Maybe some kind of collaboration with them would be possible: https://rxisk.org/prize/ ?
1 Like
Hi @awor, for those of us who are relatively new on the forum, can you tell us what happened with the BWH study?
Thanks for the responses, with what you just said, you don’t necessarily believe this is the only route for success correct? Obviously seems to be the most ideal, but the studies currently ongoing are beneficial to an extent in your mind right? I understand you are asked about Baylor a lot as you are the face of this forum who many go to in search of help, so if you don’t want to address it anymore I understand. In your opinion is the timeline so dragged on bc of a) extensive amounts of information and study (best case) b) taking the study not as serious or c) political tampering so to speak? Thank you
You have spoken about this before - about the dangers of anti-androgens of any type for potentially worsening our condition (nothing to speak of causing it). Is there a lot of evidence that people who already have pretty bad PFS can get even worse after taking anti-androgens? I know that @axolotl recently had such an unfortunate experience. (it would be nice if axolotl can talk about this as well).
I am asking about zinc in particular - because I am considering re-starting zinc after having been off it for 6 months. I never knew how bad my PFS was while I was on zinc. Now that I am off it I am worse than ever. I know zinc is supposed to mirror the function of finasteride in reducing DHT and that sounds awful as an intended effect but if I can go back to my previous baseline, I would - while other possible treatments are being investigated. I am afraid of the risks however. The way I got PFS was after I restarted finasteride after I had discontinued it for 6 months. I don’t want the same thing to happen again with zinc but I really can’t go on with my current state any longer so I might have to take the risk. How much worse can it get? My libido is already at 0…
No disrespect, but there are people here whose smallest concern is low or no libido. If libido is your main/only issue, things can get much worse. How about emotional numbness, insomnia, crippling anxiety, severe derealization where you experience life like peeking through a looking glas and stumble over your own feet? Low libido and the effects on relationships etc. suck. But there is large universe of equally if not worse side effects out there. There have been people before you who thought they had nothing loose and found out that they were mistaken. There are a lot of things that you only realize you’ve had when they are gone.
2 Likes
I am talking about this study:
They basically did not stick to the agreed protocol, took a huge amount of money, and produced a very Merck friendly paper. Merck is a major sponsor of many universities, and pays the top dogs in the field nice “consulting” fees. Go figure what happened.
This conclusion
expression levels of AR-dependent genes in skin did not differ among groups
is absolutely not possible given what the Di Loreto paper had already found (namely overexpressed AR).
Something is seriously fishy about this study. I don’t want to go on further about this in public and risk facing retaliation of some sort. Just want to say, I don’t want a repeat of this disaster.
5 Likes
Tbh, I am a little confused about the evidence. Cases with broad and strong symptoms are susceptible to get worse from taking further anti-androgens. This includes Axo and myself. Others seem to do well on Zinc for example. I don’t think anyone will benefit long term from taking stronger AA’s such as dutasteride, etc.
1 Like
I think you are severely underestimating the importance of libido for the normal psychological functioning of human beings, which is a mistake people without PFS usually make. I have all of the emotional and mental side effects you mention and much worse (I also have the standard physical side effects). Let me just say that my side effects are bad enough to be absolutely life-threatening, nothing to speak of life-destroying. And I can tell you with 100% certainty that they are all caused by severe depression which in turn is caused by lack of libido (and everything that entails). In other words, if I can recover my libido, I will recover the psychological symptoms as well. I am sure we can debate this without reaching an agreement.
1 Like
That’s for sure. I am not even considering finasteride or dutasteride. But how similar to those is zinc’s effect on suppressing DHT? I harbor no illusions that lowering DHT to any extent again can only make things worse in the long term by further upregulating the androgen receptors or alternatively from preventing downregulation. Still, I feel that I need a short-term measure to get me through the worst of this, even at the expense of long-term harm.
Hopefully people will not become discouraged to fund because of this. It’s horrible and hopefully Baylor is not as corrupt as BHW. But unfortunatelly we have no other choices. My biggest concern is that something like this may happen again, and therefore it would be great if someone like Awor and a non corrupt doctor get the right/access to supervise the process of the research.
