Testosterone Therapy and Prostate Cancer

[pjoshea13]

New review paper by Abraham Morgentaler, below.

"The saturation point corresponds with maximal androgenic stimulation at 250 ng/dL."

He's stating, effectively, that at a testosterone [T] level of 250 ng/dL, one could raise T to 500, or even 1,000 ng/dL, without "adding fuel to the fire", as some fear.

The other part of that is that during the IADT 'vacation', as T climbs from near zero, the stimulatory effect on PSA levels off before T reaches 250 ng/dL.

The irony is that many men don't get much beyond that, & as Freedland has stated, castration lasts well beyond the on-phase of IADT.  It can take more than 6 months for T to recover, & it rarely reaches the previous high.

-Patrick

ncbi.nlm.nih.gov/pubmed/271...

Urol Clin North Am. 2016 May;43(2):209-16. doi: 10.1016/j.ucl.2016.01.007.

Testosterone Therapy and Prostate Cancer.

Davidson E1, Morgentaler A2.

Author information

1Men's Health Boston, Department of Surgery (Urology), Harvard Medical School, 200 Boylston Street, Suite A309, Chestnut Hill, MA 02467, USA.

2Men's Health Boston, Department of Surgery (Urology), Harvard Medical School, 200 Boylston Street, Suite A309, Chestnut Hill, MA 02467, USA. Electronic address: [e-mail].

Abstract

Changes in understanding regarding the relationship of androgens and prostate cancer have led to changes in the use of testosterone therapy. The evidence supports a finite ability of androgens to stimulate prostate cancer growth, with a maximum achieved at low testosterone concentrations, called the saturation model. The saturation point corresponds with maximal androgenic stimulation at 250 ng/dL. Evidence is reviewed herein regarding the relationship of testosterone to prostate cancer and the relatively new practice of offering testosterone therapy to men with a history of prostate cancer. Although no prospective controlled trials have been performed, results have been reassuring.

Copyright © 2016 Elsevier Inc. All rights reserved.

KEYWORDS:

Androgens; Hypogonadism; Prostate; Prostate cancer; Prostate-specific antigen; Testosterone; Testosterone deficiency

PMID: 27132578 [PubMed - in process]

[maack1]

The procedure of participating in testosterone replacement therapy (TRT) continues to be a questionable practice, and I see Morgantaler's remark (if the above is his remark) "Although no prospective controlled trials have been performed, results have been reassuring" poses the necessity of "prospective controlled trials" to settle this issue once and for all. 

[joeoconnell]

does any one understand what is said in the above article, or is it just me that doesn't get it

[pjoshea13 in reply to joeoconnell]

Joe,

PCa cell division involves a number of factors, but most people focus on the role of the androgen receptor [AR].  For cell divission to occur AR has to bind with androgen.  Morgentaler says that there is enough testosterone [T] in the body, so that every AR in every PCa cell can have androgen bound to it, when T > 250 ng/dL.  The normal range starts at 350 ng/dL.

Morgentaler's saturation theory states the amount of T that a man has above 250, is irrelevant in terms of stimulating PCa.

As Chuck stated, this is a controversial topic.

For background on Morgentaler, read:

lifeextension.com/Magazine/...

lifeextension.com/Magazine/...

-Patrick

[joeoconnell in reply to pjoshea13]

thank you Patrick, but it is beyond my pay grade 

[Hidden]

Now, I'm a bit confused. I'm on Lupron full time now. When I was on vacation from it, my uro said that my PSA would be at nil. I understood that as meaning near zero, or there about. But, all my blood work came back at near 5, consistently. And, I only had one or two T labs done.

So, my question is, what is nil?

Joe

[pcasucks]

If you have PCa and your T is at castrate level, why would you want to risk fueling the Fire,   yes I realize that after a level above 250 or more is considered saturate levels but I still don't understand way someone would want that. That's like saying my T is a 20 that all my cancer needs so way not boost it to 600. I don't get it. I guess I could say I feel fantastic to bad it's killing me.

[pjoshea13 in reply to pcasucks]

The premise behind intermittent ADT is that QOL improves during the off-phase as T climbs.  T recovery is slow, & men who were hypogonadal (or borderline) before ADT, might not get much above 250 during the recovery.  Meanwhile, men who get above 400, say, experience the full benefit of the off-phase.

Doctors don't care how fast or how high T climbs.  The idea is to monitor PSA & switch back to the on-phase when it gets up to a certain level.  That being the case, why shouldn't T be rapidly restored?  Treatment can be reversed at any point.

Dr. Myers has a series of vblog posts on durable remission.  In the IADT off-phase, PSA is expected to rise.  Myers says that with a short on-phase, the ADT 'vacation' is invariably very short.  Ideally, the off-phase will be much longer than the on-phase.  e.g. 12 months on ADT followed by >2 years vacation might be considered a success.

The length of the vacation is important, since there is a limit to how many times the cycle can be repeated before castrate resistance occurs.  For a durable remission, Myers is therefore aiming for a very long off-phase.  He has actually said that, ideally, in a durable remission, men will have normal T.

Dr Myers has stated that the rate of PSA change in his patients is unaffected by T above 350 ng/dL.  Which means that by the time a man exits the hypogonadal range (<350), PSA behavior has become predictable, i.e. one can calculate the PSA doubling time.  [Morgentaler puts the cut-off much lower at 250.]

-Patrick