Doxazosin...treatment at the genomic level?

epigenetics
#1

https://www.physiology.org/doi/full/10.1152/ajpendo.00100.2013

according to these FREE papers

besides sensitizing leydig cells, the androgen/estrogen receptor, cAMP/cGMP + a bunch of the steroidogenic genes doxazosin modulates key enzymes that among other things decrease pregnenolone AND progesterone levels

*this obviously affects signalling which we are interested like
– pregnenolone > - allopregnenolone > - agonism at gaba receptors (which is elevated on PSSD - PFS users)
– progesterone > + estrogen receptors & - crossover with the AR(helps with the negative feedback and libido)[1][2][3]

[# Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, cAMP/cGMP signalling and adrenergic receptors in Leydig cells of adult rats - Stojkov - 2013 - Andrology - Wiley Online Library]

# Sustained in vivo blockade of α1-adrenergic receptors prevented some of stress-triggered effects on steroidogenic machinery in Leydig cells

# Doxazosin and Serotonin (5‐HT) Receptor (1A, 2A, and 4) Antagonists Inhibit 5‐HT‐Mediated Human Cavernosal Contraction

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#9

Are you suggesting we take alpha blockers like doxazosin?

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#10

im not a doctor but im taking it for 2 days and felt some weak boners this morning sensitivity is increasing too

its too early tho, the gene expression in the rat study was only elevated on day 10

ar silencing is the most researched theory i believe

doxazosin incresed expression of all the steroidogenic machinery increasing response to gonadotrophins and even decreasing progesterone
brain fog doesnt help but it seems the closest thing to a cure for me which is both otc and cheap

its also antagonist of the 5ht receptors in the penis btw

hdac inhibitors would be my next choice but they are hard to find

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#11

I took alpha blockers some years ago, aproximately one year after my first crash. Every time I took it my shrunken penis looked a little bigger (only while the effect of the alpha blocker lasted). It didn’t regain function. But I imagine the only reason behind that temporary increase in size was that alpha blockers dilate blood vessels.

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#12

not any alpha blockers are the same
yohimbine alone did nothing for me too, even with viagra and steroids in the mix
but doxazosin is working through other mechanism than adrenergic antagonism here

the fact it is the rival of finasteride for bph dont light anything up on you guys??

it is changing similar switches but on different direction

finasteride AR silencing is what causes the agressive tumor grows post usage
which hdac inhibitors reverse through hsp90 acetylation

doxazosin works similarly for BPH but on multiple pathways and WITHOUT the long term sides

just think about it

i have experience with hormones (5 year TRT + several blasts)

i think this is worth looking into

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#14

wat? a-blockers are used to treat Ed

also see this about the AR gene silencing
http://www.protocol-online.org/forums/uploads/monthly_08_2010/msg-19273-027408800%201282061244.ipb

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#15

Jesus I’m sorry, I was thinking of beta blockers and their sexual dysfunction. Beta blockers can cause ED and lower testosterone. Ironically I’m studying for a pharmaceutical test right now… guess I have to put in more hours haha.

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#16

It’s not otc in the states, is it?

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#17

Please keep us updated. I’ll be trialing impaza soon btw.

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#18

from same authors in OP

https://www.physiology.org/doi/full/10.1152/ajpendo.00100.2013?

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#19

@vanquish

seems like sildenafil upregulates some of the same genes cited in the doxazosine paper:

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#20

day 4 here feeling slightly more sensitive

tomorrow i´ll try to get some PreP to give it a go, must be synergic

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#21

i just got the strongest HIV coquetel available here(3in1 RTi’s)

should i take it now or will it interfere with the doxazosin??

https://www.physiology.org/doi/full/10.1152/ajpendo.00100.2013

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#22

That paper was dated 2013. Is it possible that nobody noticed for over 5 years…?

I mean, good luck and please let us know how you’re getting on but don’t pin all your hopes on this.

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#23

oh someone did notice:

but dont go by his talk on 5ht receptors…

also nothing to worry about with alpha blockers

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1464-410X.2005.05959.x

the degree of improvement from baseline ranged from 13% in intercourse satisfaction with doxazosin standard, to 41% in orgasmic function with doxazosin XL

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#24

so lets try again:

https://www.physiology.org/doi/full/10.1152/ajpendo.00100.2013

besides sensitizing leydig cells, the androgen/estrogen receptor, cAMP/cGMP + a bunch of the steroidogenic genes doxazosin modulates key enzymes that among other things decrease pregnenolone AND progesterone levels

*this obviously affects signalling which we are interested like
– pregnenolone > - allopregnenolone > - agonism at gaba receptors (which is elevated on PSSD - PFS users)
– progesterone > + estrogen receptors & - crossover with the AR(helps with the negative feedback and libido)[1][2][3]

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#25

Are there any serious risks about doxazosin ?

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#26

Thanks for those posts @VinnyG, sadly it’s way too complicated for me to even know if that’s a reasonable explanation of anything.

I urge you to be cautious with your health. I wish I had been more cautious with mine.

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#27

@Greek i have used the triad ssri/acc/duta so i have nowhere worse to go i believe xD

  • all this methylation/demethylation talk brought up that i may be suffering from CFS for some years now without any idea, so at least im conscious and doing something about it now, always look at the bright side :wink:
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#28

Doxazosin is otc? According to google it requires a prescription

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