Why the Androgen Receptor Theory is wrong

This is essentially the AR theory promoted by awor et al;

“Due to inhibiting DHT with Fin, ARs become hypersensitive. When Fin usage ends, ARs are saturated by the increase in DHT, there is negative autoregulation and a permanent epigenetic change occurs at the AR (methylation etc) leading to androgen insensitivity”.

There are very good reasons why receptor/post receptor androgen insensitivity cannot be the root cause of the problem. I would like to collect them in one place. As far as im concerned these are;

1• Lack of any scientific support
2• Inconsistent with hormone test results
3• Internal inconsistency & symptoms do not match theory

1• Lack of any scientific support

AR and post-Receptor defects can obviously be the cause of inborn androgen insensitivity (complete or partial) and nuclear receptors regulate themselves as a way of controlling a hormones action.

But there has NEVER been a recorded instance of any receptor becoming insensitive to any hormone in the way the ‘Androgen Receptor theory’ describes. In fact no hormone receptor has ever become permanently insensitive to its hormones under any circumstance. Any sensible idea must have support from science.

Billions of US$ has been spent on AR research for over 50yrs, both under the microscope and in the real world. And why have they never disovered that ARs turn insensitive? … because thats not the way the body works.

In fact, there is such a massive lack of scientific support the idea should be dismissed. (if you have any research that contradicts this please post it.)

2• Inconsistent with hormone test results

Lets focus any the results that are odd. 3adiolG and (apparently) neurosteroids (like Allopregnanolone).

These hormones are made by the same enzymes. Red = 5a-Reductase, Blue = 3a-HSD. 3a-HSD activates neurosteroids but deactivates DHT to 3Adiol.

Progesterone ----> 5α-dihydroprogesterone ----> Allopregnanolone

Testosterone ----> DHT ----> 3AdiolG

The ‘AR theory’ supposes that 3AdiolG is low because of a problem with the AR. ‘Doesnt deactivate DHT because cant sense there is enough’ or some such thing. But then why would neurosteroids ALSO be low?

In fact a meta-anlysis of the urine results also shows a deficiency in a range of 5aR->3aHSD reduced metabolites. Logic dictates that this is more similar to a 3a-HSD deficiency or an Endocrine disorder that prevents hormones binding to enzymes and receptors (also, both of these illnesses are already knowns to exist.) This would be a pre-receptor problem.

3• Internal inconsistency & symptoms do not match theory

The AR theory relies entirely on a change occuring after stopping, but a large proportion of members do not get worse after stopping.

This theory does not account for numbness (this symptom is traditionally ignored).

Hairloss usually continues (also ignored) even with muscle loss. Should prove theory is wrong.

Some people experience muscle loss. No scientific or theoretical explanation for this.

Some people experience new body hair growth.

Some people experience a crash up to a month after stopping - (autoregulation reaches it maximal effect at 48hrs.)

No explanation why TRT doesnt work. But plenty of ideas as to why TRT might make you worse (“negative autoregulation”!).

Theory suggests that ALL androgen deprevation side-effects are caused by epigenetic changes - simple untrue.

AR gene expression can (and has) been tested. Surely this was conclusive proof this theory is wrong?

And the rest… when i can think of them.

Please add any reasons you can think of.


Honestly, it really doesn’t matter what a bunch of people think on a message board – you, me, anyone. It’s the scientists who will be investigating this problem and will help us find answers, and they will be the ones determining most likely target areas, potential mechanisms, and designing the study protocols for investigation.

In his latest paper, Dr. Irwig concludes with:

“Further valuable research could determine who would be susceptible to finasteride through genetic studies of polymorphisms of 5a reductase and the androgen receptor.”

There is a general idea of where to focus efforts; undertaking the research is the next step.

I’ll throw in my 2 cents. I am not saying that the theory is absolutely wrong, I’ll wait for the research results before I pass judgement. Regardless, here are my major issues/questions after re-reading the research proposal theory.

  1. Too many assumptions and manipulating of statistics (clumping everyone in the same category)…

-Not EVERY PFSer has low testosterone, FSH and LH
-Not EVERY PFSer has tested low 3a-diol-G levels
-Not EVERY PFSer has low Vit D
-Not EVERONES PSA levels are low

  • A lot of the guys developed PFS while still on 5ARi

The last point is not consistent with { hypersensititvity (on Fin.)—> flooding of dht (quitting Fin.) ----> PFS } theory


Lets say you have a normal hypogonadal male. His androgen levels are going to be very very low, just like a male on Finasteride. I would assume that both of their androgen receptors have similar “sensitivity” at this point.

