So 186 up regulated genes in our brain study

I agree with your point of view. I am not good at biology, but I believe that changes in gene expression are only a result of PFS and not a cause

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The genetic expression levels are of course increased in all types of cancers , thats why it can cause unregulated cell hyperplasia.
There are obv. epigenetic factors driving those expression levels, for ex. smoking in lung cancer.
Or in our case Finasteride.
That’s why medications that regulate methylation levels of genes are used for cancer treatment.
Restoring those methylation levels woud most certainly reduce all of our symptoms, since they influence numerous pathways.
Attacking these expressions levels individually will be a difficult task if not even impossible and surely won’t translate into a treatment.
The signaling pathway that regulates the 5-alpha-reductase gene expression should def. be better understood.
This is still a black box and from my knowledge standpoint we don’t know if there’s a negative or positive feedback loop causing evident changes of the signaling pathways in the presence of a strong 5-alpha-reductase inhibitor.

Our bodies have never experienced a 50% DHT deprivation for the time of our existence.
So I wonder if the mechanisms in check to still guarantee normal cell functioning even in the presence of highly reduced DHT levels are even working properly.
Another question I might raise, is what happens to the Finasteride drug molecules that lose the competition for binding to their target receptors.
Which other receptors or molecules does Finasteride bind to?
This could potentially lead to Off-target Effects.


PfS do effect our brain chemicals, dopamine, neurosteroids and neurotransmitters genetically and derugaled. Many new gene therapy metodhs are curing different diseas. I think they Will use meds or gene therapy to regulate pfs.

It is not brain damage

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Thanks for this update. Tried GABA for two nights… Seemed to promote less stressful sleep (said my sleep monitor app/device). I used topical Finasteride for 7 weeks which produced symptoms starting week 3 so I wonder if I’m more susceptible to blood/brain barrier personally and GABA did actually cross it? L-Tyrosine made me feel kinda weird, (anxious?) I’m dealing with fight or flight feelings at night waking me up even though cortisol levels were normal in last blood test. Maybe Tyrosine’s relationship to adrenaline isn’t the right fit for me? Took 5-HTP at 4am when I woke up to try to sleep and it didn’t help but I see you suggested using that during the day rather. I’m 3 months post stopping topical Fin. No sex side effects. All cognition and sleep disturbances.

I never used finasteride; I used saw palmetto. I knew about the dangers of finasteride sometime around 2013 or 2014 when I was seeking answers for unrelated conditions. I came across a number of forums, among them a prostate forum, none of which I remember the names of, and this petition: I also found out about PSSD. I said “sucks to be them” and carried on with my life until 2020 when that midget palm tree ruined my health overnight.

accutane inhibits 5AR type 1 but not type 2. finasteride inhibits 5AR type 2 but not type 1. This would explain why the former affects acne but not hair loss and why the latter affects hair loss but not acne. dutasteride and saw palmetto inhibit both 5AR type 1 and type 2.

Vinca alkaloids used for cancer treatment are extracted from the periwinkle plant. I wonder if dutasteride and/or finasteride are extracted from saw palmetto. Anyway, I have used periwinkle, an herbal DNMT inhibitor and HDAC inhibitor, and I feel it helped me, along with countless other things I did. Alas, chemotherapy/periwinkle and other forms of immune suppression open you up to nasty infections, possibly limb or life threatening infections.

Shout-out to my ketogenic brother, @Ozeph! Keto, another thing I found helpful.


You seem to have a leaky brain barrier. It’s not unusual at all and GABA supplements are used to verify if it’s the case or not. L-Tyrosine is not for everyone. If you don’t feel good with it, stop it. 5-HTP won’t solve the real issue which is IMO excess Glutamate. A pinch of MSG (mono sodium glutamate) instantly gives me anxiety.

I’ve seen this is many PFS sufferers including myself. The Androgen Receptors have been up-regulated (or over-expressed) in response to an androgen deprivation therapy (Fin). This is not from me, it’s from one of the researches from Dr. Roberto Cosimo Melcangi in Italy. He says AR are enlarged and oval shaped under the microscope.

