The issue at the forefront

I https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083487/

A total of 626 gene promoters, out of a total of 25,437 queried genes on the array (2.46%), showed significant differential methylation ( p < 0.01); among these, 272 were hypomethylated and 354 were hypermethylated in treated versus control.

Is it safe to assume looking at the Citalopram study that genes of ours have become both hyper and hypomethylated? If this is the case then does the body write a piece of code like software as such to keep these certain genes in this state? So that even the use of a demethylating agent would be useless. Or would they be kept in place because of the overexpression of the androgens receptors themselves that may be driving this condition where the body is caught in a negative feedback loop?

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I’d like more information on this aswell, unfortunately I think it’s all unknown. Everyone seems to be trying demethylation, which assumes hypermethylation is the issue. Wonder if I could contact the people that did the study and see if they have the information on which genes where hypo/hyper methylated.

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Some studies show upregulated AR and some show down regulated AR gene expression…

I think as the old saying goes…We’re up shit creek without a paddle…

Do you have sources for the downregulated gene expression?

Just posted here in my fluid retention thread…Rat study showed down regulation…

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People blindly assume that the AR gene has to be affected. This can be affecting us at 1 other random gene and give us all these different sides.

Moderators and foundation haven’t made that assumption

Problem at the receptor genes and genes that regulate them has always been my favourite theory as it’s the only one that makes sense to every stupid reaction I have. I think some of the moderators do have strong beliefs here.

Let’s try to avoid attaching negative labels and be kinder to each other. Giving people praise and encouragement costs nothing and might give someone a much needed lift. We need to do better as a community so we don’t repeat the all out war that occurred recently on AnhedonicApes (David’s) memorial post. Thanks guys :heart:

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I’m just saying that since we know the 5ar gene being methylated or not seems unreliable, that it’s good to focus on elsewhere

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