a doctor here took allo. he sourced Sage using his doctor credentials under research purposes from a lab
ended up getting negative effects from it
I think it is a stretch to say that Melcangi is working on a cure but I do agree that finasteride’s disactivating effects on allo’s neuroprotective properties very likely plays a large role in the pathomechanism of developing PFS, at least for many patients. He’s still doing fundamental research which I think means that he might not reach a cure or treatment in the near future but the research that his lab has done and the work of Marco Bortolato are really on the cutting edge.
Epigenetic research too is at the cutting edge but my sense is that epigenetic dysregulation of genes likely comes as a consequence of a traumatic injury caused by finasteride’s neuroprotective depletion.
I understand why it’s being done but I think it is disappointing that the official position of PH is negative on Melcangi’s research when I think all these approaches are complementary. I don’t think many of the criticisms are fair or accurate which is why I felt it was important to opine.
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Well it is unfortunate that your sense isn’t really a useful tool to gauge what is true and what isn’t. And you might want to get it recalibrated since people have been banging their heads on objects since the dawn of human civilization, yet there’s no recorded cases of people’s penises disintegrating as a result of this.
There’s nothing to be disappointed about. There is no need to make the focus of research any more broad than it needs to be, and that is all Melcangi’s work has been. Broad. Without any real insight since that study demonstrating a deficiency in neurosteroids. I do not consider any research on patient’s gut microbiota to be useful insight.
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Your post didn’t make any sense, just filled with dogmatic opinion and no logic or justification. Its a huge problem on this forum.
there is a lot of substance to the Melcangi research but you clearly haven’t spent the time or effort to look into much.
For the record though, by traumatic injury i did not mean physical impact. there are a million different things that can cause adverse neuronal changes. Any kind of stress (immune, mental, social etc) can cause changes. Finasteride blocks neurosteroid production as a primary effect of the drug (by 5-AR inhibition) and it can make patients vulnerable to all different kinds of neurological and physiological harm. the fact that certain neurosteroid levels were undetectable in the CSF of every patient tested is a very strong clue. Because finasteride directly impacts neurosteroid production, it is a very strong sign that it is involved in pathomechanism of the disease if they were persistently depleted in every sample tested.
i think you guys taking at face value everything you hear. I personally trust more a university experiment, leaded from researchers, insead of “doctor”.
Which allo did he take? He has been in hospital for 3 days as pregnant woman? Did he convice Sage to give him 30$k treatment for post partum depression for his PFS ? 
Melcangi also did a study on the 5-AR gene in CSF of PFS patients and found that 56% of the patient group had altered epigenetic methylation compared to control group of 8%. Highly significant results and it shows something impt it is only present in 1/2 of the PFS group so it begs a lot of questions. Epigenetic modification is most definitely involved in PFS but it isn’t the same for all patients so there needs to be a more unifying cause. It is notable that all patients showed impaired neurosteroid levels.
It isn’t clear what this current Melcangi study is about and there’s such a large bias here that people are rejecting the work without having relevant info and just making assumptions about it.
Nice straw man argument. Your claim is that epigenetic modifications can’t be a unifying cause simply because the modifications were heterogenous for that one gene. Claim doesn’t hold up since there are 1000s of genes. Why aren’t you looking at the study that looked at AR overexpression and found that it was present in all patients that were studied? Is that not notable for some reason? Or that Baylor’s analysis found widespread epigenetic dysregulation?
For the record, you are alarmingly lacking in self awareness.
Cool. Don’t think there are any reported cases of people having their penises disintegrate as a result of adverse neuronal changes caused by immune, mental or social stress.
that’s not what a straw man argument is. But there are many many things that can cause epigenetic changes so even if you assume that there is a universal and precise epigenetic change in all PFS patients then you need to figure out how that epigenetic change was created in the first place. Neurosteroid impairment combined with some kind of other catalyst can definitely explain that and makes a lot of sense when combined with many other circumstantial factors and evidence. they are also very clearly implicated in sexual functionality so yes, there is a very strong reason to believe that neurosteroid disturbances would be responsible for the main symptom seen in PFS (but many others too).
you’re still misunderstanding what I’m saying though. there are obviously many complexities involved in PFS or it wouldn’t have continued to be a mystery for decades. there could be an infinite number of stress factors in combination with the neurosteroid depletion that result in structural damage. there is a reason that PFS happens in a minority of patients that take PFS and obviously taking finasteride would have to be a necessary component to developing PFS. the interaction is what you are misunderstanding.
