Study Shows Androgens Restrain Glioblastoma Growth

Scientists at Cleveland Clinic have discovered that hormones tied to male development, like testosterone, help curb brain tumor growth in men. In preclinical glioblastoma models, androgen loss sped up tumor growth through local inflammation and stress hormone release. Data from over 1,300 male glioblastoma patients linked supplemental testosterone to longer survival, matching the preclinical results.

Glioblastoma and higher androgen levels are both more common in men, but past work ignored androgen effects in the brain's unique setting. “The brain has evolved to keep stuff out and that includes immune cells from elsewhere in the body. It’s a delicate tissue that often doesn’t want huge immune reactions,” said Justin Lathia, corresponding author of the study published in Nature.

The study found androgens regulate the brain's protective systems differently than in other body areas. In male mouse models lacking androgens, glioblastoma overactivated the hypothalamus-pituitary-adrenal (HPA) axis, boosting stress hormones. This caused cells to strengthen brain barriers, fostering an immunosuppressive space that blocked immune cells and let tumors grow freely. Testosterone lacked this effect in female mice.

Tumor-driven inflammation in the hypothalamus appeared to trigger the HPA axis in androgen-deficient models. Future efforts will detail how tumors in one brain area affect distant regions. 

Using the NIH/NCI SEER database, researchers saw men with glioblastoma on non-cancer testosterone supplements had 38% lower death risk than others. This observational link, combined with preclinical data, calls for human trials.

“An obvious follow-up study would be to find out whether androgen deprivation, which is a common treatment for cancer, is actually detrimental for glioblastoma,” Lathia said.