I’ve read in another study that the AR are regulating the L Glutamine complex in the body. Over-expressed AR is said to create Glutamine complex toxicity, that is, too much of the Glutamine metabolites in the body. One of those metabolite is Glutamate which we end up having in excess. It’s the excitatory neurotransmitter that should transform into GABA at night to provide good sleep. For some of us, not enough Glutamate is transformed into GABA and we don’t sleep very deep or at all. Over the night, testosterone level goes up (as in all men). That makes our AR produce extra Glutamate at night and we wake up fully awake and lit up, as if we just drank 3 espressos.

There certainly has been many epigenetic alterations to counter-balance the excess Glutamine complex metabolites. In my opinion, to try and find them all is maybe educational but it misses the point. The initial problem is having been deprived of androgen and 5ar which has caused the AR to be over-expressed in order to capture what little androgen was present. I believe in putting the body in a state where epigenetic repairs can take place and then signaling to the body which direction it should take. For this, I’m fighting an androgen deprivation therapy (fin) with an androgen supplementation therapy (not TRT). It has made some long gone symptoms reappear but they are now receding. Sensitivity is much better, sleep is better on half the sleeping drugs compared to 2 years ago but I won’t know the final results until I stop the supplementation and let my androgen come back to normal. By then, I hope my AR will have adapted to higher androgen levels and normal ones will produce normal results. Let’s see.

I don’t suggest anyone try this. I’ve worked many years to make my body stabilize and my symptoms were almost all gone before I was strong enough to get worst. It still remains to be seen if I will actually get better from this. I’m a guinea pig in this experiment.

The study does not specify at what level the genes have been altered, just the overall signaling I believe.
So that means it could be at the Dna damage level all the way to RNA level.

This company could be an option for solving this

Wow. How much longer are you taking supplements in this experiment before you stop to see if your body’s androgen pendulum swings back to center?

Got my Adrenal-Neurotransmitter tests back. Took the test before trying any supplements including GABA. I have high GABA, high Dopamine and high Epinephrine, all in the red above normal range. In the yellow, slightly under normal range I have low Seratonine, Phenethylamine, and Creatinine.

Results also showed high Cortisol at night, above normal range, in the morning and before bed with low Cortisol during the day (HPA dysfunction?). And results show very low DHEA at 29, well below normal range (137-336)

This mixed with my high SHBG results. Normal Testosterone levels though. I’m now taking 4-6mg of Boron daily to try to bring that down. I’m eating greens, proteins, fats, and exercising.

Seeing my hormone doc tomorrow to discuss new neurotransmitter results.

What’s your take @Ozeph?

It shows you have deregulated genes in the brain as I believe most of us have. I sure do myself. Continue with your healthy diet and exercise, I think you can’t go wrong with that. My advise would usually be a carnivore / ketogenic diet. It shows improvements in all those who successful got into it but it’s clearly not a complete answer to our predicament.

Boron is the androgen promoter I’m currently taking. It has shown to have a very effective, fast and direct effect at lowering SHBG and thus increasing free T (and all sexual hormones as shown by the increased Free Androgen Index, FAI, results).

I took 12mg Boron per day, tested and free T was 2.25x above maximum range. I started being irritable, aggressive, sometime furious and then I blew up the top. Sex drive dropped, heavy brainfog, difficult sleep and lots of long gone PFS symptoms re-surging. 11.3mg Boron a day showed similar results but slightly less brainfog. Still unsustainable.

I reduced to 6mg of Boron a day and tested again. Free T was very high but within range, Old re-surging symptoms disappeared, sex drive, sensitivity and orgasm depth improved.

I increased to 8mg Boron a day. Tested again. Free T only 4.3% above max. No or very little brain fog, sex drive and sensitivity decreased, old symptoms didn’t come back.

All trials were done for a month before testing and correcting Boron dosage. I find it fascinating how Boron alone, via free T, can exacerbate PFS symptoms. In 6 years, with all I tried, I never had such accurate control on this disease’s expression in my body.

I currently increased to 9.5mg Boron a day. Sensitivity, sex drive and depth of orgasm are low. Slight brainfog but tolerable. No old symptoms re-surging.
In 15 days I’ll test again, post my results and then drop Boron to 2.5mg (which does nothing to SHBG) I want to see where my sexuality is without artificially increased free T. I won’t test free T, it will be within range.
If I end up with a better sexuality and better motivation compared to before I started all this, then I’ll start to believe the elevated free T and free androgen will have reversed some of the PFS epigenetic de-regulations. If not, then I did all this for nothing and spared you the trouble of making yourself worst to test a theory.

