Reversing silenced AR signal with demethylating agents - A promising treatment option?

Therapeutic Efforts Pharmaceutical
#441

Would like to bring attention back to this thread.

Are inflammation and methylation linked at all? Seems so.

onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2007.01777.x/full
ncbi.nlm.nih.gov/pmc/articles/PMC1868290/
clincancerres.aacrjournals.org/content/12/3/989.short
cancerres.aacrjournals.org/content/68/24/10280.short
cancerres.aacrjournals.org/content/67/12/5583.short
cancerres.aacrjournals.org/content/61/9/3573.short
carcin.oxfordjournals.org/content/26/7/1170.short
clincancerres.aacrjournals.org/content/8/2/514.short
springerlink.com/content/5nm52p7474w61251/

#442

[b]We cannot be insensitive to androgen (no matter what the cause may be). If that was the case, then:

  1. why do most of us have low T? The hypothalamus should sense little T and ask for more.

  2. why can somebody grow muscles on TRT/clomid (me, moonman1)?

  3. why are some people growing excessive body hair or having an increase in hair loss? If your answer is that the receptors are hypersensitive, then why don’t we have a hyperlibido?

  4. why has never awor replied to question 1, which I asked several times to him in different threads?[/b]

  5. a) The body downregulate the T to protect the cells. b) shrunken balls produce less T.

  6. Simple, cause we have div. types of 5AR and div. cell types. This is why your head doenst look like your balls. Everybody nearly has the same symptoms mostly on tne sexual part, that depent most on 5AR2. People born with a 5AR2 defici also have no problem to build up muscels. Here work other androgens, like not all have brainfog. But sometimes even a 5AR2I inhibits a part of 5AR1 too. Same for people who took accutane. This inhibits more 5AR1 but can also inhibit a part of 5AR2 thes have not so hard sexual sides, but more mental.
    Some is still working but some not, we need to find out, what is and what not. Clomid and TRT raises the Androgenlevels very high so, that a remaining part still work. But for most the effect wore off, guess why? Because the cells protect themself.
    3)If the cells are not affeced, why shall they do? look answer 2. I would say, short before the “crash” everything that raises so much up, so when you have short before the crash a super high libido, more than you had before, you can be sure this will dorp down.

  7. Honestly, because he dont have to. While studys are in proces, he cant tell to much here in a Forum and anyway, some things have to be profen first. Also, he dont have to justify. We could be happy, that someone is doing what he is doing. If anybody have other theorys, go head and prof them. For now I would say, we all are sitting in one Hell, so we should need to work together and not to fight! Only when we all work on this, and im very very sure everybody of you want a cure, we all need to give our best, to support the only real studdy on this damm PFS. Everbody can help, reading and finding stuff, looking, what can be uselfull or not, klinical findings, spending money, making it public, helping with studies, when they know some scientist, or helping as probant for the study´s. We all can do something but only if we work as a Team. IT IS TIME FOR A CHANCE!!! Please help me with the natural supp list. :exclamation:

#443

Hi Brainbug. Glad you have been thinking about things and reached the same conclusions as me.

Truth is nobody should pretend they are an expert in epigenetics. However I would add; 5) the fact is ‘PFS’ has never been recorded in 50yrs of intensive study of androgens and androgen receptors.

I think we CAN be insensitive to androgens, not in the way awor describes, but due to a pre-receptor problem;

1.) We know during the ‘crash’ LH and T goes down. Therefore a. the receptors in the pituitary are down-regulated (or b. its tertiary hypogonadism.) No other mechanisms behind this phenomena has ever been recorded in scientific texts.

2.) If the ‘damage is done’ no amount of T will help. But this is clearly an issue with androgens when TRT rebuilds muscles but makes sexual problems worse (me, 40 etc). This also more clearly points to downregulation in DHT/5aR sensitive areas. This also points to muscle loss occuring due to low biologically available T.

