haha hope that works out. i honestly don’t care to sue my doctor at this point. maybe once i recover i’ll find where she lives and terrorize her by ringing the door bell all night
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LOL…that’s not a bad idea either
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Wouldn’t it be sensible to look at AR expression in penile skin tissue of PAS and PSSD cases to see if it is also overexpressed. This has been checked twice for PFS confirming AR expression is twice that of controls. Has is not been checked in PAS and PSSD to determine AR function since the disease states are so similar?
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that is a great point man. it’s so hard to believe how many people are given these drugs, yet doctors completely dismiss the reactions people get, making it impossible to get research and fixes
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also i wonder why most people with this condition don’t respond to drugs. surely this has a direct correlation to what’s exactly going on. same with not being able to build muscle, something is not working correctly and it’s causing a great amount of issues
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AR expression is not twice. Baylor has it at just under 1.4 fold, I can’t quote the other study out of my head but it wasn’t double.
What they did say in the other study however was that the AR to serum T ratio was double in PFS patients IIRC.
But it would indeed be a good idea to check AR in PAS, PSSD and asymptomatic fin users.
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I have always wondered why they dont use asymptomatic fin users as controls. I think it would be a better comparison IMO.
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Agree. Only reason I can see for them to not do it, are because it might be hard to locate enough people.
I doubt the have asymptomatic fin users lined up to donate foreskin, lol.
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I would say the common denominator is endocrine disruption. Which either happened due to influences on the hormone balance, or influence on neurosteroids impacting hormone balances.
This has caused various degrees of changes in gene expression in people.
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The Di Loreto study showed very similar findings as Baylor (1.36 fold vs 1.4 fold increase).
As you can see it differs quite a lot between tissues though. AR density in stromal cells had roughly a 1.7 fold increase. Where epithelial “only” had 1.23 fold change, while vessel smooth muscle AR actually was slightly underexpressed (although not statistically significant).
When they end with this though it really makes one wonder. If the overexpressed theory is true, wouldn’t more AR mean more problems?
- “Our unexpected observation that percentage of AR positive stromal cells is inversely related to ASEX score, suggests that patients less able to raise AR are those with more severe side effects related to sexual dysfunction.”
I’d really want some studies looking into the local DHT levels and check the ratio to AR. If there is indeed normal DHT and still overexpressed AR we can scrap that theory for good.
This is a great read about CRPC, they show how AR is negatively regulated by androgens etc.
- Liganded AR negatively regulates its own expression by binding to a site in the second intron of the AR gene, and this repression is relieved by AR-targeted therapy.
I fully support Axo’s new research, but I still feel that checking local DHT as a intermediate step would have been a good idea.
Also since the Baylor study showed 2000+ dysregulated genes, something more than the AR has to be involved in my opinion. AR don’t modulate that many genes (from what I understand), but it might be domino effect (or due to some other pathways fin blocked).
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Anyone know how all these relate to the females? Seeing more and more affected pop up.
Good question. I don’t really have a good answer.
One of the studies that Axo quoted in his article about PFS. The one with overexpressed AR in muscle tissue which lead to SBMA phenotype, the female rats was asymptomatic IIRC unless they got androgens administrated.
There’s only been one or two human studied on fin. And the only things I remember are that they found changes in VEGF, vitamin k gene and DNA damage in white blood cells. Also it affected their periods negatively.
Baylor showed decrease in VEGF to IIRC, and people have crashed on vitamin K which makes sense if it’s also affected.
PSSD I’ve seen women also tend to have an increase in SHBG and some scientist theorized it was due to epigenetic change in the liver. Many with PFS show the same increase in SHBG, but lowering it doesn’t lead to much relief, so I think it’s more a symptom than a cause.
I would say the decrease in allopregnanolone (by potentially permanent 5ar inhibition onset by 5ari’s) only could cause severe depression.