Steroid hormone profiles in females with cluster headache: a prospective observational case-control study

Steroid hormone metabolism in females with cluster headache remains poorly investigated despite evidence of steroid hormone dysregulation in males with cluster headache. This study aimed to examine the serum steroid hormone profiles in females with cluster headache compared with healthy controls to assess potential endocrine alterations. Samples were obtained from the Danish Cluster Headache Biobank in a prospective observational case–control study. We performed targeted quantitative liquid chromatography tandem mass-spectrometry for 20 steroid hormones (corticosteroids, androgens, progestogens, and estrogens) in serum from adult females with cluster headache, including patients with chronic ( n = 28) and episodic ( n = 22 in bout and n = 19 in remission) cluster headache, with 18 paired samples obtained during bout and remission, as well as healthy controls ( n = 19). Levels of multiple steroid hormones differed significantly between patients with chronic and episodic cluster headache and healthy controls. Interestingly, pregnenolone was consistently lowered in females with cluster headache by being 39–44% lower ( p < 0.05) compared with healthy controls. Cortisol levels were 43% ( p < 0.05) lower in females with episodic cluster headache in bout. The adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate levels were lower in females with chronic cluster headache by 42% and 44% ( p < 0.05), respectively. We found no changes in episodic patients comparing bout and remission. Females with cluster headache showed lower circulating levels of several steroid hormones across different steroid hormone classes compared with healthy controls. Notably, corticosteroid levels were lower in females with episodic cluster headache in bout, whereas androgen levels were lower in females with chronic cluster headache. These findings indicate differences in steroid hormone profiles associated with cluster headache. However, further studies in larger cohorts, with comprehensive characterization of reproductive factors, are needed to confirm these findings.