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Advanced Prostate Cancer
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Testosterone Therapy & PCa Risk.

Interesting study from Germany (presented at the Sexual Medicine Society of North America 18th Annual Fall Scientific Meeting in San Antonio, Texas).

"Ahmad Haider, MD, in private urology practice in Bremerhaven, Germany, and colleagues studied 400 hypogonadal men (testosterone level of 350 ng/dL or less) who received testosterone undecanoate 1000 mg every 3 months for up to 10 years and 376 hypogonadal men who opted against TRT (control group). During a median follow-up of 8 years, 9 men in the TRT group (2.3%) were diagnosed with PCa compared with 26 (6.9%) in the control group. "

“In the testosterone group, all prostate cancers were diagnosed within the first year and a half suggesting that cancers had been present prior to initiating testosterone therapy,” Dr Haider said.

"All {9} men in the TRT group underwent radical prostatectomy (RP), and all but 1 patient had a Gleason score of 6 or less. All had a predominant Gleason score of 3 and all had a tumor grade of G2 and tumor stage T2. In the control group, 18 underwent RP alone, 6 underwent RP and radiation, and 2 had radiation alone. All 26 patients had a Gleason score above 6, and 2, 20, and 4 had a predominant Gleason score of 3, 4, and 5, respectively. Tumor grade was G2 in 6 patients (23%) and G3 in 20 (77%). One patient (4%) had tumor stage T2 and 25 had tumor stage T3."

renalandurologynews.com/pro...

Much is made of declining male fertility, but little about the concomitant fall in testosterone [T]. The study result suggests that younger men should monitor T & supplement, if necessary, to reduce PCa risk. & the target T should be much higher than hypogonadal 350 ng/dL IMO.

-Patrick

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has this been used as a treatment for P/C , if so what were the outcomes ?

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Joe,

There was a 2009 study [1]: "testosterone replacement for patients with low-risk castration-resistant prostate cancer":

Unfortunately, T never got near to 350 ng/dL.

"Only one patient {of 15} experienced symptomatic progression, and three (20%) patients demonstrated a decrease in PSA (largest was 43%)."

There was a 2009 Sloan-Kettering study [2]: "high-dose exogenous testosterone in patients with castration-resistant metastatic prostate cancer."

"Patients did not, on average, achieve sustained supraphysiologic serum testosterone levels."

"One patient achieved a PSA decline of >50% from baseline. No objective responses were seen."

In a 2013 cell/mouse study [3]:

"Testosterone boosts on CRPC VCaP cells eliminate tumor cells to a higher extent than androgen withdrawal in androgen tolerant cells. The pronounced decrease of tumor cell proliferation was accompanied by a marked downregulation of AR expression regarding full-length AR and splice variant AR V7."

Similarly, a 2016 Japanese study [4]:

"Our findings support the clinical value of testosterone therapy, including bipolar androgen therapy, in the treatment of AR-overexpressed CRPC driven by AR splice variants that are not clinically actionable at present."

...

Of course, the Hopkins Denmeade BAT trial (not CRPC) uses monthly T shots in addition to ADT.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/192...

[2] ncbi.nlm.nih.gov/pubmed/193...

[3] ncbi.nlm.nih.gov/pubmed/238...

[4] ncbi.nlm.nih.gov/pubmed/274...

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I am in a Denmeade BAT trial and it is CRPC.

Original treatment in late 2015 per CHAARTED, followed by 2016 Provenge, and now 2017 BAT for 5 months and going. Nothing obvious except rising PSA, and hoped-for benefits of reversing the ADT side effect, aside from the unobserved action against prostate cell proliferation.

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I tried it (on a trial at JH). I did not see any benefit as far as the disease is concerned, other than to make the mets show up nicely on the scans.

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So to summarise (and please let me know if I misunderstand)

1. Testosterone helps protect against PCa.

2. But if you do develop PCa, testosterone then helps support the cancer - ie we need to suppress T as much as possible.

A bit late for those of us here. But interesting nonetheless.

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Males have a good 20 years when testosterone [T] is in the upper range, & no-one gets PCa during that time. T isn't dangerous.

Suppression of T has been used to treat PCa for 70 years. Not because T causes cancer - or even drives PCa - but because it is required for PCa cell division.

Unfortunately, the castration strategy is mostly good only for 18-24 months, & comes with morbidity. One day, there will be a smarter treatment.

Morgentaler says (in effect) that those not on ADT could raise T by 600 ng/dL without any effect on PCa, since the cells are T-saturated at about 250 ng/dL.

The other side of that is one could reduce T from 850 to 250 ng/dL & it would not help control PCa. It is the elimination of T that is "therapeutic".

-Patrick

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You say " Not because T causes cancer - or even drives PCa - but because it is required for PCa cell division."

Cell division is mitosis. Testosterone, as a hormone ,has a role in gene expression. This is a different mechanism from cell division; that is, different from mitosis. Mitosis is different from protein synthesis.

Hormones are signals, and generally work by binding to a paired receptor, activating the receptor to dimerize (double up) and then enter the nucleus. The receptor has a section that binds to an appropriate section of DNA. That section varies by cell type. DNA is rolled up around a histone, ie around a screw. The part of the DNA that is exposed is what controls the behavior of the cell. It's like the page to which the blueprint is open. This video [

] goes into that in quite a bit of detail, but the point to notice, is that she is not talking about cell replication, or the portion of cell replication where the DNA replicates, or anything like that, but gene expression.

So while it must be admitted that testosterone has a role in prostate cancer, the exact connection between testosterone and cell division seems to be much less than obvious.

Something that would help illuminate the situation would be to determine if testoterone is a factor in the neuroendocrine variant of prostate cancer: small cell. In that variant, the Androgen Receptor does not play any role, so if testosterone still did play a role, that would demonstrate that testosterone has a role in the cell beyond its role in gene expression. That seems problematical to me - like a problematical system design - tieing two unrelated things together.

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Yes it is interesting.

First, they found that cutting off the testicles extended life of prostate cancer patients.

Then, they found that a drug to the pituitary to stop the production of two hormones out of the pituitary did as much. One (LH) was needed for the creation of testosterone in the testes. So stopping the testes from producing testosterone did as much as chopping off the testes.

Hormones were the early nervous system. Signals pushed into the bloodstream to control remote organs. A message in a bottle. What was the message? What did the message control? Not cell division, but the manifestation of masculine features. Gene expression. Protein synthesis.

What does that have to do with out-of-control cell replication? Not that clear. The guess, maybe one of them other dang proteins. Not PSA though, or tied to PSA expression.

The "buzzword" that people are chewing on and hoping explains something is "licensing". Licensing has something to do with the control of DNA replication. and the notion is that the androgen receptor is involved, marking starting points. Does not seem clear or even likely, since the AR binds at certain places in the DNA, so its usefulness in DNA replication would be fortuitous. The proponent of this is John isaacs at Johns Hopkins.

books.google.com/books?id=L...

en.wikipedia.org/wiki/Licen...

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