. The level of this hormone is lowest just before and during menstruation – and it is precisely in this phase that affected women experience migraine attacks most frequently. For some women, symptoms improve during pregnancy, with birth control pills, and after menopause is complete. How exactly the hormone fluctuations are related to migraines, however, is still unclear.
On the trail of migraine triggers
A team led by Bianca Raffaelli from the Charité – Universitätsmedizin Berlin has now uncovered a possible mechanism. In their study, Raffaelli and her team focused on the inflammatory messenger CGRP. “We have evidence from the animal model that fluctuations in female hormones – estrogen in particular – lead to an increased release of the inflammatory messenger CGRP in the brain,” explains Raffaelli. “CGRP stands for ‘Calcitonin Gene-Related Peptide’ and is an endogenous substance that is increasingly released during migraines and greatly dilates the blood vessels in the brain. This creates an inflammatory response that could be one of the reasons for the severe headaches associated with migraines.”
A total of 180 women took part in the study, half of them with episodic migraines. 30 of them each had a regular menstrual cycle, 30 were on the pill and 30 had already gone through the menopause. Each of these groups was matched with an equal group of participants of similar age who did not suffer from migraines. The researchers determined the CCRP level in the blood and in the tear fluid. In women with a regular menstrual cycle, they took the samples at the beginning of menstruation and around ovulation, in hormonal contraceptive women once during the pill break and once in the middle of the intake phase. Samples were collected once at a random time from the postmenopausal participants.
Hormonal fluctuations
The result: Compared to women without migraine, the CGRP level in migraine patients with a regular menstrual cycle was significantly higher at the beginning of the menstrual period. “So when estrogen levels drop to start a period, migraine sufferers release more CGRP,” says Raffaelli. “That could explain why the affected women experience more migraine attacks shortly before and during menstruation.” In women using hormonal contraceptives, on the other hand, there were no differences in the CGRP level between the two collection times and when comparing migraine patients and women without migraines. As expected, their estrogen levels hardly fluctuated. In postmenopausal women, the research team also found no significant differences in CGRP levels between women with and without migraines.
“Even if these data still have to be confirmed by larger studies: They indicate that the release of CGRP in humans is dependent on the hormonal state,” says Raffaelli. “In fact, going on the pill and coming out of menopause can provide relief for some migraine sufferers. However, as our study shows, there are women who get migraines even without hormone fluctuations. We suspect that other processes in the body play a role in causing an attack. Because CGRP is not the only inflammatory peptide that can trigger migraines.”
Therapy depending on the cycle?
The findings could also contribute to the more targeted use of migraine drugs in the future – especially those that target the neurotransmitter CGRP. “On the basis of our study, the question now arises: do CGRP inhibitors have a different effect on different hormonal states? So would it make sense, for example, to administer these drugs on a cycle-dependent basis? Further studies now have to show that,” says Raffaelli.
In the future, the research team also wants to investigate which other physical processes are influenced by the menstrual cycle and could contribute to the development of migraine attacks – for example the function of the blood vessels or the excitability of the brain. The researchers also plan to take a closer look at the CGRP levels in men of different age groups.
Source: Bianca Raffaelli (Charité – Universitätsmedizin Berlin) et al., Neurology, doi: 10.1212/WNL.0000000000207114