Estrogen, Migraines, and Men

A new study has found that estrogen levels may be elevated in men with migraine.¹ Results also showed that men with migraine also more frequently report symptoms of androgen deficiency.

“Previous research has found that levels of estrogen can influence when women have migraines and how severe they are, but little is known about whether sex hormones also affect migraine in men. Our research found increased levels of estrogen in men with migraine, as well as symptoms of lower levels of testosterone,” first author W.P.J. van Oosterhout, MD, of Leiden University Medical Centre in the Netherlands, said in a press release.

Several lines of research have implicated estrogen in the development, frequency, and severity of migraines.

Women are three times more likely to suffer from migraine than men. Changes in estrogen throughout the female reproductive lifespan have been linked to changes in migraine frequency in women. Obese individuals with higher estrogen levels have higher prevalence of migraines. Oral contraceptives are linked to both increased and decreased migraine frequency. And, transgender individuals on estrogen hormone therapy have experienced new onset migraines, while testosterone therapy has been linked to decreased migraines.

To study whether reproductive hormones could have similar effects on migraine in men, researchers measured 17β-estradiol (E2) and free testosterone in 22 men without migraines, and 17 men with migraine without aura (average migraine frequency 3 times monthly) and free of medication that could affect hormones. The men were group-matched for age and nonobese BMI.

Researchers sampled blood at morning, noon, afternoon, and early evening on a single day when men were not experiencing migraines. The blood of migraineurs was also sampled 3 to 4 times daily until they experienced an attack. Researchers also used standardized questionnaires to evaluate symptoms of testosterone deficiency like mood, energy and sexual disorders.

Key results:

Significantly lower free testosterone/estradiol ratio in migraineurs vs controls during the interval between migraines (3.9 vs 5.0, p = 0.03)

• Result due to higher estradiol (p = 0.001) and similar free testosterone (p = 0.35)

Increased free testosterone levels in men with premigraine symptoms like fatigue, muscle stiffness and food cravings (p = 0.03)

More frequent reports of testosterone deficiency in men with migraine vs without (61.1% vs 27.3%, p = 0.053)

• Androgen deficiency reports more severe in men with migraine (p = 0.006)

Take home points

• Small, preliminary Dutch study found elevated estrogen levels in nonobese men with migraine compared to nonobese men without migraine

• Men with migraine also showed evidence of lower levels of testosterone

• Larger studies needed to confirm findings and evaluate effects of estrogen fluctuations on migraines in men

Because the study was small and preliminary, larger ones are needed to confirm the findings. The exact role of estrogen in men with migraine, and whether fluctuations in estrogen may be associated with migraine activity, like they are in women, needs to be fully investigated,” Van Oosterhout concluded in the press release.

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References:

1. van Oosterhout WPJ, Schoonman GG, van Zwet EW, et al. Female sex hormones in men with migraine. Neurology. 2018 [Epub ahead of print].