3a-HSD blocks the effect of DHT. 3a-HSD needs to be removed
I understand indomethacin is a 3a-HSD blocker. Interesting treatment would be indomethacin + DHT, and whether this would permantly put our systems back into our pre pfs state.
Lets wait for the study.
I feel as though taking a 3a-HSD inhibitor would only mask the problem even if it did work. I wonder though if taking it would somehow cause a reaction like the crash some of us here experienced and reverse us back to normal. What I mean is if this inhibitor reversed the methylation or demethylation caused by propecia. But your right, we need to wait. Does anyone know when we’ll know the results though?
Before June is the best answer we have.
Both statements are completely wrong. First of all, 3a-HSD is not causative of this problem (it can trigger it, but it is not involved in the actual etiology). Second, we will also be looking at CAG repeats in the scope of the genetics study, but rather as one factor in the genotype of affected persons and certainly not as a root cause. There is no study that even comes close to linking CAG repeats with our problem, so I don’t know where Dr. Jacobs would have gotten the basis for such a claim from.
I will try to be clearer about what I meant in my post regarding antidepressants and 3a-HSD.
What I meant about 3a-HSD in relationship to “PFS” is that 3a-HSD is capable of significantly lowering DHT concentrations inside the cell by deactivating DHT into the inactive androgen 3a-diol-G. Antidepressants work by heavily inducing (activating) 3a-HSD, thereby increasing neurosteroid levels. As a side effect of this, cellular androgen levels (DHT) get reduced (because more DHT gets turned into 3a-diol-G). This is the same effect as 5AR inhibitors have, just via a different route. In other words, the androgen receptor doesn’t care if DHT levels are low because 5AR got inhibited or because 3a-HSD has deactivated some of the DHT. It just “sees” that it is not getting activated, and this leads to our problem.
This is why taking anti-depressants, in our situation, can lead to a worsening of our overall symptoms - including depression.
Bottom line is, there is no point in considering messing with 3a-HSD (nor with AR) for that matter. We have to attack the problem from a different angle.
What I don’t understand is that if our DHT is being deactivated by 3a-HSD, why do we have low 3a-diol-G? Should it be high because the DHT that we have is being converted to 3a-diol-G?
Awor, given what you know from the research, how difficult do you think it would be to fix the problem and develop a cure? Years? Decades?
In order to avoid any confusion, this conversation specifically applies to antidepressants and their interaction with 3a-HSD.
You have to think of this in terms of two separate time frames:
Is that any clearer?
That’s like asking me what the result of a fooball game will be before knowing who is playing. 
Seriously, as said before, we need to find out more about the problem before your question can be answered. What the basic problem is seems pretty clear at this point. We are talking about a problem, and this should be no surprise, which is going on at the cell level. One of the key factors determining how a cell is working, and if it is working correctly, is called gene expression. Everything which goes on inside a cell is ultimately governed by genes. Genes (combined with epigenetics) are the blueprint, which tell the cell who it is and what it must do.
Genes encode proteins and it is these proteins, which make things happen inside the cell. The steps involved in this process are called transcription, translation and post translational modification. We have basically found something to be wrong at the protein (AR) level. But we don’t know yet as to why. The next major experiment, which we currently lining up, will look at precisely that question. We will be looking at gene expression, which will tell us which genes are not behaving as expected.
Once we know that, then we hopefully will have a potential therapeutic target. But it really is like the proverbial box of chocolates; you don’t know what’s in it until you open it up and look inside. If we find 100+ genes deregulated, then we obviously will have a big problem finding a therapeutic target. If we find only a few genes out of whack, then it will be easier to potentially target the right gene(s).
The next question will be if there is a know substance that can help us alter the gene expression signature in a favorable way. There are various databases which allow you to match gene expression signatures with known substances. Such databases can help us find potential candidate drugs to attempt a therapy. But maybe there isn’t a known substance that will help us rectify the problem. We need to precisely know what we are dealing with in order to answer that.
Then, it could be that the expression of certain genes has been persistently altered by an epigenetic modification, such as methylation. This is likely and could add additional complexity to the problem. Again, we can’t really dig into that aspect before we understand exactly which genes are involved.
In short, finding a cure of some sort, or at least a substantial alleviation of the symptoms, is not impossible - but it’s no easy task. At this point, we simply need more information. It boils down to the same thing I said many times before: We need to continue going down this path in order to find out if we will get to our destination. The only thing that I can say for sure at this point is, that the other option - standing still - will get us no where. So even if this route doesn’t promise a sure outcome, it’s for sure a lot better than standing still. What at least is encouraging at this point, is that we have found very strong evidence that we are on the right path.