I don’t suggest anyone try this. Again I was quite stable and strong before I tried so I could afford getting worst in an attempt to get better.

Before doing the Boron experiment, I took a 6 months HCG treatment at 300iu three times a week. That’s very low, some 15 times lower than what the doctor prescribed to one of my friend with PFS. I did this to increase natural T production persistently. The increased T remains after HCG is stopped. SHBG was high and free T low which shows my body was correcting for the increased T. I was worst at first but became used to it and was better at the end. I took Boron afterward to stop the attempts my body was making at dampening elevated androgen. I wanted my AR to capture the new elevated androgen levels.

Curiously, 3 weeks after starting HCG and for 1 day only, sex drive was high, sensitivity and connection was very high (as I remember it when I was a teenager) and orgasm was an explosion in the brain just like old time. It was gone the next day. In my opinion, it shows that the DNA is intact underneath all the epigenetic alterations. DNA is hard to change and seldom does whereas the epigenome is fluid and responsive to changes in current conditions.It constantly changes.

Also keep in mind I’ve been on a carnivore / ketogenic diet, one meal a day, for 6 years. This has stabilized my body and according to some research I read, it promotes epigenetic repairs but without sending a clear signal to the body as to what the repairs should be.
The HCG / Boron experiment is meant to send a signal that my body is too sensitive to free androgen and thus needs to repair the AR. Increasing SHBG is the first attempt my body has made to prevent the AR from being overwhelmed. Boron makes SHBG irresponsive to the body’s attempt to do this. The theory I’m testing is that the next available solution would be for my body to downregulate the AR. I’m not saying it’s working. Let’s see.

Those are my results so far. I’ll post again in 3 weeks for those interested in knowing what happened.


Please let us know the results. I wish you good luck!

My hope is that everyone puts their differences to one side and supports all of the current and new studies, different platforms and groups.

There is freedom of speech and choice where to donate its all to help find a treatment and cure. We all have the same goal so pulling together to preserve and save lives should come first without seekng alliance to certain studies only. The more that’s being done = the better the chances.


I have a scientific question.

Does “up-regulated or down-regulated genes” mean directly “epigenetic-modifications(Methylation, histone-modification etc)” ? Altered genes expression and epigenetic-modification are completely the same thing?

According to the researches, finasteride brings out thousands of alterations of gene expressions (upregulated or downregulated) in brain and body. So, does it mean that finasteride caused thousands of epigenetic-modifications?

on the other hand, we have the theory that what causes pfs is some epigenetic-modifications which make AR-function distorted and useless. I understand it is the cause of pfs. I don’t know how many epigenetic-modifications contribute to AR-dysfunction. But, it must be not so many.

Then, do the researches reveal that besides epigenetical AR-dysfunction we have “other additional” thousands of epigenetical dysfunction? Is it truth? I feel something strange… If that so, we have not only one problem(AR-dysfunction) but also thousands of problems…

Anyone, could you teach me?

How’s it going with the self-guinea pig experiment @Ozeph? I’d love to report your experience to Dr Bouloux in London who’s interested in the data. He’s seen 300 PFS patients over the years. Here’s a summary of our call today: Success Stories Compilation

hi, heved.

30-40% of Dr. Bouloux’s patients recover close to normal eventually.

I am encouraged to hear this news! Thank you for sharing the information! Then, how long does Dr. Bouloux think it will take to recovery? Did he say something about the time?

@aki He said that everyone is different. He just said that the fact that I have found some supplements that have leveled out my symptoms means I’m likely in that 30-40% group. I’ve been dealing with this for 4 months. He mentioned others at 5+ years. I really feel what helped me also was getting the right tests. I had fight or flight sensations middle of the night so I tested cortisol. I had memory and cognition impairment so we tested neurotransmitters. That led to picking supplements to aid with imbalances according to those tests. Full blood panel and hormones check as well led to discovering high SHBG which I’ve been trying to lower (seemingly successfully) with 6mg to 9mg of Boron daily.


Thank you for your reply. I have been dealing with pfs for 8 months. it is true that experiments and facts are more reliable than pure theories of mechanism.

So, does that mean that according to Dr Bouloux’s experiments, even in that 30〜40% lucky group, some people recovered within a couple of years, but in others it takes to recover for more than 5 years?