3.) Hairloss, body hair growth is also driven by androgens. Its possible for something effecting a receptor to have different effects at different tissue.

4.) He doesnt know the answers. It would be good if one of his scientists could answer these points!!!.

#444

At the end of the day, the most important thing is we all support the research the very best we can and help out any way we can.

#445

Yes!!! :smiley:

#446

I don’t know for others but when I used Agel
1- for first few weeks I grew muscles in arms and thighs but arms were not clean and beautifully cut like before SP use.But Id did have great strength.
2- My libido shot up to 200% and erections were out of control. I had very difficult time to control my self in early days.
These muscles and libido came down slowly in 3- 4 weeks until I got to the point where I was not able to walk. My body was full of water. After stopping Agel (few weeks after) my total T and free T was the same as before going on Agel (blood test).
Now if ARs are dead why I got muscles , erections and very high libido?
suppose ARs are dead. let say 100 million. some one uses ARimidex like VincentV and get good response initially and then gradually these effects disappear. why? Do estorgen and Androgen share the same Receptors? looks like yes. that is why males grow boobs on low T or high E and FTM (females to males) grow penis by using Andractim. Now suppose arimidex made 10 million receports available so that we got positive effects.But then what happens to these new 10 million ARs. where do they go? we are not on any fin or SP now?They should stay like this and we keep using Arimidex and keep getting good benefits.
Also if the absence of DHT caused AR silincing then why children and women are not affected ( I am not a biology expert) I mean how their ARs remain intact despite no DHT or very little DHT due to age and gender. But when they are exposed to DHT or Agel they respond well( There is warning on the gel to keep it away from children and women)
I am just writing these all for the sake of knowledge. I don’t mean to dishonour Awor’s research. We must support him this is the only way to learn.

#447

If I recall the thread that AWOR made for the research, he said the action of our body shutting down these surges of androgens comes with a delay and is not instantaneous, so that seems to make sense as far as why the androgel worked for you for a period.

Also, it does seem to happen to women as well, because he also explains in the thread that SSRI’s are capable of causing the same syndrome, or accutane for example. Remember Maria? Awor states in the thread that essentially anything which lowers androgenic action can cause this syndrome.

I am not close to the smartest guy on here, and I have no problem admitting that because it is the truth, but everything in his research thread makes perfect sense to me as far as the questions people have been raising. Just my opinion…

#448

Lennon, if you cannot be bothered to do any research on the subject before offering an opinion your opinion is worthless.

Hiding behind ‘Im dumb’ is not an excuse. You have added nothing and only wasted my time because I had to read your post.

Start researching on the actions of androgens and androgen receptors first.

#449

I never said I was dumb Oscar, simply that I am not a strong scientific mind, which is the truth. However, I did read Awors thread and he does provide answers to the questions you are asking, if you look through the thread carefully. Anyways, I am not going to bother arguing with you. You are entitled to your opinion and it is no concern of mine. Feel better.

#450

Im sorry but arent you the guy that supports getting interviewed on the ‘Truther Girls’ conspiracy-theory youtube show? You are incredibly weak minded and a total waste of space. Yet you think Im not understanding something?

Let me make it simple; nothing in this thread or on this website or in any medical text published on the internet supports the idea that the androgen receptor can become permanently ‘down regulated’ as a result of androgen deprevation. Nothing. Zero.

So thats the weight of all known scientific knowledge vs. awors posts.

That by itself is pretty convincing evidence that its not happening. Really, the main reason this idea has any support is by default, it is the least worst explanation.

#451

[b]One study found that isotretinoin significantly changed the expression of hundreds of genes in skin after 8 weeks of therapy.[88]

Isotretinoin is also one of several drugs discussed in a recent study[89] examining epigenetic side effects (for example DNA methylation) of common pharmaceuticals that leads to silencing of genes.[citation needed][/b]

never reportet? This is only from Wiki

#452

Let me make it simple; nothing in this thread or on this website or in any medical text published on the internet supports the idea that Oscar ‘can’t fall in love with a woman’ after finasteride use. Nothing. Zero.

