Gliomas are the most common type of primary malignant
brain tumor and have a very poor prognosis. Little is known, however, about the etiology of these
tumors. Evidence from a number of sources suggests that endogenous
steroid hormones may play a role in the development of
gliomas. First, the descriptive epidemiology of
glioma suggests a relative protection of females compared with males, particularly during the premenopausal years. Second, some
gliomas and
glioblastomas express
estrogen receptors (ER), especially ERĪ², as well as
aromatase, the
enzyme responsible for the conversion of
testosterone to
estradiol, and possibly other
steroid hormone receptors. Third, experimental studies indicate that
glioblastomas transplanted into animals grow at a slower rate in females compared with males. Finally, experimental studies show that
estradiol,
2-methoxyestradiol, and a number of
selective estrogen receptor modulators inhibit proliferation of
gliomas and induce cell death. These hormonal agonists and antagonists may act either through classical
steroid hormone receptors or independently of such receptors. In view of these findings, further clinical, experimental, and epidemiologic studies are needed to elucidate the role of
steroid hormone agonists and antagonists in the development and proliferation of
glioma. If hormonal pathways are involved in gliomagenesis, this could eventually lead to the design of preventive strategies.