I would like to contact Mr. Bouloux and exchange with him. He has a French name and French is my first language.

So far, my body has and is reacting according to my understanding of PFS. I think my AR are over-expressed and are overwhelmed by my normal androgen levels. I theorized that too much androgen for the AR to handle would shut down sexuality in a similar way not enough androgen would.

In an attempt to get my AR used to higher androgen, I used HCG and Boron to greatly increased androgen levels. As a result sex drive dropped to near zero and sensitivity was so low and felt so disconnected that I could no longer have orgasms (not to mention the heavy brainfog). This seems to confirm that too much androgen did indeed shut down my sexuality. However, as time passed sexuality got back to where it was before this experiment (low sex drive, low sensitivity but still working) so I stopped all androgenic supplementation to see where my baseline would be.

It’s been 3 weeks now and the results are encouraging. Blood test are showing that my total T levels has gone from 33% over the maximum range (1209, normal range is 300-900) to now normal (752). Same with free T which was 133% over max,which felt horrible, and is now within range.

As for the results of all of this: Sex drive is much higher than it has been in the last 6 years since I got PFS. I want and can have sex 3 times a day. I’m looking at women with a gut instinct I haven’t felt since before PFS. Sensitivity is back to normal and orgasms are deeply felt like before PFS. Motivation is good, I’m feeling joy again and sleep is also the best it has been for a decade. I started having insomnia 4 years before crashing with PFS as I took fin for 18 years. I can now sleep a full 7-8 hours every night despite tapering down benzos. I’m now at less than half of the dose of clonazepam I was taking and no signs of withdrawal symptoms. I can’t say if I’ll be able to tapper down to zero and still sleep but I’m optimistic and I see no reasons why I couldn’t. It will take time, I’m tapering very slowly.

So those are my results. I’m stable but I don’t think I’m completely cured from PFS. I have very little symptoms left and it’s barely perceivable. Somehow, I think it’s still lurking bellow the surface. I don’t think the PFS epigenetic alterations are completely gone but it feels like they’ve been removed enough to feel close to normal even if there’s still some left. Remember, we’re talking about methyl groups inhibiting gene expression and histone alterations. This is not black and white. Some may still be left but not enough to cause major symptoms like before.

Anyway. I may be wrong in my interpretation of the results and about their cause but it remains that I sleep much better and my sex life is better than my friends that are same age as me. (and to be honest I’m a little tired of thinking about my T3 / rT3 ratio, my D3 dopamine receptors, my LH and Leydig cells etc… Those things were not on my mind 6 years ago)

I have crossed referenced my protocol with others who have “recovered” to a normal life and I think I have a better idea of the process. I’d be very interested in discussing all of this with Dr. Bouloux if you can get us in contact with each others.

I appreciate your posts on this topic and as I’ve been saying for 6 years, don’t give up guys. There’s hope !


My theory is that the epigenetic changes that occur are largely chain reactions that can occur at any dose. Some people take a single dose and go under very quickly, people like me took it for a month and initiated a longer chain reaction that eventually completely crippled me even after I stopped which I have never had happen with anything before even with things that induce withdrawals physically. As everyone knows already things up and down regulate themselves all the time in the body depending on the environment the body is in and what it’s consuming. What I don’t get either is what is so destructive about the switches made by this group of hair loss treatments that cause such a wide umbrella of equally destructive problems. Everyone with this is somewhat different too which makes it more complex. Some people may just get the sexual issues, cognitive dysfunction, neuropathy/numbness, or skin level visible changes to their body. I got all of them besides the physical changes anywhere but my genitals which technically at its worst were just much smaller.

I tried so much so far and have had individual symptom windows before but never the whole package, almost every individual window that wasn’t an improvement in my general state overall was just reverted back. A lot of things I did improve with overall I have no idea why, the only thing I can think of is that I simply induced chain reactions that epigenetically improved things again. I’ve also been shown from my windows that it seems everything in my body is still there BUT there’s something extremely dysregulated going on that is essentially locked into place whatever the stuff did. Neurotransmitters and hormones fluctuate all day long but throughout the day but I don’t tend to feel very much different anymore, it’s as if what in general happened caused my body to barely respond to anything anymore at all. My overall improvements appeared to be simply under the bubble of “body is responding” again.

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