Impact of sex in the prevalence and progression of glioblastomas: the role of gonadal steroid hormones

Abstract

Background As in other types of cancers, sex is an essential factor in the origin and progression of glioblastomas. Research in the field of endocrinology and cancer suggests that gonadal steroid hormones play an important role in the progression and prevalence of glioblastomas. In the present review, we aim to discuss the actions and mechanism triggered by gonadal steroid hormones in glioblastomas. Main body Glioblastoma is the most common malignant primary brain tumor. According to the epidemiological data, glioblastomas are more frequent in men than in women in a 1.6/1 proportion both in children and adults. This evidence, and the knowledge about sex influence over the prevalence of countless diseases, suggest that male gonadal steroid hormones, such as testosterone, promote glioblastomas growth. In contrast, a protective role of female gonadal steroid hormones (estradiol and progesterone) against glioblastomas has been questioned. Several pieces of evidence demonstrate a variety of effects induced by female and male gonadal steroid hormones in glioblastomas. Several studies indicate that pregnancy, a physiological state with the highest progesterone and estradiol levels, accelerates the progression of low-grade astrocytomas to glioblastomas and increases the symptoms associated with these tumors. In vitro studies have demonstrated that progesterone has a dual role in glioblastoma cells: physiological concentrations promote cell proliferation, migration, and invasion while very high doses (out physiological range) reduce cell proliferation and increases cell death. Conclusion Gonadal steroid hormones can stimulate the progression of glioblastomas through the increase in proliferation, migration, and invasion. However, the effects mentioned above depend on the concentrations of these hormones and the receptor involved in hormone actions. Estradiol and progesterone can exert promoter or protective effects while the role of testosterone has been always associated to glioblastomas progression.

Survival and quality of life analysis in glioblastoma multiforme with adjuvant chemoradiotherapy: a retrospective study

“…The study conducted by Bello et al established the impact of sex on the prevalence and progression of glioblastomas. Estradiol and progesterone can exert promoter or protective effects while the role of testosterone has always been associated with glioblastomas progression [ 12 ].…”

Oral Contraceptive and Glioma Risk: A Prospective Cohort Study and Meta-Analysis

“…There is some evidence that the expression of estrogen and progesterone receptors varies in glioma, and for example, higher-grade glioma is associated with lower expression of estrogen receptors and higher expression of progesterone receptors ( 4 ). Also in vitro studies, a dual role of progesterone in glioblastoma cells has been suggested: physiological concentrations increase cell proliferation, invasion, and migration, while higher doses beyond the physiological level inhibit cell proliferation and promote cell death ( 33 ). To our knowledge, only one case-control study based on the nationwide prescription registry assessed the effect of hormonal contraceptive components on glioma risk ( 17 ).…”

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“…This process occurs during the second trimester of pregnancy, developing the central part of the central nervous system [5,16]. Steroid hormones play an important role in gonadal development and eventually bring out the effect on brain's sexual development [17]. This will lead to a change in sizes of several regions in the brain, quantity of neurotransmitters, and numbers of nerve cells [5,12].…”