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Advanced Prostate Cancer
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Treating Prostate Cancer with Testosterone

Can someone explain to me what this concept is of treating prostate cancer with testosterone? I just don't get it.

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It's been known for some time that men at diagnosis tend to have lower T than matched controls, & that men in the lowest T range have a poorer prognosis.

The fact that castration provides temporary relief from proliferation does not mean that T is the cause of PCa or the primary impetus for proliferation. We still sometimes hear that T acts like gasoline on a fire & perhaps some here think that, but did Charles Huggins?:

"Hormones, or synthetic substances exerting physiologic effects similar thereto, are of crucial significance for growth of 7 hormone-dependent cancers of man and the animals. Two opposite sorts of change of the hormonal status can induce regression of such cancers: (a) deprivation of essential hormones; (b) hormone interference with large amounts of critical compounds." [1]

The androgen receptor [AR] continues to be required for PCa growth even in most CRPC cases.

In a youthful normal prostate, high-normal T does not cause uncontrolled growth. The idea that T binds to AR & cell division occurs is simplistic. There are many factors involved. If T converts to the more potent AR ligand DHT, that sets in motion the destruction of DHT & the production of the natural ligand of the beta estrogen receptor [ERbeta], which resists the growth efforts of ERalpha:

"AKR1C1 catalyzes the irreversible conversion of DHT to 5α-androstane-3 β,17 β-diol (3β-diol, a possible {likely} endogenous ligand for the estrogen receptor β (ER β, in prostate)" [2]

It is my belief that men on active surveilance should be advised to correct T deficiency/insufficiency, & that any estrogen dominance also be corrected. & that men on IADT have the option to quickly restore T levels in the off phase.

However, when CRPC happens, the changes that have occured to the AR & its environment may preclude the usefulness of T replacement. Not every man will benefit.

A new paper [3] (full text, but short) is probaly the best place to begin exploring the subject.

"In relation to PC, AR regulates proliferation as well as differentiation of prostate epithelial and cancer cells but it has not been established what conditions support one over the other. Interestingly activation of AR with excessive hormone (i.e., supraphysiological levels of testosterone; SPT) was shown to inhibit growth of CRPC in vitro by negative effects on proliferation ..."

"Multiple preclinical studies demonstrated that SPT inhibits growth of PC cells that express AR, with evidence suggesting that higher levels of AR might lead to more pronounced SPT effects in certain phenotypes of CRPC ... However, AR by itself is not necessarily sufficient for the SPT-induced growth inhibition; cellular context and AR-regulated transcriptome in its entirety will need to be assessed to delineate the molecular effect of SPT"

-Patrick

[1] cancerres.aacrjournals.org/...

[2] ncbi.nlm.nih.gov/pmc/articl...

[3] ncbi.nlm.nih.gov/pmc/articl...

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I only know of one doctor (Liebowitz) who actually did that, and the results were not good. Instead, what has been experimented with in small clinical trials at Johns Hopkins is BIPOLAR androgen therapy (BAT) - alternating periods of ADT with periods of high testosterone supplementation. The rationale for it and results so far are explained here:

pcnrv.blogspot.com/2016/09/...

There are some men who seem to do well with it, some men get resensitized to Zytiga or Xtandi, and some men have a negative response. They are trying to identify the men who it may help.

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Liebowitz had acceptable results--where are you getting your info from. His protocol required men to be PSA undetectable for 13 months before use of T. He did not receive 50% of the men staying Undetectable or having a doubling time of more than 9 months.

@ 25% of the men had long term success according to my memory---5% would be a win!

Read his book/and internal papers. The ? is which men will react positively? It is IMO a Pathology and Gene Mutational investigation to determine. Patrick j. Oshea is an excellent example of it working. He looks really good to me when I see him in person!

Nalakrats

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My information about Liebowitz comes from the data he published and which is linked in the above article. As you can read for yourself, he treated 98 men who had already received some treatment for PC but were hypogonadal after treatment. There were only 8 patients with distant metastases. The majority were low or intermediate risk and had inexplicably been treated with ADT only. 60% of those men progressed while receiving testosterone, and therapy was stopped. It did not in any way show that testosterone therapy is useful for men with metastatic disease.

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So you find no research that supports use of testosterone to treat advanced or metastatic prostate cancer.

Correct?

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In the link I gave, testosterone was successful in some men to treat metastatic PC when ALTERNATED with ADT. Read the link.

