Altered methylation pattern of the SRD5A2 gene in cerebrospinal fluid of post-finasteride patients: a pilot study

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This is huge!

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Sorry for my lack of knowledge, I understand they are saying that this methylation could explain some of the behavioural/mental problems in people with PFS?

I agree that this is huge. I don’t remember the literature that well but this might be the first time we have seen evidence for altered methylation patterns in PFS patients.

However – and I would like to read the whole paper before I stress this too much – I would be concerned if the authors insist on explaining the “behavioral disturbances” of PFS directly by another chemical imbalance theory involving neurosteroids, and not by effects of the altered methylation patterns on sexual function. The distinction between the two models is not trivial and failing to make it would lead to wasted research effort in trying to understand the causative chain of PFS, as has happened in other disciplines on a much larger scale (psychiatry) and with grave consequences.

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just came to post this and the title was taken. You’re quick on the draw @sibelio :smile:

Quel surprise. Must be the delusion the dermatologist was talking about in action I’m sure. Disappointing the symptomatic characterisation of PFS in this is still completely neurologically focused, as is the speculation which focuses squarely on the CNS despite proof in external tissue suggestive of pleiotropy. This is why the survey is so important… Baylor too, hopefully.

Tldr is the gene promoter of srd5a2 was methylated in 9 of 16 PFS patients and in 1 of 13 controls (the man with methylation of srd5a2 in the control group was affected by normotensive hydrocephalus). In the PFS patients the methylation ranged from 15.4 to 100%. Neither depression, anxiety or erectile dysfunction scoring via validated scales were related to methylation status. Methylation was not found in blood DNA demonstrating tissue specific gene silencing. Srd5a1 was unmethylated.

Note to @Awor: I’ve put this in zotero.

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full text https://ec.bioscientifica.com/view/journals/ec/aop/ec-19-0199.xml

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What insight can we draw from this?

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My understanding is it would mean the 5alpha reductase enzyme would not be regenerating correctly…

If 5ar isn’t regenerating correctly why do I continue to produce DHT and lose hair and most guys on here have normal DHT blood levels?

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From my limited understanding because the instructions aren’t correctly regenerating you may have some of the functions of the enzyme but not all…Blood levels entirely different from CSF…In my case my thin spot filled back in and never re balded…Lots of guys have dht but it is at very lower level in the blood…Maybe one of the mods chip in here…

When I had my DHT tested for TRT I was told it was in range but not high enough for the treatment. This was done through Hertoghes French lab. His testing/observations were different to that in the UK who told me everything was ok.

I would like to know in my case, since I only took a 5AR1 inhibitor.

On the other hand, the native DNA methylation pattern may change during adulthood and it is susceptible to ageing [54, 55], diseases [56-59], environmental factors and inflammation [60, 61]. Most importantly, similar effects might be triggered by prolonged exposure to certain drugs, such as
amphetamine and methamphetamine [62], inducing behavioural abnormalities.

As someone with extreme ADHD, I am absolutely fucked. Not to mention that PFS already directly and indirectly gives us ADHD symptoms.

In the study there is also my doctor Santi
All-Italian study :slightly_smiling_face:

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That is exactly what is so frustrating to me. Unless the scientists involved in the studies acknowledge all the physical symptoms of PFS (facial bone loss, penile shrinkage, collagen loss, weight gain, lower semen volume, muscle loss, hair texture changes, slower beard growth etc.) how can they formulate an accurate theory? We need to get at the root of the issue not downstream effects of the root cause that explain only part of the symptom profile.

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So there appeared to be no correlation between methylation of 5ar2 and either symptoms or hormone levels. I think this clearly demonstrates 5ar2 methylation is not the source of the problem.

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Yes but look at the low number of PFS patients. I am no doctor but how can anything be drawn from such a small number of participants (16 people)?

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They probably used a statistical method that compared the variation and range of controls to variation and range of pfs patients. I think this is called a Student’s T Test and is useful for smaller groups.

At least we can agree that they are publishing their studies quite quickly compared to Baylor or Brigham and Women.

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I am sick and tired of studies focusing on the mental stuff. If you cant explain the physical symptom list with your theory dont bother publishing it. I am not sure if this newest theory can explain the complete physical symptom list or not but as a general principle I want them to focus on the challenging part, i.e. a comprehensive theory addressing all symptoms.

I want them to address the physical symptoms people experience:

-fatique
-facial bone loss
-facial collagen loss
-muscle loss (expecially neck and forearms)
-weight gain in the midsection
-Gynecomastia
-penile shrinkage
-dry and thin skin
-hair texture changes

Why are they shying away from the real problems?

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