Persistent 5ar downregulation


Hi All,

I am new here and have been suffering PFS symptoms for about 2 and a half weeks.

This is just a thought and would explain some of the hormonal imbalances experienced by some. Feel free to shoot me down if this has already been discussed and evaluated.

It would make sense that guys are shown to have higher estrogen hormones and lower testosterone after their crash due to a reaction from the body to down regulate 5ar after experiencing abnormally high levels of DHT post finasteride cessation.

If 5ar is persistently downregulated then any testosterone produced from the testes would be unable to be effectively converted into DHT and hence will aromatise to estrogen. The result of this is hypogonadic alterations from the body to attempt to reduce estrogen levels caused by regular testosterone output being aromatised and hence why some men experience testis shrinkage.

Decreased testosterone levels would also explain loss of muscle mass and strength. I have noticed that those that have used TRT have not always recovered libido or erectile function but have gained some muscle mass, I would suggest this is to do with lack of conversion to DHT at the genital tissues which is why sexual symptoms persist. This could also explain why there are imbalances of neurosteroids related to 5ar in brain tissues, dysfunction of 5ar at these sites.

However this does not explain a failure of DHT replacement in treating ED issues.

Just some thoughts.


I think the studies showed the opposite- upregulation of 5AR. Can’t find the link now. Maybe someone will assist


I believe this is correct. The theory involves the androgen receptor in the sense that the signal of the receptor is being blocked/suppressed (not the expression of the receptor itself)

Here is a paper that a few moderators from this site put together about the topic:


The overexpression of the androgen receptor in penile tissue of PFS patients has been confirmed. Please do not confuse the androgen receptor (AR) with the enzyme 5alpha-reductase (5ar). The OP is talking about the latter.

@gonnawin You have already pointed out why your hypothesis cannot possibly explain this condition. If you were correct, supplementing DHT should help, but it doesn’t. May I also add that we see symptoms that cannot be explained by a malfunctioning of 5ar.

I appreciate that you come up with ideas. If you are interested in digging deeper, please read the paper mentioned above, the existing scientific literature as well as Awor‘s post. If you search his posts for 5ar you will find more detailed thoughts why your hypothesis can’t be correct.


Hi Northern Star

Thanks for your reply (:

Which symptoms cannot be explained? - just curious


Sorry, have little time at the moment. Please read this: Open Letter to the Advocates of 5AR2 Deficiency and Adiol-G

It is a little confrontational as the post is from a time of wild theory wars here. But the substance of it remains true.


A little confrontational, LOL :smile: I probably should have gotten banned from the forum for the tone of that post. Yes, glad those war days are over and that we found a more civil tone to discuss our views around this place.

That post of mine is so long, I did not even have the patience to read it once again after all those years. A good example of how not to write posts I suppose.

Anyhow, not fully in line with what I wrote back then, I later found an interesting link between 3a-diol-G and Testosterone values as a marker of PFS. Through some literature I found that 3a-HSD is mostly induced by AR gene products (i.e. AR gene expression). Since DHT is reduced by 3α-HSD to the inactive androgen 3α-diol-G, a deregulated 3a-diol-G/T ratio would indicate something is wrong with the functioning of the androgen receptor.

Here is an extract of that part of the paper I wrote:

The green line shows what the ratio should look like in normal men (found in literature, not shown here). Ours by contrast is pretty flat (data comes from guys who posted there test results in this forum). In other words, 3α-diol-G actually is a smoking gun, but not in the sense that some theories were trying to sell it. Rather, it supports that something at the AR level is not working correctly. In the data, one can see that some guys even have a negative response to higher T levels (where 3α-diol-G dips into the negative ref. range area). In case anybody is interested in the supporting literature for all of this, I can provide on request.

Btw, 5ARI-WS = PFS (I never liked the term PFS even though I am one of the inventors of this term, as it implies that this is a finasteride only problem).


You wrote that abstract, @awor? Just out of curiosity, is your career in research/biology and you just happened to come down with 5AR withdrawal syndrome?


Hi Awor,

Its good to see you’re still alive - I hope you’re doing okay (:

I have read this forum inside out it seems and the AR hypothesis does seem the most likely. I believe that the gut is an important factor of the symptoms but is likely damaged due to downstream effects of AR malfunction (somehow I wouldn’t really know, just a hunch).

Is there any update regarding our AR problem?

I study biomedical sciences!

Today I was thinking about situation in which if we could determine the exact malfunction of the AR (pretty bloody difficult but yano) could we use retroviruses at all sites that are affected by these faulty AR (perhaps aside from scalp!) to target stem cells in all of these tissues - eventually after continued treatment (probably a few years) we would essentially weed out all of the cells that express the faulty AR (due to correct stem cells replacing these) and our androgen pathways would be rescued. What i’m suggesting is that we essentially replace the gene and side step epigenetic reversal, I believe this is already being used to treat those with sickle cell anemia (replacing allele type that results in haemoglobin aggregation which forms rods in these cells and causes them to become sickle shaped).

This could be incredibly naive on my part and I’m not really sure how it would work in the neural tissues?

But this method of gene replacement is already definitely in the works and when the changed gene (or genes) of the AR are located I’m not sure why this couldn’t be used, maybe you could explain this to me.


I just had another thought!

I read in some literature that the degree of CAG repeats in certain genes related to the AR influences the severity of issues experienced by those affected.

If CRISPR did become functional as a gene editing device, because we already know these genes could we change the length of these repeats to get us to a DNA sequence that invariably expresses no 5AR WS phenotypes?


GW :blush:


I don’t undestand much, so it might be a very stupid question I am asking. Does this part of the study implies that AR is downregulated in accutane patients ? so it’s different from PFS overexpressed AR ? Or it has to be measured also in penile tissue ?

Recently, p53 has been identified as transcriptional inducer of FOXO1 and PTEN [156], an important observation that confirms the role of p53 in regulating multiple signalling levels of IGF-1/IGF1R/PI3K/AKT/FoxO1 signalling. AR is regarded as a sensitive marker of sebaceous differentiation [157]. Androgens induce sebaceous differentiation in sebocytes expressing a stable functional AR. DHT up-regulated the expression of genes potentially related to sebocyte differentiation such as MUC1/EMA , AQP3 , and FADS2 [158]. Remarkably, AR is a direct target of p53 and is negatively regulated by p53 [159, 160]. This allows the conclusion that all p53-activating anti-acne agents attenuate AR signalling and thus exert anti-androgenic activity, which is further suppressed via classical anti-androgens such as cyproterone acetate