Study Assesses Impact of Androgen Levels on Male Migraineurs

Results of a questionnaire-based study suggest that deficient androgen levels in men may be associated with migraine and cluster headache.

Men with migraine and cluster headache experience symptoms consistent with clinical androgen deficiency more often than men without a primary headache disorder, according to results of a cross-sectional study. Findings were published in The Journal of Headache and Pain.

Among women, migraine attack susceptibility has been associated with fluctuations in female sex hormones during the menstrual cycle and menopausal transition. However, because migraine is a predominately female disease, few studies have investigated its association with sex hormones in men.

In comparison, cluster headache has historically been considered a male disease. Furthermore, “calcitonin gene-related peptide (CGRP) is known to be involved in the pathophysiology of migraine and cluster headache. Studies have indicated that (fluctuations in) sex hormones can modulate CGRP in the trigeminovascular system,” the authors explained, adding that sex hormones may play a role via CGRP.

In an effort to compare symptoms of clinical androgen deficiency between male patients with migraine and cluster headache and controls, researchers performed a cross-sectional questionnaire study. Participants completed the web-based questionnaire between October 2019 and April 2020; individuals were recruited from the Leiden University Migraine Neuro Analysis (LUMINA) and the Leiden University Cluster headache neuro Analysis (LUCA) cohort.

All participants were between ages 18 and 80 years, and a total of 534 patients with migraine, 437 patients with cluster headache, and 152 controls completed both the Aging Males Symptoms (AMS) and quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaires. Higher scores indicate more androgen deficiency symptoms.

Researchers found that “patients reported more severe symptoms of clinical androgen deficiency compared with controls”: They had higher AMS scores (mean difference [standard error]: migraine, 5.44 [0.90]; P < .001; cluster headache, 5.62 [0.99]; P <.001) and lower qADAM scores (migraine, −3.16 [0.50]; P < .001; cluster headache, −5.25 [0.56]; P < .001).

Patients also reported to experience specific sexual symptoms (beard growth, morning erections, libido and sexual potency) more often compared with controls (migraine, 18.4%; cluster headache, 20.6%; controls, 7.2%; P = .001). Participants with migraine or cluster headache were more likely to suffer from lifetime depression compared with healthy controls.

“This cross-sectional study shows that men with migraine and cluster headache more often suffer from symptoms consistent with (relative) clinical androgen deficiency than males without a primary headache disorder,” the authors wrote. They added that their study “shows that these symptoms are more pronounced in men with chronic migraine (ie, a high attack frequency) and chronic cluster headache (ie, short or no remission periods).”

Whether findings are a result of hormonal imbalances or an epiphenomenon reflecting chronic disease remains to be determined.

The use of questionnaires as an indirect measure of hormone levels marks a limitation to the study.

Researchers hypothesized that findings may be the result of a relative androgen deficiency, attributed to either high estradiol or low testosterone levels, although suffering from a chronic headache disorder could also be implicated.

“Regardless of the cause, it is important to recognize this symptomatology in patients since this may negatively impact quality of life. We advise physicians to proactively assess mood and sexual symptoms in patients with migraine and cluster headache,” they concluded.

Reference

Verhagen IE, Brandt RB, Kruitbosch CMA, et al. Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study. J Headache Pain. Published online October 19, 2021. doi: 10.1186/s10194-021-01334-3