AR upregulation

Symptoms Sexual
#1

“The unexpected result of our present study is that the AR upregulation was detectable in the dermis of subjects long after discontinuation of finasteride use, on average at almost 5 years (mean 1672 days) of drug wash-out, in a range from 8 months to over 8 years (240 to 3010 days). Contrariwise, the hormonal alteration effects of finasteride have been reported to be shortly reversible. In fact, according to drug information provided by Lexi-Comp., after 6 months of treatment with 5 mg/day finasteride the circulating DHT levels are reduced to castrate levels without significant effects on circulating testosterone and levels return to normal within 14 days of discontinuation of treatment. An intriguing observation of our study was that the ratio of AR positive stromal cells (%) to serum total or free testosterone was 2-fold higher in former finasteride users than controls. This finding could indicate the presence in former finasteride users of an augmented regulatory feedback loop that normally serves to modulate hormonal responses [33]–[35]. Such amplification of AR levels in respect to serum testosterone levels could derive from hormonal ipo-response in the genital tissues. However, we cannot presently exclude that this apparent upregulation of AR expression is due to local low levels of androgens (particularly DHT) [36].” (Carla Di Loreto Francesco La Marra Giorgio Mazzon Emanuele Belgrano Carlo Trombetta Sabina Cauci. Immunohistochemical Evaluation of Androgen Receptor and Nerve Structure Density in Human Prepuce from Patients with Persistent Sexual Side Effects after Finasteride Use for Androgenetic Alopecia, June 24, 2014 https://doi.org/10.1371/journal.pone.0100237).

Moment. is it true, if I had a loss of androgens on the penis because of the gel that applied Diethylamine Salicylate is Antiandrogen?, did it modify my penis and brain AR? WTF? :face_with_raised_eyebrow::face_with_raised_eyebrow::face_with_raised_eyebrow:

Someone can help me to understand if the substance is antiandrogenic?

3 Likes
#2

Ha…The levels go back to normal we know they are not affected by finateride much anyway but the Androgen receptors do not and stay over expressed there by causing the horrible endocrine disruption we see after stopping…Not really the over expression but the following shut down that occurs that causes the cavalcade of side effects we expeirence…

2 Likes
#3

But I did not take Finasteride but Oxerutina (Quercitine o Rutin) and at the same time applied a Gel to the skin of the penis. After 7 days I crashed and I do not understand what happened to me. It seems that these two substances also contrast. I do not have a diagnosis yet!

#4

Its tissue specefic…Were AR upregulates more so in some areas than other areas when blocking DHT…I could only guess that a topical like this could cause this in the gential tissue…

1 Like
#5

But i beleive with time AR receptors should get sentisized again, they wouldn’t be shut down/powered off forever?

1 Like
#6

_

Since finasteride inhibits T conversion into DHT, which is responsible for most androgen activity, it is plausible that prolonged finasteride use in predisposed individuals could simulate the effects of aging in young men. Since some of the effects of androgen inhibition can not be reversed once local androgen levels are re-established, it is temping to speculate that patients could still suffer from adverse sexual effects several months or even permanently after finasteride discontinuation because of aging effects caused prematurely by androgens deprivation, namely by artificially reduced DHT concentrations. Indeed, 2 of our patients were found to have low DHT levels in the cerebrospinal fluids long after finasteride discontinuation by Melcangi et al.

This part is the scariest to me…

5 Likes
#7

Is there a way to get more DHT across the blood brain barrier? Like by injection of DHT or a DHT precursor?

1 Like
#8

Wait… but why does it happen in some men only?? Surely it means androgen receptors get activated in the others… strange

1 Like
#9

We likely have a genetic predisposition, i.e. our genetic profile is different from those other that react “normally” to this medication. It’s one of the things that we need to find out. A recent community project collected 23andMe data from users for this purposes. Hopefully, the data will be sufficient to generate leads.

2 Likes
#10

I have a 23&me profile and already got my results and everything. Can I still contribute to this?

2 Likes
#11

Please check the first post here; Important Announcement: Two Community-Led Research Projects - Please Participate

As you can see there is also a second project going on with a survey categorising all known symptoms of “PFS” (as well as PAS, PSSD etc.). In the not so distant future all of you will be kindly asked to participate.

1 Like
#12

That is the rumored epigenetic part…They stay in this state due to an unknown epigenetic mechanism…Now I also have a question that even if they did begin functioning in a normal state would the side effects even resolve then? Because remember most of these side effects I believe are due to the down stream effect on the endocrine system…I also think “how” you are effected is more genetic than “if” you are effected.

3 Likes
#13

If they do find the area of methylation, is there any treatment for something like that?

1 Like
#14

the genetic predisposition of autoimmune diseases and shifted the balance in our immune systems causing all the downstream hormonal side effects. Finding a way to balance the immune system should be a first approach.

1 Like
#15

There are demethylation agents. The problem is that we need very specific demethylation of those areas involved in PFS (if this even proves to be the problem). We do not want to demethylate areas not involved PFS, afterall Methylation is not generally a bad thing. Since we do not know yet which areas are involved in PFS, it is impossible to say whether there will be helpful agents. There are also other things going on in science including epigenetic editing with CRISPR. These tools are not yet at a stage where they can be used in humans, but their development is advancing rapidly. Hopefully, one day they will become an option.

Anyway, before we have a clear idea what is wrong with us, it is all speculation. We just don’t know.

2 Likes
#16

@axolotl Diethylamine Salicylate is Antiandrogen? If I had a loss of androgens on the penis due to the Reparil, and the body has modified the AR in my penis and brain as he says above? Could be? Let me know thanks…

#17

how is demethylating agent good if the AR is overexpressed to start with?
demethylation agents target methylated/under expressed tumor suppressor genes,not overexpressed tumor suppressor genes?
U get me right?
Tell me ur opinion :DD

#18

@zadig777, we don’t yet know why this is happening. You are correct that it is a bit presumptuous to assume non-specific demethylation will lead to positive results.

For instance, persistent overexpression of a protein that abolishes the androgen signalling pathway could be a component of this condition, and use of demethylating agents may worsen this scenario.

2 Likes
#19

wait,is it confirmed that the AR receptor is overexpressed or AR genes are overexpressed?

there is difference between gene expression and receptor

do you know for certain the answer to this?
im assuming that AR gene expressions are silenced/methylated,but i read otherwise on this forum so im confused…

2 Likes
#20

Well, the study of PFS patients linked in the opening post found twice the number of AR proteins in tissue samples taken from PFS patients compared to controls.

The AR protein is considered to be the expression of the AR gene in this context.

2 Likes