A couple reads regarding 5ARi Withdrawl Process - Possible Reasoning of Crash

General Discussion
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#1

Stumbled upon a couple good reads:

1st one points out that reducing DHT via 5AR leads to AR over expression and hypersensitivity of the AR while on Finasteride. The hypersensitive state of the AR is maintained for an unknown duration after the 5ARi withdrawal (which is why some males report being completely fine for some period of time before crashing). The combination of hypersensitive AR and the return of baseline DHT levels after discontinuing the finasteride result in a sharply over expressed AR signal. This in turn triggers an AR negative auto-regulation (mimicking what the medication was doing in the first place, however slightly exaggerated) that permanently silences the over expressed AR1 and AR2 signals (one more than the other depending on the medication).

The 5ARI-WS Theory proposes that an epigenetic process is involved, presumably in the form of DNA methylation. The resulting silencing of the AR signal leads to a downregulation of downstream processes, such as a failed induction of 3a-HSD and low 3a-diol-G values. Both of these enzymes in humans are known to be necessary in the synthesis of endogenous neurosteroids such as alloopregnanolone, and THDOC. It is also known to catalyze the reversible conversion of 3α-androstanediol to DHT.

This silencing of the AR signal effectively becomes a post-receptor form of androgen resistance. In
consequence, a broad range of side effects arise, which over time, include the atrophy of androgen
mediated tissue and the dysfunction of androgen-mediated sexual, physiological and mental
processes. These side effects remain in place indefinitely, despite quitting the 5ARI medication.

http://www.protocol-online.org/forums/uploads/monthly_07_2010/msg-19273-074754700%201280151401.ipb

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#2

The second read I stumbled upon is a study which analyzes the percentage of persistent ED in all men 42 or younger - in association with the amount of time they spent on the respective drug with < 205, or > 205 days being the cutoff. There does appear to be a positive correlation with time on the drug, and the side effects on the body as the study suggests. I know many times I heard on this website that “1 pill messed me up for life”, so I am very curious how this ties in.

https://www.researchgate.net/publication/314395519_Persistent_erectile_dysfunction_in_men_exposed_to_the_5a-reductase_inhibitors_finasteride_or_dutasteride

#3

Good posts.

We shouldn’t forget what fin does either. Killing NO. Killing glutathione levels. Killing NADHP.
Fin is a cortisol blocker. It does not convert to anything. Besides AR there are changes in other fields in the cells.
Through hormones, you won’t change a lot longterm. We must analyze how the whole system is affected as hormones, vits, minerals, heavy metals! and aminos interacts with each other. What does impair the Nitrit Oxide pathway or FAD or NADPH? Here we go.

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#4

Hi Pete, regarding the time dependent impact on ED incidences, the effect of long term deprivation of DHT is not the same as what is observed in PFS. One is an absence of potent ligand which over time can obviously lead to physiological changes, and is often demonstrated with huge doses for prolonged periods in rats. This has been demonstrated to result in incomplete return of erectile function and several other observed physiological changes. However, PFS entails a bodily response to the depletion of ligand or inhibition of the AR which is seemingly a persistent epigenetic change in cellular homeostasis, entailing a altered cellular response to the presence of ligand. The latest literature review notes pfs as occurring in as little as a few doses, whereas we’ve often seen even one pill causing PFS. I think this is the situation for user LBV amongst others.

“Moreover, the finding that DHT increases inducible nitric oxide (NO) synthase (iNOS) from DPC suggests that iNOS and NO are downstream effectors of AR” (Androgens and androgen receptor action in skin and hair follicles, Ceruti et al 2017)

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#5

@axolotl

Your response actually relates much to the first article I referenced above. If inability to successfully produce cell ligand is the root issue, this might also imply that the intracellular receptors are not functioning properly either since this is where the ligangs bind to get signal. I would also imagine that if you try to restore those intracellular structures you run some risk of denaturing them so you will not be able to do any biochemical assay with the fixed cell? it sounds like a difficult task to increase or repair specificity of binding interactions after they have been regulated/altered. Are you aware of any successful treatments or cures in similar cases? Is this something that happens a lot in medicine?

I imagine that the reversing of inhibition of 5AR is very sensitive. I can’t remember who but someone on here used a bell curve analogy that was spot on in my mind.

