Why Giving Testosterone Does Not Cause Prostate Cancer to Grow, but Lowering T levels causes Prostate Cancer to get better!

From 1996 until now, Morgantaler and others have proven everything doctors thought was true and is currently being taught about the relationship of Testosterone (T) and Prostate Cancer (PCa) is WRONG!.  So what is TRUE?

How is it possible when advanced PCa is effectively treated by lowering T levels, raising T levels DO NOT increase PCa risk and can even decrease PCa risk?   Is that crazy thinking?  Can we really treat men with Prostate Cancer with Testosterone?  What is really going on?

Morgantaler’s discovery is a true exercise in thinking outside the box while using what has been observed with T levels and PCa as part of the data.  It is the same thinking process needed when looking at Covid treatments and the Covid vaccines.  There are many many questions needed to be answered in assessing Covid treatments and vaccines.  It may not be as simple as we think.  Every reaction in the body has its origin at the cellular level where disease and vaccines are working.  In addition, once a cell is disrupted it sets off expansive feedback loops in the body changing theoretical outcomes.  There can be a huge difference in outcome when you trial a concept born in vitro in a petri dish as opposed to clinical application.  Having stated this, Morganataler took his theories of T levels and PCa straight to clinical trials with proven outcomes.

PCa screening by PSA Blood Test

Currently, PSA or Prostate Specific Antigen, level is used to screen for PCa.. It is a protein made by cells in the prostate, both normal and cancerous.  Although there is no real cutoff point, the level > 4 is indicative a man should get further testing.

Morgantaler’s Hypothesis

Morgantaler showed approximately 14% of men with a normal PSA < 4, a normal exam, and low T levels already have PCa.

From this discovery, he hypothesized there was a higher risk of PCa with low levels of T, not high levels of T.

Later it was proven the lower the T levels, the more extensive PCa will be.  (Note if the PSA is greater than 10, there is a 50% chance of having PCa.) *

Shifting the Paradigm of T and PCa: Saturation Model and Limits of Androgen-Dependent Growth

To answer why and how his clinical observations could be true, Morgantaler plotted T Therapy vs PSA levels/Prostate Cancer Growth.   He found T Therapy will increase PSA levels/ PCa growth until you reach a T level of 250 ng/dl, the lowest level in the “normal” reference range.  If someone has a T level of 250 ng/dl or more, no matter how much T you use, the PSA level does not increase, and therefore PCa does not progress!  Why?

  • At 250 mg/dl all PSA/PCa receptor sites are filled. The PSA/PCa receptor sites have reached their saturation and there are no more to fill. The receptor sites are fully saturated.
  • When you give a patient T Therapy having a T level below 250 ng/dl, his PSA/PCa growth will go up.
  • Once the T level reaches 250 ng/dl the PSA level/PCa growth will plateau and not increase as the receptor sites are saturated.

‘Although T therapy may appear to cause PSA to rise initially, more accurately, low T concentrations lower serum PSA and hence can lower the progression of PCa when they have T levels of 250 ng/dl or less.’**

Hence, there is a limit to which T Therapy can stimulate PCa growth.  This saturation model explains why you can see dramatically lowered PSA levels initially with castration and can see a minor impact with T Therapy on PSA levels in non-castrated men.  Morgantaler then showed this same saturation model also applies to Androgen (Testosterone) Receptor sites, AR. Observations noted:

Prostate growth is exquisitely sensitive to variations in androgen concentrations at very low concentrations, ….well below physiologic range…but becomes insensitive to changes in androgen concentrations at higher levels. 

A Saturation Model is proposed accounting for the seemingly contradictory results in human PCa studies. 

Changes in serum T concentrations below the point of maximal androgen-AR binding will elicit substantial changes in PCa growth, as seen with castration, or with T administration to previously castrated men. 

In contrast, once maximal androgen-AR binding is reached the presence of additional androgen produces little further effect.

Conclusions: The evidence clearly indicates there is a limit to the ability of androgens to stimulate PCa growth.”  ** 

Does Morgantaler’s hypothesis hold up in clinical practice? What happens when we extrapolate this concept to PCa in a clinical setting?  What happens when you treat men with Prostate Cancer with Testosterone?

The paradigm shift continues!

*https://www.cancer.org › detection-diagnosis-staging › tests
 **Morgentaler and Traish, Eur Urol 55:310-20. 2009 https://pubmed.ncbi.nlm.nih.gov/18838208/