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Glioblastoma multiforme is a grade IV astrocytoma arising de novo or progressing from lower grade II and III gliomas. Currently the etiology of glioma and prediction of disease progression are unknown. Recent epidemiological studies have suggested that hormonal factors, including estrogen treatment, may impact glioma risk however these studies have been limited to case-control trials and retrospective cohort studies. Here, we evaluate results from the Women’s Health Initiative, which involved 161,808 women with robust data regarding hormone exposures. During a median of 12.7 years of follow-up, 167 cases of glioma (130 cases of GBM) were ascertained. The relationship between gliomas and hormone therapy (HT; estrogen-alone [E-alone] or estrogen plus progestin [E+P]) was evaluated using Cox proportional hazards models as well as Kaplan-Meier time-to-event analysis. There was no association with gliomas for the E-alone group (HR=0.76, 95% CI=0.43,1.36) but there was an inverse association for E+P (HR=0.48, 95% CI= 0.26, 0.88, p=0.02) after accounting for patient, hormone exposure and reproductive factors. Kaplan-Meier survival analysis demonstrated a significant reduction in time-to-incidence for the E+P group (p=0.0035). Findings from the matched case-control arm of the WHI trial did not demonstrate significant impact of HT on glioma incidence. The results of this study suggest a reduction in glioma risk after treatment with estrogen plus progesterone however a further large scale case-controlled study is warranted to evaluate the impact of HT on this disease.
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GBM hospital and diagnosis characteristics among subjects receiving HT