#6

I agree @noprop successful treatment is great for short term relief, but its not a long term solution. The research surrounding the root cause of what’s happening is where I hope the time and money Is being spent.

#7

In terms of this acquisition, no, it’s novel, as per Traish’s latest paper. And treatments for what I think may be related, not yet, but they’re on the horizon. I’m working on a relatively substantial post that might be interesting to others regarding what I think could be a possibly comparable situation of the symptomatic and thus problematically causative side of PFS, independent of the mechanism of acquisition. Some recent scientific work is potentially enlightening and indeed represents an ongoing research direction that could have relevance to us.

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#8

Here we go. DHT is important for NO synthesis. But just the beginning of that pathway which also includes aminos and minerals.
That’s why you can help NO with l - arginine but it will be used up quite quickly. Ppl with high dht have ED problems.
As I said, it is more than just dht related, it is the whole path from androgens to be taken into the cell via AR and the following! paths.
And M.said dht would not be essential in adults male. They knew it. And they lied. So, I paid for this lie? I want my money back.

#9

Before my disease, L-citrulline and L-Arginine had significant positive effects on my body. Now, neither have any effect what so ever. Signaling via the receptor is necessary here and taking NO precursors will not help this if you do not have a receptor that works properly.

Please cite your sources with guys with high DHT have ED problems lol

#10

My mother’s partner.
PPL taking statins. (fin is also a cholesterol blocker)
PLL taking AB.
Cauda equinea syndrome.
There are different reasons for ED, and you can get it though having high dht levels.
As I said, erections/sexual behaviour is more than just androgens. Best

#11

I understand that, all I asked was for you to cite your sources showing that high DHT can cause ED. Giving me word salad again isn’t citing sources.

#12

I think you haven’t read my post properly.
I mentioned what causes ED even having high DHT levels. So, high DHT levels don’t mean you get an erection. There is much more involved.

If that information is word salad, hm. You might have done an interpretation.

#13

I feel that gents93 simply wanted you to cite sources rather than making an unsubstantiated claim.

#14

I feel that he should have read properly. That cannot be that difficult. Assuming something cause not understanding and on that demanding things is waste of time. And it won’t help him getting out of PAS.
Interesting are the similar sides to pfs though and the possible common roots.
Good luck.

#15

My man, you just made a claim that high DHT causes ED. Yeah, other factors can play into ED but you stated that high DHT can cause ED. You were asked to cite sources for a claim. You did not. I read your post properly as many others probably have as well.

No, asking you to cite sources isn’t going to cure me of whatever I have but you spewing out random and incorrect information isn’t going to do us any good either. Especially for the new guys that come here who have no idea what is going on with them.

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#16

Can you cite your source saying high DHT CAUSES ED? No? What a pity.
Unless you do so, you should learn to read properly and in context.
What you are interpreting, is your problem.

The kindergarten level argument, that newcomers would not understand correctly shows me you obviously know what other ppl think and understand - you are a magician.

BTW: What symptoms have you cured so far? Any? If you have, do you think you should post it?What if someone claims you did not show the studies behind your treatment protocol? I can imagine you are in a very bad situation, no question at all. It might be helpful for you to do big research what you could do re improvements.

How many useful hints based on your own experience and others have you given so far to newscomers in order to support and help them? How many?

#17

No, I can’t cite those sources because I didn’t make that ludicrous claim, you did. It’s in plain black and white text where you’re making a causation statement without a source.

I haven’t cured anything considering the etiology of this is on a molecular and perhaps a epigenetic level, and I only continue to worsen, but I am not sure what that has to do with anything that we’re talking about.

Regarding your question about helping new comers, I don’t know how many but you can peruse through my posts on PH and Solve, i’m sure you’ll find a lot. And what I post can be backed by scientific literature, so if you’d like to question the validity of what I say let me know here.

#18

Alright thats enough. Everyone here has had their lives affected in some form or fashion, we’re in this shit togerher. Stop with the bantering

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#19

You’re missing the point and driving home one that’s already understood.

Spewing incorrect information, especially with a condition like ours, could be very dangerous.

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#20

I agree with gents. It is important that we call out blatantly incorrect and misleading information which has the risk of being dangerous, as it can lead desperate newcomers dangerously astray and muddy the already exceedingly murky waters.

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