Migraine affects approximately 3 times as many women as men, with close associations with the various stages of reproduction.1 More than one-half of women with migraine have identified the time around menstruation as a trigger for attacks, with peak incidence typically occurring on the days immediately preceding and after the first day of menstruation.2 A range of research findings have shed light on the relationship between migraine and menstruation.

A population-based study published in 2000 found a significant increase in the risk for migraine without aura during the first 2 days of menstruation (odds ratio [OR], 2.04; 95% CI, 1.49-2.81), and a longer duration of migraine attacks during the 3 to 7 days before menstruation. The lowest migraine risk was observed during ovulation (OR, 0.44; 95% CI, 0.27-0.72).2

A subsequent clinic-based study found a 25% greater risk for migraine in the 5 days before menstruation, and a 71% increase in risk during the 2 days before menstruation (relative risk [RR], 1.71; 95% CI, 1.45-2.01; P <.0001). The highest risk was noted during the first 3 days of menstruation (RR, 2.50; 95% CI, 2.24-2.77; P <.0001).2 Another population-based study also reported that the highest migraine risk occurred during the first 3 days of menstruation (HR 1.96; P <.00001).2

Across multiple studies, women who experience menstrual migraine demonstrated elevated menstruation-related distress and disability.2 Less than 10% of women have pure menstrual migraine, in which there are no attacks during other times of month. Most women impacted by menstrual migraine also experience attacks at other points in time. At least 3 diary cards from consecutive cycles should be reviewed to confirm the diagnosis.2

The Role of Estrogen and Serotonin

“The very existence of pure menstrual migraine … indicates that the fall in serum estradiol values may be the most potent trigger of migraine,” as supported by the results of various studies, according to Anne H. Calhoun, MD, FAHS, partner and cofounder of the Carolina Headache Institute, and professor of both anesthesiology and psychiatry at the University of North Carolina. Estradiol may influence migraine via multiple effects of the central nervous system.3

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“Sex steroids, especially estrogens, are responsible for both synthesis and secretion of neuropeptides and neurotransmitters, including serotonin, dopamine, opioid peptides, galanin, and neuropeptide Y. When estrogen levels fall, production of serotonin is reduced,” Dr Calhoun explained in a 2018 paper published in Headache: The Journal of Head and Face Pain.3 The resulting increase in monoamine oxidase activity leads to an accelerated rate of serotonin elimination, and low estrogen also leads to reduced sensitivity of 5-hydroxytryptamine1 receptors, the target of the triptans, as well as reduced endogenous opioid activity.

This article originally appeared on Neurology Advisor