Thoughts On 5ar And Post Finasteride Syndrome

[bloom]

I've always been against SSRIs, but based on my current belief on how to beat PFS and the current situation where my brain is 100% in requirement for some sort of low dose mental drug to maintain a horrible HPA axis dysfunction issue, I am ok with using at these ultra low doses. Currently using 3.3mg. Also fluoxetine has proven to significantly decrease inflammatory cytokine TNF-Alpha which I believe ultimately may be the cause of PFS.

Adding more to this- like most with PFS, I have been one to immediately grab for the benzos during anxiety. We need to kick this. Benzo withdrawal is horrible for the vagus nerve and a major reason for vagus nerve malfunction. Everytime we take a benzo we go through withdrawal that next day. Addicted or not, we have to kick these benzos.

How do you feel the PEA is going?

 

[bruschi11]

Hard to say, I am a very tough case for this due to the severity of my issues. I had trouble without fluoxetine (raised to 5mg) over weekend so I've had to use benzos as it made me manic. Believe I am now at a dose of fluox that I can tolerate without benzos. But overall- I see PEA as more of a relaxer of the brain like a 5a-dhp. I don't see it having any effects on libido or something to heal PFS.

 

[bloom]

Here's another study which supports my idea that peripheral Androgens regulate 5ar activity in the Brain, at least in the pituitary. This study found that the activity of 5ar increased by 105% in the nuclear membranes in the anterior pituitary of rats after 7 days of castration.

[Localization of a 5alpha-reductase activity in the nuclear membranes of the anterior hypophysis of normal and castrated adult male rats]. - PubMed - NCBI

A 5alpha-reductase activity may be found in purified nuclei from anterior pituitary of intact or castrated male rats. When nuclear membranes are separated from nucleoplams this enzymic activity is recovered in nuclear membranes. Following 7 days of castration, the 5alpha-reductase activity in nuclear membranes is increased by 105 % with regard to the activity in nuclear membranes from intact animals.

I think this goes a long way in explaining why TRT doesn't work for the most part in PFS, and why it seems to makes a lot of us with PFS worse.

 

[JoeKool]

@bruschi11 I'm in agreement that the vagus looks to be a point of recovery... Some of my research brought me to Dr Eric Berg on YouTube... he has some videos on Parasympathetic Nervous system , adrenals, testosterone... though he does have a small line of supplements and I think a book, 9 out of 10 videos don't mention his products or his practice (except in references to how he has helped patients) so check out some adrenal fatigue videos and apple cider vinegar videos from him... I don't see him as a pusher and i've never bought anything from his website (which, again, I didn't even know he had from watching his videos. It was a separate search that I found his site)

 

[bruschi11]

Totally @JoeKool .... Unfortunately I'm the idiot that had adrenal fatigue and was on TRT for it before fin- and took fin to deal with the TRT cream hair loss. Yes I'm that stupid and always was a health nut before which makes even less sense.

That said- I will say that currently using just fluoxetine 2.5, PEA, and t3. I will say that size (both ***** and ****) and libido are up a little bit. Thinking allo and gaba-a modulation are important here. But that's stuff we already know- all the "expert doctors" on PFS will say that Gaba-a helps it hang etc.

But for the full package and for 5ar enzymes to return to normal in the CNS, I truly believe gut/liver--> vagus nerve-->brain must optimized which should radically decrease LPS--> TNF-alpha.

 

[bloom]

Totally @JoeKool .... Unfortunately I'm the idiot that had adrenal fatigue and was on TRT for it before fin- and took fin to deal with the TRT cream hair loss. Yes I'm that stupid and always was a health nut before which makes even less sense.

That said- I will say that currently using just fluoxetine 2.5, PEA, and t3. I will say that size (both ***** and ****) and libido are up a little bit. Thinking allo and gaba-a modulation are important here. But that's stuff we already know- all the "expert doctors" on PFS will say that Gaba-a helps it hang etc.

But for the full package and for 5ar enzymes to return to normal in the CNS, I truly believe gut/liver--> vagus nerve-->brain must optimized which should radically decrease LPS--> TNF-alpha.

That's good let us know how it goes, i'm going to order some PEA today.

 

[anotherworld]

Totally @JoeKool .... Unfortunately I'm the idiot that had adrenal fatigue and was on TRT for it before fin- and took fin to deal with the TRT cream hair loss. Yes I'm that stupid and always was a health nut before which makes even less sense.

That said- I will say that currently using just fluoxetine 2.5, PEA, and t3. I will say that size (both ***** and ****) and libido are up a little bit. Thinking allo and gaba-a modulation are important here. But that's stuff we already know- all the "expert doctors" on PFS will say that Gaba-a helps it hang etc.