#453

Doesnt mention andogens and androgen receptors. The papers it quotes dont mention androgen and androgen receptors. Im not sure what point your making, In fact your making my point for me.

Unless anyone has ANY evidence to the contrary it seems the lack of evidence is overwhelming. Androgen deprevation does not lead to the permanant down regulation of AR receptors.

#454

Oscar,

You are not in a position to challenge what Awor is stating and whether you think so or not, you simply do not have close to the amount of knowledge he does. Again, read the research thread, you will find answers to your questions there. Also, you should respect others on this forum. You seem to start fights on a fairly regular basis and I cannot think of one thing you have improved as a result.

I recall when I first came to this site reading a thread you started entitled: “why not ask merck for help?”.

Settle down, and respect your fellow forum members. Your anger for our situation is so misdirected. I am sorry you feel bad, we all do and none of us wants to be here, but it does not give you the right to act the way you do.

#455

Lennon,

  1. Not only are you gullible enough to use antifungal medication (harmless enough) you are now damaging my chances of getting better by encouraging the involvement of random conspiracy theorists. You want me to be happy about that? I would say my anger is directed pretty much in an accurate fashion.

  2. Yes i can question awor, I have discovered two new forms of hypogonadism. My whole point is that there is no information anywhere supporting his ideas. He has no secret source of information to draw upon. I know what he knows. Maybe if you werent a conspiracy theorist you can wrap your head around that idea.

But maybe Im wrong. If you have ANY scientific text supporting awors idea of androgen deprevation causing permanant AR downregulation dont keep it to yourself post a link ASAP.

#456

Oscar,

You do not know what he knows.

Again, take the time to fully read the research thread.

I am done responding to you.

Feel better.

#457

I have few more questions.
on this website there is guy who abused steriodes and became hypo. his testicles shut down completely. His total T was close to zero (1 - 2). He is from Canada you can transfer his numbers to US units. He remained in this condition for four years during which time he tried different things but could not get to normal ultimately he had to take TRT. He used TRT for many years until used fin for hair loss and suffered like us. I have had a long PM exchange with him and he mentioned to me during four year shut down period he was no where close to what PFS is. you know he was shut down for 4 years, total T to zero but got normal once jumped to TRT.. So was he not androgen deprived during this period? why got normal on TRT?
I think we should go on web site of younechs who cut off their balls to get complete androgen deprivation( sorry don’t know right english word) or MTFs and see how are they doing if they use T replacement therapy? are they close to us?

#458

Yup, exactly my point. The body senses T and takes some action. This is the definitive proof that we are not insensitive to androgen. If we were, injecting high doses of T would only increase T and E2. All the other hormones would not change. However, as we all know, they do. For example, SHBG goes up.

#459

With all due respect, people need to stop making claims of “definitive proof” about things when it comes to the “post finasteride syndrome”.

The fact is, Awor and his team hold actual results in their hands. The rest of us are trying to interpret those results blindly.

You guys can read tons of studies etc., but honestly, no one here has “definitive proof” of anything when it comes to this syndrome.

#460

Are you saying that your condition, in an of itself, is not sufficient proof to show that post-finasteride syndrome exists?

I understand where you are coming from, but this is no way to frame the discussion. When a guy develops erectile dysfunction and loss of sensation in his penis days after taking finasteride, stops the medication, and starts it again years later to face the same problems - I would say that is exceptionally convincing proof, especially when the effects do not reverse in either situation.

Due to the fact it is a rare condition, it is difficult to get it to show up in clinical trials especially when they are structured and executed by pharmaceutical companies that have every interest to have the results return in their favor. This condition is challenging to prove, but every month the evidence continues to mount stronger and stronger and eventually this will no longer be a controversial syndrome. We really just need time. Public opinion has being increasingly sympathetic and understanding in the past two years and things are continuing to accelerate.