In my humble opinion, as i mentioned already in many posts, the only possible way to understand what is going on, is to establish an animal model of our disease…Its the only way…Trying to do more research on actual human beings, when we cant even get biopsies from the prostate, let alone from brain regions that might be affected, would result in more studies that take decades, and come with laughable results (like its only in our heads)…
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we’ve already gone over that before
before we can use animal models, we need to first understand PFS much better.
so we are like 2-3 steps away from animals
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Any other country you have in your mind? EU maybe, China got good science and will be done for way cheaper than if it’s done in the US…
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what do you guy think what other country should we turn to?
Russia, India or China?
I would say ideal thing would be 2 countries at the same time and compare the results.
but life is not that easy.
I agree that we are up against an aggressive and unethical adversary. ButI think anger without action is worse than no anger at all. When we are angry we should methodically, calmly, rationally inform people around the web with short and non-nutty sounding mentions of what the long- terms side effects are and what drugs cause them. When we sit around being angry and or lashing out we don’t get anything done except making ourselves look like nuts. The worst is when we sit and complain instead of doing.
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We need a lot of effective basic science, and awareness efforts need to happen in tandem, both for scientists and the public. The clinical situation is very poorly established.
The absolute priority for us has been to establish a clear data set for the symptomatic situation of patients. Thanks to the people who took the survey and encourage others to do so, this is happening. Thank you for the kind comments on this work, and most of all for filling it out.
@Awor and I recently had a positive meeting with an accomplished biology professor and director of a cutting edge European center we are hoping to work with. They were extremely impressed by the survey and the early results coming out of it. They commented specifically on the strengths of gathering responses that answer our questions for different points in time. He emphatically urged us to do all we can to strengthen this data set with as many contributions as possible. It can support mechanistic investigation. More Isotretinoin and PSSD patients are urgently needed, but every Finasteride patient counts too. As others have said, if you haven’t taken the survey, this is an absolute priority. Please do so. It will also catalogue you on our side for contact and potential invitations to participate in the event of research opportunities derived from this effort. And regarding what I’ve mentioned: We’ll talk about it if and when we have something concrete - the ball isn’t always in our court.
Secondly, there is a dire need for outward public awareness that will garner attention and recognition of how this is affecting real people. Please think about pulling together and providing a Youtube video for the project if you’re able - we’ve only had one submission so far. We are hoping to soon reach out to the families of loved ones who took their lives to provide the same if any feel able.
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There is a generic for Propecia so Merck has already written off the profits it got before finasteride went generic, so there is really little to gain fighting Merck alone. You would have to fight the entire pharma industry. It makes more sense to me to educate doctors with the science out there so that the drug gets used less and less and eventually gets taken off the market completely.
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We have a video project, please participate.
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An across the board gene expression analysis in PFS patients will inevitably show that many hundreds of genes are disregulated. By itself, this finding is unlikely to reveal the etiology of PFS, nor will it rule out one theory in favor of another. The epigenetic silencing of just one gene, srd5aR2, the one responsible for 5a-reductase type 2, will change the expression of all androgen-dependent genes through reduction of DHT, and will also influence a cascade of other genes that are affected by related processes. There are ways to disambiguate these effects in other types of studies, however.
As an illustration of the wide range of genes likely to be affected, here is a paper which estimates the number of genes affected by finasteride - 1434 genes. A similar (in fact, worse) pattern is likely to emerge if srd5aR2 is not being expressed.
Transcriptomic profiling in Silurana tropicalis testes exposed to finasteride.
Abstract
Investigations of endocrine disrupting chemicals found in aquatic ecosystems with estrogenic and androgenic modes of action have increased over the past two decades due to a surge of evidence of adverse effects in wildlife. Chemicals that disrupt androgen signalling and steroidogenesis can result in an imbalanced conversion of testosterone (T) into 17β-estradiol (E2) and other androgens such as 5α-dihydrotestosterone (5α-DHT). Therefore, a better understanding of how chemicals perturb these pathways is warranted. In this study, the brain, liver, and testes of Silurana tropicalis were exposed ex vivo to the human drug finasteride, a potent steroid 5α-reductase inhibitor and a model compound to study the inhibition of the conversion of T into 5α-DHT. These experiments were conducted (1) to determine organ specific changes in sex steroid production after treatment, and (2) to elucidate the transcriptomic response to finasteride in testicular tissue. Enzyme-linked immunosorbent assays were used to measure hormone levels in media following finasteride incubation for 6 h. Finasteride significantly increased T levels in the media of liver and testis tissue, but did not induce any changes in E2 and 5α-DHT production. Gene expression analysis was performed in frog testes and data revealed that finasteride treatment significantly altered 1,434 gene probes. Gene networks associated with male reproduction such as meiosis, hormone biosynthesis, sperm entry, gonadotropin releasing hormone were affected by finasteride exposure as well as other pathways such as oxysterol synthesis, apoptosis, and epigenetic regulation. For example, this study suggests that the mode of action by which finasteride induces cellular damage in testicular tissue as reported by others, is via oxidative stress in testes. This data also suggests that 5-reductase inhibition disrupts the expression of genes related to reproduction. It is proposed that androgen-disrupting chemicals may mediate their action via 5-reductases and that the effects of environmental pollutants are not limited to the androgen receptor signalling.
