Might be an adrenal issue in your case I suppose, toad. We are all definately effected differently. Thyroid treatment did nothing for me. Far as TRT goes I’ve seen no improvement while on it so far.
This is what I was thinking about, maybe positive effects are just the ‘feelgood’ benefits of taking procaine and not specifically targetting the syndrome. Time will tell.
We shouldn’t get any hopes up and just allow awor to get on with it. The idea that our disease can be cure by one of our own, no matter how intelligent he is, is maybe a bit fanciful. If it works, great, but I still think if we ever make significant headway it will be from research hopefully <5 years.
I dont know. Dr. Jacobs wasn’t considering the epigentic theory until one of us here (Awor?) presented him with a paper that suggested it. Maybe something one of finds can help point one of the docs in the right direction. God knows no one else is going to go out searching the medical literature for us.
I agree with Boston332, what’s fanciful is the idea that we can simply sit back and wait for someone else to come in and hand us the cure.
Just because someone has a bunch of letters after their name doesn’t make them better than us. Don’t forget that it was people with PHD’s and MD’s who first approved and then thought prescribing finasteride for a cosmetic condition was a good idea.
Everyone on this forum is capable of reading and learning and contributing to finding a cause and a cure. I think we would be a lot closer to a diagnosis if some of the people on here put the same amount of time into research and positive discussion as they did into feeling sorry for themselves.
Perhaps this won’t be the cure, but remember that the THEORY came before the results.
This is an interesting study, scientists studied the androgen receptor methylation patterns of girls who went through early puberty and found that they had much lower methylation level, thus leading to an increased response to androgens.
Decreased Androgen Receptor Gene Methylation in Premature Pubarche: A Novel Pathogenetic Mechanism?
Conclusions: The increased AR gene activity observed in PP patients, as indicated by the reduced AR gene methylation pattern, together with the presence of shorter CAG repeats, might lead to hypersensitivity of the hair follicles to steroid hormones and therefore to the premature development of pubic hair.
Epigenetic differences arise during the lifetime of monozygotic twins
pnas.org/content/102/30/10604.long
This paper shows that dna methylation changes during a persons lifetime, It also talks about differences in promoter CpG island DNA methylation and expression profiles in twins and specifically mentions the changes in the methylation status of Androgen receptors.
Does anyone have any idea what it would cost to get a methylation analysis done to confirm or disprove this theory? And who you would need to speak to? I think once Irwig’s study is published that would be enough to get a lab interested.
I wonder if we are 1 or 10 yrs away from Irwigs study being published. It doesn’t seem even close to completion.
Obviously I’m grateful that he’s putting the effort in to help us but it doesn’t seem like it would be all that difficult to compile. It’s simply a study reporting the side effects, there’s no actual lab work or anything. I imagine it will go something like:
“In this study we report X cases of men who have complained of persistent side effects as a result of having taken finasteride - then show the raw data which will basically be the surveys we did showing how many people are suffering from what, at what degree. - In conclusion finasteride appears to cause severe and lasting side effects in a small subset of men, further testing is required to understand the nature of this problem”
Hi everyone
Sorry for my long absence from the forum. I have been enormously busy lately and was also a little confused about what was going on with me, because I indeed went through a bad phase. I was amazed at the amount of posting going on in this thread…
First of all, a short update regarding my state and the therapy. There is good and there is bad news:
The good news: The improvement in mental side effects and well being has been persistent to this day. I have regained much of my self confidence compared to pre-therapy. Looking someone into the eye does not feel uncomfortable any longer. Concentration is better and I generally feel much better with respect to my mental performance. Also, being able to ditch the antidepressants has been a HUGE milestone in my “recovery” so far. I actually found out that antidepressants reduce androgens at the cellular level in much the same way that 5ARI’s do. Not surprisingly, 5ARI’s and SSRI’s cause a nearly identical side effect profile. But this is another story and I plan on publishing an article on this in the Internet next year. Having said this, guys in our condition should absolutely avoid antidepressants AT ALL COSTS. Antidepressants can only make our situation worse!
My point regarding SSRI’s is that quitting them causes an increase in cellular androgen levels. With hindsight, this is probably what caused my temporary improvement in sexual side effects (including fuller penis, etc.). So here comes…
…the bad news: Unfortunately, the improvement in sexual sides didn’t last. Still got pretty good nocturnal, morning and spontaneous erections, but no sensitivity. Libido is also pretty much gone. After quitting the SSRI’s I did another full day medium dose i.v. procaine session. The weeks following this I had a phase of a couple of weeks where I felt pretty crappy and was generally not doing well, the same kind of effect like when I increase TRT dosing too much. Fortunately, the bad phase ended and I started feeling better again.
Just last week I did another session. This time, with the addition of a high dose deacetylase inhibitor (butyric acid). Briefly, the rationale behind this: Chromatin deacetylation often works in concert with DNA methylation to silence genes. Through chromatin deacetylation, the cell “protects” methylated DNA from active demethylation. In other words, I hypothesized that the demethylating effect could be more pronounced by the addition of a deacetylase inhibitor. Unfortunately, the last therapy had more or less no effect. All in all, I am feeling reasonably well, but remain sexually “dead”.
