Female sex hormones in men with migraine

Objective To assess the role of estradiol and testosterone in men with migraine.

Methods We measured 17β-estradiol (E2) and calculated free testosterone (Tf) in serum of 17 medication-free men with migraine and 22 men without migraine group-matched for age and body mass index (BMI), targeted at 20 to 28 kg/m2. Blood was sampled on a single, for migraineurs interictal, day at 9 AM, 12 PM, 3 PM, and 6 PM. Migraineurs were subsequently measured 3 to 4 times daily until an attack occurred. Clinical androgen deficiency was assessed with the Androgen Deficiency of Ageing Men questionnaire and the Aging Males' Symptoms (AMS) scale. We analyzed interictal data (mean ± standard error) with repeated-measures analysis of covariance and longitudinal data by generalized estimated equations models.

Results Compared to controls, men with migraine had a lower interictal Tf/E2 ratio (3.9 ± 0.4 vs 5.0 ± 0.3, p = 0.03) due to higher E2 (96.8 ± 6.1 vs 69.1 ± 5.6 pmol/L, p = 0.001) and similar Tf (357.5 ± 21.4 vs 332.6 ± 18.7 pmol/L, p = 0.35) levels. Preictal Tf levels were increased in men with migraine reporting premonitory symptoms (p = 0.03). Men with migraine more frequently reported symptoms of androgen deficiency (11 of 18 [61.1%] vs 6 of 22 [27.3%], p = 0.031), which were also more frequently severe (p = 0.006); their age- and BMI-adjusted AMS scores were higher (27.0 ± 1.2 vs 21.0 ± 1.0, p = 0.002).

Conclusions In this study, nonobese men with migraine exhibited increased levels of the sex hormone estradiol and showed clinical evidence of relative androgen deficiency. The role of estradiol in modulating migraine susceptibility and activity in men deserves further investigations.