What do you think of these supraphysiologic testosterone theories?

One road is:

SPT (supraphysiologic testosterone)

AI (aromatase inhibitor - blunts testosterone to estrogen conversion)

5-ARI (5-alpha reductase inhibitor. Blunts testosterone to DHT conversion)

Progesterone

palpable-prostate.blogspot....

[nobaday]

Thanks for the post RSH1. More data from clinical trials on high T and BAT needed to confirm/ reject the theories. Add some expensive drugs to T to encourage Big Pharma to join in.

My situation is 3 monthly Zoladex injections and 32 months of Abiraterone to keep many spine Mets in check.

Now Mets are growing ( again ) as per CT and MRI) EVEN THOUGH PSA still<0.1. As my MO does not think neuroendochrine, these are the leftover prostate cancer cells that thrive in a low T environment.

So what to do? Chemo is SOC. Lu177 I would jump at but have to travel and pay big time to get one dose, let alone 4! And still need PSMA scan to check PSMA avidity.

So I would love to try 400mg T ciprionate. But no MO will give it to symptomatic mCRPC patients, by my understanding. TA has said this too.

I have minor pain from growing soft tissue Mets, particularly at T9 to T12 on the mid spine pushing against nerves/ spine. I had spinal compression at diagnosis Nov 2017 so I recognize the pain.

I control the pain with Ibuprofen/ Tylenol. If I had more severe pain from high T I could stop and get out the opioids. But I have not got info/data on any actual cases with pain levels/any spinal compression/ affect of quick use of opioids if severe pain happens and Dara that high T could halt the growth of my soft tissue Mets.

[Hidden in reply to nobaday]

You might try contacting Sam Denmeade, Abraham Morgentaler, and Robert Liebowitz (Compassionate Oncology).

They might be able to help. At least you could get some info. Compassionate Oncology would probably want to do some SOC things before T. I think that Sam Denmeade is focused primarily on BAT. I don't know about Morgentaler. The work that I have seen from him is more SPT related.

I hear you. We need more RCTs to know what to do. As it is I am sort of self medicating. I've talked to several oncs and done some research and came up with my own SPT plan. I don't know if it works or if I've just been lucky so far. Been over a year with no issues (G9, T3, invasion of lymph nodes, etc).

[nobaday in reply to Hidden]

I might get through to Michael Schweitzer in Seattle. He was in a Q&A with Denmeade recently ( posted by George71. I think.Also he has a trial with T and Olaprib in Seattle (T and Big Ohzrma drug!).

I’m in Canada...with a COVID border closed for an easy 2 hour drive from my home in Vancouver). Apparently Zoom does not work for them.....yet!!!

We have to advocate for ourselves so good luck in your treatment decisions!

[kaptank in reply to nobaday]

Denmeade or Schwartz once talked about symptomatic pain and supra T. I don't have a ref. They generally screened out patients with symptoms of PCa but I remember that some of their early patients in BAT trials had what was thought to be arthritic pain at the start but later turned out to be bone mets at the end. Some (not all) had pain from the T injection. The pain went away as T reduced so after about 10 days they were OK. Interestingly, some of these patients elected to continue the trial and found no bad pain on subsequent injections.

[noahware in reply to kaptank]

Denmeade had said a few years back that the pain that resulted from T for these (few) men would sometimes occur within a matter of hours, so he suspected it was not some instantaneous activation of PC cells but more likely some sort of inflammatory response, but he really didn't know. If there is a more recent and more conclusive explanation for this pain, it would be interesting to check out links to any articles on that aspect of BAT that anyone here may be aware of.

[kaptank in reply to noahware]

Yes, the inflammatory response makes sense, which makes it controllable to a degree. There are anecdotal reports that supra T reduced existing bone met pain.

[Tall_Allen]

BAT is not crazy, but continuous is. It has been proven not to work except in some cases. They don't know how to identify those cases.

[Hidden in reply to Tall_Allen]

Perhaps by monitoring PSA? Seems like that is prudent, no matter what you are doing, radiation, chemo, surgery, diet, happy thoughts...

Everyone has always said that I'm a little crazy. Maybe lucky and crazy because SPT has given me almost two years when SOC docs at Mayo gave me 3 months.

Cheers!

[kaptank in reply to Hidden]

IF you are doing SPT then an aromatose inhibitor is essential. Arimidex needs to be carefully used and E2 tracked. Supplement AIs don't work so well. There is a host of info on body building sites. AIs are less important for BAT because of intermittent exposure to T. 5ARIs are a good idea and do no harm. I posted a while ago on T and adaptive pathways to resistance, there was some useful review literature.

healthunlocked.com/advanced...