1 Like
I think you severely overestimate the role of libido. And yes, I am sure we can debate this without reaching an agreement. But that does not mean it is not a debate worth having. So, please provide the evidence that made you 100% certain that all psychological side effects are caused by decreased libido. How do you know it is not the other way around?
I may be one of the few here who has taken both…Accutane as a teenager which stopped my cystic acne and I had blood tests they monitor your liver on Accutane…I stopped treatment early.
Then generic Finasteride in 2014 which didnt do anything but make my hair loss worse fast…
1mg Propecia in 2015 for 6 months gave me horrible symptoms then after stopping the following months I began a journey of health loss like I would have never thought possible…
I could be wrong but the study where they found overexpression of the AR was localized in the skin of the penis and in the BWH study they don’t say where the skin samples were taken from. Maybe it’s different depending on where the skin is taken from? Just thoughts
4 Likes
Very likely @acne1776 - epigenetic changes are site specific. I would expect the results from the coming tissue analysis to be quite different.
The skin in the bwh study was taken from the upper back (I believe in a departure from agreed protocol) and the appendices of the study (accessed separately from the main paper for some reason) suggests there was differences in “a few” androgen dependent genes. It did not specify which. They dismissed this because their correlation method did not pick up on a consistent pattern. The fact this was glossed over in a couple of undetailed sentences was disappointing, as with most aspects of this costly waste of time.
5 Likes
That is of course correct. But given that:
- finasteride is primarily an inhibitor of 5ar2
- 5ar2 is strongly expressed in the genital region (prostate, penis)
- a clear effect in the form of a deregulated AR has already been found in penile tissue
- erectile dysfunction is a commonly observed persistent adverse reaction with PFS patients
- back region has been documented to not be particularly rich in 5ar2
What was the motivation of Bhasin to choose back skin which afaik has not been documented to express high levels of 5ar2 in adults instead of previously validated penile tissue? Why was origin of skin not mentioned anywhere in the main paper (only in a separate appendix)? Why was it not disclosed specifically which androgen-dependent genes were investigated? In the appendix, it was mentioned that “a few” androgen-dependent deregulated genes had been found, but not which ones. Why was this not mentioned in the main paper?
For me, this paper was carefully designed to show that the PFS patients are simply depressed, and to distract from any cell level damage as has been previously found. The only reason I see for such a top notch scientist to produce such a lousy paper, and given the substantial budget he had, is sabotage. Anyhow, I will arrest my case now. This topic is about Accutane.
19 Likes
Something that is overlooked.
Accutane has been shown to be a very potent competitive inhibitor of RoDH4 at therapeutic concentrations of the drug and RoDH4 has been identified as one of the “molecular switches” that governs ligand access to the androgen receptor through conversion of A-diol to DHT, a so called “back door” pathway. There is a nice description of the blocking of these oxidative HSDs as a potential acne treatment in this patent application. Unfortunately, data regarding whether Accutane does or doesn’t competitively inhibit any of the oxidative 3a-HSDs except for RoDH4 appears to be absent.
This back door oxidative pathway may be crucial to maintaining DHT levels by countering reduction of DHT to A-diol.
The direct enzyme inhibition could explain the “early” anti-acne effects (and side effects) of Accutane that are observable after only 1 week and before mRNA levels of steroidogenic enzymes (such as 5ar-I, 3b-HSD, and DHSR9 (an oxidative 3a-HSD)) are significantly decreased, as they are after 8 weeks of treatment.
3 Likes
Dubya! Maybe this explains my condition. After taking the second pill of Accutane, i remember my low back hurting that morning. My lips were dry and my facial skin started to fall apart. This all went away except sexual sides. Do you have any idea why this happened to me? Maybe my prostate was prone to kind of a disease from the beginning of my life… How the hell i get this from 4 pills total. My DHT should have healed itself if it was the real problem.
I think the sharp reduction in DHT causes this problem. It doesn’t matter if DHT production returns. Putting out a fire doesn’t fix a burnt-down house.
2 Likes
Dont think so, because a lot ofmpeople feels better afternquitting, during 2,3,4 weeks, and then crashed.
Somis not dht reduction.
Regards.