This is a further report on my self-administered experiments in Bipolar Androgen Therapy (BAT). Previous reports can be found on my profile and the last was: healthunlocked.com/advanced... . It summarised my previous experience with BAT and asked the question: “Is BAT repeatable?” (at least for me). The short answer is: not indefinitely. However there is a story to it and although it’s a sample of one it may be of interest to add to the store of anecdotal experience. It sure as hell ain’t gonna get a big definitive trial (no money in it).
Up until BAT my treatment was pretty much linear SOC: surgery, radiation, IADT, ADT. When the ADT failed (castrate resistant) news of the first Johns Hopkins phase 2 trials results caught my attention and I spoke to my medical advisers who pleaded that I should at least try bicalutamide first. (Note that I am not persuaded that BAT will not work with just ADT alone. Patrick has argued that the earlier you start using the bipolar phenomenon the better) Anyway the bicalutamide failed at 12 months and I decided to go ahead despite strong contrary advice. The treatment was simple: continue ADT, stop the antiandrogen (bicalutamide), wait about a month (to let the antiandrogen wash through), then a monthly intramuscular injection of 400mg Testosterone Cypionate, continue until PSA starts rising, then rechallenge with the antiandrogen. The testosterone phase lasted about 8 months, the rechallenge lasted about 6 months before failure.
The repeat was: stop bicalutamide, wait a month, then start T injections. You don’t do a PSA test after the first month, however the PSA after 2 months showed a meaningful increase, but not above my self imposed higher limit of PSA 4-5. I decided failure was imminent. As I had already done the 3rd T injection I waited 2 weeks for T levels to lower to normal physiological levels, then re-introduced the bicalutamide. PSA halved after 2 months then increased after 3 months. I concluded that my error had been in waiting until failure before going on to the next stage and that a better procedure may be to simply do 3 months of the BAT phase followed by 3 months of the rechallenge phase, rinse, repeat. My aim in future is to try to keep PSA within a 0-5 range, the range it has shown since castrate resistance first set in. However I suspect that BAT is nearing the end of its usefulness. I am trying currently for another repeat. So far BAT has prolonged the usefulness of bicalutamide by about an additional 21 months after the initial failure at 12 months. So an acceptable but not spectacular response. I doubt it can be repeated indefinitely.
It should be born in mind that the BAT treatment has so far been shown to be helpful in cases of resistance to abiraterone and enzalutamide. Mine is the first “experiment” I know of to use it to manage resistance to bicalutamide. I have not been exposed to abi or enza (or chemo for that matter). There are suggestions it may even help after docetaxal. That would not be surprising. Abi, enza and bicalutanide are all interventions along the so-called androgen axis, as is BAT itself, so it’s not surprising that there will be similarities in the mechanisms of resistance and the means of countering them. Chemo might seem to be another matter. However its becoming likely that our nasty adaptive critter only has a limited number of ways (maybe about 8) that it can adapt to unfavourable circumstances and there is a lot of overlap, so its quite possible that there may be similar strategies for resistance even when the mode of action (of eg androgen treatments vs chemo treatments) it is resisting can be quite different.
Something about estradiol (E2) is worth noting, thanks to the discussions of Patrick and Nal. I had not previously paid any attention to E2 but during the BAT phase I took a T and an E2 test a week or so after an injection when T is peaking. Yikes! My result was 163 however it’s not quite as bad as that. The result was in different units than used in the USA. Mine was 163 pmol/L, which roughly equals 44pg/mL, still uncomfortably high. PJ and Nal argue that 12-20 pg/mL should be the aim and if it gets above 30 then seek an aromatose inhibitor to reduce the level of E2 produced in response to increased T. (this is also discussed on body building sites) In my units, that range is about 40-70 pmol/L. I did an E2 test when T was lowest (just before the next injection) and it was in a comfortable 60-70 pmol/L zone. I spoke to my onco, who snarled what do you expect for playing with hormones and no, I am not going to prescribe Arimidex. (our relationship is under review from both sides)
However there a couple of over the counter aromatose inhibitors that I am trying during the next T phase. They are obviously nowhere near as powerful as the big pharma products (which have to be used very carefully by males). They are: indole 3 carbinol (I3C), di indoly methane (DIM), bitter melon extract (BME) and Chrysin. All have been discussed on HU posts. DIM is a metabolite of I3C but I think take both. Since bio availability is an issue I also think take them all (especially Chrysin) with bioperine or a similar nutrient absorption enhancer. We shall see how things go.
