Crash Understanding

General Discussion
#1

Hi there,

Something “unique” of PFS is the crash event. Understanding what the crash is will help us to understand the root cause. I think we should focus on it, and try to understand how this event may happen.
It seems that our bodies react somehow very drastically to high levels of androgens for any reason. That is why it’s also risky to use hormone therapy to cure our problems, our body may react and crash again.
Why is this happening? Why this is something not being reported by people who is taking hormones without having PFS?

#2

Only science can elucidate it. we can only imagine.

To begin with, androgen receptor manages epigenetic modifications as I remembered. It is one of the function of AR.

Under the drug, we are deprived of 5αR(type 2 and 3) and DHT(and other neurosteroids) are reduced to 30%, in order to survive and keep functions under the such condition, our body changes its structures. For example it doubles the number of AR to amplify and boost the function of AR. Then, wenn we stop the drug, the supply of 5αR recovers suddenly, and then the function of AR becomes excess.

At that time, the overloaded AR function may bring uncontroled excssive epigenetic modifications. It may be something indescriminal destruction over the whole of life system. It may bring AR function itself epigenetically blocked in order to put the brakes on the excessive AR functions.

I imagine the crash like this.

#3

I think Aki there is right about the original problem that occurs and then downstream from that similar but different things can happen which is why there is so much wild variation in what case responds well to and whar crashes another. If we really pooled together user experiences in an organized document by substance used and side effects we’d probably be able to identify symptom clusters too. I think the damage that branches off the original problem can be pretty random though even though with the changes specific things tend to happen more often. But then for example you’ll have the one person who got a really weird roll of the dice and doesn’t respond well to something the vast majority respond well to. On your question about hormones I actually wonder the same, part of the key to this may actually lie in that answer.

Based on my personal experience with crashes the theme is that what crashes me either had the ability to mess with an androgen signalling cascade that was very weak or completely shot down something in the dopamine related excitory loop that was also in a weakened state. Like for example one of my worst was from L-theanine and another from quercetin. Just recently it would have been curcumin but I knew better when I was seeing what would happen when I tried it so I had a tiny dash, if I ate a large dose it could have been the end of months of progress in a single moment. Signalling seems to be back at a baseline where the vast majority of things can’t crash it anymore but the curcumin experience recently proves certain things can still crash it that pre-PFS wouldn’t have been able to do anything at all. I’m starting to get a good feel for what is going on in my case though because I can definitely see the patterns here.

#4

Do you think the epigenetic modification happen just overnight? It seems to me a bit unrealistic. I was on my peak after finasteride, and the in crashed very hard from one day to another.

Also, if that is the case, then, why the people gets crashing again and again when playing with hormones (increasing DHT)? I understand we can suffer a crash for that reason, but just one and we should be able to get a new balance playing with hormones again. The main problem with PFS is that it seems that when we try to do that, our system “crash” again.
Something is happening in our systems/bodies that we don’t understand and it’s key to comprehend our syndrome.

#5

I’ve had my doubts too on that myself, I think it’s more realistic that some cascade breaks down and then things go under in chain reaction after that. For me with saw palmetto things started going downhill over the month on it and got horrifically worse in the next months following it with mounting symptoms. I don’t remember exactly the day when I started getting with with the waves of dizziness, andhedonia, and severe sexual dysfunction but that definitely for me marked the beginning of the worse of it.

I never played with hormones myself because I knew from reading all over the place it never works long term and everything eventually just crashes again. I can only guess on what that implies there dysregulation of how these hormones are used and if you add more this situation just gets worse even if the person experiences a temporary improvement in some areas.Receptors numbers increase or decrease all of the time along with hormone levels so don’t think just levels or amount of receptors is the issue in itself. It could be that the issue heavily involves the hormone systems because what initially happens but then involves a mess of a large number of other regulatory functions in the body too where if you introduce more of any hormone the problems in these systems can’t sustain it and you crash. The short answer we have right now that isn’t one of the million theories out there is that nobody is sure besides the clues in what makes a lot of us better and what can generally cause a crash tells us.

#6

I don’t think this is something thaaat complicated. Maybe it is just an autoimmune disease which triggers when androgens are too high.
I think so because I got alopecia areata right after crashing, which is another autoimmune disease and it is known that when you suffer from one, you are more likely to suffer from more at the same time (like your body is prone to these).
I heart about another user with alopecia areata, that triggers when trying HCB to get better.
It makes sense for me.
Also, because usually these autoimmune disease improve with eating clean, reducing inflammation, quitting drugs…surprisingly similar to what we do to get better.

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#7

Do you think the epigenetic modification happen just overnight? It seems to me a bit unrealistic.

IN MY IMAGINATION, unfortunately it is possible. The reason why it is possible is the function of AR itself managing some epigenetic modifications. when such AR get overloaded and the modificating function itself fall into excess and uncontroled, then the unusual unrealistic event become possible.

Also, if that is the case, then, why the people gets crashing again and again when playing with hormones (increasing DHT)?

IN MY IMAGINATION, because our system is terribly distorted and already lost flexibility and resilience supported by pre-established systematic harmony which it had had before taking poison.

I understand we can suffer a crash for that reason, but just one and we should be able to get a new balance playing with hormones again.

