I understand your castrate strategy in order to re-match the overexpressed AR equilibrium. It is rational.
By the way, what do you think happened in the bodies of people who recovered over time? A few PFS patirnts recovered within a couple of years unless their recovery stories are untruth. It seems difficult to explain it by decreasing androgen level caused by aging.
I think in many cases from the crash onwards other independent mechanisms in the body can likely adapt somewhat.
So in my case from 0 hours sleep per night after a year I could have broken sleep waking up every 30-60 minutes and sleeping total of 3-4 hours on a good night. What improved? I think not the root issue but maybe my ability to create the necessary sleep hormones to a certain extent.
In most cases of improvement I would say the body likely has adapted in certain ways and also the psychology of chronic conditions like this has its own twist.
Firstly, people find a new normal and can start to forget the pre-PFS state to varying degrees.
Secondly, people want it so bad and denial is part of the psychological path to acceptance. People lie or over-exaggerate and you end up with all sorts of red herrings.
Lastly, I’d say we all have different levels of severity. If I were to say my symptoms a lot of people in the forum would be shocked. Acceptance, the body adapting and moving forward is easier if your condition isn’t extreme.
Out of all the full recovery stories I have read I think only a few rare ones actually tick the right boxes to satisfy certain issues or vibes I pick out from the stories. In most cases we also see only mild symptoms.
I think in many cases from the crash onwards other independent mechanisms in the body can likely adapt somewhat
It is likely. Some efforts probably have been made to offset the negative effects of epigenetic distortion to some extent in a patch-up manner, not at the level of the distorted gene, but at various levels above it. If that so, it itself is only an adaptation of body to our distorted genes. I am sure that it is very possible. Perhaps, thousands of up- and downregurated gene expression which is observed in researches may be rather the very such efforts.
My insomnia is as bad as yours…
Out of all the full recovery stories I have read I think only a few rare ones actually tick the right boxes to satisfy certain issues or vibes I pick out from the stories. In most cases we also see only mild symptoms.
On one hand, in many cases their symptom is mild enough that their recovery could be explained by such adaption.
On the other hand, generally speaking, epigenetic modofication is not irreversible in itself. And as you said there are rare cases which is difficult to explain their recovery only by limited adaption.
Whether the (probably epigenetically induced) AR-overexpression is (naturally) reversible or not is the critical issue.
If it is irreversible, why? Even if it is epigenetic and stubborn, it should return to normal with time, unless some factor(X) prevent it.
If it is reversible, we can definitely make some efforts as a kind of rehabilitation to encourage its slow recovery process.
What do you think about it. It is irreversible modification?
We don’t know what factor is preventing reversal and even many decades of research has not found the reason for this in CRPC.
Dr Alfonso may find something. Analysing the full genome is a new approach.
In literature there are anomalies few and far between like we sometimes see on PH.
There are possibly non-natural ways in the future. Older HDACi drugs are no good but perhaps future more targeted ones may work.
I finished reading the article: Drug resistance in metastatic castration-resistant prostate cancer: an update…
Thank you for the introduction. This scientific knowledge is definitely important. It’s also extraordinarily high level, but we can understand the outline. What a destructive and disastrous state of affairs. It seems impossible to correct these distortions.
However, all events and alterations which happen under anti-androgen therapy are really rational in themselves. Yes, our body, life system is not irrational.
In the end, as for scientific research and development of treatment, we’ll just have to leave it up to the scientists. But, I wanna believe our body’s wise and potential to re-regulate itself. Is there any idea to encourage the body’s self-repair…?
Anyway, thank you for your instruction.
Best regards
To your third bullet point, I have a couple of questions.
Firstly, why do people have different levels of severity. Why isn’t it standardised as the drug is having the same mechanism of action for everyone (I accept its effectiveness can mean people from 1 pill or 1000 can have crazy bad symptoms in developing PFS)
Secondly assuming we all agree this gene silencing or expression change is it as simple as to say those with more symptoms thus severity have more genes affected than those who are very very mild PFS case (if such a thing exists)
Or maybe EVERYONE with PFS has all these genes affected but the predispositions in our genetic make up result in how mild or severe the symptoms are
I can’t think of anything that would encourage repair. There are supplements with some HDACi properties but the likelihood of them working at all is next to none and they like many other foods can crash people.
Encouraging more understanding is important because we could create more of a think tank and it would encourage efforts to support PFS Network and the science.
