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Cluster headache -- which typically occurs more frequently in men -- tended to be more severe and debilitating in women, according to a large analysis of sex differences in patients with a verified diagnosis in Sweden.

Detailed questionnaires from over 800 patients showed that women were more frequently diagnosed with chronic cluster headache subtype than men (18% vs 9%, P=0.0002), reported Andrea Belin, PhD, of the Karolinska Institutet in Stockholm, and co-authors in .

"While the ratio of men to women with cluster headache has been shifting over the years, it is still considered mainly a disorder of men, making it more difficult for women with milder symptoms to be diagnosed with cluster headache than men," Belin said in a statement. "It's possible this could contribute to the higher rate of chronic cluster headache in women."

An active bout of cluster headache can involve up to eight attacks daily, lasting 15 to 180 minutes. Chronic cluster headache is defined as "recurring cluster headache attacks for one year or more without interruption, or with short symptom-free intermissions which last less than three months," the authors explained.

Women had longer bouts (P=0.003) and used prophylactic treatment more often (60% vs 48%, P=0.0005), while pain intensity was "equally excruciating" for both men and women, the authors noted. Overall, use of acute medication was similar between the sexes, expect for more frequent use of oxygen reported by women (P=0.013). Women also more commonly experienced ptosis (61% vs 47%, respectively, P=0.0002) and restlessness (54% vs 46%, P=0.02).

Of note, women more frequently reported diurnal rhythmicity of their attacks (74% vs 63%, respectively, P=0.002).

Neither nausea alone nor nausea associated with migraine was more frequent in women compared with men. However, as in Sweden's general population, fewer men than women had a concomitant diagnosis of migraine (12.5% vs 29.4%, P<0.0001) and tension-type headache (44.3% vs 57.6%, P=0.0002).

"This large study of rigorously diagnosed cluster headache patients mandates an elevated index of suspicion for cluster headache in women, and an awareness of possibly more burdensome disease in women," noted Richard Lipton, MD, of Albert Einstein College of Medicine in the Bronx, New York, and Mark Burish, MD, PhD, of UT Health Houston in Texas, in an .

Belin and team noted that the findings reflected previous work showing that the incidence of cluster headache peaks among both sexes -- more broadly in women -- between the ages of 20 to 30 and declines after age 50. Aside from an indication of two peaks for women with chronic cluster headache, there was no evidence of the previously reported of disease onset, which Belin and team noted had fueled speculation of in cluster headache.

More women than men had a first- or second-degree relative with cluster headache (15% vs 7%, P=0.0002). Compared with the general population, study participants had a higher mean body mass index (P<0.0001), although this difference was only significant for men (P=0.009). Men also reported higher alcohol consumption than women (P<0.0001), and were more likely to report that drinking alcohol triggered their cluster headaches (56.5% vs 40.5%, P=0.001).

Triggers that occurred more frequently in women than men included changes in weather/temperature or draft/gust (25.2% vs 11.3%, P=0.0003) and lack of sleep (14.7% vs 8.1%, P=0.037), with the editorialists pointing out that these are also "well-known migraine triggers."

"Cluster headache is still often misdiagnosed in women, perhaps because some aspects can be similar to migraine," Belin said. "It is important for physicians to be aware of how the disorder manifests differently in men and women, so the most effective treatment can be given as fast as possible."

The study included 874 individuals diagnosed with cluster headache according to the International Classification of Headache Disorders, third edition, identified from Swedish medical records from 2014 to 2020.

Mean ages of men and women were 51.3 and 49 years, respectively; 66% were men. Age at onset of cluster headaches was similar between men and women, although fewer men had onset before age 20 (16.2% vs 23.0%, P=0.020).

Participants answered a detailed questionnaire about their symptoms, medications, headache triggers, and lifestyle habits, and all variables were compared with regards to sex, the authors said.

They noted that recall bias due to use of self-reported data was possible in their study, which is a limitation.

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