Testosterone signaling slowed brain tumor growth in male mice and was linked to longer survival in older men. Digest
Glioblastoma is an aggressive form of brain cancer, and researchers are still working to understand how sex hormones influence its growth. A new study tested whether androgens, a group of hormones that includes testosterone, shape immune responses to this disease.
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The main experiments used young male mice in which glioblastoma cells were placed in the brain, with some mice undergoing castration to remove the main source of androgens and others receiving sham surgery. To test whether androgen signaling acted on the cancer cells themselves or instead changed how the brain environment responded to tumors, the researchers also grew the same cancer cells outside the brain, including under the skin. In additional experiments with glioblastoma cells placed in the brain, they used a drug to block androgen signaling in males that had not been castrated or gave testosterone back to males that were castrated. For the human analysis, the researchers reviewed health records from 1,333 men older than 65 with glioblastoma who received standard treatment, then compared those who also had supplemental testosterone listed in their records with those who did not.
- Androgen loss worsened brain tumor outcomes in male mice. In one glioblastoma brain tumor model, median survival was 26 days after sham surgery and 20 days after castration, with larger tumors in the androgen-depleted mice.
- Tumor location changed the direction of the effect. When glioblastoma cells were placed in the brain, androgen loss shortened survival. When the same glioblastoma cells were grown under the skin, androgen loss delayed tumor growth. The researchers also found shortened survival after castration when bladder cancer and melanoma cells were placed in the brain.
- Blocking androgen signaling with a drug shortened survival in male mice with glioblastoma cells placed in the brain, from 19 days to 17.5 days.
- Testosterone supplementation extended survival in mice with glioblastoma cells placed in the brain: from 20 to 22 days in castrated males, and from 21 to 36 days in males that had not been castrated or treated with the androgen-blocking drug.
- Among the men reviewed, 61 with recorded supplemental testosterone use had a median survival of 16 months, compared with 12 months in those without testosterone use. After accounting for other factors, testosterone use was linked to a 34% lower death rate over the study period.
The findings point to a brain-specific pathway affected by androgen loss. In male mice with brain tumors, losing androgen signals appeared to make the brain more inflamed. Those inflammatory signals then helped activate the body's stress-hormone system. The resulting stress-hormone activity appeared to shift myeloid cells, a group of immune cells that shape the tumor environment, toward a more immune-suppressing state, weakening T cells that help recognize and attack cancer.
The main limitation is that the causal evidence comes from mouse experiments, while the human survival finding is observational and based on medical records. If confirmed in clinical trials, the findings could especially matter for older men, whose testosterone levels are often lower due to age-related decline. But the human data in this study do not prove that testosterone supplementation improves glioblastoma survival or is safe for this use. In Aliquot #116, I discuss testosterone optimization strategies for men.