Abstract
Sex differences have been well identified in many brain tumors. Even though glioblastoma (GBM) is the most common primary malignant brain tumor in adults and has the worst outcome, well-established differences between men and women are limited to incidence and outcome. Little is known about sex differences in GBM at the disease phenotype and genetical/molecular level. This review focuses on a deep understanding of the pathophysiology of GBM, including hormones, metabolic pathways, the immune system, and molecular changes, along with differences between men and women and how these dimorphisms affect disease outcome. The information analyzed in this review shows a greater incidence and worse outcome in male patients with GBM compared with female patients. We highlight the protective role of estrogen and the upregulation of androgen receptors and testosterone having detrimental effects on GBM. Moreover, hormones and the immune system work in synergy to directly affect the GBM microenvironment. Genetic and molecular differences have also recently been identified. Specific genes and molecular pathways, either upregulated or downregulated depending on sex, could potentially directly dictate GBM outcome differences. It appears that sexual dimorphism in GBM affects patient outcome and requires an individualized approach to management considering the sex of the patient, especially in relation to differences at the molecular level.
Highlights
Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) cancer, accounting for 45.2% of malignant CNS tumors and 55% of all gliomas [1,2]; if untreated the median survival is 3 months [2]
Another study showed that reproductive factors were not associated with gliomas, especially for non-GBM tumors, but inverse associations were observed for the use of both oral contraceptives and postmenopausal hormone therapy, indicating that the protective effects are limited to exogenous hormone therapy only [52]. These findings suggest a possible association of early-life hormonal exposure with risk of glioma, along with the protective effects that exogenous hormone therapy could have on gliomas and that may be applicable to GBM tumors
This review has focused on the recent evidence indicating that GBM
Summary
Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) cancer, accounting for 45.2% of malignant CNS tumors and 55% of all gliomas [1,2]; if untreated the median survival is 3 months [2]. Primary (de novo) tumors manifest rapidly and without evidence of less-malignant precursor lesions This subtype accounts for 80% of GBM and mostly occurs in older patients (mean age, 62 years). GBM evolves through different genetic and molecular pathways, affecting patients at different ages and having distinct outcomes resulting from sex-specific features. During the past few decades, numerous studies have identified several prognostic factors in patients with GBM Clinical factors such as age at diagnosis, race, Karnofsky Performance. This review describes several differences in GBM between men and women with regard to epidemiology, disease phenotype, genetic/molecular factors, and outcomes. The goal was to understand the specific pathologic mechanisms of GBM for men and women, as well as to determine why this tumor shows such different presentations and outcomes between sexes
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