But for the full package and for 5ar enzymes to return to normal in the CNS, I truly believe gut/liver--> vagus nerve-->brain must optimized which should radically decrease LPS--> TNF-alpha.

In your line of thinking. Maybe taking probiotics which contains enzymes like Dr ohearas on iherb can help heal gut/brain/inflammation. Maybe also highly antiinflammatory compounds like turmeric, magnesium, systemic enzymes might be beneficial. Astaxanthin is super anti inflammatory with orac of over 2 million but it reduces dht by 99%.

"Your gut is the starting point for inflammation—it’s actually the gatekeeper for your inflammatory response. According to Psychoneuroimmunologist Kelly Brogan, your gut’s microorganisms trigger the production of cytokines. Cytokines are involved in regulating your immune system’s response to inflammation and infection. Much like hormones, cytokines are signaling molecules that aid cell-to-cell communication, telling your cells where to go when your inflammatory response is initiated.

Most of the signals between your gut and your brain travel along your vagus nerve—about 90 percent of them.5 Vagus is Latin for “wandering,” aptly named as this long nerve travels from your skull down through your chest and abdomen, branching to multiple organs.6

Cytokine messengers produced in your gut cruise up to your brain along the “vagus nerve highway.” Once in your brain, the cytokines tell your microglia (the immune cells in your brain) to perform certain functions, such as producing neurochemicals. Some of these have negative effects on your mitochondria, which can impact energy production and apoptosis (cell death), as well as adversely impacting the very sensitive feedback system that controls your stress hormones, including cortisol.

So, this inflammatory response that started in your gut travels to your brain, which then builds on it and sends signals to the rest of your body in a complex feedback loop. It isn’t important that you understand all of the physiology here, but the take-away is that your gut flora’s influence is far from local! It significantly affects and controls the health of your entire body."

How Your Microbiome Controls Your Health

 

[bruschi11]

Extremely true @anotherworld I mean if we look at history and all of the guys that beat this syndrome on PropeciaHelp wherever. Lifestyle #1 seems to be the common fix and the gut being #1.

Unfortunately I believe both of mine are horrible. I just have zero "good" gut bacteria.

 

[Ron J]

In your line of thinking. Maybe taking probiotics which contains enzymes like Dr ohearas on iherb can help heal gut/brain/inflammation. Maybe also highly antiinflammatory compounds like turmeric, magnesium, systemic enzymes might be beneficial. Astaxanthin is super anti inflammatory with orac of over 2 million but it reduces dht by 99%.

"Your gut is the starting point for inflammation—it’s actually the gatekeeper for your inflammatory response. According to Psychoneuroimmunologist Kelly Brogan, your gut’s microorganisms trigger the production of cytokines. Cytokines are involved in regulating your immune system’s response to inflammation and infection. Much like hormones, cytokines are signaling molecules that aid cell-to-cell communication, telling your cells where to go when your inflammatory response is initiated.

Most of the signals between your gut and your brain travel along your vagus nerve—about 90 percent of them.5 Vagus is Latin for “wandering,” aptly named as this long nerve travels from your skull down through your chest and abdomen, branching to multiple organs.6

Cytokine messengers produced in your gut cruise up to your brain along the “vagus nerve highway.” Once in your brain, the cytokines tell your microglia (the immune cells in your brain) to perform certain functions, such as producing neurochemicals. Some of these have negative effects on your mitochondria, which can impact energy production and apoptosis (cell death), as well as adversely impacting the very sensitive feedback system that controls your stress hormones, including cortisol.

So, this inflammatory response that started in your gut travels to your brain, which then builds on it and sends signals to the rest of your body in a complex feedback loop. It isn’t important that you understand all of the physiology here, but the take-away is that your gut flora’s influence is far from local! It significantly affects and controls the health of your entire body."

How Your Microbiome Controls Your Health

Any advice to achieve optimal gut flora?

 

[TubZy]

I think more than just the brain is involved definitely the liver as well which also correlates to poor glycogen storage and insulin sensitivity. Not to mention 5AR is actually located in the liver which fin processes.

 

[Progesterone]

Peripheral Nervous System Involved in Post-Finasteride Syndrome Patients with Severe Erectile Dysfunction, New Study Demonstrates for the First Time

Condition also has ‘broad consequences’ on plasma and cerebrospinal fluid neuroactive steroid levels

SOMERSET, N.J., April 18, 2017 – Post-finasteride syndrome (PFS) patients suffer from altered levels of critical brain-function regulators, including neuroactive steroids, according to a new clinical study published in The Journal of Steroid Biochemistry and Molecular Biology.

