This is my opinion on the matter. I saw Damon’s clinic report, and while he has clear ultrasound evidence of penile atrophy that other doctors of his have acknowledged, this symptom - probably one he’s 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 it’s “not reliable”. The methodology is in the paper. I doubt @Demon was given a reason for this opinion? I deeply appreciate Melcangi’s 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 don’t really consider anything particularly practical coming out of that stuff and I’m 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 Baylor’s results. This will be a real merit of the survey - making the clinical picture clear and not selective.
In regards to “are we screwed”…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 don’t 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 “PFS” 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. It’s very important to get across that “PFS” is obviously not remotely the same extent and sites across patients, and unless you decide to start on antiandrogens again I don’t see how that affects another’s 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 Melcangi’s 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 topic’s study is not correct, at least for me. It was after I crashed, wasn’t bloodflow related, and it was fast - over a few weeks. This isn’t 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, I’d imagine there’s the potential for significant improvement as this is what androgens by definition normally do to that whole business…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
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.
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.
– JK, 2018
I don’t 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. That’s my opinion, for what it’s worth.