Testosterone Does Not Drive Prostate Cancer: Presenting the New Framework of Androgen Adequacy vs Inadequacy

PURPOSE: (1) To review the evidence whether "testosterone drives prostate cancer," (2) to dissect the arguments supporting this belief, and (3) to present the new framework of androgen adequacy vs inadequacy to explain the relationship of testosterone and prostate cancer. MATERIALS AND METHODS: A MEDLINE review of the literature was performed. RESULTS: The belief that testosterone (T) drives prostate cancer (PCa) originated with Charles Huggins in 1941, led to a near-complete prohibition against T therapy (TTh) for 60 years, and persists today in regulatory warnings, guideline restrictions, and widespread clinical concerns. However, the evidence is now overwhelming that T does not drive PCa. Biopsy studies show that PCa risk is unrelated to endogenous androgen concentrations. Large randomized clinical trials reveal identical PCa rates in men receiving TTh vs placebo. TTh in men with known PCa has not shown increased rates of recurrence or progression. While androgens are required for PCa growth, PCa growth also requires other chemicals, for example, calcium. What is unique to androgens is it is the only required chemical that does not cause loss of life with severe deprivation. The key concept to understand the relationship of androgens and PCa is adequacy vs inadequacy. Adequate T concentrations for optimal PCa growth occur at a low concentration called the saturation point. Below this, cellular metabolism is compromised and cell death may occur depending on degree of deprivation. CONCLUSIONS: Testosterone does not drive PCa. Androgen adequacy vs inadequacy provides a scientifically sound framework to understand the relationship of testosterone and prostate pathophysiology.