SARMs with ARSIs: I apologize in... - Advanced Prostate...

Advanced Prostate Cancer

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SARMs with ARSIs

smurtaw profile image
67 Replies

I apologize in advance if some of this is poorly written. Xtandi is taking my brain and making it mush.

SARM = selective androgen receptor modulator. Rad-140 is a SARM with a 90:1 anabolic/androgenic ratio.

SPA = superphysiological androgens (roughly: total testosterone > 1500 ng/dl).

ARSI = androgen receptor signaling inhibitor. Examples: enzalutamide, darolutamide, apolutamide. Bicalutamide is a weaker older ARSI.

NPP: nandrolone propionate - an anabolic steroid.

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Many of us take SARMs during ADT to alleviate some of the side effects.

I have been doing this for the last year.

SARMs require open androgen receptors to work. In particular the ones in the skeletal muscles.

The one I have been using is 5 mg/day of Rad-140.

I have used Rad-140 with bicalutamide/Lupron, bicalutamide/Firmagon and Zytiga/Lupron. It has always worked to improve energy levels, provide some libido, and enhance muscle gain.

Recently I went on a Xtandi cycle (Xtandi/Lupron). Xtandi aggressively blocks the ARs. The 5 mg/day of Rad did not overcome the side effects of Xtandi. Muscle loss, fat gain, fatigue, aches and pains, lack of energy, and loss of libido. In a phrase low vitality. I feel as if I have aged 20 years in the last few weeks. It takes me a couple of hours in the morning to slowly get going. Hot bath, then massage, then cycling, and only then can I start a good workout. I have one more week to go and I hope that high testosterone will reverse this.

A side note: not many of us use NPP but it didn't seem to do anything either. It seems to work great if I use bicalutamide.

Speculations:

Any 2nd generation ARSI will exhibit the same interference.

Increasing the dose of the SARM to account for ARSI AR blocking might overcome the resistance. But will this also increase side effects? I would guess that it would.

Xtandi AR blocking is around 95%. Bicalutamide AR blocking is only 75-80% and this is possibly why the SARMs still work.

I tested out SARM effects on my PSA and had to use 50-100 mg/day to drive my PSAs up. It was very apparent - the jump was from 0.10 to 0.49 in a week. When I reduced the dose they went back down to 0.02.

Another note: the reason that I am doing a 4-week Xtandi cycle is in hopes of resensitizing my cancer to SPA. My PSA on high T cycles has been increasing cycle over cycle and hit 1.11 in the last cycle. I don't know what to make of this because my PSA on low cycles goes very low, very quickly. For example, on this cycle, my PSA went to 1.11 but then went to 0.09 within 2 weeks of reducing my androgens. In a few days, I'll have it measured again. It is at times like this that I could use input from an MO experienced in hormones and BAT.

My two questions are:

1. Since my PSA is going up on SPA cycle over cycle, but is going lower cycle over cycle during ADT what does this mean? Am I not sensitive to SPA any longer or are things going well since my PSA/scans/metrics are moving in the right direction?

2. If I am indeed losing SPA sensitivity, what should I expect to see if Xtandi resensitizes me? Will my SPA PSA be low again (0.2-0.3)?

67 Replies
Mrtroxely profile image
Mrtroxely

I was on xiandi enzalutamide for 2 weeks....For me chemo is more manageable....

smurtaw profile image
smurtaw in reply to Mrtroxely

Seems like for chemo there are more workarounds for QoL.

Mrtroxely profile image
Mrtroxely in reply to smurtaw

I know At some point I'll be revisiting xiandi/enzalutamide......

Justfor_ profile image
Justfor_

Don't know if you can make anything out of it, but my latest Bicalutamide dose halving to 25mg/week made my PSA go up and total T go down to 1600 from 2000 +/-10%. I am now on the nominal dose for 10 days to see what PSA will do.

smurtaw profile image
smurtaw in reply to Justfor_

What did your PSA go from and to and how fast?

Justfor_ profile image
Justfor_ in reply to smurtaw

Target PSA of 0.05 maintained for 6 months. Then, down to 0.036 for no apparent reason. Following monthly 0.03 (different lab). 1.5 month afterwards, at half dose, first lab 0.074, retest second lab 0.09.

Yingsang profile image
Yingsang in reply to Justfor_

What happened to your program of trying to find this constant blood state with Casodex. Your experimental work might be useful info for my Husband if he loses his undetectability. Some men use intermittent Lupron, going 3 months on and 3 off. Have only heard that initially it had been working. It is hard to keep up with a mostly full time job at the Clinic I work at.

