Can awors theory explain the fact that many people develop symptoms while on the drug? Or is it dependant on the postulation that symptoms only appear after quitting the drug?
Great info tyr…As before…Melcangi is trying to simplify the condition…I noticed he also attributed muscle wastage to metabolic disturbance but we know the over expression of ar in muscle will cause these changes etc…
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Finding a biomarker could be sig. faster than 20 years but the cure is another story completely.
Its my understanding after 10 years of just being here that pfs is caused by a combination of your specific genes…Ir gene clusters…So as years before here it was said the only way to determine this was to genetically engineer a mouse to be predisposed to develop pfs and then administer finasteride and withdraw…So…its the combo of genes that determines your pfs state as to what symptoms you get and to what degree…That has been the basis of understanding since awor…So maybe some of these rats accidentally developed the condition but how would you know? And how would you be sure as the condition has to persist for many months/years after withdrawal of finasteride and that is not what is done with these rats???
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Yesterday I looked at Altos Labs, a cell rejuvination/anti aging lab backed by bezos and others, that raised 3 billion in 2022. I felt that PFS is very similar to sped up aging (of course just another “stupid” theory), literally everything stops working in extreme cases and many sufferers are telling us that they feel like an old man. Possibly lots of bad/non functional epigenetic change happened quickly (like biological slop/littering), i.e. very similar to aging. Producing everything associated with old age: Slower metabolism, anxiety, bad concentration, no libido, fatique, collagen and bone loss in the face etc etc. Would be very interesting to see if long term PFS sufferers live sig. shorter than expected lives. But probably wont be studied, since nobody is tracking this. Also possibly PFS induced a permanent state, where the body is not able to rejuvinate and maintain bodily structures efficiently anymore, similar to the state of an old person, speeding up aging further and resulting in the deterioration of pathways/functions/nerves etc over time.
It could be that a real cure would need to come close to curing aging itself, a complete reversal of unnecessary epigentic “slop” /garbage induced by finasteride. Of course it could also be that its purely an adaptation to hormonal tinckering gone wrong, and that its easier to reverse than aging itself, if the body gets a kick from the outside, to induce it to recognize that it made a maladaption. How on earth would you however get the body to make the right change? How would you know what changes are needed? How would you safeguard against wrong changes being made? I.e. it kind of sounds a bit optimistic, more likely are thousands of changes that are hard to reverse. Very easy to destroy almost impossible to repair scenario. Especially if the disease destroys biological structures over time, i.e. due to the PFS state vital pathways are irreversibly damaged (then again you would literally need cell rejuvination anti aging tech to cure it).
I.e. my instinct here is that PFS is a disease so complex, it needs 22nd century technology to cure. Probably most diseases you need a form of complete cell rejuvination to truly cure, since the best we can do otherwise is to stop the disease from progressing, not reverse the done damage.
Anyways… hopefully the study in Finaland can enlighten us what genes make one suspectible to developing PFS. Just like with all these PFS studies however, 150 participants is not a lot for a genetic study. Ideally for a genetic study like that you would need 100x that amount (e.g. for studies on schizophrenia which has a sig. genetic component, they have 10s of thousands of participants). So we need some luck to find something.
The Kiel study only has 12 participants. Thats kind of study often gets dismissed, “too few participant”. I had that before with a doc when I showed him a PFS study, wouldnt even take it seriously due to the low number of participants.
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It’s me?
pardon me for my poor English.
observing from a functional point of view and judging from symptoms and known scientific knowledges, it seems to me that the violence of finasteride may attack all organs which relates to 5αRI and distort its cell’s program (epigenetically) and destroys its function permanently.
Depriving of 5α-reductase must be violent and destructive interference in the whole system and its harmony. Because 5α-redactase plays multiple fundamental roles in our body and has a great impact on the whole system through its homeostasis. So, the intervention definitely puts a vast burden on the system and harmony and brings huge distortion to its whole operation. Of course, our system has a flexibility to certain degree to keep its functions. But, there must be a limit. When the burden goes beyond the limit of endurance, the micro-structures which sustain various biological signals gets terribly deformed and loses their functions. (cf. Two-hit hypothesis) Such destructions may occur everywhere both in the brain and the body and at randum. Because our biological signaling system has a flexibility and its limitation and therefore all abnormal strong interference with biological signal can cause such destortions of fundamental structure, that is to say, various epigenetic dystortions . Overexpressed AR (more precisely, just as the AR system undergoes complex and bizarre transformation in the case of Castration Resistant Prostate Cancer, it is a epigenetically modified AR system that has lost its normal function) is the most decisive but one of such results.
If that so, there is no specific mechanism which causes pfs. Because if pfs had a core and key mechanism as the etiology of pfs, there should be a core and essential symptom which is directly brought about by the mechanism. Indeed the list of symtoms is limited and some of them are very popular, but we can not identify any symtom as such essential common symptom. Some patients never have sexual disorder, and others never experience insomnia. So, it seems to be simply damages of fundamental structure of our system. The only reason of its severity may be the fundamentality and cruciality of 5α-reductase. In this case, only the method of destruction, that is to say, depriving of 5AR is common. When we fire a shotgun at someone, no one knows in which the shot hits him.
I think, pfs is a kind of destruction: vast, indiscriminate, and epigenetical destruction of system; and the cause(=the violence of intaking and quiting finasteride) already had gone; unfortunately there is no cause longer and so we cannot cure it by removing the cause; there is only destructions as the result. Whatever the precise mechanism of pfs is (I really want to know it), apparently it is not difficult to imagine that it is impossible to repair this destructive damages by any artificial interference. it would be equivalent to put time back. the only chance (if it is possible) may be a self re-adjustment or re-regulation of our body through long time; only we can do is to encourage and not to disturb its process.
this is my image.
