Pls keep us updated 
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I have a thread I’ll be updating as a log. Keep yourself posted for updates 
My case exactly.
@Sibelio I’m very much following your theory and explanation. You seem to be constantly steering people back towards the underlying issue of a ‘malfunctioning’ AR, which does seem to fit with most all our symptoms and reactions to protocols.
Do you (or anyone else) have theories on how exactly taking FIN would leave some with a malfunctioning enzyme?
Epigenetic changes I somewhat comprehend, but don’t understand the full mechanism by how the drug would cause an epigenetic change in the formulation of an enzyme, leaving it malfunctioning. Otherwise, are there any other theories that could present how our conversion mechanism (the enzyme) would be malfunctioning, besides epigenetic?
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Do you know whatever happened with Mew? I guess his theory was along these lines about a decade ago. I wonder if he is still around and optimistic about prospects for recovery.
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Does anyone have advice for what I should talk about with my urologist? I have been referred to one who is familiar with PFS. Could I use any information in this thread to help him guide his hypothesis testing?
Methylation of a gene can be only in certain cells, not all cells of the body. That’s why every organ in your body is different despite they have the same genetics. So yes, there are PFS studies were methylation was seen in the cells of the brain liquid (that is difficult to get so I suppose there was no methylation in blood) cells. But I like the idea to check methylation in various tissues - it makes a lot of sense
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Castrated rats have no testicles to produce TRT, but they do have fully functioning 5a-reducrase that turns TRT into DHT and other compounds. I think that’s the difference between us and castrated rats
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5ar is not our problem. 5ar still work. Problem is the AR that doesn’t respond to the hormones.
5ar gene methylation seems to be at least accountable for the neurological symptoms. A healthy brain is also important for libido, erection, ejaculation and the regulation of sexual hormones.
I submitted a draft wikipedia article yesterday. If/when it is accepted I will post a new topic to the forum. It had extensive references to scientific papers including five meta-analyses.
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Melcangi and colleagues in Italy are looking at neurosteroids. Here’s a new article that discusses neurosteroids. Warning that it is complex and speculative. See Section 1: Introduction and section 1.2.
Post-finasteride syndrome: An emerging clinical problem
Silvia Diviccaro, Roberto Cosimo Melcangi & SilviaGiatti
Neurobiology of Stress, vol. 12, May 2020
https://www.sciencedirect.com/science/article/pii/S235228951930061X
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Thanks, you are doing a great job, man!
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Another paper I came across yesterday that discusses neurosteroids:
Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know?
Rev Endocr Metab Disord
Traish AM, Melcangi RC, Bortolato M, Garcia-Segura LM, Zitzmann M
http://doi.org/10.1007/s11154-015-9319-y
https://www.ncbi.nlm.nih.gov/pubmed/26296373/
Attaching pages 1-5 as images (can’t upload PDF). Scihub has the full text. To find it, enter the DOI: 10.1007/s11154-015-9319-y
See especially Sections 1-5.
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Unfortunately it does’t show the full article here.
I highly recommend this article to anyone who whats to understand PFS. It also explains really many of the other symptoms like neurological deficiencies, blurred vision, increased risk for diabetes, cancer, heart-disease, stress intolerance. 5ar could even explain pain and skin changes.
I find it highly concerning that blocking 5ar inhibitors lead to death of brain cells! I am highly convinced that future studies will show increased risk for Alzheimer’s and Parkinson’s for Finasteride users.
If you have problems to read the full article https://link.springer.com/article/10.1007%2Fs11154-015-9319-y, some people use sci-hub.se to get around the paywall. Probably legally gray.
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Malfunctioning enzyme is most likely an inaccurate term. What I mean is disrupted 5ar2 enzyme function. This can in theory happen in more than one ways but the evidence points towards lack of gene expression of the gene encoding for 5ar2 (SRD5A2), which essentially means the enzyme is not produced in the affected cells.
At the tissue level, some cells may still be producing the enzyme, so the enzyme will not be completely absent from the tissue but will be highly reduced in concentration (and, in many people, more so than during regular Finasteride administration).
I have no idea how this specifically happens at the sub-cellular level or what all the different ways it could happen are but all evidence indicates, in my opinion, that it happens as a response to sufficiently low or rapidly falling DHT levels, which admittedly seems paradoxical.
The evidence in support of this theory is that people can get PFS from a single Finasteride pill, without any prior exposure. The reason I believe these reports is because I myself got PFS from a single pill. It happened within 20 minutes of taking the pill so there is no doubt it happened during a phase of falling DHT.
Note that this theory is in contravention to the dominant theory of PFS, which argues that genes are methylated in PFS as a response to rising DHT levels after cessation of Finasteride treatment in an environment of upregulated androgen receptor (AR) from prior finasteride use.
The dominant theory, in my opinion, cannot explain my experience and the experience of many others who got PFS from a single pill. It can also not explain, in my opinion, the experience of people who got PFS while they were on Finasteride.
The dominant theory can only explain, to my knowledge, the experience of people who get PFS only after stopping Finasteride. I believe, however, that this is a separate type of PFS (what I have dubbed PFS type 1), which is not caused by methylated genes (and is therefore less permanent) but by the state of AR upregulation coupled with an HPTA axis hormonal crash after stopping Finasteride. This, of course, is speculative.
Likewise, the dominant theory would predict that PFS can in theory be begotten from extremely high levels of androgens from steroid abuse when AR are overwhelmed, even without prior finasteride use or AR upregulation. This does not happen to my knowledge.
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Thanks a lot. I heard from people who got PFS from a single pill, but I thought it is due to the irreversible binding to the enzyme, so that the enzyme receptor complex is slowly cleared from the blood, which itself could lead to rising DHT levels that silence the 5ar-gene in a feedback loop.
I also thought the the upregulation is just a sign, that DHT or following cascades are too low or not working anymore.
PFS within 20 minutes turns down most of the theories that made sense to me.
Because I heard people get PFS when they reduce finasteride and because of the dominant theory I decided to tapper of finasteride super slow: the first 800 mikrograms over 5 months and since 9 months I tapper down 0.5 micrograms a day.
Reaching 230 micrograms I crashed (while tappering off mirtazapine - probably I had the crash already 1 year before but could cover most symptoms with mirtazapine).
Another thing that I notice were morning errections came back in waves under 180 micrograms, but they were oftentimes so long and painful that I woke up from it (contrary to what one may think they were not coming with any pleasure or sexual desire, they were completely disconnected from my brain). These hyper errections took place until under 100 micrograms although I went down less then 0.5 sometimes just 0.3 micrograms a day! I am still tapering off (73 micrograms now in 2 daily doses). The insomnia and mental symptoms are hardly bearable. Sex life is rare and not connected to much pleasure.
I would also support that there are various types of PFS (I think it depends on which organs are most affected by the 5ar-silencing). Does your type of PFS include mental problems like insomnia? And what where the first symptoms you experienced after 20 minutes? Were they different from what you experienced after 4-6 weeks (full clearance of the finasteride-enzyme-complex)?
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This is what my experience felt like as my mileage decreased and my weight increased while energy slowly decreased like clock work…As if something was slowly leaving your body month after month until you are just now left as an invalid slob…
Does finasteride affect the brain of everyone who takes it or only those who develop pfs?
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