Vanessa's Comment:

A new study is challenging assumptions about testosterone and glioblastoma (GBM). Some previous preclinical studies suggested testosterone or androgen receptor signaling might promote GBM growth, but many of those studies focused mainly on direct effects of testosterone on tumor cells themselves, often in cell cultures (“cells in a dish”) or simplified tumor models.

This new study instead used immunocompetent orthotopic mouse models of glioblastoma, meaning the tumors were grown inside the brains of mice with intact immune systems, allowing researchers to study how testosterone affects not just tumor cells, but also the brain’s immune environment, inflammation, and the stress-response system (the HPA axis). Surprisingly, the researchers found that loss of testosterone actually accelerated glioblastoma growth in male mice. Lower androgen levels appeared to increase stress hormones and create a more immunosuppressive tumor microenvironment, potentially making it harder for the immune system to respond to the tumor.

The researchers also analyzed retrospective data from more than 1,300 men with GBM and found that patients receiving supplemental testosterone for unrelated medical reasons had a significantly lower risk of death compared with men not receiving testosterone. While the researchers adjusted for several important clinical factors, including demographics, comorbidities, and extent of surgery, this data is still retrospective and observational, meaning it can show an association but not a definitive causal relationship. The findings should therefore be interpreted with caution, and we hope to see this finding explored further in future prospective trials.

NIH-funded study suggests that testosterone suppresses brain tumor growth in males