Thoughts On 5ar And Post Finasteride Syndrome

[TubZy]

You guys are bringing being ahead of the curve to a whole new level by getting a treatment protocol down to the science.

I'm on my second cycle of 5aDHP and I am once again amazed with how obvious it is that my brain is low on this. Also I started off in late April with my first run on prog by jumping on 5mg of Prog from health natural combined with 5mg of DHEA oral. After two weeks of this I was not crazy about it because the prog and dhea gave me a weird confused feeling in my head but by no means made my condition worse or felt as if it was acting as a D H T inhibitor like some suggest it can be. Four days ago I switched the prog with StressNon and so far I'm liking the preg better than the prog and dhea.

I'm looking to start experimenting with more of this and want to contribute in any way I can with getting the "Neurosteriod restart" down to a science.

In the "Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients" study it was suggested that there may be an issue with the pudendal nerve as well as with neuroactive steroid levels. After some brief reading on the pudendal nerve it seems not only can damage to this nerve result in ED and decreased sensation but constipation as well. I though this was interesting seeing that severe unexplained constipation that does not seem to be caused by anything specific that we eat is also another trademark symptom of PFS.

I wonder if there is anything we can take to try to stimulate or repair this nerve. I noticed in one Tubzy's posts he wrote that niacinamide solved his digestion issues and gave him sensation back. I'm curious to know if niacinamide can help with any possible issues with this nerve.

Check out this thread.
Finasteride Causes Physical Damage To Nerves, Depression, ED, Steroid Imbalance

 

[TubZy]

That really is fascinating. Didn't mean to be dismissive what so ever, just was suggesting that raising DHT and hopefully AR will have long term health benefits, and hopefully short term benefits as well. What do you guys feel is the best way at alter the brain chemistry up there? There has to be a way.

On a separate note, I just found out my buddy takes Propecia and has for over 5 years. Don't want to pry into his personal life, but at the same time feel as if i should make sure he stops using it.

Didn't mean to direct at you at all, just wanted to say my experience. It is weird dude, I used those kind of supplements prior to taking fin and when I use proviron after taking fin it's like I got a half response to it. The physical effects are there but not the mental feelings like that alpha male type feeling. It like something is missing, which I why bloom's research really makes sense now and same with my experimenting with other ***t too.

Androsterone had the most positive effect out of all though but still not as good as caffeine and niacinamide. I think androsterone really only worked decent for us since it is a neurosteroid, but can also increase DHT in the body too (rather than strictly in the brain only)

 

[Jsaute21]

Didn't mean to direct at you at all, just wanted to say my experience. It is weird dude, I used those kind of supplements prior to taking fin and when I use proviron after taking fin it's like I got a half response to it. The physical effects are there but not the mental feelings like that alpha male type feeling. It like something is missing, which I why bloom's research really makes sense now and same with my experimenting with other ***t too.

Androsterone had the most positive effect out of all though but still not as good as caffeine and niacinamide. I think androsterone really only worked decent for us since it is a neurosteroid, but can also increase DHT in the body too (rather than strictly in the brain only)

Yeah, that makes sense. Combining low dose Andro/Pan works real well for me but your right - Caffeine/Niacinamide is an unreal combo. I think you and @bloom are smart to challenge the status quo and rely on how you feel opposed to what the research says. Best i ever felt was on DMAA pre workout...athletic performance was incredible, was 6% BF but still had high sex drive etc. I mention it because i know you said you used that stuff too, but also because people say its terrible for you. I looked great, felt great etc. Different methods work for different people.

 

[Orion]

Caffeine/Niacinamide is an unreal combo

Curious what amounts you used/using throughout the day @Jsaute21 @TubZy

 

[Jsaute21]

Curious what amounts you used/using throughout the day @Jsaute21 @TubZy

I don't use it every day but i have anywhere from 400-800 MG of caffeine a day typically with usually about 100 MG of niacinamide from Energin. I don't get jitters from coffee so i don't need to use too many supplements when i consume it.

 

[TubZy]

Curious what amounts you used/using throughout the day @Jsaute21 @TubZy

I was doing 600 caffeine/500 niacinamide for a while prior to receiving my thyroid stuff I just got, I'm not doing it anymore at the moment

 

[Terma]

Hey guys you have a great conversion going on here. I got the supplement PEA. Taking a large dose on its own it's weak compared to steroids, benzos and the like, not sure it's worth the money. Do you think it should work fast or that it needs a two-week course to show any difference?

