I would say it proves there is something going on, but there is a key line in that abstract as far as pinning PFS on the drug itself.
Missing data.
Now obviously if a person had this before and after, any Dr, Researcher, or Lawyer would take notice.
So maybe that would be the next step.
I guess though if PFS affects such a small percentage of those that take Finasteride that would be a hard study to pull together.
I guess some sort of reverse engineering comes to mind in our case.
Strengths & limitations: Strengths of this study include the evaluation of multiple proposed etiologies for post-finasteride syndrome. The study is also strengthened by the fact that not all data matched the initial hypotheses, qualifying the argument for the existence of PFS. Limitations include potential selection bias arising from more severe phenotypes seeking care; lack of gene expression data prior to 5ARI exposure; lack of non-penile tissue samples supposedly involved; and a lack of mechanistic data to imply causality.
This sounds like hair loss forum bullshit. People untrained in any scientific field cooking up wacky, impossible methodology to âproveâ one thing or the other on the Internet.
Science is conducted in the real world with limited time, money, resources, willing participants etc etc. Letâs work with what we have an keep the progress going. Save the hair loss forum bullshit for the incels
Unfortunately the study leaves a lot of questions unanswered. I would almost say that before a suitable therapy has been found, the probability is higher that a suitable therapy for most people will be found by accidentally.
Our data revealed differential expression of many genes in
pathways controlling gene expression itself. This may be due in
part to the fact that steroid hormones act by inducing changes in
gene expression or by AR activity, and may also explain the
nature of the persistent effects of 5ARI exposure. Namely, exposure to 5ARI could lead to permanent changes in genetic expression through unknown mechanisms which cause the changes we
were able to measure and analyze
Bottom lineâŚ
This study is more extensive than you might first think and I believe they really did try and go after the reason behind all these side effectsâŚ
An interesting read. Iâm keenly awaiting axolotlâs analysis and hearing what possible future research paths can lead on from this. I wish I was more well versed in epigenetics so Iâm unable to really impart any meaningful point of view, but the gist I seemed to get, which perhaps may also serve as a faint glimmer of hope was that itâs possible that the depletion of neurosteroids may cause downstream overexpression and underexpression of those clusters of genes. An interesting thought from Khera⌠I wonder if this would mean if somehow boosting neurosteroids though a drug may result in alleviation of downstream problems?
He also went on to mention that overexpressed AR may similarly cause the downstream problems (an idea already well established on here). Iâd imagine trying to correct neurosteroid deficits would be more straightforward than attempting to forcibly attempt to downregular AR expressionâŚ
Firstly, apologies for relative absence from the forum - I am busily engaged with many of our projects and am of course eternally grateful to the team for keeping this important resource going. As a very severely affected patient, I have to judge where to put my efforts and itâs currently managing the team, liaising with scientists and other efforts like organising/editing the video project. Iâm particularly grateful for the recent commitment of @Sugarhouse, who has been simply amazing. I am very excited about the new series of video interviews that patients, their loved ones and professionals have kindly volunteered for. Please get in touch with @Sugarhouse if you are interested in telling your story for our growing YouTube channel Itâs so important. As well as putting the issue on the map, it informs as to what is really happening to people, particularly those badly affected.
In regards to the publication, I have read it in detail yesterday and have posted a summary in the PFSNetwork science section here:
As well, with the team, have provided a broader news update on the PFSNetwork newsletter here, which contains my thoughts on the paper:
To expand a little on my thoughts for those interested, Iâm pleased by the report, despite the unfortunate delays. It is however very timely for our current efforts. I consider this to be the most significant biological investigation into PFS yet, and I am broadly happy with the analysis. Anyone who has looked at the literature review on the propeciahelp site or read my discussions in the past on this subject will probably know it is largely what I expected to see, as some have alluded to. However, thatâs different to having the results and specifics.
I consider this clear report and pathway analysis that ties the findings to biological systems directly relevant to the awful symptoms patients are reporting is extremely valuable. Throughout the paper, this is apparent. Findings of certain deregulations are interesting and serve to provide a more connected picture, as mentioned in the blog above. There are many implications from the deregulation of genes regulating reproductive, genitourinary, nervous, musculoskeletal, cardiovascular, and immune systems that are borne out in symptoms, and these are noted in the paper. This is very important, as previous hypotheses continued despite an increasing disconnection from the breadth of symptoms and peculiarities of the syndrome. Importantly, alongside acknowledgement of the biological observations, they are correlated by pathway analysis to these epigenetic deregulations.
ââŚbetter the hard truth, I say, than the comforting fantasy. And in the final tolling it often turns out that the facts are more comforting than the fantasy.â
â Carl Sagan, The Demon-Haunted World: Science as a Candle in the Dark
I hope patients take heart from this. I expect for some this might be tough to see, especially as it is complex. I would also caution against trying to make sense of this if you do not have a good understanding of the core concepts (I have recommended a good primer before in a book called The Epigenetics Revolution for those interested in gene expression). However, this hasnât changed anything for you personally since yesterday, and you may be quite a bit better off than the patients in this study - certainly than two of them, as theyâre sadly not with us anymore. We know well PFS affects people to dramatically different extents, and some see improvement. As others have alluded to, unfortunately it should be well known by now that the worst of us are dramatically and permanently physically and cognitively changed by this condition to the point we canât continue a normal life. This doesnât happen without something seriously wrong. Having important information, including this epigenetic data, will better allow us to get on in the appropriate directions to understand and ultimately address this.
