Abstract
Astrocytomas and, in particular, their most severe form, glioblastoma, are the most aggressive primary brain tumors and those with the poorest vital prognosis. Standard treatment only slightly improves patient survival. Therefore, new therapies are needed. Very few risk factors have been clearly identified but many epidemiological studies have reported a higher incidence in men than women with a sex ratio of 1:4. Based on these observations, it has been proposed that the neurosteroids and especially the estrogens found in higher concentrations in women’s brains could, in part, explain this difference. Estrogens can bind to nuclear or membrane receptors and potentially stimulate many different interconnected signaling pathways. The study of these receptors is even more complex since many isoforms are produced from each estrogen receptor encoding gene through alternative promoter usage or splicing, with each of them potentially having a specific role in the cell. The purpose of this review is to discuss recent data supporting the involvement of steroids during gliomagenesis and to focus on the potential neuroprotective role as well as the mechanisms of action of estrogens in gliomas.
Highlights
Gliomas are among the most frequent and aggressive primary tumors of the central nervous system (CNS) in adults
Several teams showed that the risk of developing GBM is reduced in women who have taken contraceptives or hormone replacement therapy (HRT) containing a mixture of estrogens and progestins suggesting a protective role of the female hormone, whereas other studies reported a deleterious effect of pregnancy on glioma anaplastic progression [50,51,52]
Epidemiological data show that men are more affected than women, raising the potential role of steroid hormones in gliomagenesis
Summary
Gliomas are among the most frequent and aggressive primary tumors of the central nervous system (CNS) in adults. The nomenclature of gliomas depends on the glial cell of origin. Astrocytomas and glioblastomas (GBMs) refer to gliomas of astrocytic origin, oligodendrogliomas of oligodendrocytes and ependymomas of ependymal cells, respectively. We will focus on adult astrocytomas, oligodendrogliomas and GBMs that represent 90% of glioma cases. Some genetic syndromes (Cowden, Turcot, Lynch, Li-Fraumeni, Neurofibromatosis type I) are responsible for increasing the risk of developing a glioma. These risk factors are very specific to few cases and do not explain the majority of brain tumors
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