Apart from E2 you need to track PSA monthly. If something goes wrong you need to be on it. What I did with BAT was set a PSA level and trend at which I concluded a failure had occurred. On reaching, discontinue and restart the last SOC (even if it had failed previously).

TA is right. We know very little about continuous SPT and PCa. I went with BAT due to an "excess of caution" - interweaving SOC with short sharp spikes of supra T didn't seem so risky on the evidence that had accumulated. There are theoretical reasons for continuous supra T being better depending on what are the predominant pathways of action of supra T in each individual case but we don't know how to clinically determine that. (eg switching off ARV7 vs double strand DNA breaks) The last reference in my post above (Mahommad et al) has a few pars on this. But in the final analysis, we really only have anecdotal data on continuous and precious little on BAT. There is lots still to be learned on how to combine and time supra T with SOC.

[Hidden in reply to kaptank]

I take an AI, cabergoline, 5-ARIs, and pregnenalone cream, among others.

uPSA, E2, DHT. T. SHBG, albumin, etc etc each month. Used to be once a week but been over a year so I've relaxed a little, I have PSA and PSADT thresholds. Multiple options driven by different thresholds. (a flow chart, if you will, to guide my decisions to make them as mechanical as possible - ex engineer and hedge fund money manager - critical for both fields)

TA is right that it is crazy? Mayo SOC uro and onc gave me 100% chance of 3 months, 40% chance of 5 years. 18% for 10 years. But only IF I did chemo, radiation, and Lupron. I watched my dad do all of those (sans Lupron). After 2 years he gave up and went into a hospice to die in peace. I felt it would be crazy to accept those treatments and odds. Essentially giving up as Patrick once said.

At one time my SOC onc thought it was crazy. She's watched however and doesn't seem to think it's crazy anymore. She told me flat out that she doesn't ever think I'll need to do ADT. And she recently talked me out of radiation. Her advice now is "do what you're doing because it's working". I consulted with a different onc and he used almost the exact same words.

Everyone has different views though and I'm sure that many would view SOC as the sane choice and deem my choices crazy.

[Tall_Allen in reply to Hidden]

Mayo docs certainly should not have given you an expiry date.

[Hidden in reply to Tall_Allen]

Not a hard date to death. 3 months to pain. 40% to get to 5 years, 18% for ten.

I decided not to quit so easily and looked for an alternative. SOC might be right about my life expectancy odds but it's been almost 2 years and I can now state that it is a fact that they were wrong about the 3 month "guarantee".

[kaptank in reply to Hidden]

Is continuous crazy? No, but it's risky given current knowledge. Depends on your attitude to risk. I agree with your advisers: if it works don't fix it. You seem to have thought this out well and you are setting fail limits and looking at what to do if they are reached. One thing: Although you do regular PSA, the gold standard test is radiological and you need Ga68PSMA PET or better scans to get an accurate picture every few years. Sometimes PSA doesn't accurately reflect what's going on and our Krazy Kritter is unpredictable. I assume all treatments must ultimately fail. That is just prudent. If I'm wrong then hallelujah and pass the snake.

Keep us informed about how this goes. It is important we exchange experiences which is what HU is about. We are learning as we go. Best wishes on your experiment of one.

[Hidden in reply to kaptank]

I agree that it is risky. The first time I injected my hands were shaking. I half expected to be in severe pain the following day and dead the next week. But the alternative was a living death for perhaps a year, perhaps longer.

I'll talk to my onc about PSMA scans.

Thanks and I will certainly keep people abreast of my progress or lack thereof.

And for all of us, PLEASE, PLEASE, PLEASE refrain from name calling. Think about it. Does calling people names or deriding their decisions make them more or less likely to listen to you. If your goal is to help, then help, diplomatically. And remember, at one time the fact that the earth was flat was equivalent to SOC. Took some time before the round earth became SOC. Same with estrogen for PCa but in reverse - used to be SOC. Now it's not. None of us, and I repeat, NONE of us, has a crystal ball and can determine exactly what works and what doesn't. If someone did, they'd be rich beyond imagine, and cancer would be cured.

[Robert_san in reply to Hidden]

In response to RSH1 and kaptank on monitoring uPSA and use of AI inhibitors...

Don't post much here as have not thought of myself as "advanced" (yet), though with my slowly rising post-RALP uPSA, may be joining the club down the road.

Thought you might like to see my uPSA charting, on which I have annotated that the times I have seen the wildest switches in my trends seem to be going on TRT injections, pausing/stopping them, or otherwise trying to play with my hormone levels through OTC approach.