The next step, however, will not be for free. For it to happen, we will need the support of every member on this forum to help fund this project. We will be looking for a sum in the area of about USD 40 - 50K. Pulling off a research project like this is not an easy venture. After a very successful first round of experiments, we have been working for many months now to prepare the next steps. Many factors have to be lined up for a project like this to work. Once we have everything finalized, and we hope this will be the case sometimes in this quarter, we will clearly communicate what has been found so far, why what we found from penile skin is relevant to the problem as a whole, and what we are planning on doing next.
It then will be up to all of us to help make it happen.
Why don’t people at merck work on fixing this problem that they caused?
One of the scientists actually approached Merck to ask them if they would be willing to support this research. It probably will come as little surprise, that they declined. It probably is not in their interest to unsettle more dust than necessary. After all, according to them, our there is no link whatsoever between finasteride and PFS. Why would they want to support research that possibly will show, beyond any doubt, that there is a link?
That would make them admit that there quilty of poisoning us.which we all know is true.I am ready to buck up to help awor I’m sure everyone on here will just to try to fix this problem the sooner the better.let us know when and how to donate I really want to help although I’m not rich I will help as much as I can.I just want to get and feel better alot of the treatments these pfs docs recommend don’t nearly make u feel like u used too.
Yes I understand. Its extremely infuriating that the big honchos up top know this is happening and all they care about is securing their wealth. They are just destroying lives for the sake of “business.” Its so fucked up that this country is set up for corporations to do whatever they want. The real terrorists that we need to go after are the pharmaceutical and bank CEOs, not foreign rulers.
Wow, great summary Awor. Sort of depressing but realistic. It is truly amazing that you are able to figure this out to this level. Also depressing as dgreene stated that people who got us into this mess bear no responsibility for helping us. Truly heartless bastards. If we already know that we need to raise 40 to 50 k probably the sooner we start the fund the better.
I am encouraged by the $40-50k price tag on the upcoming research. There are enough of us here now that a modest donation will put us at this goal in a timely fashion. If certain people are unable to contribute, it is certainly understandable given our mental and physical issues at the moment in relation to working and earning a wage, all while paying for meds etc.
Either way, that price is not a mountain for us to climb and if we pull together we can do this. I personally will contact the appropriate people and seek a donation as well.
Win, lose, or draw, we are a step closer. Awor, Mew and the rest of the gang, you guys rock. You have my unconditional support, appreciation, and respect. As of this moment, I will start making plans to seek out funds for the next step. Please let me know if there is anything else I can do to help.
I think this thread will be the only one left I will read from now 
Never in this board has been such a high hope for everyone of us, even though we’re not there yet. Thanks to you Awor, Mew, and all the others for keeping the courage to go on and work so hard in pushing the search. I’m ready to donate too, I will take in my savings, I don’t care: everyone of us must be cured, and unfortunately, others will come and join us along on this board…
How would we donate it we wanted to?
This just got interesting.
Any chance of getting Dr. Crisler and his associates to donate? Since he’s made so much off finasteride victims, but had very little success treating them, despite his best efforts. We should ask for donations from his camp along with Shippen and Goldstein.
It’s sad cause we could’ve easily covered that 40-50 k from the few guys who went to Greece. At least we know people are willing to spend a lot of money on the problem. Also, I think for every active member, there are at least 10 PFS lurkers who decide not to post–some wealthier than others. We just had a record 99 people view this forum at once! If each of those people donated $500, we’d pretty much hit our goal. So yea, the 40-50 k is a challenge, but not insurmountable.
Maybe we could start a “sign up” sheet in another thread or something simliar. And you can put down your name next to a price range you are willing to donate to better guage where we’re at.
$$$
500
400-500
300-399
200-299
100-199
<100
We’re in the process of trying to set something up for this, although it may take some time (weeks or months). So, stay tuned.
I have only just noticed that 99 users were online at one point. Wow. The number of registered users is also rising rapidly; far faster than ever before. This is encouraging stuff guys.
Just to add my 2 cents. I think we should aim to get everyone to donate at least something, don’t just give up on encouraging the guys that are broke (including myself). A one off $20 payment, $5 a month, $2 every weeks; something along those lines should be able to work for almost everyone. Please, please make a thread where we can all chat about it too, if people can see that others are donating and how much they are donating then it will have a snowball effect.
Absolutely zero chance of any of the PFS docs donating to such a fund. I think they would be baffled or maybe slightly amused any of us would think they should.
Agree entirely with your viewpoint on the monies wasted in Greece.
Hi awor, you’re doing great work and I know you’ve got a lot of people bombarding you with questions. But perhaps this protein could be a possibility to alter gene expression: JHDM2A
fpwr.org/blog/research/altergeneexpression
cell.com/abstract/S0092-8674(0600385-0 <–copy and paste, link broke
Could this protein be a possible therapeutic treatment for PFS?
I started a thread about it in the theories section if anyone’s interested in this.