The role of inflammation and potential use of sex steroids in intracranial aneurysms and subarachnoid hemorrhage

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) continues to be a devastating neurological condition with a high risk of associated morbidity and mortality. Inflammation has been shown to increase the risk of complications associated with aSAH such as vasospasm and brain injury in animal models and humans. The goal of this review is to discuss the inflammatory mechanisms of aneurysm formation, rupture and vasospasm and explore the role of sex hormones in the inflammatory response to aSAH. METHODS: A literature review was performed using PubMed using the following search terms: “intracranial aneurysm,” “cerebral aneurysm,” “dihydroepiandrosterone sulfate” “estrogen,” “hormone replacement therapy,” “inflammation,” “oral contraceptive,” “progesterone,” “sex steroids,” “sex hormones” “subarachnoid hemorrhage,” “testosterone.” Only studies published in English language were included in the review. RESULTS: Studies have shown that administration of sex hormones such as progesterone and estrogen at early stages in the inflammatory cascade can lower the risk and magnitude of subsequent complications. The exact mechanism by which these hormones act on the brain, as well as their role in the inflammatory cascade is not fully understood. Moreover, conflicting results have been published on the effect of hormone replacement therapy in humans. This review will scrutinize the variations in these studies to provide a more detailed understanding of sex hormones as potential therapeutic agents for intracranial aneurysms and aSAH. CONCLUSION: Inflammation may play a role in the pathogenesis of intracranial aneurysm formation and subarachnoid hemorrhage, and administration of sex hormones as anti-inflammatory agents has been associated with improved functional outcome in experimental models. Further studies are needed to determine the therapeutic role of these hormones in the intracranial aneurysms and aSAH.