Titled Neuroactive Steroid Levels and Psychiatric and Andrological Features in Post-Finasteride Patients, the three-year study also uncovered evidence of neuropathy of the pudendal nerve among those with severe erectile dysfunction.

In all, 16 men with PFS and 25 control patients were evaluated in the study conducted at the University of Milano’s Department of Pharmacological and Biomolecular Sciences by a team of 12 researchers led by Roberto Cosimo Melcangi, Ph.D. The PFS patients had discontinued finasteride for a median of 5.4 years at the time of evaluation, and had no prior history of erectile dysfunction or depression prior to finasteride use.

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.

In plasma, statistically significant decreased levels of DHP and allopregnanolone, and increased levels of pregnenolone, DHEA and testosterone were observed.

Decreased plasma levels of allopregnanolone and decreased CSF levels of progesterone are common features of anxious/depressive symptomatology. Important physiologic effects of neuroactive steroids on brain function include neuroendocrine control of reproduction and sex behavior, synaptic plasticity, morphology of neurons and astrocytes, maintenance of cytoskeleton proteins and myelin, adult neurogenesis, and cognition-related functions.

The study also identified, in 25 percent of PFS patients, the first objective evidence of abnormal somatosensory evoked potentials (SSEP) of the pudendal nerve. Abnormal SSEP findings were observed in PFS patients with severe ED.

Peripheral neuropathy of the pudendal nerve, the major nerve supplying the genitals that is critical for peripheral neurogenic control of erection, in PFS patients is a novel finding that demonstrates for the first time involvement of the peripheral nervous system in PFS patients with severe ED.

Additionally, 50 percent of the PFS patients were diagnosed with major depression based on the results from validated questionnaires, the Mini-International Neuropsychiatric Interview, the Beck Depression Inventory and the Beck Anxiety Inventory.

Such depression represents the first confirmation of findings in research led by Shalendar Bhasin, MD and published last year in The Journal of Clinical Endocrinology & Metabolism (Characteristics of Men Who Report Persistent Sexual Symptoms after Finasteride Use for Hair Loss), which suggested that men who experience persistent sexual dysfunction after discontinuing finasteride have “neurobiological abnormalities.”

“Among the most important milestones of Professor Melcangi’s research is that it builds directly on Dr. Bhasin’s work,” said Dr. John Santmann, CEO of the Post-Finasteride Syndrome Foundation, which sponsored the study.

“Medical science is now one step closer to characterizing the underlying biologic mechanisms of PFS, which in turn promises to pave the way for the development of effective therapies,” he added.

The full JSBMB study is available here.

 

[TubZy]

"In plasma, statistically significant decreased levels of DHP and allopregnanolone, and increased levels of pregnenolone, DHEA and testosterone were observed. "

So it seems it is strictly down a lot soley towards DHP and allopreg only. Preg and DHEA, test etc. are raised probably cause the can't convert to DHP/allopreg downstream.

 

[sladerunner69]

"In plasma, statistically significant decreased levels of DHP and allopregnanolone, and increased levels of pregnenolone, DHEA and testosterone were observed. "

So it seems it is strictly down a lot soley towards DHP and allopreg only. Preg and DHEA, test etc. are raised probably cause the can't convert to DHP/allopreg downstream.

Holy ***t. this may explain why supplementing dhea makes us irritable and tired. Because we already ahve high dhea, and the 5ar isn't there to convert it downstream to dht.

What do you think about combining dhp, progesterone, and androsterone? Also taking caffiene and niacinimide for thyroid support. Would I be better off combining dhp with just pregnenlone? Or maybe simply progesterone and androsterone. I want to refill all the critical downstream 5ar hormones but at the same time am wary of lowering my cortisol too much...

 

[REOSIRENS]

Holy ***t. this may explain why supplementing dhea makes us irritable and tired. Because we already ahve high dhea, and the 5ar isn't there to convert it downstream to dht.

What do you think about combining dhp, progesterone, and androsterone? Also taking caffiene and niacinimide for thyroid support. Would I be better off combining dhp with just pregnenlone? Or maybe simply progesterone and androsterone. I want to refill all the critical downstream 5ar hormones but at the same time am wary of lowering my cortisol too much...

The coping mechanism that body uses sometimes to fight stress is by raising protective hormones(pregnenolone/dhea/testosterone)... So if they come elevated under stress doesn't mean your system have loads of them... Means that your body is battling stress with these hormones... To the point you stop having raw materials to manufacture them... and then body crashes and ask for last resort fight or flight cortisol/adrenaline... And if stress continues it becomes a syndrome (you run out of defences)...

