Everything Epigenetic

General Discussion
#122

@Dubya_B It looks like this was addressed to me, although it wouldn’t be obvious, if it weren’t for the capitalized “you”, by which I somehow inferred you meant me. Still, this is most helpful, thank you!

Maybe you can answer the question @Borax did not want to/couldn’t answer. Let me copy the question again here:

Let me also copy an excerpt from the paper you just posted. I would like to have my question answered, if at all possible, in light of this key passage from the paper, which I think sums up the theory well:

<<We postulate that a significant 32%-94% reduction of serum and cellular concentrations of DHT, depending on the 5ARI medication, and the resulting DHT surge following 5ARI withdrawal, can trigger the above listed molecular mechanisms and resulting persisting effects.

We propose that reducing DHT (via 5AR inhibition) leads to AR overexpression and hypersensitivity of the AR while on the medication. This hypersensitive state of the AR is maintained for an unknown duration after 5ARI withdrawal. The combination of a hypersensitive AR, and the return of baseline DHT levels after 5ARI withdrawal, results in a sharply overexpressed AR signal. This in turn triggers an AR negative autoregulation mechanism, which silences the overexpressed AR signal.>>

#123

Hi guys, I know that Propecia and Isotretinoin are strong anti-androgens. Do you really think SSRIs are strong enough anti-androgens that it is highly probable that PSSD is primarily the same thing as PFS and PAS? Just curious. People on SSRIs get numb genitals on their first pill whereas people on the other two drugs generally do not, possibly implying a different initial mechanism. However, long term the symptoms seem to be the same. Just asking because I took Accutane initially and then got much worse on Trazodone. I wonder how much hope I might hold out for epigenetic treatment outcome from Propecia sufferers.

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#124

This is a futile exercise. I can give you n number of reasons why what I’m saying makes sense to me, and you can give me n number of reasons as to why what you’re saying makes sense to you, but at the end of the day, we are both speculating. No matter how right it feels to you, in the absence of a study, it is just speculation. To not acknowledge that would be both arrogant and dangerous.

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#125

I believe adverse reactions are just an extreme case of this. For whatever genetic reason, these drugs either cause a more extreme depletion of DHT and/or receptors are already in a sensitive state before hand and it just causes a shit storm or extreme depletion and over-expression. Either way the methylation can happen immediately and symptoms happen immediately.

#126

There are some key differences in PSSD and PFS. namely PSSD seems to not effect the body as greatly as PFS (muscle wastage, prostate problems, gyno etc…). These sides are not frequently associated with PSSD, suggesting that different mechanistic actions maybe involved. Although the admins on this forum seem to think that both illnesses have identical pathogenic mechanisms. Which is conceivable considering that both drugs inhibit major neurosteroidogenic enzymes (SSRI’s don’t inhibit 5ar but others like CYP which finasteride inhibits). It’s possible that receptor silencing doesn’t just occur with AR but also with GABAa and other receptors that are regulated by neurosteroids which would account for some overlap. In fact I tend to believe that not just the AR is downregulated. Especially after that one guy trialed synthetic allopregnenolone and became worse (surging neurosteroids further pressures hypersensitive receptors and causes further silencing)

Thats just my two cents either way

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#127

@heymomlook, I used to believe the symptom profiles should be different because of the differences in mechanisms of action too, but the survey results show an almost-identical condition shared by people who took finasteride, SSRIs, and Accutane.

I also noticed that there seemed to be a bias against discussing side effects not related to sexuality in the PSSD community in the past. Some members of the old forum were told their physical side-effects (that developed along-side the sexual side effects) were not related to PSSD. Even anhedonia was said to be due to something else for a time.

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#128

At the moment, unfortunately, especially in the case of PSSD, the similarities or not with the PFS are educated guessings. PSSD and PFS could have the same causes or not, I think it is still better to verify it, if in a first study significant differences should emerge (for example in PFS there are alterations of the androgen receptor and not in PSSD) it would be better to know it and then go on in a different way. But it would still be useful to know, a biological veirfy is needed. Then if it were shown that instead they have even similarities better. Keep in mind that the PSSD community does not currently have the organizational strength of that of the PFS, so for us (PSSD) it is certainly better to team up with the PFS.

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#129

I’m pssd user. Since i got pssd, i had muscolar wastage. After try tribulus, i got all pfs symptoms. I’m one of worse cases of people that didn’t killed himself, for the moment. So I think that pssd and pfs are related.

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#130

Why stop at one gene or set of genes?

Gene expression profiling of skin from 8 patients treated with isotretinoin was performed to gain insights into its mechanism of action. Skin biopsies were obtained from the patients at baseline and at 8 weeks isotretinoin treatment. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays in order to examine changes in gene expression as a result of treatment. After treatment, 784 genes were significantly changed: 197 up-regulated and 587 down-regulated. The majority of genes that were up-regulated at 8 weeks encode structural proteins of the extracellular matrix such as collagens, fibulin and fibronectin. The preponderance of genes that were down-regulated at 8 weeks are involved in the metabolism of steroids, cholesterol and fatty acids.

#131

definitely intriguing that tribulus gave you pfs symptoms. like I stated above, SSRI’s do inhibit neurosteroidogenesis so its possible that the two conditions share the same pathogenesis

#132

Does anyone know what work is currently being performed on discovering what epigenetic changes we have are? Is that something that will ever even be practical to do? I don’t know the first thing about genetics, really. Would love to self-educate just don’t have the time right now very busy with work.

#133

Call and asked this guy…

#134

Don’t know if you are being serious or not but if we haven’t managed to do anything except sit and wait for Baylor for 10 years then we are pathetic.

#135

I’m absolutely serious…This guy knows more about it than any other living human on the planet…When it comes to Gene’s and post finasteride syndrome it’s the only investigation I know of at this level and its rumored he found the same thing…Gene’s up and down all over the placd…Then after it was completed somebody must have put their thumb down on the journal not to publish it…

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#136

extremely interesting Dubya_B
extremely interesting…

#137

So does this mean that theoretically a potential cure would work for PFS, PAS, and PSSD?

#138

Maybe. Being that there is currently no standard diagnostic for any of these conditions, we can’t know with certainty they are the same. We only have the similarities in post-drug symptoms, the overlap in effects of the drugs, and a small body of biological research on PFS patients.

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#139

Well, I’d be curious to see what the basis of those rumors is. There was a member of the board here who flew across the world to visit him and was told personally that he basically had no idea what PFS is. So, I think sitting and holding out hope for an outcome from Baylor is an extreme example of the Mark Twain or Ben Franklin or whoever it was definition of insanity.

What happened to the 23andme data? Did not enough people here contribute to it or what? Could that find what we need?

#140

They didn’t get enough samples really to do anything I don’t believe…Moonchild said he thought he was clueless as well but said he told him he thought genes were “off”…I was told by others here genes were deregulated…point is that’s all we got and no other such study has or will be attempted as I know of…Nobody has the money to do anything…

#141

The problem is simply that we haven’t provided enough incentive for scientists to investigate us. We haven’t given them anything. We’re just sitting here talking. Scientists have no incentive to help us until we provide it to them. We will sit here forever or until we get organized, get the survey filled out by thousands of people, get our condition publicized, and generally stop being useless. The way science works is that scientists can easily get millions of dollars from NIH and other funding agencies. They just need to have evidence to support a hypothesis in grant proposal. Right now they have nothing. If we get them some data then they can put that in grant proposal and in come the millions of dollars.