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Glioblastoma Multiforme (GBM) is an aggressive brain tumor with an extremely low survival rate with the current standardized treatment protocols. Despite the similarity in clinical presentations between men and women diagnosed with the same tumor grade, there are many differences in the tumor microenvironment that contribute to the response to certain treatments and survival timeline. The goal of this paper is to highlight the sex differences in the pathophysiology of GBM with a focus on factors that contribute to the microenvironment of the tumor, such as hormones, metabolic pathways, the immune system, and genetic and molecular changes in both men and women for better treatment and management of the disease. Current drugs don’t consider these individual microenvironment differences, rendering many of these drugs ineffective in treatment and disease management. Therefore, further investigations of genetic differences can play a significant role in the development of better, more effective treatments and in the early detection of disease.

To accomplish this, a comprehensive literature search was conducted utilizing PUBMED, Google Scholar, and the Cochrane Central Register of Controlled Trials. The search incorporated keywords and phrases such as “sexual dimorphism in GBM,” “treatments for GBM,” “microenvironment of GBM,” “precision treatment of GBM,” and “GBM growth in sex-specific contexts.”

Our literature search revealed that, among many specific phenomena that contribute to sex differences in the pathology of GBM, estrogen enhances the Th2 response in women and suppresses inflammation. In contrast, testosterone suppresses the Th2 response, contributing mainly to the survival timeline and response to surgery and current treatments.

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