Am not sure what it all means for me. Have been thinking it is related to my unifocal margin+, 3mm, Epstein graded at 3+3=6. Maybe the ups/downs of my T and estradiol is affecting the margin tissue? Will need to make a decision down the road whether to hit prostate bed with SRT, or wait and hope the scans get better so the true source can be located and zapped. Hopefully not micromets, but who knows.

Am not in a major city. Have been with my uro all the way--a City of Hope guy--he supported Morgentaler's ideas so was ok with giving me TRT after RALP. Even had nurse train me to self-inject. Cheap, and was easy to do. I was the one that got nervous and stopped it myself after uPSA rose. I did get an appt. with an endocrinologist after a nine-month wait. Jan '20. She was pretty anti-TRT for my case and didn't want to treat my (above standard range) E2, saying it wasn't bad enough yet. My self-treatment OTC attempt to get hormones in line didn't go so well. So have gone about as far as I can with it all.

Anyway, thought the data points might help someone.

i.imgur.com/zkKTzmu.jpg

[Hidden in reply to Robert_san]

I don't see a huge influence from TRT. Maybe but maybe not.

From the research I've seen it looks like you could divide serum test vs. PCa into 3 bins.

1) Low (castrate). Deprives PCa from some fuel. Eventually PCa adapts and you're CRPC. That's bad news and statistics say that the future might not be bright (but there are exceptions).

2) Medium - normal levels. Normal TRT would be included here. Bad for PCa. Gives it "food" and test isn't high enough to damage the PCa cells.

3) High - SPT. Some evidence that high levels might kill some PCa cells and keep it under control without CRPC happening.

What were your serum overall test, free, and bioavailable levels if I may ask?

And I target E2 between 15-25. I think that higher might be bad news. Lower is probably not desirable either because you could hurt yourself if you don't have enough E2.

I have some info about my particular SPT program on my blog: prostatecancer.health.blog/...

And all of this is of course my opinion. You might hear other opinions. Which is right? Is there only one way to skin a PCa cell? Are there any ways? I will readily admit that I do not conclusively know how to contain PCa, and based on the history of our medical care I suspect that nobody knows.

[Robert_san in reply to Hidden]

RSH1,

-------------------------------------------

"I don't see a huge influence from TRT"

Yeah, I'm just guessing, too. Morgentaler's saturation theory says TRT above castrate range will have "little to no" effect on PCa. Guess I may be in the "little" area - it is kinda hard to see, if there is a connection in my case. But my test readings were looking strange enough to spook me off TRT. Just didn't feel the docs had the whole picture of things. To reiterate, I live in a smaller town and not a top-flight institution like MDA/Mayo/MSK close by. And I really do not want to do SRT unless I have to.

-------------------------------------------

"What were your serum overall test, free, and bioavailable levels if I may ask?"

i.imgur.com/bbRL2e1.jpg

That is the chart I presented to endo at Jan. 2020 appt. As I said, she just kinda blew me off. She said, twice, that being on TRT for me would be like "adding fuel to the fire". And that my hormones *were* a little out of whack, but treating them would require a lot of med fine-tuning. My uro, as I stated, had no issues with my TRT. Funny that they are both in the same hospital system and just across street from each other.

-------------------------------------------

"I suspect that nobody knows." -- yeah, sadly, you are right, that is the case.

[Hidden in reply to Robert_san]

Looks like your testosterone is in the not great area of zone 2.

Estradiol is rather high. I don't think high estradiol is good for PCa. I'm surprised she said that dialing it in is hard. Maybe she meant other hormones?

All you'd need is a low dose AI to get it lower. You monitor your labs so it's amazingly simple.

But pretty much the story I got from most SOC docs though. Can't change cholesterol without a statin. No way to change RBC or WBC. Before I did estrogen ADT I talked to 4 SOC docs. They all said it wouldn't work. 5 months of undetectable T. Obviously worked. I saw another doctor afterwards and he said it was lab error! (20 measurements and 3 different labs?. Seriously?)

[Hidden in reply to kaptank]

Kap, could you comment on this: prostatecancer.health.blog/...

[kaptank in reply to Hidden]

Thanks, very interesting. I'm starting to see what you are trying to do: start on SPT, when/if it fails go to a long term BAT type arrangement of 1 month of continuous SPT, followed by a couple of months of of androgen blockage. Learning as you go. I agree with setting failure limits: very necessary. But there's no great reason to continue any treatment to failure. I think now cycle treatments regularly.

A couple of comments.

