This is not to say that NOT mean that we should not keep hope, I simply say what they told me. At the moment it is incurable and they are too far away, words of Cosimo Melcangi.
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I understand your words. Melcangi said cure is impossible at the monent. But other study(Baylor) is going on 5+years with scientists and awor. And axolotl is helping awor for find a root cause. I believe them and hope we can get out of this disaster.
We have to keep hope!
Anyway just waiting for Baylor study results.
Thank you demon for giving information.
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I give you the text of my diagnosis in this regard:
To date it is not possible to establish the specific cause of these symptoms which appears to be due to the reduction of neurosteroids. There are currently no treatments.
I add that Melcangi and Santi do not consider the problem to be in the AR receptor and that Di Loreto study on receptor overexpression is unreliable. They told me this.
As soon as I have news from them I will let you know.
Thank you for the clarifying words. Even though it is not very promising but I already lost hope after 10 years living in this mess. Fortunatelly I am still able to work and except excessive sweating and sometimes anxiety symptoms +Ed and some shrinkage I am still able to live with it. But in the next two years I really hope that there are some studies to at least get full financial coverage from my health insurance, because there seems to be no way out anymore. I will need a penile implant. I always hoped that there is a cure but for me all hope has gone now.
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Friend the same goes for me, I canāt even work and I have serious physical symptoms that keep me closed at home and need daily care to live. Iām struggling legally to get justice and make the syndrome recognized for all of us. I will do my best I promise.
The changes in genital tissues and āvenous leakageā found in multiple PFSers can be reversed when our AR is back to functioning normally. When the Baylor results are published very soon we should get a better idea on what to pinpoint in on.
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Thanks, you know I am not even able to participate in a class action because my case is too old. I took it at the age of 19-20 only 11months. It is a radical step but I have still some libido left and if it is only the ability to get a good erection why should I live another 10 years with it.
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For Melcangi, Santi and also Harvard the problem is not the AR, so what are we talking about? Of hot air. Yes, we are waiting for Baylor, letās see what will come out. I will update you regarding Melcangi.
If you have calcification why do not try shockwave therapy? There are some studies ensuring this works for that, and also some user in the forum.
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What do you think about Demonās talking?
@axolotl and @awor.
Just curious why they published conflict results?
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This is my opinion on the matter. I saw Damonās clinic report, and while he has clear ultrasound evidence of penile atrophy that other doctors of his have acknowledged, this symptom - probably one heās talked about the most - was not even included by the doctor. They made time to mention they believe the syndrome is caused by neurosteroid disruption. I would have hoped this would be secondary to an accurate clinical profile.
Regarding the Di Loreto study: It was a very straightforward IHC stain so I do not see any reason itās ānot reliableā. The methodology is in the paper. I doubt @Demon was given a reason for this opinion? I deeply appreciate Melcangiās primary research on patients that has been very useful for the issue and his strong expertise in his field. However, my opinion is theory has to fit reality, and he does not acknowledge (in his publications) a large amount of the symptoms, novel experiences and secondary diagnoses. I donāt really consider anything particularly practical coming out of that stuff and Iām not even sure the kind of tech is there to go much further besides keeping feeding finasteride to rats, which in the absence of knowing the predisposition to make a model, transgenic or otherwise, is not PFS. I hope he might reconsider his opinions after Baylorās results. This will be a real merit of the survey - making the clinical picture clear and not selective.
In regards to āare we screwedāā¦Firstly, if you are having a bad psychological reaction to what other patients have experienced, or reading a study like this, you can reflect on how much you have to be thankful about. Some of us donāt need a study to tell us lasting damage has occurred in some patients, believe me. @Awor wrote ten years ago in his paper:
There is much evidence that not all individuals are affected in the same way or to the same degree. Some get only weak side effects such as mild ED or depression, while others get a very broad range of serious side effects, which include strong muscle wasting, life threatening depression, metabolic syndrome, osteopenia/osteoporosis, destruction of penile structure and complete loss of all sexual function. There appears to be a broad range between those end-points, which presumably is determined by individual genetics.
For an example of this in my own case, I had weight loss and muscle wasting with exercise. I had no wider physical, mental or sexual effects at all ever for the many years I had āPFSā without knowing, until I took it again. I could not in those years have imagined what I experienced after taking it again, which onset like a truck hit me, and my condition since is not remotely comparable. If I had not done so, I would still be happy and have no idea this was possible. Itās very important to get across that āPFSā is obviously not remotely the same extent and sites across patients, and unless you decide to start on antiandrogens again I donāt see how that affects anotherās prognosis. As we know, some patients describing more variable and functional effects have had improvements to the point some within that are able to function happily.
Do recall objectively 25% of studied patients in Melcangiās 2017 study had pudendal neuropathy, with severity variable within that correlating directly to self reported extent of sexual dysfunction. That means 75% did not. Like in this ultrasound study, such neuropathy had previously been diagnosed in other patients before it was confirmed in a study. Atrophic changes in PFS patients are acknowledged in many studies and reviews now and diagnosed across the forum. Deleterious tissue effects are of course a firmly established consequence of finasteride as evidenced by dozens of histological studies on animals outside of PFS, which is distinct.