IN MY IMAGINATION, unfortunately maybe no. It is quite easy and in a flash to destroy a beautiful and erabolate work of art or a historical sublime architecture, but it is nearly impossible or at least extravagantly difficult to restore such ruined works as before.

it will be very long time before our body gloss over the structual distortion and then improves to a certain degree as far as possible. It is probably certain that our body has such power of repairing.

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Oh! Sorry, now I just realized I was confused. Without doubt, I thought “I” was asked, because your post is replying to mine formally. Forgive me…

#8

I’m not sure about it. It’s like…“hey we don’t really know what is happening here, so let’s assume is an epigenetic modification (being something you cannot test)”. If it is an epigenetic modification, and we have another equilibrium in our bodies, then…we should be able to “play” with that new equilibrium with hormones. However, it seems there is something in our body that doesn’t allow us to do that.
Like if there is something in our bodies that triggers when androgens are going up again. I don’t know if it is autoinmune, or there is something different playing a role here, but deffinetively there is something missing.

Also, AND I AM NOT RECOMENDING ANYBODY TO TRY IT, but I think maybe the poor equilibrium we have now is due to a sharp reaction from our body (crash) reacting very bad to high androgens (for any reason), but I am sure this was not necessary to happen and most people just felt better after finas discontinuation (like I also felt) but without any crash. Therefore, MAYBE if our body goes through the same process…is it unrealistic to think that we may recover another equilibrium (low DHT and then high DHT) without suffering a crash…? Just wondering.

#9

Testosterone bell curve…Androgen receptor overexpression is an epigenetic change itself…

It won’t go back…THe bell curve is where testosterone has detrimental effects…the more you increase it the worse it gets…

#10

to Mr. holyhead

I agree with your opinion that “the more you increase it the worse it gets…”.

On the other hand, I don’t think “it won’t go back.” Do you think ARoverexpression as epigenetic changes is irreversible?

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When we examined time since smoking cessation, we found that the majority of the differentially methylated CpG sites observed in analysis of current versus never smokers returned to the level of never-smokers within five years of smoking cessation. This is consistent with the fact that risks of many smoking-related diseases revert to nonsmoking levels within this period of time. Our results also indicate that cigarette smoking induces long-lasting alterations in DNA methylation at some CpGs. While speculative, it is possible that persistent methylation changes at some loci might contribute to risks of some conditions that remain elevated after smoking cessation.

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I don’t have scientific knowlege. But I read this article recently and now I think that epigenetic modifications are never irreversible. Even if not all of them are reversible.

#11

I think so…atleast not on its own it won’t…Also I think this much different than changes that everyone talks about…like diet, smoking and exercising etc…it’s a much more severe an extreme change in epigenetics

I think the lady nadine hornig in Germany will eventually tell us what went wrong but how long it will take to do that I don’t know…

#12

I agree with you.

I think that epigenetic distortions caused by fin are reversed enough in the body of recovered (from true pfs) people. So, such epigenetic distortion itself should be not irreversible, as like in the case of smoking.

But, as you say, something should be different. I think so too. Because some people cannot improve. I do hope Dr. nadine hornig and other scientists elucidate the mechanism.

It seems to me that it is something systematic trouble which arises from and on the epigenetic chaotic modifications. IN MY IMAGINATION, It may be a kind of systematic inconsistencies under the modifications (not merely modification itself as distortion), that is to say, for example, for one distorted part of the life system a certain level of androgen is too strong, but at the same time it’s too weak for anothor distorted part. In that case, androgen function might be forced to swing between two (or many) inconsistent requests and such inconsistent condition should prevent our body from reversing the epigenetic modifications. Yes, it’s just like the famous Buridan’s ass!

it is different from the cases of smoking or specific excercising which bring “non-inconsistent” modifications in the whole life system.

Epigenetic modification itself is normal event of our life system. However it is structually detetminating event of our body and therefore it should not and can not be inconsistent in the system. It is usually impossible. But unfortunately excessive AR function caused by finasteride (the first crash) may make it possible… I imagine so.

#13

I think the main problem is the androgen receptor protein itself…its expression has changed and Nadine hornig hints at that in her interview…

It’s not being made normally anymore or something :confused: 🤷

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#14

(Needless to say my amateur imagination is worthless. )

I watched her interview. she looks wise. I’m not good at English. It’s too difficult for me to catch and understand such specialized discussion…

from my poor understanding,
Usually when AR catch DHT, AR starts to operate and produce some proteins each of which plays various role in the body.

I think the main problem is the androgen receptor protein itself…It’s not being made normally anymore or something

Does “androgen receptor protein” mean such produced protein? If that so, the main problem is that AR can not produce such proteins normally, probably because some troubles happen in the production process (for example transcription). Is this what you mean?

So, such AR-disfunction itself also should be caused by epigenetic modifications.

And such dysfunction should bring and keep AR overexpressed and prevent other thousand epigenetic modifications from recovery.

Is this what you mean?

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I read the article “Differential Gene Expression in Post-Finasteride Syndrome Patients” Skyler Howell et all.

I know AR itself is overexpressed.
And I know “AR function is complex and involves many genes separate from AR.” “other genes involved in AR signaling” are over- or underexpressed.