Keeping an eye on most recent papers as they come out is important. Who knows something might work and we could piggyback off whatever information is found.
AR expression varies across the body. It is higher in prostate, skin and brain tissues.
The differences between people result from a mixture of over expressed, highly expressed and normal expressed tissues. Which tissue has been impacted more varies between each individual.
Highly-expressed tissues can be seen from the hyper masculine effects e.g. increase MPB hair loss, increased sweating etc
Over-expressed tissues can be seen from loss of anything masculine in certain tissues as the AR does not function properly under normal hormone environment
I have noticed I tolerate alcohol extremely well if I have taken estradiol the same day.
I can finally feel drunk again.
I also suspect my gut to be an issue, and I have done 3 FMT.
No change, don’t bother.
Yes same exact experience. I can now get drunk again very easily since E.
Regarding the gut, gut issues appear to be a downstream effect because estrodiol also has mostly fixed my gut. Only as a treatment, but it works long term and treats all symptoms apart from erection quality which hasn’t changed much.
Edit - still some remaining gut issues but 70% better since using E. Overall I have only some gut and sexual issues remaining since treatment. Sexually the type of libido has changed but it is there and it wasn’t before E.
This is going from one of the worst cases e.g. extreme insomnia, worst imaginable IBS-D, genital / testicular / prostate pain, extreme disabling brain fog, slurring words, anhedonia, loss of energy, metabolic issues, food intolerances, fight / flight response, frequent urination without being able to fully relieve, dry skin, peripheral neuropathy, issues regulating body temperature and whole bunch of other symptoms.
I really want to try estradiol only for a period of time and have the courage to get off T and DHT, but I am so scared to get feminizing effects I can’t pull the trigger.
I am almost certain it would make my achy joints and my back feel a lot better, but I can’t risk turning into a woman.
Maybe adding HCG would correct that ?
Maybe makes turn into females only when they take estradiol WITH androgen blocker ?
Firstly, can I ask you how expensive the patches are for you? I imagine you have to buy them yourself off of grey zone pharma vendors.
Secondly … That article was interesting - I think you’re right that PFS is similar to that. I’ve read similar articles but concerning breast cancers (my issue has started after AIs so was looking more into estrogen-related stuff).
However I’m pessimistic with regards to most of the research about these things. This genome approach does not make sense to me as well.
All this research is to me very myopic and narrow-minded - but this to me is actually in line with how the academic-medical system functions in the capitalist system. The research has to produce very measurable results and it has to produce results that point to the possibility of creating new and marketable (profitable) drugs.
People with biochemical perspectives see these things differently.
People with cancers get cancers for very concrete reasons. It’s because their antioxidant systems and detox pathways don’t work. Glutathione-ascorbate cycle is impaired, possibly because of some bacterial and viral infections.
The methylation cycle is impaired in people with prostate cancers and demethylating enzymes do not work properly because they depend on a working glutathione-ascorbate cycle, iron and copper metabolism (ceruloplasmin metabolism – which does not work in people with chronic conditions because a working antioxidant and aldehyde system is needed), glutamate metabolism etc.
Of course that then adding these stupid castrating drugs will result in a disaster. Body will not be able to bounce back because it cannot undo the epigenetic changes (demethylases and TET don’t work properly). And the original offender of the cancer is not removed (still heavy metal toxicities exist, still some latent viral or bacterial infections exist and so on).
@Tyr
To me, your treatment is absolutely fantastic, especially considering the severity of your case. And I do agree with your point on the acceptance of this condition.
But I don’t agree that solving this mess is something best left to researchers. It is most assuredly not.
The big issue is that as it stands now people are left to experiment with high-risk protocols. Some recover, some get worse. We know that it is possible to recover from PFS, even some severe cases were recovered. But there will never be a one-pill treatment for this.
Tyr hasn’t turned into a woman, as we know haha.
If you’re on TRT then your HPA is inhibited enough to do a quick test of just E2.
If you feel too weird, just stop E2 and continue with test.
Also, for your trial, you also should try adding T3 to your protocol. So TRT/DHB+E2+T3.
And try to experiment with every RoA. Some people feel better on injections, some on creams, some on oral pills.
Probably has to do with how the body controls E1:E2 ratio and especially with the state of STS system (sulfate stores)
Further to this as fyi.
My latest experiences from trying androgens, rapidly worsening and then stopping and going back to just E2 has been that a sudden switch seems to occur 4-6 weeks after last injection of propionate form of androgen.
