Hey guys, this topic was only to briefly explain what is meant by methylation, which has been proven and reported site specifically in PFS patients already. Theories are therefore not relevant to the content here as this is just a basic mechanism of cellular biology. This ties into a broader framework most users don’t have, so therefore might be handy as it’s unlikely the last you’ll hear of it.
Regarding theories, the microbiome is almost certainly disturbed in PFS as both ADT and tissue AR dysregulation is proven to do so. I’ve linked to a study regarding this some time ago that I believe you recently posted. That is therefore supported by evidence as a plausible consequence, of which there are many, and is not a site-specific cellular mechanism nor is it capable of causing what we have seen for the past fifteen years.
@pvdl, as I’ve said we’re working on a project that should hopefully answer all your questions, but it’s taking some time as it has to be robust and comprehensive. There’s a lot to cover and it is simply not suitable for a forum post format. There’s a lot of recent science we haven’t discussed (as I’m considering submission to peer review) that we feel very significantly ties into the bigger picture. And whether you find it hard to believe or not, many of the most severely affected members took one pill or less. This includes myself. While a single epidemiological study of 5ari use in general found length of use of 5ari to increase risk of lasting erectile dysfunction, every single study of PFS that profiled symptoms with validated and as hoc instruments concluded that severity had no correlation to exposure in their samples. The entire reality of a post drug syndrome is out of the realms of what makes “common sense”, so I find it quite incredulous when people with at least some degree of lasting effects start picking at other members because to them it seems rather far fetched to them. Your case does not seem any less far fetched to the millions on this drug with no significant detrimental consequence to their quality of life, otherwise your doctor would be up in arms and no one would take it. It’s important to bear in mind there is obviously something different about susceptible patients, and significant variation within that. Many years ago Crisler phrased it as there being something about our endocrine systems that “is all set up to get broken” when he was explaining that he was repeatedly seeing patients with PFS who did not respond to treatment, and in layman’s terms that’s the long short of it. Precision medicine study by Cauci et al already correlated both exposure and PFS symptoms/severity to AR polymorphisms, so the “something” I mention is likely to be genomic, epigenomic or both. That’s why we’re taking a look at what we can ourselves with the 23andme project. It’s a serious long shot, but it’s worthwhile in the meantime.
Let’s keep this topic on track now as others can be started regarding unrelated stuff or theories.