Nevertheless, I am very happy with the mental improvements I was able to make so far, because otherwise my career would have been at serious risk. However, I am perplexed at the fact that I didn’t manage to keep sustainable gains on the sexual side. This DOES NOT mean that methylation is not involved, but rather that the approach is either insufficient or too unspecific. What I mean by this is that research has shown that re-expression of genes typically occurs after 72 hours of high dose treatment. I so far have only had about 4 hours in all at a low to medium dose. By unspecific I mean that global demethylation can potentially increase the expression of genes which actually act to downregulate AR expression. To date there unfortunately is no available technology to selectively demethlyate DNA regions. At the moment it’s pretty much all or nothing.
Personally, I am not prepared to globally demethylate my DNA in a substantial way by going for high dose/long duration therapy. I understand enough about the crucial role that methylation plays in gene regulation, and proof reading during DNA replication, to know that intensively pursuing this route is highly dangerous. I was hoping that a little demethylation would be enough, which seemed to be the case mentally but not sexually. Additionally, it may well be that additional factors are involved and that demethylation alone is not sufficient.
This brings us back to the point where we need to get work done by scientists in a lab. We absolutely need to get a better understanding at what we’re dealing with at a molecular level. All these things we are talking about (methalyation, hypersensitivity, post translational modification, AR gene expression levels, etc.) CAN be verified by people that know what they’re doing, have access to the right equipment and funding. It will only be with that understanding that we can advance further with therapy concepts. I am part of a small group of members on this forum that is actively working the science side of things. We are in contact with a number of scientists which are interested in working on this problem. The main obstacle at the moment is priorities and mostly funding. The most effective thing we can all probably do at the moment is start putting aside some money to assist in the funding of a future initial research project.
Btw, I would like to make a big compliment to all of the posters in this thread. The level of discussion is very sophisticated, and even practicing doctors may find our discussion hard to follow. Long gone seem the days where everyone was running around this place claiming that their 5AR2 was permanently damaged or that our hormones are simply out of whack. I think many people have come to realize that gene regulation is at least as important as circulation hormone levels. As I said before: If the light bulb is switched off, it doesn’t matter how many volts you apply to it - it will stay dark. The more educated we become, the better our chances are of moving this tanker into the right direction…
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Thanks for your efforts awor.
Thanks for the update Awor.
How much $$ do you think we will need to get a research project going?
And, whats next for you?
Thanks awor. It was fun thread whilst it lasted!
Next step is to get tested at a cellular level to find out whats going on. Simply cycling through all the experimental anticancer drugs that alter gene expression is potentially dangerous. That being said, if the problem is methylation i’ll gladly shoot up with as much Azacitidine as it takes to get better - I cant imagine any side effects being worse than the situation im in.
I thought I’d share my thoughts on the matter:
Firstly thanks awor for your input its been most useful.
I think we should not dismiss this theory for our side effects. The reasons being firstly awors mental side effects and well being have improved substantially afterwards in a way that couldn’t be put down to procaines MAOI qualities. Surely this is a sign.
Now although he had no sustained sexual gains I’d like to make the point of “depth”.
Awors treatment was not very deep in the sense he took a low to medium dose of procaine for a short period of time and as awor points it it takes 72 hrs after high dose treatment to become effective. There are dangers to high dose demethylating agents for a period of time. I need to read up on this area as to see the risks. If anyone can enlighten me with the risks would be much obliged. There are dangers to deep treatment.
But then there is a variability in us as sufferers as to the “depth” of our problem. Some display hardly any androgen action such as no hair loss, slow beard growth, no libido, muscle loss. Some still show some androgen response. So I ask depending on the depth of our problem we require different depths of treatment. Deeper treatment would be stronger and more prolonged. So I’m still open to trying the procaine treatment.
It will take a long time to get the specific research we need done so I am intrigued to know how deep can treatment go before the risks outweigh the potential benefits? I think this is the problem. I intend to review all the literature over the next two weeks and find out more about methylation in general, the side effects of meds, what happens when sufferers of Myelodysplastic syndrome take it for long periods of time. If you want to help me out be very kind of you.
We should still pursue the research option. Question arises who will do it? And how much money is needed?
Thank you for your efforts awor,
I would also like to reiterate what others have said, can you give us some idea about what sort of money we are talking about here? $100,000? $250,000? $1,000,000?
I am sure given the impact that this disease has had on all our lives the is really no reason why every member of this forum shouldn’t be able to contribute at least a couple of hundred dollars each.
Also, i thought given that persistent side effects are already recognized in Europe then this would be the best place to start in applying for a grant into research. I don’t know whether we would get any kind of special consideration given the nature of our problem but perhaps in the proposal we would could emphasize the importance of understanding the true long term impact that pharmaceuticals have on the human body at the epigenetic level.
I noticed the same when coming off Prozac last year. Was on it for a month and it gave me bad shrinkage which I don’t normally have, and I didn’t wank for a month. Got back to my low, normal post-fin level when I quit. Was going to update a thread about this where I’d almost encouraged SSRI use which was not a good idea. I did feel less depressed but looking back that was due to other factors, not the drug itself.
Needless to say, SSRIs are bad news.
Agree with Luck there. Shippen said SSRI’s are almost as bad as Fin. Deplin and Wellbutrin seems to have helped me with depression at least to the extent that I can cope somewhat and get things done. Of course there still are bad days.
Thanks for your efforts Awor! I’ve been checking this thread almost everyday and still believe this is our best chance of getting better. Like the other guys, I’m curious what amount of money we’re going to need to fund the further testing that you discussed? I’m more than happy to chip in several hundred dollars or even more if this is something we can make happen within a reasonable time frame.