Justfor_ profile image
Justfor_ in reply to Yingsang

Seems that my 1.5 months ago dose halving was a bad decision resulting in an out of range PSA rise. I can hypothesize two reasons for this: a) There is a min concentration level bellow which linearity is lost, sort of a hysterisis like effect. b) I have reached the point where Bicalutsmide stops working, instead reverses and feeds PCa. To discern between the two I am taking the nominal dose for 10 days after which I will have new labs. A PSA drop will weight in favour of hypothesis a) while a rise towards b). In a couple of days I will know better.

Yingsang profile image
Yingsang in reply to Justfor_

As a medical professional I was hoping for your success. As my husband one day may lose his low undetectability, and was again hoping that your experiment would work. There is one member doing intermittent Lupron. 2 months on and 2 months off. Not a lot of data. But initially working. Let me know if you obtain any breakthroughs.

KocoPr profile image
KocoPr

how long are you doing SPA for? Maybe shorten the cycle for a little while. Also try increasing the RAD 140 to 10mg to get rid of xtandi SEs. Im doing Osterine 10mg + cardarine 10mg along with Orgovyx and darolutamide. Neither Org/Daro crosses blood brain barrier so maybe you can try to get Orgovyx instead of lupron

After 6 months of ADT i have very minor side effects. Still it is scary doing n=1, but no matter what i do I will still become castrate resistance so I might as well have QOL

smurtaw profile image
smurtaw in reply to KocoPr

I started with 1–2-week cycles and eventually went to 1-2 months. Then back down to 1 week (this was my first one-week cycle and I was shocked at how fast my PSA rose).

I preferred Orgovyx but my insurance preferred cheaper stuff. I haven’t had any issues with Lupron. Perhaps there is an interaction with Xtandi?

I just increased the Rad. I’m going to try 20 mg/day for this last week. It’ll give me a data point.

In addition to having a much greater affinity to the ARs than bicalutamide, Xtandi also works in a few other ways. I don’t know how it restores SPA sensitivity outside of simply upregulating the number of ARs in response to a low T environment. But if that was the case, Zytiga should also work but it doesn’t. I also don’t know if all SARMs will suffer the same fate as Rad-140. Pseudo-SARMs like Cardarine and Stenabolic don’t act on the ARs, but I don’t know of any that help with joints and muscles.

I’ve done several 1-day SPA bursts (oral T undecanoate can be used - and for slightly longer pulses I use Androgel). My PSA reacted favorably. A caveat is that I never measured it during a cycle – only a measurement before the bursts and after they were done. If my SPA PSA is still high, I might try some more of them. Seems like I could do a fast pulse and at the top of the pulse compare the PSA change to my free T or DHT. That should allow me to determine the PSA expression increase per SPA level. We know that androgens increase PSA expression and Xtandi masks it. But how much? Xtandi supposedly masks it about 90% and the data that I have seen on testosterone shows a 5x increase for SPA. It can't be digital though and it would be nice to know the analog response. It would make PSA/cancer calculations SO much easier. Heck, I might find out that I'm concerned about my high SPA PSA levels for no reason at all. My SHBG is low and my total T was around 3000 so perhaps the increase in PSA was right in line with undetectable PSA on a low cycle. That would fall in line with my ADT PSAs and my rapid PSA decreases. Hope I'm making sense.

To quote Churchill, “A riddle wrapped in a mystery inside an enigma”.

Sometime you might want to add some SPA cycles to your ADT program. Try to stave off CRPC. Alternatively, you could wait for CRPC and then try BAT. The good thing about that is that we should have more data and most of it applies to CRPC men.

Like you, I'm very much about the QoL. Keeping this animal at bay is a big part of it though.

KocoPr profile image
KocoPr in reply to smurtaw

it is difficult to put myself in your analytical mind while im not actually going through your experiences with all your data points over specific time references! Lol!!! Hope that makes since hahaha.

All kidding aside you certainly could be making a mountain out of a mole hill.

When you do your cycles are you lengthening your ADT cycle while shortening your SPA cycles?

If you were becoming CRPC I can’t imagine enzalutamide creating it’s known AR mutations while on BAT. I also can’t see Your beast working around the any other ENZY non AR resistant pathways since your feeding the beast T enough to keep it slightly fed.

It certainly is a “A riddle wrapped in a mystery inside an enigma”.

smurtaw profile image
smurtaw in reply to KocoPr

When I do my cycles I typically do an ADT cycle for 4 to 6 weeks. It takes that long for my PSA to drop to low levels (<0.1). This time it went to 0.09 in two weeks. The velocity of the decrease is extreme (1.1 to 0.09 in 14 days).

I'll go you one step further. Instead of making a mountain out of a molehill, perhaps I am trying to make a volcano out of a lake.

I don't suspect that I am becoming CRPC. I was afraid that I was becoming resistant to SPA. That's how most men "fail" BAT. SPA no longer kills their androgen-insensitive cancer cells.

