Men with PCa Given TRT Had Unpredictable Results

[gusgold]

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

Gus

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

[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.

[pjoshea13]

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 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 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 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 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 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 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]

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?