Now when that hypogonadal male goes on TRT, he is going to have a “floodgate” of androgens come back…akin to the male “quitting Finasteride”.

Now, why is it that this “floodgate” of androgens mixed with a “hypersensitive adrogen receptor” does not cause PFS in hypogonadal men on TRT? Even if its a genetic subset of men that get PFS, why have we never heard of a single case of someone getting PFS symptoms from trying TRT or high doses of testosterone (steroids).

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I’ll wait to hear results as well before concluding anything, but I’ve asked some of these same logical questions before. It was disappointing not to hear any attempt at counterpoint or explanation.

Particularly, as far as explaining how this concept applies to people experiencing severe side effects while ON finasteride. Is there some nuance I’m not appreciating?

Are the side effects while ON the drug, just the “side effects” that pop up after 9 years on the drug? And then quitting the drug BECAUSE of the side effects brings on the “flood of DHT” and switches off androgen receptors permanently? And what % quit “just because” vs. quit precisely due to the side effects which end up persisting?

And why do some have mid-range or high DHT, others like me have low DHT?

I’m truly not looking to politicize this, I’d love to have this explained by someone who strongly understands and supports this theory.

Mew, Dr Irwig’s study is almost totally focused on neuroactive steroids, in fact the quote you give is the ONLY TIME he mentions Androgen Receptors (and is likely a reference to CAG repeats). Thats probably why the full quote is this:

“… It is important for physicians to acknowledge with their patients the current limitations in medical knowledge, particularly as it relates to neuroscience. There is no known blood or imaging test to study or measure neuroactive steroids or their metabolites in different areas of the brain associated with sexual function. One possible avenue for future human research is the measurement of neuroactive steroids in the cerebrospinal fluid via lumbar puncture, a relatively low-risk procedure. Further valuable research could determine who would be susceptible to finasteride through genetic studies of polymorphisms of 5 a reductase and the androgen receptor. Further research with validated instruments is needed to study the nonsexual persistent side effects associated with finasteride…”

See there is no way of knowing what is right. I agree that AIS is hard to believe, I don’t think everyone is resistant to androgens, more like changes to androgen receptors.

It’s hard to understand some guys can get errections, grow facial hair. Some have high androgens some low, some suffer mental, some suffer both, some suffer just physiological changes.

It’s really hard to pin points where to start when addressing this problem. It’s not consistant.

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I realy dont understand the purpose of this treat or the aim?

i agree with brainbug… what is the actual purpose of this thread?

leave the science to the scientists in my opinion, no one on this forum is going to solve this syndrome, no matter how many materials they absorb

What is a forum? It’s a place for discussion. I haven’t seen any scientific evidence done in a LAB yet. There is nothing wrong with sharing points, his done this well by providing evidence. Let him have his say.

i think we differ on the definition of “evidence” … anyways, you guys go for it, i wont bother you, good luck

Let me rephrase he gave educational theory on his thoughts, there is nothing wrong with sharing information. We are all on here trying to help eachother out. It’s good to see that people question and are open to discussion.

But then again who are we to question what has not been proven.

yeah lets discuss PFS away!

Let me rephrase, on the one hand we have running studies, on the other a discussion. Mhhh
I´m out of this discussion.

Just PM me when you find the cure please.

It could be that the theory is correct. But still what could a possible treatment consist of other than the means we have today?
I mean we have tried pretty much everything known as far as treatments are concerned and even some unknown things not even close to mainstream medicine.

The one issue i always bring to my mind is Chronic fatigue syndrome, another enzyme related disorder (see L Rnase enyzme related problems/complement system disorders) similar things pretty much happen as in our case, when between two individuals affected by some strong trigger, let it be drug/virus/bacteria/long stress periods one exhibits decreased cortisol receptor sensitivity patterns while the other remains completely unaffected and his whole HPA works steadily/so does his immune system.

When this affected individual is treated with normal or high dose cortisol nothing happens instead he only sees side effects. Low dose cortisol however does some work (5mg/day or every other day) in restoring his energy and immune profile to some extend.

In this case too there is dampening of the whole HPA, that means if you measure cortisol activity it is less active, there are lower burdens of adrenal cortisol even under stimulation or even at some cases intermittently higher but not at a steady state.