 

[TubZy]

Explains why people have recovered from GHB. Seems like it addresses every angle that fin shuts down in the brain. If only this stuff was easier to get lol .

In male Wistar rats, GHB dose-dependently (75-1000 mg/kg, i.p.) increased AP, THDOC and their precursors pregnenolone and progesterone in brain cortex and hippocampus.

GABA(B) receptor-mediated increase of neurosteroids by gamma-hydroxybutyric acid. - PubMed - NCBI

 

[bloom]

That is awesome man, thanks for that you read my mind haha. How much niacinamide and diamant are you doing? I'm going to dose it before bed tonight. I think niacinamide benefits come more from acting as a cofactor (from increasing NAD/NADH etc.) in the brain for neurosteroid synthesis rather than just acting on the GABA-A receptor itself.

I thought this aswell, but then I tried Nicotinamide Riboside, it didn't produce the same effects as Nicotinamide. I have a suspicison that Nicotinamide a CLASS 3 Histone Deacetylase Inhibitor (HDACI) increases 5ar gene expression. I can't find anything on Nicotinamide increasing 5ar, but there are a few studies showing that Trichostatin A a class I and II HDACI increases 5ar gene expression.

Trichostatin A enhances glutamate transporter GLT-1 mRNA levels in C6 glioma cells via neurosteroid-mediated cell differentiation. - PubMed - NCBI

Based on these findings, histone deacetylase (HDAC) inhibitors are assumed to induce glutamate transporter-1 (GLT-1) gene expression probably through the promotion of glial cell differentiation. Then, we examined the effects of HDAC inhibitors on GLT-1 mRNA levels in rat C6 glioma cells and found that trichostatin A can induce GLT-1 gene transcription following steroid 5α-reductase and GFAP gene expression.

While it doesn't specifically mention Nicotinamide or class III HDAC inhibitors, it's possible especially considering how remarkably Nicotinamide can improve my symptoms, in a different way to Valium or any other direct GABAA agonist.

 

[bloom]

Hey guys you have a great conversion going on here. I got the supplement PEA. Taking a large dose on its own it's weak compared to steroids, benzos and the like, not sure it's worth the money. Do you think it should work fast or that it needs a two-week course to show any difference?

I wouldn't get your hopes up too much with PEA, Etifoxine and the like. If you look at the study just released it strongly suggests the 5ar is impaired in the CNS, I'm not sure these things will increase 5ar significantly, in the same way that direct GABAA receptor agonists seem to.

Peripheral Nervous System Involved in PFS Patients with Severe ED, New Study Demonstrates - The Post-Finasteride Syndrome FoundationThe Post-Finasteride Syndrome Foundation

Key findings of the study include broad effects on plasma and cerebrospinal fluid (CSF) neuroactive steroid levels observed in 14 PFS patients, as compared to 25 controls. Statistically significant decreased levels of DHT, pregnenolone, progesterone, 17-beta estradiol and dihydroprogesterone (DHP), and increased levels of DHEA, testosterone and 3-alpha diol were observed in the CSF of PFS patients.

Increased Testosterone and DHEA, with decreased DHT and DHP in CSF is very suggestive of impaired 5ar activity. I'm looking into increasing 5ar in the Brain which doesn't just involve hitting the GABAA receptor. But for the time being that seems to produce the best results, not just for me but for others.

 

[sladerunner69]

Explains why people have recovered from GHB. Seems like it addresses every angle that fin shuts down in the brain. If only this stuff was easier to get lol .

In male Wistar rats, GHB dose-dependently (75-1000 mg/kg, i.p.) increased AP, THDOC and their precursors pregnenolone and progesterone in brain cortex and hippocampus.

GABA(B) receptor-mediated increase of neurosteroids by gamma-hydroxybutyric acid. - PubMed - NCBI

I've been on the hunt for that stuff for a long time. I could never find any so then I considered somehow crafting it myself, but it was too complex so I gave up.

 

[sladerunner69]

I thought this aswell, but then I tried Nicotinamide Riboside, it didn't produce the same effects as Nicotinamide. I have a suspicison that Nicotinamide a CLASS 3 Histone Deacetylase Inhibitor (HDACI) increases 5ar gene expression. I can't find anything on Nicotinamide increasing 5ar, but there are a few studies showing that Trichostatin A a class I and II HDACI increases 5ar gene expression.

