The Post-Finasteride Syndrome is a Neurological Disorder

General Discussion
#1

This theory puts forward the idea that the root cause of PFS is an inflammatory disorder of the nervous system preventing nerve cells from communicating (demyelinating), similar to MS.

Evidence

The most common symptoms are all neurological in nature.

• Erectile disorder – neuropathy has been confirmed.
• Orgasm disorder – peripheral nerves or brain.
• Libido disorder – Originating in the brain (amygdala, hypothalamus other limbic areas, etc)
• Another very common symptom is ‘brain fog’

In fact most people with PFS only display these symptoms, although other problems exist.

Also, all doctors that have studied this problem and published peer-reviewed papers believe the root cause of PFS is neurological, Prof Traish, Dr Irwig etc.

Problems with this idea

• There is not thought to be any 5aR type 2 in the human brain. viewtopic.php?f=1&t=5960

(It should also be noted that almost all of the studies on the effects of 5aR inhibitors on the nervous system are Rat studies. This is misleading because Fin inhibits 5aR type 1 and type 2 strongly in Rats, unlike humans. Secondly the Rat brain also contains 5aR type 2.)

• Neurological problems are all focused on areas of sexual function. Need a reason why this should be the case.
• Problems can get worse after stopping.
• Low 5aR -> 3aHSD reduced metabolites such as 3adiolG, Neuroactive steroids etc.
• Why should Fin trigger a neurological problem.





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Solutions to these problems

This is how I would explain these problems. My assertion is that the antigen (‘target’) of the autoimmune/inflammation reaction in the nervous system is the 5aR type 2 enzyme.

• A reaction against 5aR may cause problems with paracrine hormone metabolism causing low 5aR -> 3aHSD metabolites.
• The regeneration of 5aR may cause the disorder to get worse after stopping (this has been shown in other drug-induced autoimmune disorders.viewtopic.php?f=27&t=5589&start=240#p52471 )
• Neurological disorders cause low neuroactive steroids in spinal fluid. ncbi.nlm.nih.gov/pubmed/20492360
• 5aR type 2 is present in genitals/prostate and its inhibition causes neuropathy in this sensitive region. (There is also evidence that Dutasteride causes all-over numbing viewtopic.php?f=25&t=1919&p=10049#p10049 ).

Therefore the only problem is why sexual regions in the brain are affected. I can think of three ways around this problem:

  1. Studies on human brain 5aR have missed the fact that the only areas of the brain with 5aR type 2 are small parts of the limbic system like the amygdala. The recent 5aR type 3 study does show some type 2 enzyme ‘somewhere’ in the whole brain (see graph)

  2. The part of the primate brain with the densest concentration of 5aR type 1 is the limbic system. ncbi.nlm.nih.gov/pubmed/3536457 If there is also a smaller reaction against 5ar type 1 it may have an amplified, focused effect in this small area (this may also be why ‘brain fog’ increases over time).

  3. PFS sufferers uniquely have 5aR type 2 in the brain. (worse).

How this solution may explain other symptoms:

Other neurological problems – The area of brain effected also controls emotions and memory. And more.
Loss of visual acuity – Optic nerve passes these brain structures affected.
Worsening of symptoms with TRT – due to an increase of 5aR
Bloating – 5aR type 2 is also found in the small intestine, spleen, liver etc. (Bloating is common in MS)
Muscle loss – 5aR type 2 is found in muscle. A different kind of tissue but even a small amount of neuropathy may cause weakness and/or muscle atrophy.
Fasciculations, fatigue, tinnitus – neurological in nature.

I would also assert the following:
PFS is not as severe as MS due to the fact the antigen is different and because it is localised. Neuropathy may also be a secondary indirect effect of a reaction against 5aR.
A reaction against 5aR (cytokines, antibodies, whatever) may also inhibit 5aR metabolites from binding to intracellular receptors.

#2

So what is the solution? Take a bullet to head or take some cyanide to solve the problem.

