How does that suggest that lack of 5ar2 is not causative for PFS, combined with your subsequent statements which seem to acknowledge that 5ar2 is not primarily responsible for neurosteroids?
Because the subsequent quote states that there was no correlation between methylation status of 5AR and any other symptoms either?
We next evaluated whether the clinical parameters reported earlier (18) were related to the SRD5A2
methylation status. No differences were observed in the degree of erectile dysfunction (P=0.362, Pearson’s chisquare test). Accordingly, the five international indexes of erectile function (IIEF-15) domains, identified as erectile function, orgasm, sexual desire, intercourse satisfaction and overall satisfaction, did not differ between groups
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That’s your second, independent reason, I thought. So your first reason, about 5ar2, is not relevant?
As for the second reason, no correlation between methylation status and symptoms - that could easily be explained if the people with unmethylated 5ar2 had symptoms secondary to a different reason. In other words, there may two types of PFS. I believe this conjecture is supported by a lot of other evidence as well.
An alternative explanation is that 5ar2 not in spinal fluid but in other tissues is primarily responsible for sexual dysfunction in PFS. Therefore, 5ar2 in spinal fluid will not be correlated with sexual dysfunction.
With my first point, I was clarifying that 5AR2 being a cause of PFS was unlikely to explain the mental symptoms people were facing (if they are caused by a deficiency in neurosteroids).
As for the second reason, no correlation between methylation status and symptoms - that could easily be explained if the people with unmethylated 5ar2 had symptoms secondary to a different reason. In other words, there may two types of PFS. I believe this conjecture is supported by a lot of other evidence as well.
Except that’s just speculation on your part. None of the research done on PFS patients so far explains that, and if we’re considering anecdotal experiences, neither does the vast majority of patient experiences (not all, but most). It is of the essence that we unite behind a single theory, not just because for research it’s the ideal scenario, but because it is what appears to be the most likely.
There’s an unbiased study that showed AR overexpression in the penile tissue of all the PFS patients it surveyed, and found a correlation between the degree of overexpression and symptom severity, why aren’t you giving that more weight in your thought process?
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Many of our symptoms relate to testosterone and dht deficiencies. What if the underlying issue is simply that our bodies couldn’t deal with dht suppression and became sick. No single switch to turn back on. We start by trying to restore correct methylation throughout the body that relates to testosterone and dht. We ensure that the body has correct amounts of testosterone and dht in all relevant tissues. Receptors should be functioning properly by correcting methylation. That’s a big task in itself.
Nobody knew that dht inhibitors could cause so much damage and nobody really knows what will happen if we try to undue the damage one step at a time. Melcangis work does not relate to every area of the body that’s been affected. I don’t believe we need to find the bottom of the rainbow to fix PFS and we won’t really know until we try.
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This is an old post, but some good points still. Receptors have always been the most promising theory, I just can’t believe 10 years later we still haven’t been able to test the methylation of these genes and regulating genes.
Because Andrew, if it were as simple as that a vast majority of people would’ve gotten better from Testosterone or DHT supplementation. And that hasn’t happened. For every guy who said he’s benefitted from it on this website, there are 10 who’ve either gotten worse or had no therapeutic benefit.
We need to unite under a single front. I’m not asking you to blindly have faith in it, but to look at all the information we have at hand and decide accordingly, so we can all live better lives sooner rather than later. If you look at the history of this place, you’ll see this debate has been going on forever. There’s people who believe in a theory because it’s convenient or because it happens to fit into one person’s symptom profile, and it causes more divide amongst the community.
We need more people to make this happen faster, but we all need to work towards a common goal. I see some members posting random studies and discussing the science like it’s going to make a difference. We’re past that stage, we have one strong theory that has so far, been supported by studies done on PFS patients and I think it would be prudent to apply Occam’s razor here. What we need to do is figure out what is different in us genetically/epigenetically compared to normal people. And the way to do that, is to conduct studies. The way to conduct studies is to get researchers interested in our problem, and the best way to do that is to strengthen the data set we have (i.e. the survey).
I know a lot of you have been ambivalent about the survey at best. Trust me, in the beginning, I was too. I didn’t even really understand the point of it besides, well, why not? But it’s what gets scientists/official bodies interested, so if you guys want to make this progress faster, figure out how we can get more people to take it. @Sibelio @Andrew35
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The simple reason is the Foundation studies were geared towards proving the existence of PFS with the goal of taking Fin off the market. We are simply spectators watching the latest episode of Foundation vs Merck.
