Abstract

Background
Although cluster headache (CH) is well known as a disorder of predominantly young males, the male to female ratio decreased from 5-7:1 before 1980s to -2:1 in the 2000s and afterward in Western observational studies. It is unclear whether this represents a true rise of CH in women or better recognition of CH in women. We sought to assess whether the sex ratio of CH were changing or not in randomized controlled trials (RCTs) over time in accordance with observational studies.
Methods
We included RCTs regarding pharmacologic medication, as well as procedural and surgical treatment, devices. Time trend of sex ratio was compared among 3 different publication era (1985-2000 vs 2001-2010 vs 2011-). Sex ratio between different cluster headache type (Episodic vs Chronic) was also compared.
Results
22 acute treatment trials and 25 preventive treatment trials were initially selected for inclusion. 5 acute treatment trials and 10 preventive treatment trials were excluded due to small sample size (n<20) and/or no demographic information. All studies were underwent in western countries. Of 32 trials finally included, 10 studies were published between 1985 to 2000 (1^st era), 8 studies from 2001 to 2010 (2^nd era), 14 studies after 2010 (3^rd era). Of the 2,476 patients, 80% were male. Secular tendency of decreasing male predominance was shown over time. 542 of 623 patients (87%) were male in 1^st era, while 83% were male in 2^nd era, and 75.3% were male in 3^rd era (p<0.001). Male to female ratio was 6.7:1 in 1^st era, 4.9:1 in 2^nd era, and 3:1 in 3^rd era. In chronic CH, 28% of subjects were female, while in episodic CH, 14.6% were female (p<0.001)
Conclusions
As suggested by observational and registry data, the population enrolled in the RCT also exhibited a decreasing trend in male predominance over time in CH.

• Keywords: Cluster headache, Randomized controlled trial, Sex ratio, Secular trend