Men are three times less likely than women to experience migraine, and now we may finally know why.
A team from the Leiden University Medical Center in the Netherlands has published a small study showing that men who suffer from migraine have significantly more estrogen in their blood than those fortunate enough to have no history of the debilitating brain disorder.
Writing in the journal Neurology, the group explains that previous investigations suggest fluctuations in sex hormone activity in women and adolescent girls is both a risk factor for developing migraine and a trigger for more severe and/or more frequent attacks. Such variations in hormone activity occur naturally during puberty, menstruation, pregnancy, and menopause, and may be induced by hormonal medications. Past research has also indicated that giving women testosterone therapy can reduce migraine symptoms and frequency and that male-to-female transgender individuals taking estrogen combined with male hormone blockers often develop migraine.
Although the molecular pathways underlying this phenomenon require further study, it is believed that female sex hormones increase the brain’s susceptibility to waves of electrical cell signaling (called CSD) and over-activate sensory neurons wrapped around cerebral blood vessels in the head, jaw, and neck – two hallmark features of migraine pathogenesis.
Until now, however, no research had assessed the role of sex hormones in men who were not taking level-altering medications. So, the Dutch team led by Dr W.PJ. Van Oosterhout enrolled 17 otherwise healthy men who reported suffering an average of three migraines without aura per month and 22 controls. Estradiol – a form of estrogen – and testosterone levels were measured in all participants four times across one day (to account for circadian variations). Then, those with migraine had blood draws each day until they experienced an attack.
Men with migraine were found to have an average estradiol concentration of 97 picomoles per liter (pmol/L), compared to 69 pmol/L in those without. There was no significant difference in average testosterone concentration between the groups, yet interestingly, a survey revealed that 61 percent of those with migraines noticed symptoms associated with low testosterone – such as mood, energy, and sex drive issues – compared to only 27 percent of those without.
“Estrogens seem to have a positive and androgens a suppressing effect on nociceptive transmission, with higher estrogen levels reflecting higher activation states of these mechanisms,” the authors conclude. “Overall, the differential effects on CSD susceptibility and trigeminovascular activity might well explain, at least partly, why migraine is so much more prevalent among women and why periods of major sex hormone fluctuations are so often associated with marked changes in migraine activity.”
Due to the study’s small size and reliance on patient’s self-reporting of symptoms, Dr Van Oosterhout is calling for future studies to confirm his team’s findings.