Men with PCa Given TRT Had Unpredicta... - Advanced Prostate...

Advanced Prostate Cancer
10,722 members12,834 posts

Men with PCa Given TRT Had Unpredictable Results

gusgold
gusgold

Nalakrats go fishing and forget about TRT or you might be swimming with the fish

Gus

ncbi.nlm.nih.gov/pubmed/215...

10 Replies
oldestnewest
Hidden
Hidden

I do not understand the theory of this study. It is:

"To assess the evidence for the concept that the androgen receptor of prostate cancer (PCa) cells becomes saturated when testosterone values exceed castrate levels, so that testosterone administration in hypogonadal men with untreated PCa does not stimulate tumour growth"

"Castrate" means remove the testes. You have no testes. Castrate levels (of testosterone) means the level of testosterone if you have no testes. If at that level, your AR (sic) is "saturated", why do men even have testes?

Maybe the problem is what they mean by "saturated" receptor(s). What?

So the theory of this study makes no sense to me. The question can remain, can something be made of the trial data? Maybe.

Gus,

Note that TRT is not a cure for PCa. However, low free T is associated with more aggressive disease. Thus, increasing T might, paradoxically, slow down the cancer.

But, I think we need to distinguish between border-line hypogonadal & near-castrate. In the first case, there is already enought T to facilitate growth. TRT should not have much immediate effect on PSA. In the latter case, the man is effectively on a form of ADT. In some cases, TRT will expose aggressive disease. Fortunately, discontinuation of patches is followed by rapid clearance of T - & PSA falls.

By the way, the criteria used for hypogonadism was <10 nmol/L (<288 ng/dL).

"In others, the use of intermittent therapy resulted in synchronous changes in PSA levels. Interruption of TTh invariably translated into a decrease in PSA to pre-therapy levels."

See my response to your Dr Bob post.

"Hypogonadism associated with untreated PCa is not common ..."

A number of studies have noted lower T numbers in PCa. In addition, Patrick Walsh has reported that T increases after RP. So that statement is incorrect. Added to which, hypogonadism is not uncommon in the age group.

...

Here is a ref. to the study:

"In another 2011 study, Morales [57] reported his experience with testosterone therapy in seven patients with untreated prostate cancer. Six men had low risk disease while one had high risk Gleason grade 4 + 4 disease. Two were given testosterone intermittently. The author recommends proceeding with caution as the PSA responses in this small series were erratic. It must be noted, however, no follow-up biopsies were performed in these patients and only PSA kinetics was studied [57]. Although the use of testosterone therapy in men on active surveillance may appear to push the limits of safety, it is worth noting that low free testosterone concentrations were found to be an independent predictor of disease reclassification (ie, progression) in a study of 154 men on an active-surveillance protocol [58]."

Only 7 patients!

Here is Morgentaler's comment:

"A cautionary note was raised by Morales, who reported variable responses to T therapy in six men during T therapy while on active surveillance. Although a rise in PSA in a few men was concerning, no follow-up biopsy results were reported to document progression." ... Actually, 7 men.

-Patrick

Hidden
Hidden in reply to pjoshea13

"However, low free T is associated with more aggressive disease. Thus, increasing T might, paradoxically, slow down the cancer."

Are you adding new ideas to the study, ie free testosterone, or did they mean that anyway without having said it?

Low free T is "associated", so that it may not be a necessary condition, a cause. But of course, low T does select for cells that can survive in low T. It is Just not clear what the effect of raising T is after the low T cells have been selected. Potentially, the ones that survive in higher T begin to replicate, and replicate faster than the ones that need low T. What are the odds?

pjoshea13
pjoshea13 in reply to Hidden

Studies that look at total T seem to assume that it is a surrogate for free T.

But if SHBG is high, free-T can be low, even if total-T is high. SHBG- bound T is not bioavailable. About 50% of T is bound to SHBG. Almost all the rest is bound to albumin. Only 1-2% T is free.

SHBG tends to be high when E2 is high & T is low. Increasing T lowers SHBG levels.

-Patrick

Hidden
Hidden in reply to pjoshea13

where does SHBG come from? The thing that makes it is affected by testosterone levels? Testosterone acts as an agonist? The pituitary? The pituitary watches over testosterone levels I think. That would mean that an increasing the T sex hormone caused the pituitary to reduce the amount of sex hormone binding globulin. Some globulins are hexagonal constructions of antibodies, I think. LIke IL-2. Could be wrong.

pjoshea13
pjoshea13 in reply to Hidden

The liver produces SHBG.

When estradiol rises, SHBG rises too. But it has much more of an affinity for T than E2. Doesn't seem fair, but E2 comes from aromatization of E2.

When T rises, SHBG declines.

-Patrick

Hidden
Hidden in reply to pjoshea13

[from aromatization of T]

Wait, I am missing something

1. some (free) T->E2

2. Rising E2 raises SHBG

Rising T should elevate SHBG

3. Rising SHBG binds (free) T

=====

Or alternately

aromatization T->E2

lowers T (its consumed)

raises E2 (its created)

pjoshea13
pjoshea13 in reply to Hidden

With lower T, aromatase increases.

With low T, muscle mass declines; fat mass increases. Fat secretes E2.

Normal-high T brings everything back in balance.

Hidden
Hidden

is it that free T (the smallish testosterone molecule) can diffuse through the cell membrane, but bound T (the molecule attached to a bigger one) needs the transport mechanism of the androgen receptor?

Gus, I plan to go fishing for sure--leaving in 2 weeks from today. Going to have lunch with a mutual friend--hopefully next week. I think I will let all you experts fight it out about the use of T---All the papers are 2005, 2011, it is almost 2017 and we know a whole lot more.

The first premise is that men with low T tend to get Prostate Cancer

The second premise is the lower the T, over extended years the more likely to have Gleason 8's and 9's

The next premise is that those that supplement their normal T levels, with any T preparation, the body does not recognize that it is now in a high T state. The body still thinks it is low T. Granted you can lift more weigh have better sex and stay lean from the foreign T--but the body still says you are low T.

To make a point---a retired Urologist who wrote a book long ago--would test any man over 55 for T. If a man had low T, he did a PSA. Even if the PSA was 1 or 2, anything under4[Normal], he would biopsy the patient--even though the PSA was Normal and a Digital was perfect. What he found was that 20% of these men with Low T and perfect Digitals and PSA's had prostate cancer--deep inside and undetectable by standard examinations, and blood work.

So we do have paradox's. We have known it for years. One--why does the 25 year old with 1100 ng/dl as to T, not get Pca--and the Man of 60 with a T of 250 ng/dl get Pca--but not just any kind--usually very aggressive Pca?

Another Paradox as proven by Leibowitz, and now dozens of Oncologists and Urologists, show that men with low T especially those that have become castrate resistant, can have their PSA's reduced more than 50%. Some use BAT, some use straight intermittent, others just high T with no other drugs.

So we have a problem and there are partial solutions, which indicates to me we may not be looking in the right place yet. I have certain theories, and I am not where I want to be yet. But sometimes to solve a mystery, who have to work backwards. So instead of the cause to the effect--you work backwards from the effect to find the cause. As an example, when doing a difficult maze puzzle, I do not start at the entrance. I start at the exit.

So I will let you girls argue out the papers, clinical trials, articles, testimonials etc. as to the use of T. I just had my last PSA result today before leaving for Florida, and I am still undetectable. So I will stay tuned, but while you girls argue back and forth, I am going fishing.

Nalakrats

You may also like...