@Renegade What helped you if u don’t mind me asking
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I’ve theorized the same as you before, but after reading multiples studies and I find it unlikely that we still have finasteride lingering in our bodies.
What I think is quite clear though, is that for some reason 5AR stops or decrease it’s enzymatic activity in the brain. I haven’t seen any evidence that’d its due to permanent methylation to the gene however. According to Melcagnis study, the patients with no methylation of 5ARD2 still had low 5AR metabolites (among other neurosteroid changes).
Further people have tried DHT supplements with slightly positive or negative outcome.
This is likely due to supplementing DHT will not help with all the other neurosteroid production. And recent studies have also shown that DHT won’t readily cross the blood brain barrier.
I do however believe that some of the physical effects of finasteride can be mitigated with DHT supplements.
Mainly penile and/or prostate issues. But the issue here is that you can’t supplement DHT alone, but you’ll need a full blown HRT regime.
In healthy young men your T to DHT ratio should be 1:10 - 1:20 (5-10%). Supplementing with T has shown to keep this ratio. In older men the ratio doesn’t stay consistent, as 5AR methylation is a normal part of aging.
One test that could be conducted to check for 5AR activity could be to increase onces T level and check if the ratio stays 1:1. Unfortunately I cannot test for DHT in Sweden, otherwise I would try it out myself.
However this is not the whole extent of the issue. In rat studies it’s been shown that finasteride treatment lead to changes to the estrogen receptors, even after a wash out period.
The result was increase in estrogen receptor alpha and decrease in estrogen receptor beta.
ERb knock out mice have some traits that reminds me of PFS.
-Reduced social interactions with same-sex.
-Impaired aggressive behavior.
-Reduced or unaffected stress response, but during forced swim test they took longer to start swimming, and didn’t swim as long (eg. less will to live).
-Decreased RNA expression oxytocin (love hormone).
Among others.
Another interesting part is the increase in negative allosteric modulators of the gaba system, coupled with a decrease in positive modulators.
Again, in a study done on zebra fish and opioid self administration, they saw that finasterid greatly decreased self administration, and there was a significant increase in DHEA-S. DHEA-S is a negative allosteric modulator of the gaba system.
My own blood work show I have elevated DHEA-S. Which could be due to finasteride, but since I don’t know my value pre-fin I can’t say for sure.
Also fin inhibit 5AR2, 5AR3 but also 5BR2. This itself has affects on us that I think many people overlook, as when you read about finasteride it’s mainly advertised as a 5AR2 inhibitor.
I haven’t had time to research how everything is connected yet to the extent that I would like. But one thing is sure and that is that finasteride affect much more than we once thought.
I’m a firm believer that even if we can’t “fix” all our issues, we can alleviate our symtoms to a degree where we hit a quality of life high enough to live a fulfilling life.
But with the information we currently have, it’s unlikely it will be as easy as to swallow a pill. But rather we need to adress our issues from many different angles.
Going forward I’m going to try different remedies on myself and posting what happens. Sadly in Sweden HRT and TRT are basically non-existant and it’s hard to get your hands on experimental stuff life peptides. So it’s likely going to take time, since I don’t want to put any subpar suppments in my body.
As we all know, it’s much easier to destroy something, than it is to build it up again…
If anyone want sources about anything I’ve just said, just say and I will post (posting this from my phone and I have many papers downloaded on my pc).
Edit: And I just want to adress anabolic steroids.
There is no anabolic steroid (which I know of) that is as androgenic as DHT. Many people are talking about Proviron but it’s not oral DHT, and Masteron is not injection DHT. Neither of those steroids are as androgenic as DHT. Most anabolic steroids is made to be less androgenic, and more anabolic than T/DHT.
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I am the OP of this thread and after 5 and a half years I have done nothing but worsen each year to the point of permanent physical disability now…
I’m sorry to hear that.
I’m also sorry for going off topic in a thread this serious.
Have you ever considered trying some kind of treatment?