FWIW, I am failing to gut out the Xtandi. Perhaps it's hit me harder than most guys because I have joint pain that makes sleep difficult and sometimes impossible.

If I can find out how fast PCa can grow I can try to figure out how much my PSA is overexpressed from androgens. I hope it will be more apparent when my brain returns. Right now it is becoming hard to talk coherently. Hormones: powerful things!

Seasid profile image
Seasid in reply to smurtaw

Why do you have a joint pain? I also can't bend my knee fully but it is not so bad to disturb me during sleep, only if I am running, not even then.

Can you ask for MRI, or at least ultrasound of your painful joint?

I had the ultrasound and looks that nothing is really broken.

Maybe you have a tear in your ligaments? Can you ask your doctor or ask for referral to a specialist?

smurtaw profile image
smurtaw in reply to Seasid

I'm fairly sure it is Xtandi taking away all androgenic action that is needed for my joints. It started a week after starting Xtandi and then got worse. I took my last dose of Xtandi two days ago. Xtandi is still active in my body (about a week half-life). If I still feel pain in my joints in a few weeks I'll talk to my MO.

Seasid profile image
Seasid in reply to smurtaw

Maybe it is just a sign that Xtandi is working well? I don't really know. I am just concerned for you. You are trying lots of medication.

Maybe your body just need to adjust to the new drug, but you are doing cycles and it is impossible.

Maybe so many starting stopping is not good for you?

For how long you are on and for how long you are off?

I thing you said 1 month low testosterone and 3-4 months high testosterone.

But you also said that you are now doing rapid cycling? Like 1 week?

What's the purpose of this?

Are you monitoring the number of tumor cells circulating? How are you making a decision about the length of the cycle?

Some people do intermittent ADT.

You never came to the idea about that? Why not? Maybe you could give a break from the medication to your body?

My first MO wanted me on intermittent ADT, but I was to scared to do that with 15 bone mets in my spine etc.

Where are your mets?

Sometimes the cure is more dangerous than the disease.

TA said that BAT does not extend life.

I understand you.

When did you have a bone density scan?

Why don't you contact Dana Farber or similar just to see what will they say? You don't have to act on the advice.

That is why you are J because you set your goal and you want to achieve it with BAT.

smurtaw profile image
smurtaw in reply to Seasid

With all due respect to TA, I do not agree. In clinicals BAT was shown to resensitize most men to Xtandi. That alone is huge and extends life. And in clincals, it was shown that using Xtandi AFTER BAT extended the effectiveness of Xtandi (I don't recall the numbers but it was something extreme like 2 times as long). It even extended Zytiga. More clinical trials are in progress to investigate the Xtandi effectiveness. It resensitized once. If it can do it over and over. My MO and I think that if this can be done, for some of us PCa might become like diabetes. A treatable condition. Denmeade thinks it might work.

As of a few months ago I did not have any mets. No signs of cancer on a Pylarify scan. TMB decreasing. PSA decreasing. Bone density increasing. Liver enzymes decreasing but seem to be plateauing in the bottom half of the normal range.

I do not rule out intermittent ADT and have this as a backup plan (intermittent ADT/Zytiga with SARMs and possibly NPP). During the SPA phase of BAT I have 5-15x a week libido and muscle gain that I haven’t had since I was in my 30s. During the ADT phase of BAT I have 1-2x a week libido and muscle plateau.

Stopping and starting meds was hard for me when I did ADT in 2019. On SPA it seems like my body is almost impervious to side effects. But this time it was during the ADT phase and it hit me very hard.

I monitor PSA to determine when to end the ADT phase of BAT. Using CTCs would be interesting. I don’t think my insurance would go for having me test my CTCs every week though.

My SPA phase was 1-2 weeks, then progressed to 1-2 months, this time around it was 1 week. For the time being, I think I’m going to loosely align it with most BAT programs for 2 weeks. I’ll look at PSAs starting a week after SPA ends and enter the next SPA phase when my PSAs reach some predetermined level - I have a slowly rising bias in the threshold. Knock on wood, my PSAs on my last few cycles have cruised well below the threshold, and this time around they dropped below it in under 2 weeks.

In the future, I might do rapid cycling. There is some evidence that this might work. I’ve done it 8 times, and my PSA has gone down each time. I was doing 2-day cycles using oral testosterone undecanoate. I’m not convinced that my T went high enough so might go 7-day cycles using Androgel or even two-week cycles using propionate. Cena is using oral T undec in her BAT clinical. I think I am going to try to consult with her.

BAT is one therapy of 4 that I have done. I have another 14 in waiting (only half of them do not involve some form of BAT). Constant SPT was the best that I have done but only lasted 2 years. BAT is pretty darned good though. So, you are right, I do want to accomplish my 12-year goal with BAT. If I can't, I can't. But if I don't try, then, of course, I can't.