So to say, the whole HPA is affected due to an error in the enzymes which are responsible for stabilizing the complement system and the immune pathways as a whole. This is expressed through a defect in cortisol binding to its receptors. Then there is the complex pathways involved in higher cns centers with somewhat of a similar pattern being followed among CFS sufferers (like overwhelming serotonin activity-in contrast to depressive disorders where serotonin levels are generally low/exhausted).

Anyways, any sort of receptor dysfunction could cause an array of such problems, shifting of neurotransmitter production/ atrophy of brain centers etc etc and thus dampening of a whole system like HPA/HPG.

Likewise here we are playing on a different axis mostly the sexual one HPG but if you take into account the previous syndrome it is more or less one of the same kind, just different key hormones /receptors involved but the pattern remains.

Whether our problem stems from dysfunctional neurotransmitter handling or levels, which we cannot measure at this point due to lack of proper testing (lack of pet scans or diffusion measurements) or if it is solely a hormonal problem which is highly doubtful there is some role of the AR receptor down there.

Libido for me is highly enhanced when using damiana, a psychostimulant substance with serotonin/ and FSH exerting properties and i mean several fold but this is not a steady process. Next day i am back to average/low libido. Hormones on the other don’t do nothing to me, as a matter of fact they make me worse, much worse.

On the other hand because of direct effect of finasteride on ones prostate and testicles issues become even more complicated. How many people have discovered urinary symptoms post finasteride, i read more and more about it in several forums. Offcourse libido cannot be so much related to prostate issues, but penile numbness and urinary issues could be.
Even so in prostate inflammation the AR is in fact a place to blame.
Two individuals with similar bacterial profile and one gets symptoms the other one doesnt. One has normal hormone levels the other one dont.

We are stuck in a labyrinth of problems stemming from our genital to our most complex brain areas.
We cannot measure neurotransmitters affected. Neurotransmitters build up neurohormone levels like GnRH/Fsh/LH. Shifting of their levels and their relations/frequency of production makes it hard for a steady amount of GnRH being produced. Most of us show drop in FSH levels production. I don’t take into account LH because it is never a steady measurment.

I think we will be at a loss for many years to come, i am not very enthusiastic about receptor research its too theoretical but it is a good step and good for them who participated and organised and put time and effort in it.

I am mostly concerned about the immense problems i keep facing like testicular atrophy, prostate issues. Libido i can correct even with those means mentioned above so i am partly happy

imao, since we r not scientist, every effort in theorizing is a waste of time

could be good only if other researchers pick up different way to approach pfs


I also don’t agree with AR theory but will support Awor’s study 100%, what other options do we have? I hope we will discover something through this study.
If some body can launch a parallel study /Research based on body’s reaction or autoimmune that would be great.

Precisely. This is an anti-theory thread.

And the ‘Androgen Receptor’ theory is a particularly bad theory. It goes against the grain of known science, it doesnt even match the symptoms. I think treating this idea with any undue respect simply encourages other random theorizing without reference to reality, or creates the perception that the answer isnt already documented in some form.

Lets get away from theories.

Given the chance everything known to science that can effect hormones needs to be tested first. Hopefully that logic is accessible to everyone reading this thread.

And why? Quote the writen theorie.

Honestly? You have absolute no clue what you are talking about you totaly are missing the Topic and the aim of the research. In Germany we would say. Sit down 6. Missed topic!

Could you please quote any of your statements?
Oh and even when this does not belong to the main Topic of awors theorie… There are forms of AIS that have a unclear genesis btw There are many good works in German. Anyway, do you know how signaling works? Do you have any science or medical backround or is this just you are Prof. Dr. Google? here google this: aeaAndrogenresistenz unklarer Genese.

yeah go away from Theories, this would be the best thing

I still dont understand the aim of your treat.
What is wrong with you? viewtopic.php?f=33&t=6581
Try to read this a few times, may be you will understand it than and yes read on a bit more for the just till the first Projekt about the AR.

Sorry, shall the running studies be stoped, just because, Prof. Dr. Google Oscar with non medical background. Says it? Do you realy think, you know it better than the Scientist who are working on this???
What is the aim of this Treat? Messing up? We all are sitting in the same boat, so dont shit inside! This is a free Forum everbody can have his ideas. But messing up people, like awor who realy build up something big, trying to help us, pisses me realy on. We all could thank him for all the work he is putting inside. What have you done oscar? What is your aim with this treat?
Showing the world that the PFS guy are all totaly brainfoged and stupid, because they are fighting each other about theories and belive wars?

agree with brainbug, 110%