All the benefits I get seem to rapidly return like a switch. So maybe 4-6 weeks is needed for some who have just stopped TRT.
Re feminisation, I’ve not had much at all. Some improvements of my skin which I like. My face is super susceptible to changes in hormones, but a stable estrodiol dose has me looking very much still male.
That’s apart from fluctuations. I might experience short lasting feminisation for a day or two before that reverses.
I know one person who says he has used vials of E2 and no facial changes at all. They just have improvements in PFS. So facial changes are individual. If you also look at transgender communities, feminisation usually takes years.
If anything I actually want to be more femme, but PFS hinders that for sure and at times even more masculine than before!
@LazarusRy has seen my facial changes. He could say his observations.
Initially I purchased $60 vials of estradiol valerate from grey zone vendors. They also sell gels.
About 2 years ago now I explained the science to my GP, asked for an endocrinologist referral and explained to the endo. He couldn’t help because he “could lose his license prescribing E2 to a male”. I didn’t catch on until after I answered but he asked what gender I am in a very obvious way. If I had said female I suspect the outcome would be different.
I then managed to get a referral to a gender dysphoria specialist endocrinologist and didn’t mention PFS. I described gender dysphoria as a strong desire for the effects of estrodiol, i’m on estrodiol diy, and I’m non-binary. I was prescribed 2 x estradot 100mcg to be applied twice weekly.
For about 6 months now I’ve been using patches that were prescribed to me for gender dysphoria. They cost £10 per month as a national health prescription in the uk (all prescriptions cost the same one off fee).
Re your opinion on the research, I disagree. It would likely be extremely improbable that a more widespread approach to research would be fruitful. It would likely lead to the same red-herrings that CRPC has.
Regardless of cause / effect for many of our issues one of the potentially multiple cures is more than likely related to gene therapy of some sort. It is the top of the chain for many processes (a narrow but also a widespread approach) and Dr Anfonso has in mind the thought something abnormal will be found that is involved in the regulation of AR.
I’m more than pleasantly surprised with both the direction of PFS research and also the lead scientist.
I feel the title of this thread should change now lol.
Ha, smart, you did well for yourself.
About the research (just this, then we can finish this discussion) - 2 points. First, imo the genome approaches are the big thing right now, and they are so in an important part because they seem to reflect the progress of medical technology. (The big breakthrough in this field was the discovery of MTHFR gene mutations imo.) But to me, they are mostly a fine way to produce schizo-knowledge. Nothing actually actionable. This PFS research is hopefully gonna discover some important things (about the regulation of AR) but they will not discover anything that we cannot already hypothesize with decent confidence. Their approach to this is just an expression of how medical science currently constructs reality (decontextualizing) - it does not mean that it is the best approach.
I do think medical science must move in this “genome” direction but I also think that only in multiple decades will we be able to transform any of the potential discoveries into applicable treatments (which will be very expensive). But as of now, we already know enough to actually make a difference. This leads me to point 2.
My point was basically to say: in the context of how science operates now, it does not make sense to research things in a way that I vaguely suggested in the previous comment. This is a matter of politics of scientific research. My frustration is a response to this rigid politics.
If “science” did not operate in such a fragmentary fashion (multiplicity of disciplines reflect the bureaucratic impulse of the last two centuries), we wouldn’t ever have created such things as finasteride … That’s how I see it.
Ultimately I think the most important thing to note is that there is nothing about these syndromes that make them incurable in principle.
Yeah I get your point regarding the way science works in general not being optimal.
The information from the study will likely help decrease our time to an official gene therapy cure even if it doesn’t result in immediate actionable therapy. I don’t see a better way forward tbh. Maybe if we worked towards gaining official approval to trial other methods within CRPC research such as PARP or HDAC6 inhibitors.
We might be one of the first bunch of conditions to actually be cured with gene therapy within the next 1-3 decades. There may even be increased financial motivation to cure our condition genetically with there being a strong linkage to CRPC. We are like those patients but we haven’t got imminent death sentences, so perhaps better patients for a clinical trial of this sort? It may be important if we ever get to market our condition for funding for therapy. Full genome understanding would open up doors and be great in marketing it.
One possible benefit to genetically understanding this condition is other studies can piggyback off this and I would imagine it be possible to create an animal model with confirmed PFS.
We have to be forward thinking and the Alfonso study should be a part of our decision as to what is next. There is no benefit to debating the study itself anymore.
Yeah, definitely.
I agree with you.