Seasid profile image
Seasid in reply to smurtaw

I am just curious what would an endocrinologist say about all this cycles to your body and endocrine system?

I understand that you feel more comfortable as your PSA is down. That is good for your cancer but is it the best for your body?

I am not saying that they (endocrinologists) know everything but still worth talking to them.

Maybe your cancer already died out? (I don't believe but hope)

If you would go back to normal life without ADT and BAT, what would happen?

You could always go back to ADT or BAT if you want and don't have symptoms.

You can use PSMA PET scan and FDG PET scan MRI to feel comfortable.

You should not rely on PSA alone.

That is why I am following you.

Professor Richard Epstein my first MO said that CTC test is rubbish. He had a fairly strong feeling about this.

I believe your goal is not to kill the cancer but to stay alive until the cure will be available.

I just warning you not to over medicate yourself.

Talk to an endocrinologist and contact Denmeade as soon as possible over an easy email.

smurtaw profile image
smurtaw in reply to Seasid

I don't think that Denmeade will help. I'm HSPC. Before I realized that he wouldn't be of any help I sent him a few e-mails and even called once. No replies. Soon after that I talked to a friend who was shut down cold by Denmeade. I think his response to anyone HSPC will be simply "don't do BAT. Have a nice day."

The hormonal swings are part of BAT.

Seasid profile image
Seasid in reply to smurtaw

Maybe he is right?

smurtaw profile image
smurtaw in reply to Seasid

Schweitzer, Lieberman, Morgentaler, and Friedman, and my own personal experience (PSA 0.17 down to 0.02, TMB dropping, Pylarify negative, MO telling me to continue because this is working) are wrong? Was the BATMAN trial done wrong or come to erroneous conclusions?

I appreciate what you are saying. Always entertain the possibility of being wrong and changing course (I had to learn the hard way during my hedge fund years). But there are reams of data showing that this is not correct. He admitted choosing to attack the CRPC SOC therapy space because "it is easier to get into". That tells me a lot.

So, yes, maybe he is right, but so far I haven't seen that his opinion is data backed.

Seasid profile image
Seasid in reply to smurtaw

I believe that he said it was never easier for him in his life until now to get funding for his work than for BAT. The grants are piling up.

smurtaw profile image
smurtaw in reply to Seasid

The VA is getting involved. BAT is spreading its wings. Hope to have more HSPC BAT trials soon.

cigafred profile image
cigafred in reply to smurtaw

Same experience with Denmeade, and no response from Antonarakes (sp) when he was still at JH. Tulane was welcoming and I saw Dr. Baratta there about BAT (he has since moved to somewhere in Ohio). Schweizer at U. of Washington was most welcoming but said it was unlikely he would prescribe BAT for anyone castrate sensitive (despite having done the BATMAN trial on the CS, as you know).

smurtaw profile image
smurtaw in reply to cigafred

Good info. I thought that Schweizer was a possibility. Perhaps Sena or Antonarakis (his receptionist said that he would consult with me).

Seasid profile image
Seasid in reply to smurtaw

The Strengths and Weaknesses of Bipolar Androgen

Therapy

A. Edward Friedman

Abstract: It has been shown that when the amount of intracellular androgen receptor in prostate cancer is

greatly amplified, such as in the cell line LNCaP 104-R2, then testosterone will stop the growth of those

cancer cells. This is the principle behind bipolar androgen therapy, which alternates amplifying

intracellular androgen receptors by using very low levels of testosterone with supraphysiologic levels of

testosterone. This approach has achieved some limited success in human patients. However, as these

cycles continue, some mutations are expected to arise that give the cancer cells a selective growth

advantage and lessen the effectiveness of bipolar androgen therapy.

CAMPSOUPS profile image
CAMPSOUPS in reply to Seasid

If you read this thoroughly from beginning to end I think you will better understand smurtaw's approach and will help you ask better questions.

onlinelibrary.wiley.com/doi...

Seasid profile image
Seasid in reply to CAMPSOUPS

Thanks I will try. There is a clinical trial offered to me in my local hospital in Darlinghurst, Sydney to do BAT but maybe in the future as at the moment I am reasonably fine.

My biggest concern now is that I turned osteoporotic. It looks that I have to work on that, but I am not in a big hurry.

smurtaw profile image
smurtaw in reply to Seasid

I was osteoporotic years ago and it was getting worse. It probably would be osteoarthritis by now. This was one of the reasons I went to BAT (many other reasons).

My BMD by DEXA scans has gone up for the first time in my life. Average is +5.20%. I'm now in the normal zone for the first time since in the last decade.

I wouldn't advise that you consider BAT without having an MO on board or being in a clinical trial. Outside of a clinical trial or without an MO I think it is an early option. My opinion is that if you have some headroom you can recover from a therapy gone wrong. Shooter1 had terrible results and didn't have the headroom to easily recover. Some of us have had great results. Seems like the earlier we get it started, the better the results. PJosh has been using some form of BAT for 16 years. He still isn't CRPC.

