Background and objectives: Cluster headache is considered a male-dominated disorder, but we have previously suggested that female patients may display a more severe phenotype. Studies on sex differences in cluster headache have been conflicting; therefore, this study, with the largest validated cluster headache material at present, gives more insights into sex-specific characteristics of the disease. The objective of this study was to describe sex differences in patient demographics, clinical phenotype, chronobiology, triggers, treatment, and lifestyle in a Swedish cluster headache population.

Methods: Study participants were identified by screening medical records from 2014 to 2020, requested from hospitals and neurology clinics in Sweden for the ICD-10 code G44.0 for cluster headache. Each study participant answered a detailed questionnaire on clinical information and lifestyle, and all variables were compared with regard to sex.

Results: A total of 874 study participants with a verified cluster headache diagnosis were included. Of the participants, 575 (66%) were male and 299 (34%) were female, and biological sex matched self-reported sex for all. Female participants were to a greater extent diagnosed with the chronic cluster headache subtype compared with male participants (18% vs 9%, p = 0.0002). In line with this observation, female participants report longer bouts than male participants (p = 0.003) and used prophylactic treatment more often (60% vs 48%, p = 0.0005). Regarding associated symptoms, female participants experienced ptosis (61% vs 47%, p = 0.0002) and restlessness (54% vs 46%, p = 0.02) more frequently compared with male participants. More female than male study participants had a positive family history of cluster headache (15% vs 7%, p = 0.0002). In addition, female participants reported diurnal rhythmicity of their attacks more often than male participants (74% vs 63%, p = 0.002). Alcohol as a trigger occurred more frequently in male participants (54% vs 48%, p = 0.01), whereas lack of sleep triggering an attack was more common in female participants (31% vs 20%, p = 0.001).

Discussion: With this in-depth analysis of a well-characterized cluster headache population, we could demonstrate that there are significant differences between male and female participants with cluster headache, which should be regarded at the time of diagnosis and when choosing treatment options. The data suggest that female patients generally may be more gravely affected by cluster headache than male patients.