Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study

DOI: https://doi.org/10.1186/s10194- 021- 01334- 3

Abstract-Summary To compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls.

We performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls.

As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically dif- ferentiate androgen deficiency symptoms from (comorbid) anxiety and depression.

2.5 Hormones

413

Patients reported more severe symptoms of clinical androgen deficiency com- pared with controls, with higher AMS scores (Aging Males Symptoms; mean differ- ence ± SE: migraine 5.44 ± 0.90, p < 0.001; cluster headache 5.62 ± 0.99, p < 0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: − 3.16 ± 0.50, p < 0.001; cluster headache: − 5.25 ± 0.56, p < 0.001).

Both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001).

Men with migraine and cluster headache more often suffer from symptoms con- sistent with clinical androgen deficiency than males without a primary headache disorder.

Extended: We performed a cross-sectional questionnaire study among men with

migraine, men with cluster headache and male controls without headache.

Men with migraine (episodic or chronic) or cluster headache (episodic or chronic) that fulfilled the International Classification of Headache Disorders (ICHD-3) crite- ria, and men without a primary or secondary headache disorder (apart from an occa- sional episodic tension-type headache), who gave written informed consent to be contacted in case of future research, were identified.

Introduction With migraine being a predominantly female disease, a limited number of studies has investigated sex hormones in men, but one small scale study showed a decreased testosterone/estradiol ratio in males with migraine [732].

Recent studies show that cluster headache occurs in women more often than

previously assumed with a male to female ratio of 2:1 [733].

Calcitonin gene-related peptide (CGRP) is known to be involved in the patho-

physiology of migraine and cluster headache.

As relative androgen deficiency has been suggested in men with migraine, but may play a role in cluster headache as well, we aimed to compare symptoms of clinical androgen deficiency between male migraine and cluster headache patients and controls.

Methods Migraine and cluster headache patients were first asked to fill out a validated web- based screening questionnaire with a sensitivity of 0.93 and specificity of 0.36 for migraine, and a sensitivity of 1.00 and specificity of 0.58 for cluster headache [14, 734].

Patients who fulfilled the screening criteria for migraine or cluster headache, were sent a validated web-based extended migraine or cluster headache question- naire, based on the International Classification of Headache Disorders criteria (pre- viously ICHD-2, now ICHD-3 version) criteria [735].

As both the AMS and qADAM questionnaire contain multiple items associated with anxiety and depression, which are more prevalent in chronic headache disor- ders, we performed a secondary analysis determining the number of patients report- ing to score below average (≥4) on four selected items of the AMS scale regarding sexual symptoms (beard growth, morning erections, libido and sexual potency).

414

2 Mechanisms

Results The mean AMS scores were higher in patients with migraine compared to controls (mean difference ± SE: 5.44 ± 0.90, p < 0.001), and cluster headache compared to controls (5.62 ± 0.99, p < 0.001).

Mean qADAM scores were lower in patients with migraine compared to controls (− 3.16 ± 0.50, p < 0.001), and cluster headache compared to controls (− 5.25 ± 0.56, p < 0.001).

Men with episodic cluster headache out of bout still scored higher on the AMS (4.72 ± 1.04, p < 0.001) and lower on qADAM (− 4.62 ± 0.58, p < 0.001) than non- headache controls.

Discussion 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.

Our study shows that patients with migraine and cluster headache suffer more

frequently and more severely from these symptoms than men without headache.

A recent study in male migraine patients showed symptoms of a relative andro- gen deficiency with a higher estradiol/testosterone ratio compared to controls, which was attributed to higher estradiol levels [732].

These presumed differences in estradiol/testosterone ratios may be responsible for the symptomatology described in the present study, which would strengthen the hypothesis of hormonal imbalances in men with migraine and cluster headache.

Our study shows that men with migraine and cluster headache more frequently report symptomatology consistent with androgen deficiency than males without a primary headache disorder.

Acknowledgement A machine generated summary based on the work of Verhagen, Iris E.; Brandt, Roemer B.; Kruitbosch, Carlijn M. A.; MaassenVanDenBrink, Antoinette; Fronczek, Rolf; Terwindt, Gisela M. 2021 in The Journal of Headache and Pain.

High rates of (treated) hypothyroidism among chronic migraine patients consulting a specialized headache clinic: are we missing something?