Itâs also important to reflect on expectations of this study. âThe Baylor Studyâ had become an emotionally charged subject in patient discussions, somewhat disconnected from the reality of its design. The study was designed to deliver this RNA microarray analysis, and I think the paper could be considered to be a near best case scenario. There are inherent limitations in the fundamental design, including the lack of proven causation, the low power due to the amount of patients involved, single tissue analysis, lack of genomic data, and mechanistic implications that arenât yet clear, but the study makes sensible recommendations for further pursuits which I endorse.
So, further pursuits: As @Sugarhouse alluded to, despite our good relationship with the PFSF - I hope to partner with them on these projects and am in touch with them - we needed our own charity infrastructure now. The burden of this platform and everything weâre trying to do beyond that is significant. We will be eligible for certain things we need if registered as a charity, so we are currently setting this up. We are in good talks with scientists and have a working group we hope to expand through a conference later in the year with professionals. Nothing is fixed yet as the professor of genetics we are talking to and hoping very much will help us is not yet clear they will have time. They are well published in their field (including in Nature & Cell) and experienced in resolving population questions regarding rare diseases, so I, and the other excellent scientist I am extremely pleased to be helping us, are keen to defer to her advice if possible in regard to the next steps in looking for a predisposing factor. If this was obtained, a true animal model would be possible, and this would resolve a lot of questions and challenges including the great difficulty accessing CNS tissue from patients and of course attempting treatments. This is a priority for the team and I. It is also critical for the safety of consumers who are STILL unbelievably without anything CLOSE to appropriate warning for a cosmetic product. As well, we have discussed studies in other directions building on the findings here and prior work.
The staff team will be able to commit a significant amount and hopefully get these initiated, but we will need to engage a lot of fundraising activities through the forum here and through the new content we are preparing - as well as helping with personal campaigns. I am sorry this isnât faster, but our issue is rare, we do not have endless money, and we need to be very clear on what we will be pitching is justifiable as our best option, taking full account of the clinical picture and peculiarities of this syndrome. This is why we have consulted so many scientists over the past years, and have not gone with the first option available just because itâs âsomethingâ. The moderator team will keep you updated.
Finally, I would like to say a quick word on self experimentation based upon this. I know some patients are frustrated with the slow pace of understanding, and see the release of publications like this as potentially providing clues to google and in the hope of finding a therapy to attempt. I understand. I am suffering intensely and would give anything for a treatment. This paper has not presented us with actionable information in regards to treatment. Substances that downregulate/interrupt AR signaling, or inhibit androgens, have peculiarly provided relief across the history of patient forums. They have also - sometimes not long after for the same person - caused significant worsening that has in some cases preceded suicide. The moderators endlessly warn patients of the dangers of further antiandrogenic substances in PFS. This is a demonstrable common pharmacodynamic of the substances that cause unfortunate people to end up here in the first place. I just want to reiterate for those that might not be aware and might think to do so after reading this paper: In my view as the administrator of propeciahelp, and somebody obviously invested in this subject, it is not safe for PFS patients to take antiandrogenic substances. This is especially important to consider if you are severely affected, or developed PFS after very little exposure to finasteride.
While this may look like a sobering report, in my view this step forward should be seen as a source of hope and vindication. Key factors (including the AR) are master regulators of the epigenome, and have enormous downstream implications. The technologies to interact precisely with these problems are not here yet - but they are rapidly on the way, independent of us. We need to get on and get the answers we need so the future will see a treatment. And, with more understanding, I donât preclude the possibility of some relief with tools available. Please keep hope, pull together and get involved how you can - @Sugarhouse would love to hear from you.
Finally I would like to thank the PFS foundation, Awor, and Dr Khera and team for organising this study, and deeply thank the staff team here (and non-patient volunteers) for the tireless job they do keeping the forum available. Thank you to all patients banding together, particularly those who have or are going to contribute to our video series.
Thank you to all patients for your courage in persevering with this condition, and your empathy to each other. Love to you all.
I already warned in this forum that there was a high level of broscience. Nothing we donât know was show in this study. Finasteride an endocrine disruptor that produces a cascade of metabolic, genetic and androgenic changes.
Solution same experimenting with testosterone, hCG etc.
Mild cases: diet, sport, androgenic substances.
Severe cases: hormones.
I may be in over my head here but arenât there things to do to reverse epigenetic changes? Keto / Carnivore diet supposedly normalizes DNA. Lifting weights and exercise causes epigenetic changes too. Might explain why some have gotten better with diet and exercise
I think Dr. Marco Bortolato did a controlled study with rats who were intentionally stressed (I think simulated drowning) and they found that the rats administered with finasteride had a dysregulated stress response. Humans and animals experience stress differently so it is hard to compare.
Melcangi also did some studies with rats where I think he knocked out the 5AR II gene but I donât remember the finding
I know the study didnât address this and wasnât supposed to but what about the âcrashâ many experience where all function returns to normal Or close to normal for a couple days to a month from what Iâve seen. What the hell happens that people wake up different overnight