#3

What appears clear to me, is that the graph you posted states we are probably f____ up widespread. What is scary is the massive expression of 5AR3 all over the body. For what I know the majority of the theories so far have focused on 5AR2, which is obviously not necessarily the main contributor to the syndrome. And since everybody is different (which means all those parts of the body can be differently affected in the sufferers) it explains to me also the difficulty in getting a characterization of the syndrome and the differences in the behaviors of the symptomatology. It is to be considered also that there are really few studies on 5AR3, complicating the things to a fateful destiny.
For the theory in itself, I don’t know. There are so many variables that even professionals would freak up quite easily. I wouldn’t shoot myself tough, at least for another 1-2 years. Some studies are coming out and there is some interesting data arising from a couple therapies.

#4

What concerns me is even if the foundation or whoever figures out the cause in however many years, we then have to get lucky that it can be cured with current medications. Developing a new medication costs billions of dollars and will never happen.

#5

its allllll speculation and opinion right now, at least everyone who is posting here … this is a time for optimism and team work … lets get realistic and start donating to the pfs foundation … they are our best, if not our only hope of getting ourselves better … this is just simple fact and the sooner we can all come to terms with this FACT, the better off we will all be and the closer we will put ourselves to first understanding, and then fixing this whole mess

i will say though, those graphs on 5ar3 sure are eye catching … either way, there is no sense in non scientific minds like us trying to figure out the science of this mess

lets get real here and put our efforts towards things that we are capable of controlling and understanding

stick together, and stay organized people … we will not get another chance if we fuck this up

#6

Why isnt this thread about sticking together?

Most evidence points to PFS as neurological in nature. Remember, Prof Roberto Melcangi who is “Leading international efforts to investigate PFS” is an academic and expert in neuroendocrinology. Dr Irwig and Prof Traish who are in contact with Melcangi both later published papers stating the root cause is neurological. Tests on the CNS and peripheral nerves have shown there to be a neurological problem (Hopefully this info will soon be published, or at least posted here).

Im just trying to connect it all together but obviously I really dont know anything.

Yes 100%. The average is 11 years and 1.1 billion for a new drug.

#7

I guess the biggest thing we can hope for is to utilize what is all ready avalible, it has been stated here before that we can potential benifits from cancer research. There are alot of drugs out there, the likely hood that we can at least get some relief I would say looks pretty promising. I think going at this disorder with a positive attutde/mindset makes life a little more enjoyable. We hopefully will get a bomb if information dropped on us this month, at least we can say forward progress is being made.

#8

Oscar I agree with you 100%, IMO it seems pretty clear that it is neurological in nature and it does seem that the research is pointing that way. The only thing I would add to this and I think this is major that a lot of people ignore, there is some undeniable cycle to this. Some hormonal change having seemingly cascading effects on our body.

#9

Because this is my first post on this forum, I feel need to say that I’m recent victim, I’m sorry that I haven’t posted on member stories, mostly due to fact that I have most of the symptoms other members share. So much of introduction. I just wanted to add that my impression is that if we need to identify something as the ‘root cause’ of our trouble, first thing on the list is reduction in 5ar. So, instead of wasting time creating new and new theories, we and doctors, of course, should focus on finding way to increase 5ar. If there is a way to inhibit it, then I’m really convinced that there is way to reverse that. There is no need for years and years of researching, like I said, the first, and I’m really convinced, only thing pfs foundation should do is to find a way to reverse 5ar inhibition. So far, googling, only thing I found that can act that way is protodioscin. I’m planning to try that stuff in couple of days.

#10

I wish you luck in whatever you try, and I hope you feel better … but people need to stop acting as if they are more qualified than the REAL researchers on where research should be headed, and what should be tested … seriously, the notion is absolutely absurd and it really needs to stop… leave the science to the scientists people

feel better and good luck

#11

Re-training the brain

Techniques used in the Dynamic Neural Retraining System™ are based on neuroplasticity therapy, which rewires the limbic system to build more functional neural pathways.

It is the disorganization of neural networks that occur during trauma that can cause deep protective mechanisms within the limbic system of the brain to fire more rapidly and inappropriately. This results in a heightened chronic stress response that may affect many systems of the brain and body, especially those involved with emotion, sensory perception and cognitive function. Additionally, symptoms may include chronic inflammation, poor memory, brain fog, digestion issues, lowered energy levels, numerous sensitivities, chronic pain, and a host of other ailments. Functions such as detoxification, absorption of nutrients or cellular communication can also become compromised.

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What I believe PFS is