Seasid profile image
Seasid in reply to smurtaw

I believe that Creapure also help with the bone matrix not just BAT alone.I believe that the p51?? mutation comes later that is why the BAT is more successful later ones you are CRPC.

As TA said, Sadly BAT does not extend life.

I have a clinical trial running for BAT 400 m from my door step.

I am fine now but it can change

I would like to live in peace with my cancer. I will not push it too hard. I love the sleeping cancer concept.

My goal is not to kill my cancer just to live with it in peace. If you push too hard it will be a lost battle.

smurtaw profile image
smurtaw in reply to Seasid

It extends life. It resensitizes to Xtandi. It makes Zytiga and Xtandi work longer. You just have to know how to use it properly. Friedman and others think that earlier is better than waiting for CPRC and mutations to set in.

It has given me a minimum of 16 months of extra time before CRPC. I hope to be like PJosh and extend that for decades. SPA extended my time before CRPC by 2 years. So, we're looking at 3 1/2 years of extra time. Advanced HSPC -> CRPC time is about 2 years (range less than a year to many years). The median time for me is well past and still no sign of CRPC. Mayo predicted that I would have a 25% chance of being alive at this point in time and they expected hospitals, pain, progression, and radiation within the first year of my surgery (3 months max was their "guarantee").

But, and this is a big but, I started when I was HSPC. As Friedman says, it is optimal to start early and not wait for CRPC.

You have mets so I wouldn't advise it at this point.

Seasid profile image
Seasid in reply to smurtaw

It is like a religion. Either you believe or you not believe.

smurtaw profile image
smurtaw in reply to Seasid

Clinical trials aren't a religion to me.

A minimum of 3 1/2 years of CRPC delay is not a religion.

Xtandi resensitization in 75% of men is not a religion. Nor is the extended use of Zytiga and Xtandi.

Perhaps you are saying that you either believe in science or don't. I'm an INTJ so have little doubt that science is, well, science.

I've said it many times though, I don't think BAT is a good fit for you. It isn't for men with mets and is better suited for HSPC men or early CRPC men with wiggle room. We do not know who will respond and who will not. I was a responder. PJosh is a hyper-responder. MB is having success. But Shooter1 waited until his cancer had progressed. When he did BAT his cancer progressed rapidly.

Seasid profile image
Seasid in reply to smurtaw

I know that is a problem.

TA said that sadly BAT does not extend life.

Maybe you don't understand that way, but I did understand very clearly that BAT is inherently only useful for CRPC. And per definition not useful for HSPC.

I am very surprised that you didn't get it and I see it after reading only one page of information about BAT and a way how it works.

The idea of the BAT is to kill all the prostate cancer which adopted to the low testosterone levels by growing androgen receptors.

I am actually confused and surprised that you don't see it.

Seasid profile image
Seasid in reply to Seasid

This is the clinical trial in my local hospital in Darlinghurst:

clinicaltrials.gov/ct2/show...

smurtaw profile image
smurtaw in reply to Seasid

I read the clinical trials. They speak louder than any of us internet doctors; even the confused ones. Did you read BATMAN, updated BATMAN, RESTORE, TRANSFORMER, etc?

Seasid profile image
Seasid in reply to smurtaw

I don't understand your question. Could you please rephrase it?

You mean why do I see that BAT can only have effects when used during CRPC phase and not during HSPC phase?

During the CRPC phase the cancer androgen receptors are mutated and enlarged. Therefore killing the mutated prostate cancer is easy by providing them with lots of very high level so called supra physiological levels of testosterone.

During the HSPC phase the cancer is still not adopted to the low so called castrate levels of exogenous testosterone.

Please explain if I overlooked something. (Probably I did overlooked something?)

smurtaw profile image
smurtaw in reply to Seasid

Did you read BATMAN, updated BATMAN, RESTORE, TRANSFORMER, etc? I have posted them and many others many times. Go to clinicaltrials.gov. It would help you.

In a nutshell, ask yourself if you think that ARs are upregulated in a digital fashion? (10 ARs to say 1000 in a femtosecond). If your answer is no, then why do you think it is useless to attempt to delay CRPC? Go one step further and try to explain away BATMAN, Lieberman, Morgenthaler, Friedman and their results/studies.

Seasid profile image
Seasid in reply to smurtaw

I just started. Does BAT has toxicity on you?

smurtaw profile image
smurtaw in reply to Seasid

No. Just the opposite. Watch your hematocrit. Some men need to go through a simple procedure if it gets too high. Rare on BAT. Never happened to me during SPA or BAT.

Seasid profile image
Seasid in reply to smurtaw

Why is hematocrit rising?