Trichostatin A enhances glutamate transporter GLT-1 mRNA levels in C6 glioma cells via neurosteroid-mediated cell differentiation. - PubMed - NCBI



While it doesn't specifically mention Nicotinamide or class III HDAC inhibitors, it's possible especially considering how remarkably Nicotinamide can improve my symptoms, in a different way to Valium or any other direct GABAA agonist.

Is there much difference between nicotinamide and niacinimide? The former is rather expensive

 

[bloom]

Is there much difference between nicotinamide and niacinimide? The former is rather expensive

They're the same thing just different names.

 

[TubZy]

I thought this aswell, but then I tried Nicotinamide Riboside, it didn't produce the same effects as Nicotinamide. I have a suspicison that Nicotinamide a CLASS 3 Histone Deacetylase Inhibitor (HDACI) increases 5ar gene expression. I can't find anything on Nicotinamide increasing 5ar, but there are a few studies showing that Trichostatin A a class I and II HDACI increases 5ar gene expression.

Trichostatin A enhances glutamate transporter GLT-1 mRNA levels in C6 glioma cells via neurosteroid-mediated cell differentiation. - PubMed - NCBI

If it is due to the HDACI, diamant has strong HDACI properties as well, so that is interesting.

 

[sladerunner69]

They're the same thing just different names.

Okay I already take 500mg every morning. I am considerring upping the dosage but high doses tend to make me tired maybe because of the increase need for sugar.

 

[TubZy]

Haha cheers man i'll look into the LEF version on amazon. Yeah nicotine is very hit and miss for me. It can improve my brain fog libido ect. Then sometimes it makes me depressed and and anxious. Nicotine is a 3a HSD inhibitor, the enzyme responsible for producing Allopregnanolone, THDOC, and 3a-diol.

Nicotine and cotinine effects on 3 alpha hydroxysteroid dehydrogenase in canine prostate. - PubMed - NCBI

If nicotine inhibits 3a HSD, how does it still increase allopreg in the brain then?

Neurosteroids in nicotine and morphine dependence. - PubMed - NCBI

Acute intraperitoneal administration of nicotine (0.3-2 mg kg-1) or morphine (5-30 mg kg-1) induced dose- and time-dependent increases in the cerebrocortical and plasma concentrations of pregnenolone, progesterone, and allopregnanolone.


Also, I found some more info on morphine and is more recent.

In the present study we determined the gene expression of the two main catabolic enzymes of T and we showed that morphine treatment significantly changes 5aR-1 and AROM mRNA expression in different body regions. There was a significant increase in the expression of one or both of these enzymes in the brain as well as in the liver and testis, suggesting a pro-metabolic action of morphine.

In our adult male rats, AROM was much more highly expressed in liver than in the diencephalon and testis; nevertheless, its physiological role is not very clear since liver is generally considered a non-steroidogenic tissue [35,36]. However the huge increase in 5aR-1 in the liver can be explained by the need to eliminate androgens and protect against excessive hormone levels; the pathway responsible for the switch from T to DHT activity involves the irreversible reaction catalyzed by this enzyme [37].

Aromatase and 5-alpha reductase gene expression: modulation by pain and morphine treatment in male rats

 

[TubZy]

And also based on your study from the original post of this thread? Why is that all these hard drugs increase 5AR, even meth..lol wtf

"...Diencephalon 5 alpha-reductase activity showed a highly significant increase (p less than 0.01) after a single administration of carbamazepine, reserpine, diazepam, phenytoin, phenobarbital or disulfiram. A significant increase (p less than 0.05) was also found after a single administration of methylphenidate, caffeine or methamphetamine."

 

[bloom]

If nicotine inhibits 3a HSD, how does it still increase allopreg in the brain then?

Neurosteroids in nicotine and morphine dependence. - PubMed - NCBI

Acute intraperitoneal administration of nicotine (0.3-2 mg kg-1) or morphine (5-30 mg kg-1) induced dose- and time-dependent increases in the cerebrocortical and plasma concentrations of pregnenolone, progesterone, and allopregnanolone.


Also, I found some more info on morphine and is more recent.

In the present study we determined the gene expression of the two main catabolic enzymes of T and we showed that morphine treatment significantly changes 5aR-1 and AROM mRNA expression in different body regions. There was a significant increase in the expression of one or both of these enzymes in the brain as well as in the liver and testis, suggesting a pro-metabolic action of morphine.

