Sex differences in cluster headache: insights from the Chinese Cluster Headache Register Individual Study (CHRIS)

BACKGROUND: Sex differences in the clinical characteristics of cluster headache (CH) remain controversial in both Eastern and Western studies, and such differences have not been thoroughly investigated among Chinese patients. METHODS: This large-scale, multicenter cohort study included 1,206 patients from 31 provinces across China diagnosed with CH between May 2021 and December 2024, and was conducted within the framework of the Chinese Cluster Headache Register Individual Study. Demographic and clinical data were systematically collected from each participant using an electronic structured questionnaire, and compared all variables between sexes. RESULTS: In total, 1,206 patients were enrolled, with a female-to-male ratio of 1:3.94. Demographic analysis revealed that female patients had an earlier mean age of onset, higher educational attainment, and fewer unhealthy lifestyle factors compared to male patients. Female patients were also more likely to have comorbidities such as migraine (28.28% vs. 15.90%, P < 0.001) and psychological conditions, including anxiety and depression, and to use oral rizatriptan for acute treatment (27.78% vs. 15.80%, P < 0.001). With respect to cranial autonomic symptoms (CASs), female patients experienced eyelid edema (18.85% vs. 12.47%, P = 0.010) and ptosis (56.97% vs. 49.90%, P = 0.048) more frequently, and reported migraine-associated symptoms more often. Conversely, male patients more commonly presented with conjunctival hyperemia (56.03% vs. 38.52%, P < 0.001), rhinorrhea (47.92% vs. 38.93%, P = 0.012), and facial sweating (38.15% vs. 30.74%, P = 0.032). Female patients had significantly higher frequencies of attacks during the early morning hours (2:00–8:00), whereas male patients experienced significantly more attacks during midday (10:00–14:00) and evening (16:00–20:00). CONCLUSION: This study provides the first comprehensive analysis of multidimensional sex differences in Chinese patients with CH, encompassing social characteristics, clinical phenotypes, psychological burden, and circadian attack distribution. These findings offer valuable evidence for developing precision medicine approaches and sex-specific clinical management strategies for CH.