"On SPT you can not become CRPC ." Unfortunately we don't know that. It is perfectly possible that our Krazy Kritter can develop a work around for SPT just as it easily develops resistance to super low T. Certainly Denmeade et al have shown that their version of BAT usually fails after a time. In my case, about 8 months.

"Another option is to use testosterone propionate since it has a shorter half-life and should be eliminated in a week or so." DANGER DANGER!! This stuff has post injection pain like a kick in the thigh by a very angry bull. I've had both and I know. Body builders use it for short term sculpting and just "man up" to the pain. Definitely not for PCa patients.

I note you take abiraterone and I hypothesise that it has something to do with success so far. Avoiding resistance to abi is a good long term aim.

I concluded from my experiences trying to replicate the first overcoming of resistance to my androgen blocker was: don't wait for failure. Don't continue treatment until there is a definite uptrend. Stop after a month or 2 while things are going well and do the opposite, again for a few months, stopping, letting your antiandrogen wash through, then restart a SPT phase again. In your case the anti androgen is abi, so short half life and quickly washed through.

[podsart in reply to Tall_Allen]

As you might remember, I have been at supra T levels since starting Xtandi (been on only 3 pills per week for a long time now). I am trying to find anything related to supra T, including the failure cases. Any references would be appreciated.

Do you think that since my Supra T results apparently from the Xtandi, my situation is different than those who are introducing T from external sources?

I remember Dr Friedman discussing the need to use bio identical T if you want to T from external source. Do you think he’s correct?

[Hidden in reply to podsart]

Your super T is very different than SPT. Via Xtandi, you are blocking the androgen receptors but not blocking your T production. Therefore your T is going high but it is "useless" in a sense. That's why the serum level is high - not much can be taken up by ARs.

SPT relies on T interactions with the ARs. Xtandi (and Zytiga) block them. I'm on Zytiga and SPT. I know from what I feel like however (massive gym gains and very good libido) that the exogenous T is swamping out the blocking affects of Zytiga. When I was on Zytiga/Casodex/dutasteride I had almost zero libido and very little gym gains. But my serum T was over 2000.

As an aside, none of the doctors that I have talked to know what Zytiga is adding to the SPT program. The advice from two of them is essentially, ain't broke don't fix it.

I think Dr. Friedman might be correct wrt bio-identical T. Cypionate is one of the cheapest and most common testerones available. Testosterone cypionate-ester has an ester molecule and that allows it to be suspended easily in a solution. It is considered to be bio-identical once in the body (body strips the ester from the cyp). In contrast, there are many man-tweaked T drugs that are not natural forms of T. Their use is mainly for bodybuilding.

en.wikipedia.org/wiki/Testo...

Here are some links. I think that the youtube video with Morgentaler discusses some failures.

youtube.com/watch?v=wafNZV-...(Not working as expected?)

bmccancer.biomedcentral.com...

ncbi.nlm.nih.gov/pmc/articl...

sciencedirect.com/science/a...

academic.oup.com/carcin/art...

academic.oup.com/endo/artic...

cdmrp.army.mil/pcrp/researc...

grandroundsinurology.com/te...

medicalxpress.com/news/2019...

ncbi.nlm.nih.gov/pmc/articl...

frontiersin.org/articles/10...

molecular-cancer.biomedcent...

cancerres.aacrjournals.org/...

mdpi.com/2072-6694/9/12/166...

pubmed.ncbi.nlm.nih.gov/296...

onlinelibrary.wiley.com/doi...

pubmed.ncbi.nlm.nih.gov/312....

ncbi.nlm.nih.gov/pmc/articl...

Lots of info and videos here:

compassionateoncology.org/

There is some discussion about failures as well as successes.

But, again, with Xtandi, you're not doing SPT so these don't really apply to you.

Russ

[podsart in reply to Hidden]

Thanks for this treasure trove of related info

[Tall_Allen in reply to podsart]

Xtandi monotherapy keeps your cells from utilizing testosterone. It therefore accumulates in your serum. It is unusable, though. Very different.

[podsart in reply to Tall_Allen]

thanks

[nobaday in reply to Tall_Allen]

Hi TA

You seem to be calling continuous SPT crazy but you are not calling RSH1 crazy , RSH1 who seems to be benefitting greatly from his anecdotal SPT program.

I’m surprised because Usually you use great data and research to backup your comments. You say BAT is not crazy, yet the main high T of >1500 is the driver behind both SPT and BAT.

Do you think any of Denmeade, Liebowitz, Morgantaler or Schweitzer are crazy. They all appear to be involved in great high T research.

Have I misunderstood your comment?

