Also receptor silencing absolutely fails to explain why men feel worse on TRT and the temporary windows after certain events
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 arenāt replentishing (which receptors do) would be gene silencing. Itās 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.
I feel you, Iām the same way and my life is fucked legit 180. Itās just an absolute massive leap to suggest that all those receptors got āturned offā. 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 arenāt keen when others post comprehensive theories so Iāll 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 Iām just going to say these are all my opinions, based on being here way too long.
Iāve 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 itās 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 donāt 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 āthese results are inconsistent with those presented in the available literature.ā 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 Iām not sure what all of these studies being talking about are. If Iām 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.
Youāre 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 donāt 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 weāre seeing.
Right, the point Iām trying to make is, one thing is for sure, is that the AR gene isnāt at the root of it. Didnāt 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 Iāll assume you understand all this better than me from a technical level. I am just focusing on bigger picture
Yes, Iām happy to agree to disagree along as thereās 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 ātorturedā with emotional blunting but never once felt suicidal? Iām just trying to understand. It doesnāt 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 wouldnāt return via homeostasis doesnāt make sense.
I have special mental toughness
Oh okay
gotta exercise and eat a more nutritious, lower calorie, nutrient-dense diet. Those 2 things arenāt optional.
Wow thanks I had no ideaā¦
Super simple concept my man. Executing it daily is the tough part
I was a 160lb distance runner u really think thatās why Iām here for tips?? If thatās all pfs was I would have been gone from here years agoā¦my body is gone and another example of people who are affected entirely differently by this syndromeā¦No answers to these riddlesā¦
Not trying to discount your symptoms or story man. I donāt doubt any of it. I wouldnāt have believed any of this shit would be possible unless it happened to me, and it did. But what I am saying and what I am focusing on is that we have to be giving ourselves a fighting chance. Every time you eat something that is not healthy for you or rub chemicals on your body in the form of shampoo, body wash, etc, there should be alarm bells ringing in your head saying, āwhoah, what the hell are we doing?ā
Saying that, as long as Iāve been a member of this forum, Iāve received absolutely zero input or advice from you. Iāve asked you about your diet, exercise, Iāve asked you to talk on the phone, private messages, nothing.
But youāre right, my two cents about the diet and exercise was uncalled for and off-topic. Hope you are doing well man.
I guess the important thing to point out here that itās not just upregulation and downregulation. There has been a huge oversimplification of these things in the medical community which has lead to an understanding that is too basic that is subsequently hurting people. This idea that once you take the drug away the brain will just bounce back to the way it was before, itās harmful. The brain is way more complex then just increasing and decreasing the number or receptors. The theory here is the receptor is stuck being hypersensitised to the androgen due to the unnatural depletion. This means not only increasing the number or receptors but it increases its affinity and binding potential so more androgens bind to each receptor. Maybe a number of other ways also. Some sort of over expressed state. Receptors getting stuck in this state via epigenetic means is the problem at hand in line with this theory. This is causing a downstream silencing of the receptor upon any further stimulation for too long. No other receptors have been doing this because depleting androgens or neurotransmitters to this extent is not something that happens in nature. From what I know. Our brains tried to adapt and it messed us up.
No thats fine itās not directed at you personallyā¦I havenāt given you any advice because I donāt know anyā¦Iāve tried a multitude of things as you probably know myy long historyy hereā¦few things have helpedā¦
Ok now I know the part that confuses me. If itās overexpressed and hypersensitive wouldnāt that make u more responsive to androgens? Or are u saying androgens rush back in this overexpressed state and causes a massive down regulation? Thanks for explaining this stuff to me.
yes, if you donāt have enough receptors or they are silenced it doesnāt matter how sensitive they are to the androgen. You wonāt be getting enough.