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I agree. There could be no rhyme or reason to it. Thousands of things could be destroyed. AR overexpression may be one of them but not the only one and also not the central switch. Its basically chaos theory in action. Thats why I think its akin to trying to cure aging. Its multicausal and parallel and self reinforcing. PFS has basically sped up processes typically seen with aging (“epigenetic drift”). Like with curing aging, you are trying to put back together a city, which has been severely damaged by a tornado/storm. Its theoretically possible but akin to turning back the clock. And imo this kind of tech will only arrive next century. I summarize this as the switch theory vs the chaos theory. The switch theory (awor), says that if you solve one central problem, the entire system will come back to health (AR overexpression). The chaos theory says that many parallel and independent but also self reinforcing parts have been randomly changed (epigentically), with no particular reason for it, other than that we were particularly vulnerable for drifting into epigentic chaos (akin to aging) via this outside “chemical attack”. Since its everywhere and random its essentially only curable by rejuvinating everything.
Chaos theory imo is what Melcangi is going with and its sig. more negative than switch theory.
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An analogy I keep coming back to is that of an ecosystem collapse. Finasteride didn’t just impact one component; it was like removing a keystone species. The initial, specific event—the epigenetic insult to the Androgen Receptor system that AWOR’s work points to—is the “switch.” That’s the extinction event. But the consequences aren’t linear. What follows is the “chaos”: the unpredictable collapse of the entire ecosystem. Predators starve, rivers get clogged with algae, invasive species take over. You can’t understand the full scope of the disaster by only studying the empty niche where the keystone species used to be. You have to study the whole broken system. This aligns with Melcangi’s work on neurosteroids, the gut, and inflammation; these are the downstream consequences of the foundational imbalance.
The problem is how to prove it. The scientifically ideal study—the one that would connect all the dots—is a logistical nightmare. You’d need to take tissue biopsies to confirm the AR dysregulation, draw cerebrospinal fluid to analyze neurosteroids and inflammation at the source, and profile the gut and blood all from the same large cohort of patients over time. Let’s be honest, this is practically a fantasy. It’s incredibly invasive, prohibitively expensive, and requires a level of institutional support that simply doesn’t exist for a controversial, unacknowledged condition. This is the great wall we’re up against, and it’s why progress is glacial and why the small, isolated studies, while important, never feel like they move the needle.
So, if that’s the reality, maybe we need to shift the goalposts. Maybe the immediate objective isn’t finding a “cure.” Maybe the most critical, immediate goal is just getting undeniable proof of the pathology. To get one properly funded study that moves the “persistent AR dysregulation” hypothesis from a compelling theory into a medically recognized, demonstrated mechanism of disease. That victory alone would change everything. It would end the gaslighting from the medical community and force the regulatory agencies and pharmaceutical companies to take this seriously.
From that foundation of proof we wouldn’t be looking for a magic bullet to reverse the entire ecosystem collapse overnight—the “22nd-century tech” sentiment is probably correct for that level of restoration. Instead, we could search for leverage points. Can we find a way to interrupt the most damaging feedback loops? Can we stabilize one part of the system to prevent further decline? It’s about damage control and symptom management based on the actual underlying pathology. It’s the difference between trying to regrow an ancient forest and simply stopping the fire from burning what’s left.
This is a grim, long-term fight. With a solid scientific foundation in maybe 10 or 20 years, no one would have to go through this with the added horror of being completely disbelieved and abandoned.
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Agreed - I think natural recovery as we’ve seen in some people in likely the only hope.
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Follow up interview with Prof. Roberto Melcangi. If he is working downstream then its of course not as potent as reverting the primary change (which could be androgen receptor related).
Natural recovery is a pipe dream for serious cases.
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Awor echoed the same sentiments back in 09…If it turns out a receptor related problem all we can do is try to give the body time and what it needs to recover naturally best it can…And support each other because the tech to intervene in such matters is not here yet basically…
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Natural recovery for many cases is not possible though. So for them its a bit annoying to keep hearing about it.
Tell me about it 
Melcangi is sounding like a nothing burger as well…
A slow deterioration is much more likely than a natural recovery for serious cases.
They should be able to test new treatments on PFS patients who have nothing to lose instead of waiting for so called ethical approval which could take many years.
I cant imagine any other drug could do as much damage to the body as Finasteride.
Over the years Ive taken many different drugs and treatments which have not caused me any long lasting harm unlike Finasteride.
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You’ve recovered a good amount correct?
pvdl, holyhead, I think both you are right.
On one hand, “Natural recovery is a pipe dream for serious cases.”
On the other hand, “all we can do is try to give the body time and what it needs to recover naturally best it can and support each other because the tech to intervene in such matters is not here yet basically.”
It is probably the conclusion we have reached from our many years of experience on this forum. It is the cruel reality. But we should not look away or escape from the reality.
Being a very serious case, I probably cannot live on. My insomnia is getting worse and worse. On the other hand, several Japanese patients I am in contact with had milder symptoms than I did, and after a few years, they have improved somewhat and returned to their daily lives.
It seems certain that our bodies have the ability to correct distortions to some extent over time. However, this ability is very weak, so improvements take a long time and are limited, and in severe cases, it seems to be relatively ineffective.
So, In a sense, the situation is simple. We have already been fundamentally destroyed, there is no room for medical treatment, and our remaining capacity for reconstruction is limited and weak. That is all.
I’ve recovered by over 70% but I still have problems.
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Yes I’m not saying you will recover with time…That is truly not the case for the majority of pfs sufferers…As I myself after 10 years am only worsening with time and am in a truly perilous state of health now with no job after years of contributing to both organizations and participating in all the data sets and genetic studies i could…
I’m just saying its the only option we have…
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