Migraine and menstruation: what’s the story?

All the statistics show that migraine affects women more than men, but experts disagree on what causes this gender gap. The role of sex hormones as migraine triggers is a hot research topic these days.

Many women notice a link between migraine and their period. So is there a connection between migraine attacks and the natural fluctuations in hormone levels during the menstrual cycle, especially in the days leading up to your period? For a brief rundown of where the science is at on the migraine-hormone connection, read on. What do we know, what don’t we know (yet) about menstrual migraine? First off: the connections are extremely complex and research on this topic still has a long way to go. But with researchers around the world busy investigating and hypothesizing, we may be closing in on the answers. Meanwhile, as far as migraine prevention goes: 1) Keep working toward a lifestyle your head will love you for (key migraine facts are here; lifestyle tips on prevention are here). 2) Stay on top of the latest research insights – read our article updates for the latest developments on the big issues in headache prevention research.

Are sex hormones involved?

Christian Wöber, head of the headache outpatient clinic at Vienna General Hospital, gave an interview to the Austrian Broadcasting Corporation's science magazine program on the migraine gender gap. Reporting from the front lines of headache management, Wöber says he sees numerous indications in his female patients that sex hormones may be involved in triggering a migraine. More specifically: the fluctuations in hormone levels that are a natural part of the menstrual cycle may precipitate migraine attacks. Women with migraine often see an improvement after they have gone through the menopause. A reduction in migraine burden during pregnancy is another common phenomenon, Wöber says. Estrogen levels are consistently low after the menopause and consistently high during pregnancy. It is reasonable to conclude that the absence of menstrual fluctuations in estrogen levels in these two stages of life may be responsible for the observed improvement in the migraine burden.

Natural hormone fluctuations regulate the menstrual cycle

A typical menstrual cycle looks like this: The cycle begins with the first day of your period. The uterine lining (endometrium) built up during the previous cycle is shed during menstruation. At the start of the cycle, estrogen levels are fairly low. They start rising when egg (oocyte) maturation starts in the ovaries. This part of your cycle is called the follicular phase or pre-ovulatory phase. Follicles are little pods in the ovaries. An immature egg sits in each follicle. A single dominant follicle usually develops, and the egg contained in that follicle grows to maturity. Rising estrogen levels ensure that the lining of the uterus builds up. The endometrium thickens and receives a rich supply of blood and nutrients to provide the ideal nest for a (possibly) fertilized egg to grow. Estrogen levels continue to rise until the ripening egg is ready for release. The dominant follicle bursts, expelling the ripe egg from the ovary (ovulation). The egg travels through the fallopian tube toward the uterus. Ovulation marks the beginning of the luteal phase of your cycle. The dominant follicle produces the ‘corpus luteum’, which starts producing progesterone. This hormone thickens and preserves the uterine lining previously built up under the influence of estrogen. If the egg is not fertilized, the corpus luteum breaks down and progesterone production ceases. Both estrogen and progesterone levels drop. As the levels of the two hormones fall, the blood and tissues lining the uterus start to come loose. Your body sheds this material during your next period and a new menstrual cycle begins.

The complexity of the hormone connection

In 2018, a Spanish research team published a review of the existing literature on the role of sex hormones in precipitating migraines. Analysis of the available studies indicated that female migraineurs in their fertile years with a typical menstrual cycle are significantly more likely to have a migraine attack around menstruation. The menstrual phase – during which migraineurs are thought to be particularly vulnerable to migraine attacks – extends from the two days before your period to the three days after. This phase of the menstrual cycle is associated with a major shift in estrogen and progesterone levels. The authors point out that the role of sex hormones in triggering migraines is a highly complex affair and say that a lot more research needs to be done to get to the bottom of what’s going on. In particular, there is a lack of long-term clinical trials that would deliver reliable data on the relationship between the menstrual cycle and migraine, the authors say.

Estrogen and the trigeminal nerve – a bad influence?

They do come up with an interesting hypothesis, however: that the fluctuations in estrogen levels during the menstrual cycle might affect cells in the trigeminal nerve. The trigeminal nerve is a cranial nerve thought to play a crucial role in mediating the factors that trigger migraine attacks. One theory is that nerve impulses mediated via the trigeminal nerve inflame the blood vessels in the membrane layers that protect the brain (meninges), resulting in the throbbing pain of a migraine headache. The Spanish research team suggests that sex hormones might make the trigeminal nerve more receptive to the particular signals that lead to migraine attacks. The researchers hypothesize that this sensitization happens when the sex hormones act on the TRP channels – ion channels in the cell wall of pain receptors – around the trigeminal nerve.

Mounting evidence supports a role for estrogen

Three Italian researchers explored the theory of trigeminal nerve involvement in migraine events in a review published in 2020. Their hypothesis is that sex hormones affect both the frequency and the severity of migraine attacks. A US review published in 2020 compares regular menstrual migraine in women in their fertile years with the migraine burden in women going through the menopause. A common feature in both these situations is an increase in migraine burden as estrogen levels drop. In menstrual migraine, the authors say, the risk of migraine attacks increases with the sudden drop in estrogen levels around menstruation. A similar situation applies when estrogen levels start declining in pre-menopause and during the transition to postmenopause (the stage in life after your last-ever period).

Where is the research at?

In a review paper published back in 2014, a team of US researchers wondered whether the possible link between increasing migraine symptoms and declining estrogen levels might be a starting point for further research into using hormonal contraception to manage menstrual migraine. A lot of women with migraine are asking themselves the same question, but science does not have the answers yet. The authors of all the studies done so far emphasize the complexity of the sex hormone-migraine connection. We need to take the proposed explanations for what they are: hypotheses that will hopefully pave the way to a better understanding of migraine in the near future. The reasons for the gender disparity in migraine burden are likely multifaceted and require further dedicated research on many levels.