Cleveland Clinic scientists have found in a new study funded by the National Institutes of Health (NIH) that hormones associated with male development may play an important role in limiting the growth of brain tumors in men. The research team found that in a preclinical model of glioblastoma, loss of androgenic hormones such as testosterone promotes tumor growth by inducing local inflammation and triggering the production of stress hormones. Analyzing data from more than 1,300 men with glioblastoma, the authors found that testosterone supplementation was significantly associated with improved survival, consistent with preclinical experiments.
The results are a welcome surprise and could provide clues to new treatments for certain cancers that are more deadly in men. ”
Anthony Letai, MD, Director, National Cancer Institute (NCI), NIH
Because glioblastoma and androgens also have a higher prevalence in men, many researchers suspect that these hormones are part of the problem. However, previous studies have not investigated the effects of androgens on tumor growth in the unique environment of the brain.
“The brain has evolved to protect against foreign invaders, including immune cells from elsewhere in the body. The brain is a delicate tissue and often doesn’t want a large immune response,” said corresponding author Dr. Justin Lacia, professor of cancer science and scientific director of the Cleveland Clinic Brain Tumor Center.
Lacia and his colleagues discovered that androgens in the brain, unlike elsewhere in the body, play a critical role in regulating the organ’s safety system. Reducing androgens in mouse models of glioblastoma puts a neuroendocrine system called the hypothalamic-pituitary-adrenal (HPA) axis into overdrive. This triggered a surge of stress hormones, which then caused a subset of cells to further isolate the brain from the rest of the body.
Increased security created an immunosuppressive environment in the brain, reducing the number of immune cells available to reach the growing threat, allowing tumors to progress largely unchecked. The authors found that testosterone did not have the same effect in female mice.
The researchers determined that the HPA axis is likely driven by inflammation in the hypothalamus caused by tumors in androgen-deficient mice. Future research will determine exactly how tumors trigger this response in entirely different areas of the brain.
To investigate the relationship between androgens and brain tumors in humans, researchers analyzed existing clinical data available through the NIH/NCI Surveillance, Epidemiology, and End Results (SEER) database. Researchers showed that men with glioblastoma who took testosterone supplements for reasons unrelated to cancer had a 38% lower risk of death than patients who did not take the same supplements.
Although a causal relationship has not been established, Lacia and colleagues believe that this observation, together with the preclinical results, warrants clinical trials for further study in humans.
“An obvious follow-up study would be to find out whether androgen deprivation, a common cancer treatment, is actually harmful to glioblastoma,” Professor Ratia said.
sauce:
National Institutes of Health (NIH)
Reference magazines:
Lee, J. others. (2026) Androgen loss accelerates brain tumor growth via HPA axis activation. nature. DOI: 10.1038/s41586-026-10451-5. https://www.nature.com/articles/s41586-026-10451-5