You are right - it is not a strawman argument. I have my logical fallacies mixed up because I am constantly seeing them on this forum.
No matter what way you spin it, the biggest issue with considering neurosteroid impairment as the root cause of this issue is that it does not explain how androgenic dependent issue literally disintegrates in some patients. Why consider an answer that can’t explain all the symptoms patients are experiencing, when there is an answer that does?
The jump from all of the negative effects of neurosteroid depletion to having androgen dependent tissue disintegrating is a huge one. I’d be willing to consider the possibility (and honestly inclined to, because it would make solving this problem a lot easier), but I don’t see how it’s possible to make that jump.
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I’m not sure exactly what you mean by ‘androgen dependent tissue disintegration’. But I would consider posing your question to Dr. Melcangi before assuming that the explanation does not exist.
Epigenetic modifications are a really hot new topic in biology and nearly everything will cause epigenetic modifications. Psychological stress or PtSD will cause epigenetic changes. I do think it is worth exploring PFS from every angle, obviously including epigenetic research, but I don’t think it makes sense to categorically reject neurosteroids other than competition for donations which I don’t even think is so practically relevant here. I think Melcangi’s studies will likely get funded without donations from the forum but I just don’t think it makes sense to categorically dismiss it.
Everything here is still largely in the exploratory phase and it will take a long time for the science to catch up here. I’ve been living with this for over a decade and have seen the pace at which things move so I’ve decided to focus on trying to bolster my health more holistically. I still have an interest in having the science get figured out though.
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Um. Allow me:
I’m not going to argue with you; I just want to say I’m frustrated we can’t agree about the obvious basics of our condition around here.
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It’s really hard to do that because there is so much diversity among people claiming to have PFS, there definitely may be multiple forms of PFS, and some ppl may be lumped in with PFS patients that have other problems unrelated to PFS.
We’ve identified a bunch of biomarkers in different studies. this is a multi-systemic illness so there will be a lot of interconnections that are going to be hard to discern and there may even be multiple causal factors required for PFS to develop in the first place.
Epigenetics seems very likely to be involved in some capacity though it is unclear yet in what way or how it may be treated if we identified a precise epigenetic issue. Some studies show biomarkers that are present in all PFS patients (like neurosteroid depletion) which warrants serious consideration and some show biomarkers present in some patients which would be more indicative of a correlation or indirect connection but definitely requires an explanation.
We have fairly strong epidemiological evidence and internal Merck evidence to show that this long term condition is real.
that seems to be the state of what everybody can really agree on today given the evidence. I happen to think there are a lot of strong causal mechanisms and evidence that show neurosteroid inhibition was a significant factor in causing PFS but there are strong reasons to believe that epigenetic modifications are involved as well. there isn’t enough evidence at this point to really say there is a clear path forward so I think it is foolish to close the door at this point on certain areas of explanation. I know people want to find answers and get to a cure as soon as possible but wishful and close-minded thinking will risk setbacks.
university research initiatives get corrupted all the time.
literally happened to us
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That’s like saying anger toward Merck is a biomarker of PFS.
Actually anger toward Merck is probably way more specific to PFS than neurosteroid depletion.
Anger is an emotion where allopregnanolone is a neurosteroid blocked by finasteride that was found to be undetectable in the CSF of PFS patients. I’m not sure what point you’re trying to make. If dht were undetectable in every single pfs patient in which it is measured (it isn’t), that too would be very notable.
So it’s better to follow all the ways indifferently and simultaneously? I agree with you in this.
We can’t figure it out what was wrong with us until we don’t try all the strategies
Guys, if you want to donate to the study…donate to the study. It’s pretty simple. Nobody is stopping you.
I’m not sure what this circular discussion is achieving.
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Guys, what about the research in Kiel? What is the reason for the delay? I read about 3 researchers who can help us there - it’s a strong and young team.
Is it really hard for us to find 12 sick people in Europe?
No, I’m asking without pretension.It’s just discouraging.