I dont know how much could be fixed for me personally. This hypothesis in the topicās study is not correct, at least for me. It was after I crashed, wasnāt bloodflow related, and it was fast - over a few weeks. This isnāt a variable change some describe, I would describe more as erosion. However, I am at the extreme end of PFS. I have symptoms such as autonomic issues that are rarely described. If we get a treatment, or someone not so bad has an improvement, Iād imagine thereās the potential for significant improvement as this is what androgens by definition normally do to that whole businessā¦except in the case of dysregulated transcription factor. Examples such as blackfox applying andractim to his penis and having it get paradoxically and rapidly worse shows something is very wrong. There are numerous studies showing in castrate animals, administration of androgens rapidly restores form and function.
Androgens regulate trabecular smooth muscle growth and connective tissue protein synthesis in the corpus cavernosum. Further, androgens may stimulate differentiation of progenitor cells into smooth muscle cells and inhibit their differentiation into adipocytes. Thus, we conclude that androgens exert a direct effect on penile tissue to maintain erectile function and that androgen-deficiency produces a metabolic and structural imbalance in the corpus cavernosum, resulting in venous leakage and erectile dysfunction
ā Traish, 2005
Castration significantly reduced trabecular smooth muscle content, and this reduction was restored by testosterone (but not estradiol) treatment. The results of this study demonstrate that androgen deprivation alters the functional responses and structure of erectile tissue.
ā Traish, 1999
combination treatments led to complete restoration. The combination treatment also prevented decreases in histological indicators of cavernosal integrity, including smooth muscle actin and collagen III expression levels and fat globule accumulation and sinusoidal density. These synergenic effects of [GH & T] on penile growth may follow changes in androgen receptor expression levels and were accompanied by decreased testicular volume losses.
ā JK, 2018
I donāt have time to go through my notes but you get the point from a quick google of some I recall. On that basis I would be inclined to agree with @moonman1 that if we sort it out the dysregulation of this critical transcription factor things will improve considerably, possibly resolving for many, and probably quite quickly. Thatās my opinion, for what itās worth.
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Man in less than a month how is it even possible?! , what did the doctors say regarding the doppler. Please tell me. Was the doppler made with prior injection to your penis because it says ābasicā in your photo youāve posted,Or was it really a basic doppler without injecting alprostadil or whatever substance to artificially gain a erection? I am refering to your doppler photo by the way
The problem is yeah in my case it was also like yours more of a erosion but realistically for many users here the critical factor is time. You can maybe restore tissue after a time frame of about half a year but everything above is unfortunatelly not possible with the latestest technology/research. Even if it is we normal human beings wouldnāt even have the money to buy the treatment. Even Sage therapeutics denied a clinical trial with pfs patients. So how should it then be possible to get our hands on a more advanced technology like reactivating smooth muscle cells or whatever. In 20 years maybe but not at the current state of research.
The idea is that all our problems are related to a lack of androgenic signaling and as @Axolotl has pointed out, there is reason to believe that the return of proper androgenic action may result in a reversal of our symptoms. This is supported by the brief honeymoon periods that some people experience during the use of anti-androgenic substances. People have described quasi miraculous recoveries on such substances, which toally makes sense in the light of the theory that is currently investigated.
Sage Therapeutics is targeting the market for depression treatments. This is a multi-billion dollar market. Of course, they are not interested in doing a trial for a small group of patients that suffer from a very rare condition that is not widely accepted and often rejected. Thatās because commercial drug development is highly expensive and there is no additional benefit in including us. If they capture the market for anti-depressants theyāll make billions. Why would they waste any time on a small and irrelevant group like ours?
The fact that we as a community are so small and irrelevant is why the admins here have decided to branch out. As you may have read here already, it turns out other conditions are likely driven by a very similar or identical mechanism. Hence, it makes sense to join forces with the respective communities to make our problem bigger and more relevant. The more relevant we are, the more resources we can gather for our cause. Thatās why everyone from these communties needs to support the survey and 23andme project.
Still, it is unlikely that a drug will ever be developed specifically for our condition. However, our problem is closely related to key issues in prostate cancer research. And billions are invested in prostate cancer research which may result in benefits for us.
While a drug may never be specifically developed for us, we may get lucky and profit from efforts in prostate cancer research or may have at least some therapeutic benefits from developments like Sage-217. But there are also technologies like Crispr that are fast becoming powerful yet cheap tools that may not need billions of developmental costs to be applicable to us.
@Axolotl has explained it in a different thread:
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This thread is too doom and gloom. Myself and many others have experienced full recoveries at times. My longest lasting was from cyestine and histadine, actually. I got everything back within DAYS. It was miraculous. Oilyness, drive, sexual health, hair loss. All within 3 days a flip was switched. And this lasted for many months and may have last for much longer if I didnt mess around with minox and 5htp. Theres many other things Iāve done that have helped as well, but one thing that was made clear was just because I was āturned back onā didnt actually mean I was healthy. I just had the opposite problem. I was too sexually stimulated and had too many dht symptoms. We need to find the middle. Iām more balanced now but not 100% where I want to be, and Iām fighting fibrosis with shockwave, which more should get on (I think everyone) as a preventative as it is the only researched solution.
I know we can reverse it. But i dont want to just reverse it back to how i was before. I want to be healed. And that is a much more complicated picture.
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CRISPR do it only in China and not on humans.
I wonder if the same results would appear in men who have ED not caused by pfs (something crazy like 1/4 have it). Especially if they had it for a while.
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Can u tell your āgenital storyā here briefly please? I tried to find yours but couldnāt manage to do so.
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