Why is increased Androgen Expression a bad thing or considered causative in PFS?

I assume overexpression of the Androgen Receptor is the same as increased expression past the norm?
I know this is a basis of the theory on the homepage.

I could pull this line right here though,
“Increased androgen receptor (AR) expression and activity are pivotal for resistance to androgen-deprivation therapy.”

But then I see mention of gene silencing in PFS, which would mean reduced AR expression.
So is AR expression increased or reduced?
Increased AR expression seems it would be protective.
Anyone want to clear this up?

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Increased AR “expression” and “density” are basically interchangeable. Sometimes people also use “sensitivity” to mean the same thing, although technically there is a very slight difference.

The theory is that our androgen levels and/or androgen output/products (proteins made when AR system works appropriately) drop after exposure to 5ari’s, anti-androgens, etc.

Our body then compensates by increasing the amount of receptors (ARs) in order to try to get more of the endproduct made (proteins).

When we stop taking the 5ari’s or antiandrogens or whatever caused the drop in AR, you get a tital wave of androgens back in the system while the system still has high ARs. This basically nukes the AR system (too many AR endproducts/proteins). In response (I’m guessing here but potentially to mitigate cancer risk among other things), our body then silences the AR in certain tissues by adding something like a methyl group (there are a few other “things” our body can add to silence) so that no matter how high or low androgens or ARs go, it sort of doesnt matter since the gene itself is now silenced. So no more/way less endproducts/proteins being made = PFS.

Now, how does that fit into people’s stories that got PFS while still taking finasteride? They didn’t stop the medicine and then have that tidal wave. It could be complicated interactions with other medications or even stress responses (i.e. Glutathione and allopregnenelone are severely affected).

So to answer your question, a silneced gene means no protein being made. No protein being made means our body is increasing AR in order to try to get protein made. For some reason, our gene(s) are stuck silenced. Some type of faulty mechanism not allowing it to de-methylate. CRISPR seems like the most likely treatment method, although there is a chance that in time, the gene(s) could re-methylate.


I’m one of those who had sides on fin (erection, penis size, mild brain fog) but they were not as bad as month off when I crashed.

Thanks for taking the time on that.
Im still getting hung up on this part though, the AR gene is silenced (reduced expression) , but at the same time overexpressed (increased expression)?
Or one leads to the other?

the AR gene is silenced (reduced expression) , but at the same time overexpressed (increased expression)?

The AR gene is silenced (reduced output) and expression (number of receptors) is increased.

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Ok how about this. Maybe you’ve seen a few of my posts.
Lets start from scratch, not having taken any drug and no theories.

Again just a patent, maybe nothing to get too excited about, could be nothing.

Maintenance of male phenotypes
As a result of isolating vesicles derived from bacteria belonging to the genus Propionibacterium in vitro and evaluating therapeutic efficacy thereof, it was confirmed that the vesicles exhibited an anti-inflammatory effect and an effect of inhibiting the death of keratinocytes, and as a result of evaluating the mechanism of the vesicles, it was confirmed that the vesicles increased the expression of male hormone receptors

^Sounds good right?

Then apply the drugs, apply the theories.
Still good?

Just to pivot here a little bit, this alone could be a big deal when looking at overall skin health and thickness. Not only that, but drug induced hair loss as well. Im thinking about Accutane here mainly.
Another “just in case”

“Protection from skin and hair follicle cell death.”

I wonder do I have increased androgen receptor expression after I got so fucking hairy in my early teens after isotretinoin, despite having my androgen levels on the low side. Would that show in somewhere else?

This is where I pulled that line from the patent.
“it was experimentally confirmed that, when vesicles isolated from in vitro cultured Propionibacterium acnes , which is one species of bacteria belonging to the genus Propionibacterium , was administered to mice, the expression of an androgen receptor in prostate tissues was increased”

^On the flipside of the coin, if the androgen receptor is overexpressed and thats a bad thing, bacteria might play a role in that too.

Can you or someone help me out one more time here that knows the history or studies.
Are there some real world examples (meaning studies and such) that show this theory as a possibility?
Increased or overexpressed AR gene actually leading to a type of androgen deprivation?
Id check myself, but that doesnt seem like the simplest thing to find real quick.

Yes, there are a few. But primarily one that showed increased AR in a part of the genitals.

> Differences in AR expression and nerve density in different portions of dermal prepuce were evaluated in the 2 groups. Density of nuclear AR in stromal and epithelial cells was higher in cases (mean 40.0%, and 80.6% of positive cells, respectively) than controls (mean 23.4%, and 65.0% of positive cells, respectively), P = 0.023 and P = 0.043, respectively. Conversely, percentage of vessel smooth muscle cells positive for AR and density of nerves were similar in the 2 groups. The ratio of AR positive stromal cells % to serum testosterone concentrations was 2-fold higher in cases than in controls (P = 0.001). Our findings revealed that modulation of local AR levels might be implicated in long-term side effects of finasteride use. This provides the first evidence of a molecular objective difference between patients with long-term adverse sexual effects after finasteride use versus drug untreated healthy controls in certain tissues.

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