[Tall_Allen in reply to nobaday]

Yes, you have completely misunderstood my comments and obviously misunderstand the different therapies involved. Here's why I wrote that:

prostatecancer.news/2016/09...

Anyone who follows the anecdotal report os a single patient who doesn't supply full data on his diagnosis is crazy as well, imho. No one knows what would have happened with a different strategy or what will happen in the future because of it. That's why God invented clinical trials.

[Hidden in reply to Tall_Allen]

Relying on one article? Have you read the case studies of Libowitz?

Many success stories. There are failures also. SOC therapies also have failures. Understanding how to integrate new procedures with old is important to beat this beast yet live the life intended for us. And that's what we're all trying to do and we all have different views of success (mine is to be a man, even if that means I check out in a year - been over a year so far and I'm still here).

[Tall_Allen in reply to Hidden]

I actually have followed it for a long time (those articles were written in 2016 and updated frequently). Liebowitz has published nothing since 2009 - I assume that's because his patients are dropping like flies. I wasn't aware that Morgentaler treated men with prostate cancer - do you have a reference? I'm glad that you are happy with this, but I think a patient would be crazy to follow your lead. You are just one patient, and it is not at all clear what your real situation is.

Men are men even without testosterone.

[Hidden in reply to Tall_Allen]

Not men in the bedroom or gym or wrestling mats. At least not 100% IMHO and experience. As I've said countless times, each person has their own definition. Yours is simply different than mine. Nothing wrong with that and please don't read anything into what I am writing.

That said, if 6 months of ADT would guarantee me 30 additional years. I'd do it because I could gut out being a woman for half a year in exchange for being a man for 30. But Mayo couldn't even guarantee 50% odds of living 5 years. No thanks!

Also, I am one patient, with one phenotype/genotype. I've been pretty clear about my staging, prognosis, and history. I also have them clearly laid out in my blog. I send that info to anyone who asks. I hesitate to call someone crazy simply because they choose to try something that I disagree with. And I don't think that it is logical to say that I am the only person in the history of the world who has done SPT with some success. If this were the case, then perhaps I would indeed be one isolated case. But it's not so I'm not.

Everyone is entitled to their own opinion. Since yours is "crazy" unless that opinion adheres to RCT and SOC so be it I guess. Personally, I try hard not to judge others. My opinion was that it would have been crazy for me to continue ADT knowing how much Jiu-Jitsu, weight lifting, and sex mean to me (as you can see, I judge myself but if you go through my posts you'll see that I try not to judge others).

[George71]

SPT is not a shot in the dark by any means in my opinion, Dr. Leibowitz and Dr. Morgantaler have been doing it successfully for 20 years... I've posted their videos --.

[Hidden in reply to George71]

Of course you know I agree. Otherwise I would have tried something else. My plan is actually a BAT plan but with an indeterminate high phase driven by thresholds. And my plan isn't strictly BAT because there are other steps I'll take if certain PSA and PSADT thresholds are exceeded. But if all else fails, as a last ditch, I'll go into a low phase.

I started low for 6 months, went high, haven't met any thresholds so am continuing high and it's been over a year.

[George71]

Yes of course -- thats why you are doing it -- I was commenting in support of your plan .. I am not sure others realize the distinction you are making -- it isn't IADT or BAT in the traditional sense --- what you are doing is much better IMO ... ... when rotating off and on BAT every month or (3 months) on a timed schedule ... each time you are on the ADT cycle you are moving slowly toward CRPC. where as -- staying on super high T you may never have to go to the on ADT cycle for years or at all.

Even a slow crawling PSA increase if slow enough will take decades to matter,,, meantime new immuno therapies are being developed as we speak.

IADT is similar but it only stops the ADT and waits for your T to return slowly over months (if at all) --- that is when any remaining PCa cells recover and survive -- whereas if SPT had been initiated immediately at the start of the off cycle they may go years with SPT and choke off the remaining PCA cells and PCa cells may never be able to regroup... as Dr. Khera's study showed..

What you are doing has a much greater chance of success for the reasons just stated ... I know you know this -- thats why you are doing it the way you are.

[Hidden in reply to George71]

Thanks George. I know you support SPT if done logically.

I'm hoping that the high cycle lasts until I die of old age. But if I ever feel that I need to go into a low cycle, it falls out of my flowchart. And of course there is some possibility that SOC may include a new powerful treatment (given the progress since the "war on cancer" in the 70's I'd say unfortunately that this is not something I want to rely on).

[j-o-h-n]

I would like to make a comment.... but I lost my place....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 10/13/2020 9:30 PM DST