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.