In our adult male rats, AROM was much more highly expressed in liver than in the diencephalon and testis; nevertheless, its physiological role is not very clear since liver is generally considered a non-steroidogenic tissue [35,36]. However the huge increase in 5aR-1 in the liver can be explained by the need to eliminate androgens and protect against excessive hormone levels; the pathway responsible for the switch from T to DHT activity involves the irreversible reaction catalyzed by this enzyme [37].

Aromatase and 5-alpha reductase gene expression: modulation by pain and morphine treatment in male rats

***t I don't know man haha. Like I said it's hit and miss sometimes it improves my libido, Brainfog, other times it makes me worse. Could ultimately increase allo since it increases progesterone, but initialey decrease it by inhibiting 3a HSD. Human biochemistry especially Brain chemistry is extremely complex, you can never really know for certain what's going on. What's most important is observing how you respond to a treatment and not be so hung up on theory.

Also what's interesting to me is that with morphine based drugs they do improve my brainfod and mood to a degree, but do nothing for my libido. There was a study I was reading a little while ago which could explain this, i'll go find it.

 

[TubZy]

***t I don't know man haha. Like I said it's hit and miss sometimes it improves my libido, Brainfog, other times it makes me worse. Could ultimately increase allo since it increases progesterone, but initialey decrease it by inhibiting 3a HSD. Human biochemistry especially Brain chemistry is extremely complex, you can never really know for certain what's going on. What's most important is observing how you respond to a treatment and not be so hung up on theory.

Also what's interesting to me is that with morphine based drugs they do improve my brainfod and mood to a degree, but do nothing for my libido. There was a study I was reading a little while ago which could explain this, i'll go find it.

I know man it is very complex...lol. Yeah, I know what you mean, I was prescribed percocets while on fin for two surgeries I had and I used them both while on and after fin. It does improve mental feelings but didn't do much at all for libido, I think it is due to the fact that opiates can lower T. Amphetamines and their derivatives I used in the past like DMAA, increased libido for me.

For anyone that has the balls to try any of these drugs that were very effective on 5AR in the brain from the study

("...Diencephalon 5 alpha-reductase activity showed a highly significant increase (p less than 0.01) after a single administration of carbamazepine, reserpine, diazepam, phenytoin, phenobarbital or disulfiram. A significant increase (p less than 0.05) was also found after a single administration of methylphenidate, caffeine or methamphetamine.")

This site has many of them (it is legit as many people order thyroid from them from this site)
Meds.com.mx

 

[bloom]

OK holy ****, I think I found an explanation for why T and DHT can have prosexual effects but makes guys mental states deteriorate. I initially I thought that the isoenzyme 5ar2 was not expressed in the brain, I'm wrong on that. So basically this study found that T increased 5ar2 mRNA levels in the CNS of rats. But decreased 5ar1 mRNA levels. The study also states that 5ar2 is thought to be responsible for

sexually dimorphic functions of the male

whereas 5ar1 is responsible for

catabolic and neuron protective role

Effects of testosterone on brain mRNA levels of steroid 5alpha-reductase isozymes in early postnatal life of rat. - PubMed - NCBI

The enzyme 5alpha-reductase (5alpha-R) (EC 1.3.99.5) exists as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2), and both are present in the brain. 5alpha-R1 has been proposed as a constitutive enzyme that essentially plays a catabolic and neuron protective role whereas 5alpha-R2 has been associated with sexually dimorphic functions of the male

In this work, we studied the effects of testosterone (T), the masculinizing hormone of the central nervous system (CNS), on mRNA levels of both 5alpha-R isoforms in the prefrontal cortex of male and female rats during the postnatal sexual differentiation of the CNS in the rat

We found an increase in 5alpha-R2 mRNA levels in both male and female rats after T treatment, while 5alpha-R1 mRNA levels were decreased in the same experimental conditions. Our results clearly indicated that T regulates the expression of both 5alpha-R1 and 5alpha-R2 genes in an opposite manner and independently of the sex. This could point to a crucial role of T in the sexual dimorphism for both 5alpha-R isozymes in the neonatal brain. These results open up a new research line that could improve understanding of the role of 5alpha-R isozymes in the physiology of the CNS.

This can explain why Morphine based drugs don't improve my libido but do improve my brain fog, memory and mood. The studies mention that morphine increases 5ar1, not 5ar2@TubZy