What is the simple procedure if hematocrit starts to rise?

The cancer should be cured in real life with multimodal therapies exept when you are on a clinical trial but that is not a real life. Clinical trials are for science. You can't learn how to treat your cancer from a clinical trial alone.

Clinical trials try to figure out which therapy work.

Seasid profile image
Seasid in reply to Seasid

Don't focus on BAT only and on BAT clinical trials only if you want to cure your cancer.

You need a good doctor. Not me as i am only an internet doctor and I am now in my BAT phase learning and that is my baby.

smurtaw profile image
smurtaw in reply to Seasid

Hematocrit is the % of red blood cells by volume in your blood. It can start rising in response to high testosterone or androgens.

The simple procedure is medical phlebotomy (bloodletting). Or just give blood. I’ve never heard of it not working.

My hematocrit stayed normal throughout SPA and on BAT. But it is something to monitor.

Seasid profile image
Seasid in reply to smurtaw

Are you dehydrated? What is the underlying reason for the increase of the hematocrit?

What is a concerning level of the hematocrit?

I believe that people with an uncontrolled asthma have problems with the blood draw. Their blood has difficulty to flow.

smurtaw profile image
smurtaw in reply to Seasid

My hematocrit stayed normal throughout SPA and on BAT. It can start rising in response to high testosterone or androgens.

Seasid profile image
Seasid in reply to smurtaw

What do you think that is the underlying reason for hematocrit rise?

Do you stop breathing during the night when you sleep? Are you sweating, do you have a headache after waking up? Any indication for sleep apnea? How many times do you have to go to the toilet during the night? Do you have any other symptoms?

smurtaw profile image
smurtaw in reply to Seasid

My hematocrit stayed normal throughout SPA and on BAT.

Seasid profile image
Seasid in reply to smurtaw

Ok, I thought that it doesn't happen in a Femtosecond (fs).

How long did you try Supra physiological testosterone? You said during the first 2 years.

How long did you keep high your testosterone? After that you stopped for how long? Was it effective on your PSA? The mutated cancer dies and the PSA dropped?

smurtaw profile image
smurtaw in reply to Seasid

2 years. PSA <0.01 to 0.17. Then BAT for last 16 months. PSA down to 0.02.

Seasid profile image
Seasid in reply to smurtaw

What do you think about the BAT clinical trial in Sydney? I live there not so far away.

smurtaw profile image
smurtaw in reply to Seasid

Not bad if it is applicable to you. I rated it as a 4 on a scale of 1-10. I hope it pans out. If it was applicable to me and I felt I needed support I would certainly try to get in the trial.

The thing I see with it is that they are using enanthate. It will not clear. So they are going to essentially go high testosterone to lowish testosterone. The half-life is a little less than cypionate. But they are using 500 mg injections (probably to increase the high T pulse-width to match cypionate).

400 mg of cyp gets total testosterone from a high of around 2000 ng/dl down to 145 ng/dl during the cycle.

500 mg of enanthate gets total testosterone from about 2850 ng/dl to 155 ng/dl.

Each person’s biology is different and you can see that from the raw data from the trials. The cypionate numbers are what I observe in myself (when I did SPA and when I came off of it). These are just total testosterone numbers though. Free, bioavailable, and DHT are what are important. The free T and bioavailable T numbers are impacted heavily by SHBG. My SHBG is low so I get great free and bioavailable T numbers.

Seasid profile image
Seasid in reply to smurtaw

I am not an internet doctor. I am just trying to understand the purpose and usefulness of BAT etc. available to treat my cancer.

What worries me is that the cancer always finds it's way around.

And that lots of things even the best ones are only prolonging life by 4 months. Therefore to understand the best timing of any procedure is essential for me.

Does BAT has toxicity?

Seasid profile image
Seasid in reply to smurtaw

That is a problem that not everyone will be a responder.

We know that people with certain mutations (they usually develop later during the CRPC phase) will respond better.

In a BAT clinical trial in my local hospital they are taking people who developed that mutations. They will also administer them carboplatin chemotherapy.

I am fine with my results that I don't have visible mets.

If I develope visible mets (CRPC) I would SBRT that visible mets if it is possible to do so. Therefore I would kill the CRPC.

Ok, BAT is useful of course but we should be realistic that the cancer will find it's way to mutate out of control again.

That is a beauty of the cancer.

And even if we kill all the cancer with chemotherapy and radiation the remaining cancer stem cells will regrow the cancer again.

The new trend in oncology is that the aim is not to kill the cancer but to live with it. (I believe BAT is only one tool from a tool box). I believe combining therapies would be useful.

I am doing it but I am not bragging about it.

Seasid profile image
Seasid in reply to smurtaw

This is a BAT clinical trial in my local hospital:

clinicaltrials.gov/ct2/show...

