Sex Differences in the Formation of Intracranial Aneurysms and Incidence and Outcome of Subarachnoid Hemorrhage: Review of Experimental and Human Studies

Intracranial aneurysms are defined as pathological dilatations of cerebral arteries and rupture of intracranial aneurysms leads to subarachnoid hemorrhage (SAH). The goal of this review was to outline the sex differences in the formation and progression of intracranial aneurysms as well as sex-related differences in incidence and outcome of SAH. The literature review was performed using PubMed with a combination of these search terms: "subarachnoid hemorrhage," "incidence," "outcome," "sex," "gender," "male," "female," "experimental," "mice," and "rats." Studies written in English were used. Female sex is thought to be a risk factor for aneurysm formation, especially in postmenopausal age populations, suggesting the potential protective involvement of sex steroids. Female sex is also considered a risk factor for SAH occurrence. Although incidence and mortality are confirmed to be higher in females in most studies, they elucidated no clear differences in the functional outcome among SAH survivors. The effect of gender on the pathophysiology of SAH is not very well understood; nevertheless, the majority of pre-clinical studies suggest a beneficial effect of sex steroids in experimental SAH. Moreover, conflicting results exist on the role and effect of hormone replacement therapies and oral contraceptive pills on the incidence and outcome of human SAH. Sex differences exist in the formation of aneurysms as well as the incidence and mortality of SAH. Potential therapeutic effects of sex steroids have been replicated in many animal studies, but their potential use in the treatment of acute SAH in human populations needs more future study.