Hi everyone, I’m sure everyone is quite aware of the AR upregulation theory. I think this is undoubtedly the case. AR upregulation can explain A LOT. This study found low levels of key neurosteroids in the CSF of men with PFS, the androgen receptor decreases expression of the enzymes which are responsible for their synthesis https://pubmed.ncbi.nlm.nih.gov/28408350/
‘Indeed, decreased levels of pregnenolone, progesterone and its metabolite (i.e., dihydroprogesterone), dihydrotestosterone and 17beta-estradiol and increased levels of dehydroepiandrosterone, testosterone and 5alpha-androstane-3alpha,17beta-diol were observed in CSF of PFS patients.’
Overexpressed AR can explain low progesterone it negatively regulates the enzyme responsible for progesterone synthesis: https://pubmed.ncbi.nlm.nih.gov/9432137/
Overexpressed AR can explain low Pregnenolone it reduces expression of StAR https://academic.oup.com/endo/article/145/3/1269/2878129
Overexpressed AR can account for low DHT and high T in CSF it negatively regulates 5ar1 expression an isoenzyme found abundantly in the Brain https://www.researchgate.net/publication/10635616_Differential_regulation_of_steroid_5alpha-reductase_isozymes_expression_by_androgens_in_the_adult_rat_brain
Now if it is the case that an upregulated AR is the cause of PFS why is it that men generally get worse when we take something which decreases the AR? I think the reason is that when you ingest something to lower the AR it increases the activity of 5ar in the tissues that substances reaches and a result the increased 5ar activity causes an increase in DHT which interacts with the AR where it is high thus you get a worsening of symptoms. It goes something like this:
ingest substance to lower AR---->increase 5ar, increase DHT---->DHT interacts with AR where it is high---->worsening of symptoms.
This explains why when you take a substance to lower the AR some symptoms can improve others get worse. I think predominately the problem with severe PFS is high levels of the AR in the Brain this would mean taking something to lower the AR is a bad idea and would make the situation dramatically worse as one of the last places things you ingest end up is the Brain because of the blood brain barrier (BBB). So the situation when taking something to lower the AR looks something more like this:
Ingest substance to lower AR----->substance accumulates in body (less so in brain)----->5ar, and DHT increase peripherally------> DHT interacts with high levels of the AR in brain-----> Dramatic worsening of symptoms.
This would mean that ingesting something to treat PFS should be scrapped for the majority of us, especially bad cases (such as myself). What i’ve some to realise is that you want a treatment which targets the brain specifically and nowhere else, i think I have found that treatment it is called low level laser therapy (lllt) or Photobiomodulation therapy (pbmt). I read about it in a book called ‘The Brain’s way of Healing’ by Dr Norman Doidge .
PBMT has a long history of use and has been found to be very effective in improving cellular health. I wont go to far into the specifics of how it works exactly but I will post some links. The short of it is it works by increasing ATP synthesis in mitochondria, it also works by hormesis, there are multiple mechanisms of action some known, some not.
I purchased a couple of PBMT devices from a company called vielight. The use of these products has helped me dramatically in terms of cognitive function, depression, sexual function and so on. I also have been seeing a Dr in Sydney Australia (near where i live ) who practices the therapy and it has been very beneficial.
I will also add that I am not a mild case, from 2015-2019 I was in and out of psychiatric hospitals constantly as a result of having the condition, I have lost teeth my dental health has deteriorated, I have experienced extreme pain in my genitals and prostate on and off during that time as well as extreme depression and anhedonia. The PBMT has all helped dramatically with those symptoms as well as some lifestyle changes. Don’t let anyone tell you severe cases can’t improve, it’s not true.