The AR gene is absolutely affected it has to be if we’re still producing the same levels of hormones and don’t feel the effects anymore. Loss of smooth muscle all over my body speaks to that
I only have neurological side effects and my dht levels are normal.
Plus one of the studies already shows that some people With PFS have AR methylated and others don’t.
If it was that easy we’d all be undoing the mechanism at the AR gene right now. Unfortunately it’s deeper
Does it matter if AR is methylated or not? We re still producing DHT
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Genetics and epigenetic in solving medical issues has been nothing short of an colossal failure across the board with trillions of dollars spent and researchers now realizing it wasn’t what it was all cracked up to be
Who cares if DHT is being produced if it’s not not being RECEIVED by some of us? Yeah the AR, the dopamine receptor, acetylcholine, GABA, and whatever the fuck other receptors that are silenced or destroyed are kind of important.
Totally agree, but I’m just saying it’s incredibly incredibly incredibly unlikely the theory about “silenced” androgen receptors. I enjoy a healthy debate. Most of us still have pretty good signs of androgen receptors working. Also there has never been a case of androgen receptor silencing unless I am wrong. An old post made a good point that silencing of the AR would’ve been eaten up by big pharmaceutical companies and quick.
Also receptor silencing absolutely fails to explain why men feel worse on TRT and the temporary windows after certain events
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Well I have no signs of androgens working. Or dopamine. I have a numb, shrunken dick, no libido, no emotions, insomnia, memory loss, dry skin, etc. And drugs of all kinds (benzos, marijuana, alcohol, dopamine promoters) have little to no effect now. How is that explainable any other way? And unless there is actual, physical microscopic damage to some of us (not counting that out) the only possible explanation for why receptors aren’t replentishing (which receptors do) would be gene silencing. It’s obviously a genetic response being that 99.9% of people taking SSRIs, Propecia, or Accutane never experience permanent damage. And certainly not being completely destroyed physically, emotionally, cognitively, and sexually like I am or like the worst cases are. So idk man.
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I feel you, I’m the same way and my life is fucked legit 180. It’s just an absolute massive leap to suggest that all those receptors got “turned off”. We can PM more if u want and I can share my complete theory and maybe provide some hope but I realize ppl on here aren’t keen when others post comprehensive theories so I’ll leave it at that brother
i think its clear that other genes are methylated. though i just read your post where you said you disagree with that theroy.
i guess we will all have to just wait like we have been
Before I start I’m just going to say these are all my opinions, based on being here way too long.
I’ve read hundreds of theories and it took me years to believe any theory. Nothing has ever made sense to every part of my condition like this.
As it’s been stated here before there a types of PFS. Those who have the most severe type- (no windows, increasing and decreasing androgens worsening symptoms, dont respond to androgens properly anymore) are the ones who tend to agree with this hypersensitive theory. It fits in every way. I feel like those without these markers have a lot more flexibility trying to treat this and I completely understand why they don’t agree with the receptor theory.
This is an oversimplification. If you read the study it goes into the variables and what usually happens when there is an overall decrease in androgens (upregulatution). This is a quote from the study “these results are inconsistent with those presented in the available literature.” Studies unfortunately are not bulletproof. There is always studies that contradicting each other in almost every area. Studies done on rat brains are not comparable to ours or even monkeys. If you read lots of studies you will see these often contradict each other also. Methods, date of study and bias are also huge factors. Whether participants actually has PFS or just took the drug is a huge factor. Epigenetics goes a lot further than just up and downregulation of receptors (these things happen daily). The first study to have covered what we are talking about is Baylor so I’m not sure what all of these studies being talking about are. If I’m wrong please correct me with links.
This is untrue. This has been proven to be extremely hard to do. There are a lot of current studies based on trying to do this with CRISPR.
Same
As far as I know if is one of the main markers to why this is the theory, because the receptors are hypersensitized they continue to downregulate when exposed to testosterone for prolonged periods of time. You have lot of receptors so even if some of them are switched off the remaining receptors will still be doing the job, just not enough to reach your normal baseline.
You’re wrong. Receptors are silenced in many cancers. Hence the use of demethylating drugs. Also its a relatively new thing and hard for anyone to prove especially with rare disease. It could be the reason for a bunch of problems we don’t know about.
Hey Lakehouse, I actually read your story out of interest. I. guess you could say you were a little more lucky than some people here (you still got fucked obviously). My theory for you is still an epigenetic one. Different tissues can be effected differently by methylation etc. It is possible that only the tissue in your brain was effected due to previous epigenetic changes in your life or that you were born with. Just like different receptors in different brain regions can be hyper sensitised to mental or environmental changes. This is also why I believe in this theory so much, because it accounts for a lot of the variation we’re seeing.
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Right, the point I’m trying to make is, one thing is for sure, is that the AR gene isn’t at the root of it. Didn’t say that we would successfully reverse it, but would be attempting right at it with therapeutics.
We still have to dig deeper.
Yes I did get lucked out, though my emotional blunting does feel like torture and I did waste 5 years of my career
But never once felt suicidal and feel more positive than ever. Really wish everyone was in the same state of mind as myself.
As for most of your post, at this point I’ll assume you understand all this better than me from a technical level. I am just focusing on bigger picture
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Yes, I’m happy to agree to disagree along as there’s no misinformation going around. I would take being sexually disabled over blunting any day, so I feel your pain. I want more information also, hopefully soon.
How can you say you were “tortured” with emotional blunting but never once felt suicidal? I’m just trying to understand. It doesn’t seem to match.
Thanks for your response. Very knowledgeable. I guess I have trouble with the fact that receptors could downregulate that much. No other receptors in the body do that - that acutely. None. Additionally why they wouldn’t return via homeostasis doesn’t make sense.
I have special mental toughness 
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Oh okay
gotta exercise and eat a more nutritious, lower calorie, nutrient-dense diet. Those 2 things aren’t optional.
Wow thanks I had no idea…
Super simple concept my man. Executing it daily is the tough part 