Tried them all…father time has done more than anything…That and baking soda…
Don’t worry about going off topic it’s been very constructive but for some people nothing works.
I’m sure something works for everyone, but since we have no way of knowing what’s wrong, it makes everything we do a shot in the dark.
And sometimes you’ll hit, but most of the times you won’t.
I’d really like to read your story but I had a hard time finding it. Would you mind giving me the title of your thread or link it?
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Baking soda? Like ot helps you?
Could you please link this study?
There you go bro!
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I still wonder why most people however don’t seem to suffer from lasting effects from Finasteride treatment.
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Well, I’ve tried probably hundreds of things but here is the quick and dirty of what I benefited from over the years…Just FYI, they all weren’t done at once and there are a LOT of specific details to each one:
Wellbutrin XL
Trt
Proviron
SJW (hypercin)
Arginine
Running (3 types)
Probiotics
ALCAR
Rhodiola
Fish Oil (just for overall health)
Ubiquinol (same)
Magnesium glycinate (for sleep)
Melatonin (same)
Low carb/paleo diet
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So not just the skin.
Some of these effects persisted (i.e., the upregulation of the androgen receptor in the cerebral cortex)
This is a horrible name for a thread btw.
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Yeah, but androgen receptor change is to be expected. Lowering the most potent androgen will lead to adaptations to make less potent ligands more potent.
What’s interesting is that I always suspected ER was involved but this is the first time I’ve actually seen is discussed in a scientific paper.
Now I wonder if it’s due to the inhibition of DHT and thus depletion of 3b-diol that we get these changes?
As we’ve seen in prostate cancer cells during ADT, cells either express more AR to get the same androgenic activity with less potent ligands OR change it’s dependency all together eg less expression of AR (androgen resistant prostate cancer).
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@Cbrandel, compared to many posters on here you seem to be quite logical and have a reasonable working level understanding of the systems at play. It’s refreshing.
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The more I read about PFS the more I think our issues stem from issues with the endocrine system.
After all, hormones are strong regulators of gene expression.
Now people are going to disagree with me, but our system is finely tuned during puberty and doing what we did, to basically cancel out one of the most potent hormones there are is going to come with consequences.
Our system feeds of multiple feedback loops and hormones express themself differently in different tissues. That is why it’s not as easy as supplement with X because then Y will change. Or X won’t reach where we need it.
Some people are more resilient than others when it comes to this kind of things, their system is more robust. This could be genetic.
Another thing that makes your system more robust is age, or time. The more time you do X the better you get at it. Our internal systems work the same way.
That is likely why younger guys are at a higher risk to develop PFS. As older guys endocrine system is already “set” at what they want. So if they stop the pill they have an easier time to reset to baseline.
Of course this is a generalization, even older guys can develop PFS.
And thank you for the nice words @orthogs
I only try to look at the data and what we know, and draw some conclusions. But as the data is thin, and I don’t have equipment to test most of my theories myself I’m not sure how much help I could actually be of.
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I understand what you’re saying. At first, I also saw a generalized hormonal and neurotransmitters imbalance (and some other proteins). I later read that it was all about androgen receptors being silenced/hypersensitive and it was messing up the hormonal and neurotransmitters balance. I though alright, could be !
I later read that fin had a lasting effect on 5ar producing cells. It was my interpretation that some fin could be stuck there, but it could as well be that the 5ar cells didn’t recover. I like the later version better because epigenetic changes to those cells could be a cause and that’s something I can do something about.
There are many ways that will make a cell behave differently. One is a change of hormonal stimulation and /or inhibition. It could be a change in mineral balance (like electrolytes), could also be the central nervous system for some cells. But epigenetic changes are taking place all over our body every days, and normally not to a degree that would disrupt the whole body homeostasis. Epigenetic changes, by definition, change how a cell behave.
Changes in minerals have been tried and yes, it does something but it’s not a cure. Changes in the hormones and neurotransmitters is definitely something I take as a fact (and also changes in many other proteins). We can supplement just like with minerals but in my case and from what I’ve seen, it’s not a cure either.
