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

Therapeutic Efforts Pharmaceutical
#331

Hi everyone

Just wanted to drop a line to let everyone know I’m still alive. As I said before, this is not a recovery thread. But given that I let people know that demethylation has helped me, I think it’s time to give you all an update.

As stated previously, a demethylation therapy using intravenous procaine did wonders for me. So much, that I decided to dump all other medication (mainly two antidepressants). This led to a further improvement in my condition, including sexual sides (fuller penis, usable erection, libido). Antidepressants work by increasing neurosteroid levels. They achieve this (just about all of them), by increasing induction of 3a-HSD. This, unfortunately, causes a reduction in androgens at the cellular level.

So dumping my antidepressants had the effect of giving me an androgen boost, which made me feel better for about a week or two following quitting. In my case, increasing androgens eventually always makes me feel worse. So going off the SSRI’s eventually caused me to crash again and I was feeling pretty shitty for quite a few months. Since about a month, I am starting to feel better again. Some libido, often good morning erections. But if I do anything to raise testosterone (ejaculation, too much exercise), I feel bad, depressed and get shrinkage. So not really useful from a sexual perspective.

Since 6 months I am completely off any medication besides TRT. The procaine therapy seemed to have weakened my immune system because I was coughing almost all winter. This appears to have gotten better now. Global demethylation is not the magic bullet because it messes with too many other mechanisms in the body and can cause other, serious problems. My personal focus is still on getting scientists interested in working the basic science side of things. We need a more detailed understanding of what’s wrong in order to assist with a more targeted therapy. I hope we can start initiating some molecular level studies in the foreseeable future.

Take care all.

#332

Thanks for the update.

I am not sure I agree with your statement on global demethylation as the majority of the epigenome would be far more resilient to demethylating therapies than the ones that have been altered. It is not like people who have taken azacitadine suddenly find their bodies acting in a completely different manner. Most of the more fixed gene expressions will return to their normal function by process of remethylation or would not necessarily demethylate in the first place. Given this and the fact you improved on procaine wouldn’t it suggest that it could help. If I’m wrong about this could you point to examples where demethylation has messed things up permanently for people. Also have you retained any benefit from the procaine therapy or do you think you suffered from remethylation? If so again what reasoning and evidence do you have to suggest a longer therapy would cause more harm than good?

Thanks.

#333

But they dont, thats what Im saying.

No. Gynecomastia always needs surgery. Look it up.

If testosterone isnt working there must be low estrogen effects too - else it would be obvious from the symptoms reported.

[Size=4]NAME ONE.[/size]

This supports what Im saying. If E is working but T isnt why should a person even need to boost there estrogen levels before they feel E sides? (Anyway provide some proof grapefruit juice does this).

There is no “everything else” - THERE SHOULD BE - this is the point that Im making.

I welcome a counter arguement. Otherwise the conclusion must be as follows: Either both androgens & estrogens are working or neither are working. Its not as ‘simple’ as just an AR problem.

#334

Your tone is very confrontational. I hope you are ok.

To answer your questions. Gynecomastia can be go away by itself if the hormonal abnormality is corrected, or through medication. However, if left untreated it can persist then surgery is an option. You obviously have not looked this up. Even wikipedia gives this info.

No testosterone and estrogen do not bind to the same receptors. Therefore one can work when the other doesn’t if hormonal levels are normal.

One problem of high estrogen - gynecomastia which Mew has had issues with. Not everyone will have these issues as not everyone has complete inactivation of their AR signal. For example some people can still have morning erections.

Grapefruit juice - maturitas.org/article/0378-5122(9490012-4/abstract

I hope this helps. And please you’re going to wind a lot of people up if you continue in your confrontational manner. Present your findings in a fair manner. Let the science speak for itself.

#335

Ok. The main point is it doesnt go away without intervention. But gynecomastia, which Mew has, as opposed to pseudogynecomastia - always needs surgery. Either way - it IS NOT a sign of high estrogen.

en.wikipedia.org/wiki/Gynecomastia

Who said they did?

So…why isnt it?

This developed on the drug, has not got worse, and would not necessarily resolve. Therefore in the whole forum NOT ONE EXAMPLE OF HIGH ESTROGEN AFTER QUITTING!

But they should - an inactivation of AR (even partial – as you say) would cause a massive estrogen dominance.

You have provided no argument to counter what I am saying, nothing scientific, nothing at all. Unless you can find an example of high estrogen after stopping and not simply something that developed on the drug and never went away, I must be correct. Its only unfair to deny such blatant and obvious facts. Pull yourself out of your mindset.

#336

Again with the aggressive manner. Your logic doesn’t add up as there are people with high estrogen.

I will answer your questions:

First off. Gynecomastia is a range of disorders ranging from whether adipose tissue is formed or breast tissue is -pseudo is primarily adipose tissue. It may improve upon resolving the hormonal issue:

Treating the underlying cause of the gynecomastia may lead to improvement in the condition. Patients should talk with their doctor about revising any medications, such as risperdal, that are found to be causing gynecomastia. Often, an alternative medication can be found that avoids gynecomastia side-effects while still treating the primary condition (e.g., in place of taking spironolactone the alternative eplerenone can be used). Selective estrogen receptor modulator medications, such as tamoxifen and clomiphene, or androgens (typically testosterone) or aromatase inhibitors such as Letrozole are medical treatment options, although they are not universally approved for the treatment of gynecomastia. Endocrinological attention may help during the first 2–3 years. After that window, however, the breast tissue tends to remain and harden, leaving surgery (either liposuction, gland excision, skin sculpture, reduction mammoplasty, or a combination of these surgical techniques) as the only treatment option.

