Estrogen May Also Trigger Migraine in Men

Megan Brooks

June 28, 2018

Estrogen, a well-known trigger for migraine in women, seems to also play a role in migraine attacks in men.

In a Dutch study, men with migraine had increased levels of estradiol, as well as symptoms consistent with relative androgen deficiency, compared with men without migraine.

"Higher levels of estrogen seem to make male individuals more susceptible to migraine," W.P.J. (Ron) van Oosterhout, MD, neurologist and headache researcher at Leiden University Medical Center, Rotterdam, the Netherlands, told Medscape Medical News.

"Up until now, no extended studies into the role of sex hormones in men with migraine had been performed. This is the first study to show that differences/changes in sex hormone levels are associated with migraine in men too, and not only in women," he noted.

"Fluctuations in estrogen, and mainly the drop in estrogen prior to the menses, are considered triggers for migraine attacks in women. Our study now shows that estrogens seem to play a role in migraine pathophysiology in men as well," said van Oosterhout.

The study was published online June 27 in Neurology.

Hormones in Flux

Participants included 17 nonobese men (mean age, 47 years) who experienced migraine headache an average of three times a month. None were taking medication known to affect hormone levels. They were compared to 22 men without migraine, matched for age and body mass index.

In all participants, researchers measured estradiol levels and calculated free testosterone levels in serum at four time points during a single day, each 3 hours apart. For men with migraine, the first blood samples were taken on a nonmigraine day and then three to four times daily thereafter until a migraine attack occurred.

Compared with migraine-free men, men with migraine had higher estradiol levels between migraines (96.8 vs 69.1 pmol/L; P = .001), but similar free testosterone levels (357.5 vs 332.6 pmol/L; P = .35), which resulted in a lower ratio of testosterone to estradiol in men with migraines (3.9 vs 5.0; P = .03).

In addition, men with migraine more often reported symptoms of androgen deficiency, such as mood, energy, and sexual disorders (61% vs 27% for controls; P = .031), and their symptoms were more often severe.

"We can only speculate on possible mechanisms of action," said van Oosterhout. "High levels of estrogen might increase the brain susceptibility to cortical spreading depolarization — a spreading 'wave' of hyperactivity of neuronal cells followed by a silenced phase — which is considered the underlying mechanism for migraine aura, and a putative trigger for migraine headaches," he explained.

"The role of testosterone, however, is less clear," said van Oosterhout, noting that in this study testosterone levels increased before a migraine attack only in men with premonitory symptoms.

"Testosterone is known to rise in concentration in stressful situations," van Oosterhout said. "Therefore, we are not sure if the increase in testosterone just prior to a migraine headache actually is a migraine specific change, or a more general response of the body to the stressful situation of being aware of a forthcoming migraine headache is something that patients might base on the experience of these premonitory symptoms," he explained.

A Hidden Minority

The current findings probably don't have immediate clinical implications, van Oosterhout said. "For example, hormonal treatment has not yet been proven to be effective in women with migraine, so it is too early to speculate on possible effects of hormonal treatment in men with migraine," he noted.

Noah Rosen, MD, director, Northwell Health's Headache Center in Great Neck, New York, agreed.

"This is an interesting finding in men, but I'm not sure how it necessarily changes management," he told Medscape Medical News.

Nonetheless, Rosen, who wasn't involved in the study, said he's "glad to see this study because it's actually kind of unusual to see any type of research focusing on men with migraine.  In some ways, men are the hidden minority" because three times more women than men experience migraines.

Migraine is often as troubling in men as in women, said Rosen, yet it may not garner as much attention. "In my office last week, I had a young guy who has had migraines most of his life, more than 20 years, and he probably was not as well treated, either he wasn't diagnosed properly or his condition was minimized. I think that is an issue," said Rosen.

The study was funded by the Netherlands Organization for Scientific Research, Spinoza Premium, and the European Commission. The authors and Rosen have disclosed no relevant financial relationships.

Neurology. Published online June 27, 2018. Abstract   

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