Sex-specific clinical differences in cluster headache: A systematic review and meta-analysis

Sex-related differences in cluster-headache (CH) have been reported with inconsistent findings across studies. This systematic review and meta-analysis aimed to reveal sex differences in clinical features, attack characteristics, autonomic symptoms, associated features, and comorbidities in patients with CH.

This study was conducted accordance to PRISMA guidelines. Observational studies reporting clinical features in both sexes among patients diagnosed with CH were identified through searches of PubMed, Embase, Scopus, and Web of Science up to July 2025. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS), and studies with NOS scores≥ 7 were included in the quantitative meta-analysis. Pooled odds ratios (OR) and mean differences were calculated using a random-effects model.

Nineteen high-quality studies were included. No significant sex differences were found in age-at-onset, attack duration and attack frequency, pain intensity, attack lateralization or diurnal and annual rhythmicity. Most cranial autonomic symptoms were comparable between sexes, although eyelid edema (OR=1.94, CI=1.62-2.33) was more frequently observed in females who had also higher rates of migraine (OR=2.72, CI=2.58-2.88) and psychiatric comorbidities (OR=1.73, CI=1.32-2.27) and were less likely to smoke (OR=0.33, CI=0.16-0.69) or consume alcohol (OR=0.32, CI=0.15-0.69).

This meta-analysis suggests that CH has a largely similar clinical phenotype across sexes. Some differences were observed in lifestyle factors, comorbidities, and accompanying eyelid edema, that may reflect a combination of biological, behavioral, cultural and reporting-related factors. Given the observational nature of the included studies, mechanistic conclusions could not be drawn.