A new theory about why PFS happens

General Discussion
#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.

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#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.

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#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.

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#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.

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#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

#71

Well I thought Brigham looked at the different lengths of repeats in ar…Been awhile since I read that study.

#72

INTRODUCTION: Long-term adverse symptoms of men who used oral finasteride against androgenic alopecia have been recently described as post-finasteride syndrome (PFS).

RESULTS: Median age was 32 years, duration of finasteride use was 360 days, and time from finasteride discontinuation was 1,053 days. We observed several frequency differences in symptoms according to (CAG)n and (GGN)n repeat numbers. Three AMS items were worse for medium (GGN)23 than for long (GGN)>23 carriers and one item was worse for short (GGN)<23 carriers. The AMS item for decrease in sexual desire or libido was worse for short (CAG)9-19 carriers than for medium (CAG)20-24 carriers. Through the ad hoc questionnaire, significant findings in (CAG)n and/or (GGN)n repeats were obtained for penile discomfort, loss of scrotal sensitivity, scrotal discomfort, less pubic hair, loss of perceived perineal fullness, increased sperm density, involuntary muscle spasms, loss of muscle tone, increased weight (>2 kg), increased skin dryness, and onset of symptoms after finasteride use.

CONCLUSION: This study showed that short and/or long (CAG)n and (GGN)n repeats had different frequencies according to symptoms reported by patients with PFS, likely reflecting the vast array of genes modulated by the AR. This study showed a U-curvilinear profile of (CAG)n repeats for skin dryness symptoms, where the two extremes exhibited a worse condition than medium repeats. Further studies are necessary to investigate the PFS pathophysiology using a precision medicine approach.

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#73

@skorpio88
Some who reacted nothing or worsened because of tribulus can all improve by your protocol,taking soys and so on?
Also why do you think only a few can recover completely(means 100%)by tribulus?In what I saw,most of them seem not to achieve recovery.On the other hand,the fact that a few guys like April1989,recovered is interesting though…

#74

You have to differenciate with tribulus brands and MediHerb Tribulus … complete different things.