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Sibelio, what do you think should be done now? What pathway do you see toward corrective therapy?
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I think it would be great if someone with the necessary background to understand things well could write a quick explanation of why or how PAS, PSSD, and PFS might be related so we could take it to other communities for the purpose of acquiring more survey completers. I would love to do that writing myself, but I’m not remotely knowledgable enough on the science. Would be more than happy to serve as messenger, however.
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I currently take transdermal DHT, which helps my joint pain tremendously. I have other positive effects from it as I have described elsewhere.
My longer term hope is that the epigenetic changes in PFS can be reversed by strenuous exercise. There is evidence this might be possible, as showcased in this thread: Exercise and Epigenetic Regulation
I have already begun my exercise program but have suffered a temporary set-back due to injury. I will resume shortly and hope to accelerate fast.
I also can’t exercise because of joint pain. Are there any safety concerns with transdermal DHT?
Of course. It is a very imperfect method of replenishing lack of tissue production of DHT, which I believe I have.
You have to dose it right, at a minimum. I would say you have to be within the normal serum ranges to make sure the effect on non-affected organs and tissues is somewhat limited.
It increases hair loss tremendously. It also affects my mind in a negative way - makes me more impulsive, aggressive, and a less deep and creative thinker.
Also, if you put it on genital skin, which I do, it may increase cancer risk.
Still, the benefits outweigh the costs for me for now, as I literally can’t walk or do anything with my hands without it.
Aren’t you concerned that most DHT is produced and consumed locally (so high serum levels aren’t helpful but rather mostly just cause disregulation of other hormones via the HPA)? I experienced zero benefit whatsoever from TRT.
If it’s really helping your joints then fair enough, but I personally would not be interested in disrupting my hormones without good reason.
I am concerned but I think the tissues do get some DHT from serum, especially if starved completely. Some tissues need less DHT than others and these can benefit more from systemic supplementation.
I had the following changes after I started taking DHT:
Progesterone has dropped from 0.805 nmol/l to 0.541 (up to 0.474) and is almost in range now. This is a 33% reduction!
Estradiol has also dropped from 95 to 72 pmol/l (41.4 - 159.0), which is a 25% reduction.
DHT went up from 175 pg/ml to 605 pg/ml (300-850).
Free Testosterone went up from 29.27 to 32.32 pm/ml (7.0 - 22.7).
Total Testosterone stayed the same at 23 nmol/l (9.9 - 27.8).
SHBG went up from 33.4 to 56.08 nmol/l (18.00 - 54.00).
The Free Testosterone measure seems paradoxical and might have been a fluke. Need to repeat all these at some point.
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Is your libido any better?
It is only better when I apply the DHT cream locally on target tissues - i.e. the genital area.
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Interesting that it is apparently affecting your brain (libido) only when you put it on your dick? Does it help with genital numbness?
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Hi @vkg1, thanks very much, I’m sure that will be a big help. @Northern_Star had some success doing so. We have an internal literature review that does cover this in detail, but A) it is huge and B) we need further feedback from scientists who have indicated they may be able to help advise us on how to best use parts of it for more effective dissemination, possibly via a journal, so it isn’t shareable at this time.
Regardless of any scientific justification, I think the case for “how they may be related” at the level of patients taking a survey (which is really quite a low bar of effort to clear) should be a case that can be simply made by demonstrating the persistent symptom profile in the literature reviews of PFS in line with what many pssd patients and post accutaners plainly describe. Healy et al. (2017) already have published results of a far more limited survey in medical literature drawing attention to a symptomatic and behavioural overlap across the 3 groups. Like post-finasteride patients, post-accutane and post-ssri patients are a heterogeneous group in symptoms and severity. Establishing the existence of the clinical profile and, secondarily, analysing the significance of overlap in the data should be a priority before needing a clear explanation of why. After all, although many users have their idea of what the symptom profile is, it would be wrong to assume the scope is adequately acknowledged either broadly within the patient community or in wider appreciation of the condition - it isn’t. This is a priority before any explanations, and the survey has been designed by complete review of related literature, complete review of cases on this site, and collaboration with other patient communities to achieve that aim as best possible (with acknowledgment of the problems of any such surveying, e.g. recall bias). It is purely to establish the clinical situation.
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