Seasid profile image
Seasid in reply to smurtaw

I googled Friedman and ADT. Here is the result:

The Strengths and Weaknesses of Bipolar Androgen

Therapy

A. Edward Friedman

Abstract: It has been shown that when the amount of intracellular androgen receptor in prostate cancer is

greatly amplified, such as in the cell line LNCaP 104-R2, then testosterone will stop the growth of those

cancer cells. This is the principle behind bipolar androgen therapy, which alternates amplifying

intracellular androgen receptors by using very low levels of testosterone with supraphysiologic levels of

testosterone. This approach has achieved some limited success in human patients. However, as these

cycles continue, some mutations are expected to arise that give the cancer cells a selective growth

advantage and lessen the effectiveness of bipolar androgen therapy.

researchgate.net/publicatio...

smurtaw profile image
smurtaw in reply to Seasid

I use an aromatase inhibitor and started a 5ARI yesterday. My choice was finasteride so that I can switch gears if need be. Dutasteride is stronger but takes almost a half a year to wash out.

"However, it is possible to add other treatments to BAT in order to prevent the increase in ER-α and to kill PCa after the amount of mAR increases. In order to prevent the increase in ER-α, an aromatase inhibitor should be used to prevent E2 levels from getting high enough to give a selective growth advantage if the amount of ER-α increases. If mAR increases enough, this will avoid the apoptosis that otherwise would occur when exposed to BAT. A 5AR inhibitor can be used to reduce the total androgen binding to iAR and with sufficiently high levels of T thus cause the apoptosis expected to occur when there is much more binding to mAR than to iAR [14]. In theory, high levels of T along with a drug to block iAR plus an aromatase inhibitor should be even more effective, but no research has yet been published using this protocol."

Seasid profile image
Seasid in reply to CAMPSOUPS

I also Googled BAT. Here is a result:

The Strengths and Weaknesses of Bipolar Androgen

Therapy

A. Edward Friedman

Abstract: It has been shown that when the amount of intracellular androgen receptor in prostate cancer is

greatly amplified, such as in the cell line LNCaP 104-R2, then testosterone will stop the growth of those

cancer cells. This is the principle behind bipolar androgen therapy, which alternates amplifying

intracellular androgen receptors by using very low levels of testosterone with supraphysiologic levels of

testosterone. This approach has achieved some limited success in human patients. However, as these

cycles continue, some mutations are expected to arise that give the cancer cells a selective growth

advantage and lessen the effectiveness of bipolar androgen therapy.

researchgate.net/publicatio...

Seasid profile image
Seasid in reply to smurtaw

Do you have an endocrinologist? You are experimenting with hormones.

My MO referred me to the endocrinologist because I developed an osteoporosis 4 years on ADT (Degarelix).

He referred me to professor Greenfield here in Sydney, Darlinghurst, Australia to the st Vincent's Private Hospital.

I don't want to pay 550 A% to the consultation therefore I am waiting until February next year to see maybe his registra in a public hospital setting for free.

Here in Australia Enzalutamide is on PBS for free ones in your lifetime until it stops working.

After that even if you had a chemotherapy and the drug either Enzalutamide or something similar would start working again you can't get it for free anymore. Only ones in your lifetime!

Therefore I am saving money for that.

If you want you could maybe contact Professor Greenfield and ask him questions if you have any. He probably knows more than our average MO?

Or just contact someone in the USA or even Germany?

smurtaw profile image
smurtaw in reply to Seasid

Enzalutamide is free for me. I have commercial insurance (my wife's employer). With manufacturer assistance, my payment is $0.

Zytiga was $10 a month. Similar assistance but they didn't pick up 100% of the bill.

My first battle with hormones was ADT. I didn't want to lose more bone density. Estrogen was the way I went.

I had osteopenia since my first bone scan a decade ago and it continued getting worse. Last year I worked on it, my bone density increased by 5.20%, and I am back in the normal zone.

I used to ask my NMD about hormones (he used to be a bodybuilder, so hormones are like the English language to him). While a good endocrinologist should know more about hormones than I do, the way I use them is very niche. Someone involved in cutting-edge androgen/PCa research might be a better bet. I asked my MO for a consultation referral. It's been a few weeks, so I'll probably wait until my next appointment to ping her again.

Seasid profile image
Seasid in reply to smurtaw

Contact the endocrinologist recommended by my MO.

He is charging 550 A $ per consult.

Professor Greenfield ár St Vincents private hospital in Sydney, Darlinghurst, Australia.

Ok, he was recommended for my osteoporosis, but maybe he knows more.

Have a look a research paper what he is doing and make a decision.