Secondly show me evidence that estrogen isn’t working or is low in individuals. My estrogen was in normal values. Why do you think it is so important? What you are saying is that if androgens are not functioning estrogen would dominate completely and cause a cascade of symptoms. However, you do not see this happening. What are you implying? Estrogen resistance as well? Then why the response to estrogenic substances? It doesn’t add up. Keep in mind we still have normal androgen levels and a varying degree of function of the AR and what happens after it.

This guys estrogen was raised and you yourself told him so.

Check out: viewtopic.php?f=4&t=4827

Also: viewtopic.php?f=4&t=4406

I don’t know why you’ve come up with this idea. Show me evidence it is the case and then maybe I’ll believe you. But at the moment all you tell me is I’m categorically wrong which is not only unconstructive but is unprofessional.

#337

Either way, it doesnt mean estrogens are still high, not at all. (Also, your quoting from the same source as me which elsewhere clearly supports what I have said!)

Im not talking about levels or ranges.

Yes EXACTLY. Or at least it would be reported quite often, instead of never.

Yes. Thats what I have said. We are not responding to estrogens properly too, otherwise low response to androgens would lead to high estrogenic effects, and someone at some point would at least have reported them. Getting effects only after boosting estrogens (if indeed thats what did happen) proves my point.

It does add up. It must be both androgens and estrogens, else those people with low function in their AR (as you say) would have at one point reported gyno.

So? Nothing to do with this discussion.

What a strange thing to say. The facts are 100% in support of what im saying. Thats why I came up with this idea. There are NO SYMPTOMS of high estrogen reported on this board. Thats the fact of the matter, that is conclusive evidence. This MUST happen if the AR is not working.

I am correct, so its time to progress the conversation accordingly. Not a lot else needs to be said.

#338

This would happen if the AR is completely dead. I do not think this is so. For example I still lose hair and have morning erections yet I suffer from many sexual sides and a crippling fatigue. I see your point Oscar but do not feel the balance is so out that it would directly cause symptoms of increased estrogens and i do not feel the AR is so dead to not have any effect. Construct a test to determine whether I’m wrong. But at this moment I am not convinced.

Maybe get a DEXA scan. Oestrogen is important for bones.

ncbi.nlm.nih.gov/pubmed/10209570

#339

It’s common

Myself and 1750 are good examples.

As my estrogen levels have risen post-finasteride my symptoms have worsened.

Seriously man you’re barking up the wrong tree on this one. If we didn’t feel estrogen either we’d be 10x worse again. We’d all have weak joints and all sorts of issues.

#340

No. Bodybuilders get gyno and they have normal response to androgens.

If you think the AR isnt working in some that would put the estrogen/androgen effect ratio out - for those with no response to androgens they (at the very least) would have a massive estrogen/ratio problem. They do not report these symptoms, thereofre i must be correct.

The fact no one reports estrogenic side effects after quitting is 100% solid proof.

Im actually trying to get one sorted out at the moment. That wont prove Im right though.

Im not saying estrogen has stopped working in everyone. But in those people for whom testosterone has stopped working so must estrogens, otherwise the effects would be obvious.

Either both androgens & estrogens are working or neither are working. Its not as ‘simple’ as just an AR problem.

#341

I disagree with the idea that there are no symptoms of high estrogen on this board. My gyno has got gradually worse and become moobs. Also, tons of guys become ‘emotional’ when they quit as there are no androgens to offset these sides. This is one thing we have in common with BB’ers who report the same thing when they come off the juice. Thank Christ this seems to go away.

The problem isn’t so much high estrogen as no androgens to counteract normal levels.

Even Crisler used to joke that his office was full of gifts of flowers, cards and pen sets from PFS guys, ie we were a bit wussy and low in t, high or unopposed in E.

#342

You are wrong oscar.

About 3 weeks after quitting fin i developed lumps behind my nipples. They were diagnosed as gyno by my doctor. They have since resolved themselves without any assistance, took about 2 months for this to happen(resolution).

So you are wrong…

#343

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#344

Has anyone else tried any demethylating agents - apart from awor?

#345

Why should anyone do it, since it didn’t really work for him? Furthermore, it is my impression that the methylation theory fails to explain a few recent recovery/improvement stories, while, as awor says, it should explain all stories on this forum.

Given these two facts, it is understandable why nobody has started a potentially harmful treatment such as global demethylation.

#346

It did help awor. Yes it didn’t stick but that is because he most likely didn’t hit it hard enough and remethylation took place. Which stories don’t fit in?

#347

Recoveries from:

hCG
Synthyroid
T3 and Preg
Arimidex
Vitamin D3
Prednisone and Dox

don’t seem to reconcile well or at all IMO.

#348

I disagree. I have shown how all these things in this thread link in with this idea. Also I have pursued most of them and none of them have helped. Show me consistency in these treatments in terms of results. Our bodies don’t respond to testosterone as it should. Hormonal levels have little effect.

#349

In cases such as this it can be proof that there are non-hormonal problems not just a really complex unprecented acquired partial androgen resistence. More realistic non-hormonal problems can be anything from liver to CNS to brain to prostrate or a combination. It’s been shown that gut wall infections and suchlike can cause subclinical problems to both adrenals and thyroids, also. I think these are the areas worth exploring first and foremost.

#350

I think the problem is most certainly to do with the lack of response to androgens. It is the most realistic explanation at present. Other hormonal treatments have not helped in a repeatable way and i have shown can act on the response to androgens. A change in the biology of our bodies is most likely the thing to explain the reason for the crash after stopping rather than a pathological explanation like an autoimmune process or a leaky gut.