Low Testosterone Linked to Higher Risk of Aggressive Prostate Cancer Progression
New research suggests that men with low testosterone undergoing active surveillance for prostate cancer may face a greater risk of developing more aggressive disease.
A retrospective study of more than 900 men with localized prostate cancer found that low testosterone levels were associated with a higher risk of progression to aggressive disease during active surveillance. The findings challenge the long-standing belief that higher testosterone necessarily fuels prostate cancer growth.
Study Details
For decades, the dominant medical view has been that testosterone promotes prostate cancer growth. This belief stems largely from early research showing that lowering testosterone through androgen deprivation therapy could shrink prostate tumors in advanced disease.
However, newer research by University of Texas MD Anderson Cancer Center in Houston has begun to question whether this relationship is always straightforward, particularly in early-stage prostate cancer.
In this study published in the Journal of Urology, researchers examined whether baseline testosterone levels influence disease progression among men enrolled in active surveillance, a management strategy where low-risk prostate cancer is closely monitored rather than immediately treated.
Researchers analyzed outcomes in 924 men diagnosed with localized grade group 1 or 2 prostate cancer who were enrolled in active surveillance between 2005 and 2024.
Methodology
Researchers conducted a retrospective cohort analysis of men undergoing active surveillance for prostate cancer. Baseline testosterone levels were measured before surveillance began, and participants were followed over time to monitor whether their cancer progressed to higher-grade disease. The analysis adjusted for several factors known to influence prostate cancer risk, including age, PSA density, body mass index, and tumor volume measured on biopsy.
Key Findings
Low testosterone (≤300 ng/dL) was linked to a 61% higher risk of progression to grade group 3 or higher disease.
Low testosterone was not significantly associated with progression to grade group 2 disease, suggesting the relationship may specifically involve more aggressive tumors.
About 29% of patients had low testosterone levels at baseline.
During follow-up, 23.2% of patients experienced grade group 2 progression, while 9% progressed to grade group 3 disease.
Among those with grade group 3 progression, over one-third advanced to grade group 4 or higher.
Implications for Practice
These findings contribute to a growing body of evidence suggesting a more complex relationship between testosterone and prostate cancer biology.
Researchers point to the testosterone saturation hypothesis, which proposes that prostate cancer cells respond strongly to testosterone only below certain threshold levels. Once that threshold is reached, additional testosterone may have little effect on tumor growth.
If confirmed in future studies, testosterone levels could become a useful marker in prostate cancer management.
For patients, this may eventually help doctors determine who is most suitable for active surveillance versus early treatment. For clinicians, incorporating testosterone measurements into prognostic models could improve risk stratification and monitoring strategies.
However, experts caution that the study does not support routine testosterone replacement therapy in men with prostate cancer at this stage. Prospective studies will be needed to determine whether modifying testosterone levels can influence disease outcomes.