So: conclusion. BAT for me is a useful but limited means to control resistance to antiandrogen therapies. There is a high variability in individual responses to BAT. We don’t really know who it will help although most people so far have benefited in some way and generally very few have ended up any the worse for a carefully conducted BAT. I would suppose that my experience is fairly average at best. Many do better and some do worse than me. But small samples.
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kaptank
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Before switching to Arimidex, I was using chrysin successfully. The liver destroys a great deal of an oral dose, so it is important to take Bioperine (piperine) at the same time. Piperine inhibits the CYP3a4 enzyme.
Note that LEF's MiraForte uses chrysin (750 mg) & Bioperine (75 mg) to inhibit aromatase.
I have been on DIM-PRO 100 (Pure) twice a day since stopping ADT in March. T is 700+ now and my E2 just measured last week is 32 so either it is not enough or I need something else. I may try the BME and the Chrysin (with Bioperine) to see that helps. However, I do not anticipate another E2 test for a few months so next report will be awhile.
Patrick' suggestion above about LEF's Miraforte is useful - a more powerful pill. I made a mistake about BME. It's not an aromatose inhibitor but it is a natural PARP inhibitor that I take in the high T phase.
It is often said that patients shouldn't try to prescribe for themselves. That task should be left for experts. I kinda sorta agree with that but there's a problem. A lot of doctors are less expert than their MD degree might indicate they would be. I wonder how many oncologists remember the biochemistry and molecular biology they studied in college and med school, and how many of them have continued to study after they got out of school - sometimes 20, 30, or more years ago.
If you want to experiment with hormones I suggest that you be sure that your oncologist really understands them well enough to help you out. If, for example, your doctor can't explain the biochemical function of testosterone in prostate cancer other than to say "it feeds the cancer", he's not the guy to advise you on anything other than standard therapies.
One good place to look for oncologists who can do better than that is the research and teaching hospitals. See: cancer.gov/research/nci-rol...
Thanks Alan. Yes, even today textbooks repeat the "T is fuel for cancer" myth despite definitive evidence that it ain't the case and things are a good deal more complex.
Cesces, thanks for your concern. I am aware of the Dunning Kruger effect, the thesis that idiots generally have an elevated opinion of their own competence. However it applies more generally as a general characteristic of our whole species. I have been privileged to know maybe 3-4 genuine geniuses in various fields. Adding to a touch of Aspergers, they were all case studies in Dunning Kruger. That is how they became geniuses. They extended themselves way beyond their initial competence.
In my rather more humble case this experiment was not undertaken lightly. I have posted on this forum my reports and reasoning from start to now (see my profile). I thought it important to leave a record for others to learn from my mistakes. My risk analysis was deep and searching. I went in to this with eyes open and a good understanding of how things could go wrong and what to do. I had long and maybe heated arguments with my Onc. I investigated every point she made. Then I decided. The first few injections were with trembling hand.
I totally agree with the substance of your advice. Professional advice is essential, if it is available. In my case, it wasn't. No one wanted to know. There are compelling legal reasons for this where I am (Australia).
There is no treatment at our stage that does not have serious risks. This one has so far given me about 21 months I may not have had. My aim is to manage the bastard until I die of suffocation in the bosums of numerous well endowed ladies.
Thanks for that suicide thought j-o-h-n. Whoar Arrrrggggggggg.
There are all kinds of nuances you are almost certain to be missing.
And bat as I understand has a success rate of 25 to 50 percent.
You want a doc with experience reading for signs. This is sort of life and death.
You want a doc with oncology training and experience, who has done 20 or 30 bats.
You seem pretty bright. Listen to yourself:
"I have been privileged to know maybe 3-4 genuine geniuses in various fields. Adding to a touch of Aspergers, they were all case studies in Dunning Kruger."
I agree: human beings on average tend to overestimate their abilities. There is enormous variability in such self assessments. The best we can do is turn up the gain on our sceptical instincts and do as much research and risk assessment as we can as honestly as we can to stack the odds in our favour. I think BAT has much better "success" rate than 50% when rechallenge with previously failed antiandrogen is included. We can debate what we mean by "success" but I have noted that the great majority of "failures" were not proper BAT. eg many did not involve true supraphysiologic T and others were continuous T rather than the bipolar kind.
I regard the DK thesis as trivial. I do not say it is pseudo science but it is most definitely "folk science".
I don't think DK applies here. While some poor performers overestimate their ablities, the other part of DK is that succesful people tend to underestimate their abilities. I have known a few men who have self-treated with crazy protocols & quickly exited the stage, but others, as a logical reaction to poor survival odds for mPCa, have used complementary approaches to improve the odds. I think that is a sane response.
Putting aside the 'DNA double strand breaks' aspect of BAT, the great idea in BAT is that progression can be slowed or halted via short frequent periods of testosterone [T] restoration. This is an important concept for younger men faced with ADT-Abi-Enza failure within 5 years.
