New research involving male-to-female transsexuals lends further credence to the theory that sex hormones are involved in migraine generation, physicians report in the medical journal Neurology.

“We know that migraine is more frequent in women than in men,” co-investigator Dr. Tamara Pringsheim told AMN Health, “so a lot of research goes into what estrogen does to the brain.”

A new way to examine this issue, she added, is to look at a population of genetic males who take antiandrogens and estrogen to induce female sex characteristics.

Pringsheim, at the University of Toronto, and Dr. Louis Gooren, at Free University Amsterdam, distributed questionnaires regarding headache symptoms and frequency to 50 transsexuals who had recently undergone sex reassignment surgery, all of whom were taking hormonal therapy.

Thirteen (26 percent) fulfilled criteria for migraine or probable migraine, similar to the number of cases of migraine in genetic females that would be expected. In contrast, the expected number of cases of migraine in genetic males is significantly lower.

Pringsheim and Gooren theorize that the increased prevalence of migraine is related to the effect of hormone therapy on nitric oxide, a known migraine trigger.

“Normally, vascular reactivity is different in men than in women because of estrogen’s effect on nitric oxide,” Pringsheim explained. “Interestingly, cardiologists who have studied vascular reactivity in male-to-female transsexuals found something similar - that they have enhanced arterial activity - so we know the hormones are doing something to the blood vessels.”

She acknowledged that other mechanisms may be at play, such as the stress of gender reassignment or adoption of a female gender role. Follow-up studies that include headache histories and neurological examinations to confirm the diagnosis of migraine should shed more light on these issues.

SOURCE: Neurology, August 10, 2004.