A new theory about why PFS happens

General Discussion
#51

I also want to add that this theory reliably explains why some guys paradoxically experience an increase in baldness or at the very least experience a shed when they go on propecia; its possibly because they had low androgen receptor density to begin with and propecia increased their AR density, thus increasing their baldness or causing a massive shed. Anyways the reason I bring this up is to demonstrate that propecia reliably upregulates androgen receptors and this is something that can help us understand its mechanism of action better.

@slick1
thanks for sharing your experience. My own person suspicion is that the androgen receptors are easy to upregulate but are harder/more resistant to downregulation. Anecdotally I have read about similar stories to what you say regarding creatine and it appears that the side effects associated with taking creatine (for a normal, non-PFS guy) do not eventually resolve themselves by continuing to take creatine (which would suggest the body naturally downregulating androgen receptors in response to the high creatine dosage), but rather the negative side effects persist until the person stops taking creatine. In this regards, I think that maybe all receptors are not the same; some receptors (like dopamine receptors) are much more sensitive to downregulation while others like androgen receptors are much more resistant to downregulation. This is just my guess anyways, I have no scientific evidence to back this up.

#52

I don’t see how this theory explains hair loss. Hair loss is an androgenic feature and in general, androgenic features are muted in PFS, which we believe is due to AR overexpression.

#53

@arkaeik

I said that some (many?) people that go on propecia experience an initial increase in balding or shedding when they first go on propecia, I wasnt referring to something that happens after PFS is acquired.

#54

I would say that pssd community gone much further in understanding mechanism of pfs/pas/pssd.Check this, its a blog of pssd member
https://www.theresearchzone.com/blog

also this thread quite interesting
http://www.pssdforum.com/viewtopic.php?f=5&t=3195

And propecia is focused only on 5ar2

#55

the different lines of research are not mutually exclusive. Everything helps

Its going to be a mistake to assume that PFS/PAS/PSSD all have the exact same mechanism behind them. Its possible that they might, but there is literally no reason to confidently assume that this is the case. To give you an example of this I will provide an excerpt from the very page you linked (which has awful and hard to read punctuation btw):

Serotonin REDUCES PPARy which normally ACTS to INITIATE Androgen Receptor (AR) activities; that’s WHY we get DOWNREGULATION of androgen receptors with SSRI - because the “nuclear” receptor of PPARy is being downregulated (persistently) by SSRI’s - which causes a continual reduction in Androgen Receptor amounts (densities) and activities. SSRI’s like Luvox & Prozac “get in the middle” and cut off the “supply and demand” connection to nNOS from the Androgen Receptor - leading to LESS neuronal nitric oxide synthase and NO non-contact erections (erections without touch). STUDY -->

It is well known that PFS is associated with the androgen receptors being overly dense and upregulated, NOT with them being not dense enough and overly downregulated. From the page you posted alone its clear that the etiology of PSSD is different than that of PFS. Im all for cross research into PFS/PAS/PSSD but I disagree with this idea that PFS/PAS/PSSD must definitely have a common cause.

1 Like
#56

At the moment i am convinced all of them have VERY similar mechanism, if not the same. and 5HT system is involved into this. Too many similarities across each aspect, from symptoms to drug reactions and recoveries.

#57

You are convinced but why is this? I showed an excerpt from the very page that you linked which shows evidence that the etiology of PSSD is different than PFS, why do you ignore this?

Just because there are similarities doesn’t mean that PAS/PFS/PSSD have exactly the same root cause. Its possible that some of the same body systems (IE dopaminergic) are affected identically in each of these disorders but its also equally likely that there are some body systems (androgenic) that are affected in different ways according to each disorder as well. You are trying to oversimplify the issue here. Just to be clear, I am very open minded to the idea that there might be a root cause for all of these disorders, but I disagree with the confidence that some people have for thinking that this is so.

4 Likes
#58

The word ‘‘convinced’’ was too strong. yes, that difference you pointed out is correct. But its just one of the theories, so it can’t serve as evidence. Once more studies are released we will see.

1 Like
#59

fair enough, I have an open mind about this

#60

i am actually on anti androgenic combo now . Downregulating AR with resveratrol and inhibiting 5AR with zinc. Also taking loratadine to inhibit H1. My erection quality improved from 40% to about 70 -80%. Libido on a lower side, but from my experience i its different 5ht receptors should be targeted to fix libido.

And good bonus from resveratrol:

The administration of resveratrol upregulated the expression of SIRT1 and restored erectile function. In contrast, resveratrol downregulated the expression of p53 and FOXO3a, which regulate apoptosis and oxidative stress.

(it’s proved that isotretinoin upregulating p53 and foxo3a) So worth a try hitting them. Sirt1 is also assicoated with pssd.

1 Like
#61

https://onlinelibrary.wiley.com/doi/full/10.1111/andr.12353

#62

thanks for sharing man. BTW have you taken resveratrol in isolation? It sounds like something interesting that I might consider experimenting with. I recall taking it a long time ago and it slightly weakened my erection quality, but I didnt take it for very long. I would be open to give it another shot though

#63

yes, I’ve been making 2 hours window between intakes of zinc and res. The problem is its hard differentiate if loratadine contributed also. Rigidity is definitely improved.

1 Like
#64

Likewise mate and 8 months later

#65

is this androgen receptor upregulating in weightlifting good for your libido ?

#66

the differing responses that guys have to weightlifting supports this theory; some guys experience improved libido from weightlifting while others crash from it or have negative results. There is no way to know for sure though, im guessing that its possible that weightlifting could upregulate androgen receptors in a negative way though

#67
#68

This looks interesting

2 Likes
#69

Didnt Brigham look into this and it had nothing to do with pfs…Niether did 5ar

#70

If you refer for my link;

This only assesses difference of pfs sides depends on ar genetic variants