We know that the androgen axis often remains important in CRPC, which is why BAT (& Abi too) has some success even at that stage. However, where there are AR-V7 & similar cells, restoration of T will not control their progression.
If BAT is started along with ADT, there is a good chance that the mean-time-to-failure can be vastly improved, IMO. When BAT begins much later in the game, we must assume that cells no longer dependent on androgen or the AR axis will eventually come to dominate. The challenge is to target those cells while using BAT.
Patrick, I am coming around to your view about starting BAT with ADT. I looks to me to be a useful management tool to delay failure. I wish I knew what I now know when I first started ADT. Sadly the possibility of serious definitive trial is zero. It would be a brave doctor and a brave patient that would do it so early when the "T is cancer fuel" thesis is still in textbooks waiting to be quoted in court by the relatives of a dead patient. After all, we do have a terminal illness. Litigation against oncos for varying SOC has reached alarming levels here.
I encourage anyone who has done it to describe the results in HU to add to the anecdotal evidence.
"SPT produces a durable response in AR-pathway inhibitor ENZ CRPC that is associated with sustained suppression of ARv7 and E2F transcriptional outputs, and the DDR transcriptome, highlighting the potential of combination treatments that maintain suppression of these programs to drive a durable response to SPT."
Partial translation:
Supraphysiological testosterone produces a durable response in AR-pathway inhibitor ENZ CRPC that is associated with sustained suppression of AR-V7 (androgen receptor splice variant 7) and E2F (cell cycle activators) transcriptional outputs, and the DNA damage response transcriptome, highlighting the potential of combination treatments that maintain suppression of these programs to drive a durable response to supraphysiological testosterone.
Interesting that SPT seems to attack over multiple pathways (in vitro and in vivo). This is a review of high dose T experience and pathways. The authors make the point that so far there is only limited experience of truly supa physiological T. I've posted this before but it bears second and third readings.
Thank you again for posting your detailed and most informative post on self directed BAT. I also want to commend you on your courage to undertake the trial. Several months ago I asked my MO if he would support a trial of at least 2-3 cycles of BAT but received an unequivocal no - he became upset and said he would fight me on this issue and I believe would ask another MO to handle me.
I agree with you that waiting for failure may have contributed to a shorter period of BAT efficacy, but failure may have to be better defined. The following are my thoughts and opinions: waiting until the PSA increases from a baseline of 1, for example, to 3 may not be the same as going from 1 to 1.5. The latter may be considered “early” in the failure phase, whereas 3 may be “late”. Early detection requires that the PSA tests be performed more frequently (monthly) so that linear regression can be performed on 3 to 5 points and a reasonable trend (unfortunately always upward) confirmed with a correlation coefficient of 0.8 or better. The aforementioned assumes that there there is a good relationship between PSA level and population size of the resistant PCa cells. This would not be the case if the PCa is starting to acquire a more neuroendocrine character (and emitting less PSA).
I agree that the efficacy of BAT will vary from individual to individual, just as most people respond differently to the SOC therapies. I suspect that patients with gene repair defects will benefit more from BAT, because high doses of T while on ADT leads to DNA double strand breaks. Cells that have defects in repairing DNA die.
One question I have is whether you remained on Lupron throughout your BAT trials?
I will be conducting a trial with the COC protocol this fall and will be following the procedure I mentioned above.
Phil, there was no great science involved in deciding failure: 2 successive rises in PSA or 1 rise if it's large. (monthly PSA tests) I am now thinking its better to bail early than late.
Your suspicion is widely shared about DNA repair defects. There are trials going on now to combine BAT with PARP inhibitors. But there was a "super-responder" (PSA undetectable 2+ years out) in the early Johns Hopkins trials. There was nothing special about his DNA profile. BRAC2 and Pten (I think) but plenty of people with those didn't respond in that way, so who knows? My conclusion was that the best, cheapest and most accurate way to find out if you are responsive you are to BAT is just do it. Carefully with the help of a professional (if possible)
I continued ADT throughout (zolodex, similar to lupron)
In most developed countries there is a small but thriving black market for hormones of that type servicing the body building fraternity. More risk and more care needed. Usually a search of body building sites will give an idea of trusted suppliers. Often they have a private members section for discussing steroids. Not hard to join, usually free. One rule of thumb is that anyone NOT using bitcoin or the like for payment is almost certainly a rip off.
I now remember a previous post on HU (probably by you) about obtaining sources via the bodybuilding community. The bitcoin qualification is very interesting and allays my fear about quality. Much appreciated.
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