In my humble opinion, the epigenome is the balancing system you’re talking about, the one formed during puberty and the overseer that smoothed out an otherwise random selection of genes from either of our parents. There has to be a harmonizing system because some of those genes would have opposite instructions and the way the epigenome dynamically works, by trials and errors, fit the bill IMO.
And on top of that, after destabilizing the epigenome of some specific cells, there’s certainly a feedback loop between the epigenome and the unbalanced hormones and neurotransmitters.
Let me give you an example: alcoholism is mainly caused by epigenetic changes (I’ll argument that point below). But being alcoholic makes the body build tolerance / dependence, and when tolerance is high, a sudden stop can kill the alcoholic from unbalanced hormones and neurotransmitters and/or some other things that made the tolerance / dependence possible. However, if the alcoholic manage to stop and remain sober for 5 years, then one day takes a drink, he is almost certain to relapse and get back to where he was 5 years before, and that within just a few weeks. That’s the epigenetic part: the memory of how the body react to alcohol…
So they took mice and made them cocaine addicts (because who doesn’t like cocaine addicted mice ?). Then, they withdrew cocaine from the mice and after a period of anxiety on withdrawal, the mice began to act normally again. They divided the group into two: a test group and a control group. To the test group, they injected an epigenetic reset drug that erased all epigenetic markers and reset the histones.
Then they put the two groups in a single cage, with cocaine. The control group went straight to partying while the test group with a blank epigenome had completely lost the “psychological” addiction to cocaine and didn’t touch it.
The 5 year sober alcoholic still has his epigenome modified. If he takes alcohol, he’s back on the ride. Were he to be injected with the same drug as the mice, I believe he would drink like a normal person and sure, maybe develop alcoholism again later on. But not within a few weeks. (the drug exist but the article I read didn’t say if the mice survived it later on)
So my point is, the 5ar cells, the androgen receptors and obviously many other things are deregulated. There could also be feedback loops from an unbalanced system that unbalances another, and another, which ends up unbalancing the first one too. But I believe it all started by the epigenome and considering everyone has a different DNA and a different state of his epigenome, that would explain why most people don’t get pfs while some do, and why those who do all have a unique set of commonly shared symptoms. Also to note, other epigenetic diseases have a very similar set of symptoms which manifest differently for each one.
So, I’m certainly open to any suggestions on supplements, drugs or activities that can contribute to getting better but at the same time I’m having steady results in doing things that repairs the epigenome. I will continue and at the same time, please share what works for you !
@Cbrandel, I don’t see any contradiction in what you’re saying and what I’m saying. I am taking amino acids and supplements as well. And I diet and do tricks that are said to repair the epigenome. I think we all have to gain from me, trying this experiment. If it doesn’t work beyond what it has done already, no lost efforts to anyone but me. But if it works ! We just need one cure and the epigenetic approach could be a common cure to all ! I just wish I had a more definitive treatment than just being ketogenic plus a few tricks. I’d sure like to know more about the drug that was used on those mice !
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Might be this study you mean?
But yeah, I’ve read a few and they use HDAC inhibitors.
This have been proposed as a cure for a long time and I think some of the OG members on here even tried diffent HDAC inhibitors but with not to much effect?
This is a nice, although heavy read about epigenetics.
Theres some discussion how hormones affect epigenetics (DNA hypo/hypermethylation) etc.
Also how big of a factor the parents life choices are for the offspring, before they are even born. It’s super interesting, but also a little bit scary to realize.
Thanks for the links. I will read those. Yes there’s something scary about it. Epigenetic, just like this disease, shows how little we control our thoughts, our decisions (because of what motivates them) and our actions.
Nonetheless, we are standing here, aware of our existence, and we can choose not to act on an instinct or to ignore anxiety and depression (it’s just caused by the disease) and just do what we have to do.
Not sure we can simulate empathy while we have anhedonia…
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Those are anti-androgen without being pro estrogen ?
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