KocoPr profile image
KocoPr in reply to smurtaw

I did not know that SPA is the predominant reason BAT fails. I always thought it was the ADT that failed to drop the PSA. So while on high T do you expect your PSA to drop at any time during that phase or that when your PSA climbs to a self imposed number and you jump back on ADT it doesn’t drop below your base threshold?

The other question is on joint pain.

I don’t know if your doing this, but take it easy on weight lifting while on ADT phase as your not feeding your muscles and ligaments and joints with T. Maybe You should try uping your RAD140 to 10mg to see if both less exercise and or more RAD140 helps.

I know when I dropped my Osterine and Cardarine from 10mg/day to 5 my loint pain started again. Presently on 10mg i have 0 pain.

smurtaw profile image
smurtaw in reply to KocoPr

I read in an article that SPA desensitization is the primary reason that BAT fails to work. That makes some sense to me because BAT requires both phases to work. Increase ARs on the ADT phase while controlling the growth of AR+ cells and then decrease ARs on the SPA phase while controlling the growth of AR- cells. I don’t know if that was proven though, and using my brain to think of things feels like trying to run through waist-high mud.

I don’t expect my PSA to drop during SPA. I’ve never seen it do that. PSA always goes up on SPA. In trials and in practice. SPA increases the expression of PSA per viable cell. Lab studies show it is about 5-7x. I’m not sure if that was a saturation point though or if higher and higher androgens would make the expression go up more and more.

I’ve looked at many PSA/T BAT charts and I don’t recall seeing one that is a funnel – higher highs and lower lows. That is what interests/scares/excites me. Is this working better than I could have ever anticipated? Or is it failing in a manner that will leave me incapacitated in months?

I was following a self-imposed number for PSA. I think I’ll change that to a constant duration and just focus on the ADT phase. I’m not knowledgeable enough to figure out what this inverted funnel means. I could speculate but that and $2 buys me a $2 cup of coffee. Xtandi brain isn’t helping. I vaguely recall that last night I told my wife about a theory I had to explain the higher-highs/lower-lows but I can’t remember it now.

Taking it easy on weightlifting is a given. I don’t have the energy, strength, or joint health for hard workouts.

I stopped the Xtandi and started bicalutamide. This ADT phase is over in a week. Until then I think I’ll try just light lifting with BFR bands. If I was going to use Xtandi again, I’ll try 10 mg/day of Ostarine. Perhaps it would work where Rad failed.

FlyJ profile image
FlyJ

I have often wondered and looked for data on the pharmacology of ARSI's to ascertain if SARM's might be useful while on ADT. You have given reference to their blocking strength "Xtandi AR blocking is around 95%. Bicalutamide AR blocking is only 75-80% and this is possibly why the SARMs still work". Can you tell me where you found that information?

smurtaw profile image
smurtaw in reply to FlyJ

I don't remember. I think I read it more than once but Xtandi mush brain...

If I find it I'll let you know.

I looked a lot and found this article that states that bicalutamide blocks 90-95% of DHT. Xtandi not only inhibits DHT more effectively, it also operates a few other ways. I went to the reference article and it referred me to another article - the reference did not exist. That makes me take this with a grain of salt.

Anti-androgen hormonal therapy for cancer and other diseases - ScienceDirect

sciencedirect.com/science/a...

SARMs didn't seem to do anything for me while I was on Xtandi and the joint pains were excruciating last night. I'm throwing in the towel and going to use bicalutamide/SARMs/NPP for the next week or so and then go high T.

MateoBeach profile image
MateoBeach

very good insight about the SARMs not being effective with deep AR blockade. I only use my (not a SARM) and Osterine while I am on my SPA cycles of modified BAT. This is to support body composition and strength program while on high T.

If I end up adding Nubeqa to during my castrate cycle (one month) I will not bother and just cruise through that period.

I think that your lowering PSA levels during castrate cycle show the program of mBAT is working well! Regardless of higher PSA during SPA periods. That is what it is supposed to be doing! Alternating competing sub populations of AR+ and AR -/resistant to maintain a constrained balance in the cancer ecosystem. Paul/MB

BTW I don’t even measure PSAs during SPA phases so far.

Seasid profile image
Seasid in reply to MateoBeach

Good

Seasid profile image
Seasid in reply to MateoBeach

The Strengths and Weaknesses of Bipolar Androgen

Therapy

A. Edward Friedman

Abstract: It has been shown that when the amount of intracellular androgen receptor in prostate cancer is

greatly amplified, such as in the cell line LNCaP 104-R2, then testosterone will stop the growth of those

cancer cells. This is the principle behind bipolar androgen therapy, which alternates amplifying

intracellular androgen receptors by using very low levels of testosterone with supraphysiologic levels of

testosterone. This approach has achieved some limited success in human patients. However, as these

cycles continue, some mutations are expected to arise that give the cancer cells a selective growth

advantage and lessen the effectiveness of bipolar androgen therapy.

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