We donated towards the Foundation studies because they cleverly tacked on a sentence or two saying they hope therapies would come from the studies. I feel like we got played on numerous levels.
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I have left out references to Dr’s and studies on Dht and T it’s been done enough already. While we don’t know for certain why the majority dont respond we could start with receptor expression and Methylation as a probable cause. Those who do respond to treatment likely have functioning receptors that can utilise Dht and T. We could run tests on these patients.
Sibelio has shown by applying dht to certain tissue that he was able to improve symptoms. So can we assume there is also a tissue problem that needs addressing which goes beyond the limitations of Melcangis study.
All of this costs money, money which we frankly, as a community, aren’t in abundance of. Which means that we’ve probably don’t have a ton of shots at getting this right, so we need to go with what’s most likely, and what makes the most sense.
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That’s seems like a lifetimes work. Before we took these androgen inhibitors I believe many of us functioned normally and well. Who is to say that we cannot function like that again if we restore methylation and receptor expression. We may have a genetic weakness to these drugs and nothing has really changed within us. So we restore the necessary functions, and continue living and obviously don’t take any substances that could recreate the effects of Finasteride. How many here would prefer that option over waiting a possible lifetime for the answer.
The first goal should be to restore health. The second is to achieve this following the path of least resistance.
I think we are all pretty much in alignment with our main theories on PFS. However some of us want to start addressing a possible solution while others want to know the route cause. It sounds like the testing for methylation will be cheaper than finding the route cause which requires 7 figure investment that can only be conducted by a limited number of researchers.
They are codependent goals Andrew.
There are plenty of supplements/drugs that people take that lower AR expression as a direct effect or a consequence, and that clearly does not fix the problem (permanently) for majority of people on this website. A lot tend to get some degree of relief temporarily, followed by a loss of efficacy, or some relief followed by a worsening of their condition.
Let’s make this very clear, I haven’t spoken to the other moderators but I believe they feel the same way. If there was a solution right now, we would take that. None of us want to go through PFS, and the main reason we want to understand it is because that is a prerequisite for safely treating it (or treating it at all). Not because we have a deep passion for steroid biology.
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I don’t know how methylation or demilitarization is related to brain damage.
I just don’t understand the connection.
We don’t know specifically how much AR expression is altered using supplements or we’re exactly is this being affected in the body. We don’t know how many receptors are affected it could be too many at once which the body cannot handle. So we’d look to focus on one receptor and have control over what we target.
We would be restoring normal function to the receptor this is not the same as using a supplement that could be influencing other parts of the body. It’s a blunt instrument. People get PFS in stages by going on and off the drug so it’s possible we could recover in stages.
We could also be sat here in 10 years time still discussing PFS theories. Progress has been slow over the past decade. That’s no attack at people here doing their best. People sat back and put their faith in others. That simply hasn’t worked and the community won’t get those 10 years back. We can go back and forth but I will leave it here, enough information has been exchanged for people to think about.
Thanks Borax for taking the time to respond you are a good guy and I always appreciate your help and support 
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I feel extremely annoyed and bored that I have to explain the same things a hundred times. I may do that, again, if and when I have the time and am in the mood. @borax
I don’t know why are you arguing here about something you don’t understand 
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It’s not because no one understands Sibelio, it’s because your hypothesis doesn’t hold up to scrutiny. It REQUIRES US TO SPECULATE A LOT MORE than the predominant one, and has literally ZERO EVIDENCE (no studies done on PFS patients to support it), which would’ve been fine if it at least supported all anecdotal experiences, but it doesn’t.
I’ve capitalized the important parts so hopefully, you don’t miss them.
You seem like a smart guy, and I don’t know how the issues I’ve raised haven’t changed your mind.
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Article discusses recent methods to improve safety.
Russia announces 1.7billion investment in gene editing.
Yi Li, a plant scientist at the University of Connecticut in Storrs, says that the programme’s launch is “a significant move” both for Russia and the world. He says that it could prompt China to invest more in gene-editing technologies, and help to fuel growing enthusiasm for such technologies in the United States. “For European countries, this can be a very interesting development in the light of the European court of justice ruling on genome editing,” he adds.