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quoting your reference:

"

Schweizer et al. conducted a pilot test at Johns Hopkins. They treated 16 asymptomatic men who were diagnosed a metastatic and castration-resistant. They were all still on ADT. "

Not alternating ADT. It continues.

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No. They alternate 3 months of ADT with 3 months of high-dose testosterone.

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ADT is continued, not suspended, in Denmeade's protocol at Hopkins.

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Tall Allen, Nice Blog:

pcnrv.blogspot.com/2016/09/...

This testosterone treatment is very scary.

Are there any U.S. Docs that are using this as part of their treatment protocols (as opposed to doing exotic one-off clinical trials)?

I noticed Dr. Drake's name in the Lancet. When I was looking for a Dr. Myers replacement I contacted his office, but he was focused on research and wasn't taking new patients then.

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I agree that it is scary. They carefully choose asymptomatic or minimally symptomatic men. Even so, many men progress on the therapy and there is no current way of predicting who will progress from who won't. That's why it should only be done as part of a clinical trial where patients are monitored very closely.

Michael Schweizer, the lead author, has since moved to UW Seattle, and he may be following the JH protocol - I really don't know.

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I recollect that either Patrick or Tall Allen take some form of testosterone supplementation.

Is that correct?

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I used T continuously from 2 years after diagnosis for 5-6 years. PSADT had been <6 months following RP & salvage radiation. PSA did not move for 6 months & then gradually. PSADT was >2 years for much of that period, but eventually shortened.

So I began alternating between T & castrate T (3 months each for about 6 years).

Because of the BAT research, I have now switched to the BAT monthly cycle. One month is not long enough for my PSA to fall to near zero. Can't say what my month-end trend is yet.

I was comfortable with the 3-month cycles.

-Patrick

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I use TRT - but I am cured.

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What is try?

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TRT=testosterone replacement therapy

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"I use TRT - but I am cured."

Please explain, If you are cured why use TRT? As a prophylactic to prevent the return of the cancer?

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Because my natural testosterone levels are too low. I feel better with normal testosterone levels.

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Any Good Urologist or MO who concentrates on Prostate Cancer will tell you that T does not cause Prostate Cancer. Having low T can!

Nalakrats

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Cause is a funny word. Testosterone suppression is the strongest treatment path available, and in use for the longest time.

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Yes after you get Pca--again T does not cause Pca--because a treatment for Pca is T suppression, does not mean it was causal.

This is the enigma many researchers have been trying to figure out for decades. We do know that men who have low T before getting Pca, are likely to get Pca.

Nalakrats

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My husband has low T

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Does he have Pca?

Nalakrats

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Aggressive PC? Yes

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Am I missing what you are asking--these short blurbs back and forth--I am confused, as this subject was on an old thread.

Nalakrats

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Hi heard Dr Dawn Lamaine of oregonio.com speak at a conference, her talk was on PCA and treatment. Her presentation stated that:

Castration therapy --> castration resistent PCA in some time, still PCA, just cancer morphs from one type to the other.

Without specific details her tactic was to alternate (as said above) the protocol.

I learned that cancer is not a static, is rather smart and adaptable. Starve one food source it learns (morphs) to consume what is available. I've heard the comment that PCA does not respond to the low carb/high fat paleo diet. I have not seen research, even if I did, it would have to say ALL PCA does not respond to low carb.

Applogies, I'm wandering to say all PCA variants responds indefinitely to androgen starvation also doesn't make sense from my info gleaned. Now? Where the heck are we re tests, strategies? I wish the better practitioners wrote more that we might pick apart.

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My experience is that of one. My PSA had been undetectable for 3 years; my T averaged 11 ng/dL during that time. Never went above 15. Quality of life was nonexistent and it was recommended that I begin TRT. Oncologist started me on Androgel about 10 months ago. Next blood test came back with T at 380ng/dL. Next month was 800 or so. But the second month the PSA became .1. Next month, .2. The PSA is increasing so far .1 per month. Not sure how far I want to go with it. The change in QOL has been extremely dramatic. I didn’t realize how bad the QOL was.

Is it worth it? I can’t say. It is hard to know that the cancer is gaining momentum and curiosity is would ADT slow it back down?

But, on the empirical evidence of one, the T does seem to be providing the PCA with some energy.

Alan

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So you are doing just straight testosterone, not bipolar where you alternate it?

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I’m doing just TRT. Purpose was nothing more than to provide some quality of life. I’m not sure how long my Oncologist wants to go with it. I will say that my QOL was as low as it could get!

Alan

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