Saturation theory and testosterone effects on end organs

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The variation in the effect of testosterone on different end organs is likely due to the saturation theory, which suggests that supplementing serum testosterone to higher levels may positively impact muscle growth but have limited effects on prostate growth and prostate cancer development. Tissues like hair follicles and prostate are similar due to high densities of 5-alpha reductase, allowing conversion of testosterone to DHT. This variation in testosterone effects is not unique to the androgen receptor and may apply to other receptor superfamilies.

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Ted Schaeffer is an internationally recognized urologist specializing in prostate cancer and a returning guest on The Drive. In this episode, Ted provides insights into the role testosterone plays, or doesn't play, in the initiation and progression of prostate cancer. He unpacks the findings and limitations of the recent TRAVERSE trial, exploring the complex relationship between testosterone and prostate cancer. Ted delves into the molecular nature of prostate cancer, explaining the androgen receptor saturation theory and the potential impact of testosterone on cancer growth. He also discusses the use of the Decipher test to predict cancer aggressiveness and guide targeted treatment. Furthermore, Ted shares how he counsels patients regarding testosterone replacement therapy (TRT), including its safe administration in patients with low-grade prostate cancer. Additionally, he highlights advancements in prostate cancer therapies and biomarkers that help develop precise treatment strategies while minimizing the need for broad androgen deprivation therapy.

We discuss:

Background on the TRAVERSE trial: insights into exogenous testosterone and prostate cancer risk [3:00];
The androgen receptor saturation theory: how different organs respond to varying levels of testosterone [10:30];
The relationship between testosterone levels and prostate cancer aggressiveness: how aggressive prostate tumors have lower androgen receptor activity and rely on different growth mechanisms [16:15];
Using the Decipher score to assess prostate cancer aggressiveness and guide personalized treatment strategies [23:45];
Considerations for testosterone replacement therapy: how Ted counsels patients, how TRT can be safely administered in patients with low-grade prostate cancer, and more [31:15];
Advancements in prostate cancer therapies and PSA as a biomarker for precise treatment decisions, minimizing the need for broad androgen deprivation therapy [38:30]; and
More.

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