Supplemental testosterone may improve survival outcomes for men diagnosed with glioblastoma, according to a study published in the journal Nature. Researchers at the Cleveland Clinic found that while testosterone is often linked to tumor growth in other cancers, its absence in the brain can trigger neuroinflammation and immune suppression, ultimately accelerating brain tumor progression.
Why Does Testosterone Affect Brain Tumors Differently?
The traditional medical understanding of testosterone is rooted in prostate cancer research, where androgen-deprivation therapy is used to slow tumor growth. However, the brain operates under different biological constraints. According to lead author Juyeun Lee, DVM, PhD, who is now Assistant Staff at Cleveland Clinic’s Florida Research & Innovation Center, the systemic interaction between the body’s systems is critical when evaluating brain pathology.
In preclinical murine models, the research team observed that removing testosterone through castration led to increased neuroinflammation. This state activates the HPA axis, which increases glucocorticoids production. These hormones suppress the immune system, leaving the brain less capable of controlling glioblastoma and metastatic tumors. Unlike in other parts of the body where testosterone fuels cancer, the brain requires a different hormonal balance to maintain immune surveillance.
Researchers confirmed these findings by injecting exogenous testosterone into their models to validate that the tumor activity was testosterone dependent. They observed that the brain’s response to cancer is distinct from the rest of the body.
What Do Clinical Outcomes Reveal?
To validate the laboratory findings, researchers performed a retrospective analysis of 1,333 men with glioblastoma using data from the Surveillance, Epidemiology and End Results (SEER) database. All patients in the study underwent surgical resection and radiation therapy.
The study identified a clear survival difference based on hormone exposure:
- Supplemental testosterone and temozolomide group: 61 patients achieved a median survival of 16 months.
- Temozolomide alone group: 1,272 patients achieved a median survival of 12 months.
Justin Lathia, PhD, who oversees the Cleveland Clinic lab involved in the study, noted that the team used models putting the tumor not in the brain but in the flank. They observed opposite results compared to the brain models, confirming that there are major differences in how the brain responds to cancer compared to the rest of the body.
How Will This Change Future Treatment?
The medical community is now evaluating the potential for early-phase clinical trials to test supplemental testosterone as a therapy for glioblastoma. Drs. Lathia and Lee are currently in discussions with their colleagues in neuro-oncology and endocrinology to potentially study this question in an early phase clinical trial.
Future research will also focus on the role of testosterone in brain metastasis, seeking to determine if similar immune-protective mechanisms can be leveraged to treat cancers that have spread to the brain from other organs.
Frequently Asked Questions
Does testosterone cause all types of cancer to grow?
No. While testosterone is associated with increased growth in other systems, this study suggests it may have a different effect in the context of glioblastoma.
Why were men historically thought to have worse glioblastoma outcomes?
Historically, men with glioblastoma tended to have more aggressive disease and poorer outcomes than women, but the reasons were unclear. This study suggests that progressive testosterone loss in aging men may have an impact on cancer.
Is testosterone therapy currently a standard treatment for glioblastoma?
No. These findings are based on preclinical models and a retrospective analysis. Drs. Lathia and Lee are in discussions to potentially study this question in an early phase clinical trial.
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