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

Area of Science:

• Urology
• Endocrinology
• Oncology

Background:

• The long-held belief that testosterone (T) drives prostate cancer (PCa) has influenced clinical practice and regulatory guidelines for decades.
• This belief, originating in 1941, led to significant restrictions on testosterone therapy (TTh).

Purpose of the Study:

• To critically evaluate the evidence linking testosterone to prostate cancer development and progression.
• To dissect the historical arguments supporting the notion that testosterone drives PCa.
• To introduce a novel framework of androgen adequacy versus inadequacy for understanding the T-PCa relationship.

Main Methods:

• A comprehensive MEDLINE literature review was conducted to gather relevant studies.
• Analysis focused on biopsy data, randomized controlled trials (RCTs), and clinical outcomes of TTh in men with and without PCa.

Main Results:

• Overwhelming evidence indicates that testosterone does not drive prostate cancer.
• PCa risk is not correlated with endogenous androgen levels, and TTh does not increase PCa rates in large RCTs.
• While androgens are necessary for PCa growth, the critical factor is androgen adequacy, not just concentration, with optimal growth occurring at a specific saturation point.

Conclusions:

• Testosterone is not a driver of prostate cancer.
• The concept of androgen adequacy versus inadequacy offers a scientifically robust model to explain the complex relationship between testosterone and prostate pathophysiology.