Treating Prostate Cancer with Testosterone

[cesanon]

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

[gusgold]

telegraph.co.uk/science/201...

[pjoshea13]

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...

[Tall_Allen]

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.

[cesanon]

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

Is that correct?

[pjoshea13 in reply to cesanon]

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

[Tall_Allen in reply to cesanon]

I use TRT - but I am cured.

[cesanon in reply to Tall_Allen]

What is try?

[Tall_Allen in reply to cesanon]

TRT=testosterone replacement therapy

[cesanon in reply to Tall_Allen]

"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?

[Tall_Allen in reply to cesanon]

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

[Tall_Allen]

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.

[cesanon in reply to Tall_Allen]

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

Correct?

[Tall_Allen in reply to cesanon]

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

[Hidden in reply to Tall_Allen]

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.

[Tall_Allen in reply to Hidden]

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

[Hidden in reply to Hidden]

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

[cesanon in reply to Tall_Allen]

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.

[Tall_Allen in reply to cesanon]

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.

[Hidden]

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

[curt504a]

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.

[Kimmilemo]

My husband has low T

[Kimmilemo]

Aggressive PC? Yes

[agyoung]

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

[cesanon in reply to agyoung]

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

[agyoung in reply to cesanon]

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

[lewicki in reply to agyoung]

Hi Alan, Just read this. How are things going now. I am thinking of this should my cancer raise its ugly head.Thanks

[agyoung in reply to lewicki]

Hello lewicki,It’s going well with the quality of life. It took a while of using the Androgel to notice a difference and I can say it is huge. However, the PSA is climbing 0.1 each month. It seems to be a linear increase but I think that when I see Dr. Sartor in February he will probably have me quit using it and see if the T goes back to around 11 ng/dl. Hopefully it will and I won’t have to do the Lupron and Bicalutmide mess.

Not sure if I answered any questions but would be happy to.

[lewicki in reply to agyoung]

Hello AG, Thanks for the answers. I have been to Germany four times for AC-225 and LU-177. PSA is now 0.1. I have a oncologist willing to give me High T if and when my PSA starts going up So I think I read you are only on T ,no other drugs and continuous. How long have you been doing this and has your doctor written on this for me to read? I have not been on any ADT for 14 weeks and already I am felling much better. Testing PSA and T this coming Wednesday.

[agyoung in reply to lewicki]

Hello lewicki, Yea, I am using Androgel every morning. My T was around 80 ng/dl for about 4 years. I didn’t feel too badly. But for some reason it dropped to around 10-11 ng/dl and remained that way for about 3 years. That is when I began being “flat” emotionally, according to my oncologist, Dr. Sartor. He saw in me what I couldn’t see. I was quite uninvolved in life. Absolutely no energy, everything seemed to hurt ( bones in my legs primarily) and no drive or desire to do anything but survive. Dr. Sartor gave me the option for supplemental T to try to give me some quality of life, with us each knowing the PSA will rise. As he explained “do you want to live maybe 4 more years with zero quality of life or maybe two years with some quality of life”. I decided to try it. It took a while but I am amazed at the difference, for me at least. It is troubling to put that stuff on knowing that your PSA is climbing.

I am taking no other medication yet. I’m afraid because the PSA is climbing fairly rapidly that I will have to cease the Androgel and see if the T drops back down to a castrate level. If it doesn’t I gues it’s back to ADT that will hopefully work. For some guys not having T is quite debilitating. For others it doesn’t seem to be too bad. For me, it seemed ok at about 80 ng/dl but when it dropped to about 11ng/dl g ft or several years is when I became pretty much useless.

The high T regiment wasn’t discussed. Dr. Sartor just wanted me to have some QOL. He has said many times that I present a rather unusual case and he is not sure how to handle it.

I think that a very high T course can be beneficial in some people (at least according to what I have read. If you decide to go that way I hope it works very well for you.

As far as Dr. Sartor writing anything about my case I don’t know. I have been on Androgel going on 2.5 years, every day. The T came back quickly. First month it was 320 ng/dl, the second month was 838 ng/dl and stayed that way for several months and then dropped to around 230 ng/dl and that is typically what it has been to several years.

Your T may come back to a normal level after cessation of ADT. Mine never did. I think the testicles tried and finally went on permanent strike. Hopefully your T will return to normal and the PSA will stay at 0.1. That would be a great outcome.

I hope I have answered some of your questions.

Have a Happy New Year.

[lewicki in reply to agyoung]

Thanks for your reply. Most appreciated. Sometimes I wonder what I did to deserve this curse. I just keep smiling. Good luck to you.

[agyoung]

I guess one contribution to society is why I must have come down with it. My prostate is encased in wax as a display at the Tulane Cancer Center. They weren’t going to operate because they thought it was too advanced. Curiosity got the best of them and they wanted to see the thing. It was the size of a grapefruit. Hard as granite. 7 of the 12 biopsy needles were bent during the biopsy retrieval. The urologist said he had never seen that before. Anyway, that must be my contribution to society! All 12 cores were Gleason 5+4 except two that were 4+5. Crummy disease for sure.

Take care,

Alan

[lewicki in reply to agyoung]

With AI in the medical field perhaps a cure is around the corner for us.