From studies made...
you all recover creating a balanced system between stimulation (Progesterone and triiodothyronine) and glucose promoting agents (dhea... magnesium... potassium...palmitic acid. ...thiamine ... Niacinamide...retinol)

And environment is essential to stop further stress... So avoid isolation...get plenty of light... Have goals and achieve them... The success that comes with realizations will make you forget the past pain and move on... Dopamine is a powerful analgesic agent(both for mind and body)

 

[TubZy]

The coping mechanism that body uses sometimes to fight stress is by raising protective hormones(pregnenolone/dhea/testosterone)... So if they come elevated under stress doesn't mean your system have loads of them... Means that your body is battling stress with these hormones... To the point you stop having raw materials to manufacture them... and then body crashes and ask for last resort fight or flight cortisol/adrenaline... And if stress continues it becomes a syndrome (you run out of defences)...

From studies made...
you all recover creating a balanced system between stimulation (Progesterone and triiodothyronine) and glucose promoting agents (dhea... magnesium... potassium...palmitic acid. ...thiamine ... Niacinamide...retinol)

And environment is essential to stop further stress... So avoid isolation...get plenty of light... Have goals and achieve them... The success that comes with realizations will make you forget the past pain and move on... Dopamine is a powerful analgesic agent(both for mind and body)

Did you read the study? The only thing that seems to be low is DHP/allopreg really, which is actually kind of a relief somewhat.

Adding DHEA to PFS people makes them worse majority of us here have tried that and confirmed it too.

Adding something like DHEA when the body is already in a stress state can make it worse, Peat mentions this.

I think an interesting combo could be diamant and 5a-DHP and possibly T3.

 

[REOSIRENS]

Did you read the study? The only thing that seems to be low is DHP/allopreg really, which is actually kind of a relief somewhat.

Adding DHEA to PFS people makes them worse majority of us here have tried that and confirmed it too.

Adding something like DHEA when the body is already in a stress state can make it worse, Peat mentions this.

I think an interesting combo could be diamant and 5a-DHP and possibly T3.

If you add dhea alone you will not succeed for sure... I have always mentioned dhea with pregnenolone... And progesterone with magnesium... I have always said you have to raise the big three(dhea/progesterone/pregnenolone) not just one they work together

I know a guy doing pretty well with
5mg 7-oxodehydroepiandrosterone with 30 pregnenolone... He can handle stress pretty well and I see his body well trimmed and face young again and he says it helps stop gut inflammation...and he takes low dose Progesterone with tailored b vitamins and is doing pretty well... Never liked dhea even in low doses as stand alone procedure to fight stress... I just take 7-oxodehydroepiandrosterone with pregnenolone when I feel stress is running wild and this combo shuts down stressful reactions quite fast...

PS 7-oxodehydroepiandrosterone I don't take more than 5mg twice daily with pregnenolone


Some people make the mistake of taking hormones in high doses and when body starts to complain they blame the hormone and catalog it as being bad... Hormones should be taken in low balanced doses and in pure pharmaceutical grade... Not any brand fits the bill...

I will give you an example... To save money I bought once source naturals pregnenolone and it was a big mistake because it didn't feel pure pregnenolone so went back to pure encapsulations pregnenolone and felt amazing

 

[REOSIRENS]

Do you really think pfs guys are floating with testosterone dhea pregnenolone... From studies frontal cortex is clearly damaged and frontal cortex is full of testosterone/dhea receptors and pregnenolone plays a stunning protective role in the frontal cortex...

Sometimes body elevates dhea and pregnenolone to fight back against stress

PTSD suffers have at times elevated dhea... But why 7-ketodehydroepiandrosterone is being studied as treatment for post traumatic stress disorder

Glycine is elevated in some stressful situations... And will you say that Glycine is bad to fight stress

 

[TubZy]

Do you really think pfs guys are floating with testosterone dhea pregnenolone... From studies frontal cortex is clearly damaged and frontal cortex is full of testosterone/dhea receptors and pregnenolone plays a stunning protective role in the frontal cortex...

Sometimes body elevates dhea and pregnenolone to fight back against stress

PTSD suffers have at times elevated dhea... But why 7-ketodehydroepiandrosterone is being studied as treatment for post traumatic stress disorder

Glycine is elevated in some stressful situations... And will you say that Glycine is bad to fight stress

It doesn't work that way for PFS though, I would look through the previous pages on this thread and you will understand why. I agree that certain metabolites can be increased in certain conditions but that route you are talking about (preg, prog, dhea) have been tried before and if it that was soley the issue. The downstream effects of both preg and prog convert to the metabolite that was shown in the last two studies to be low (allopreg/DHP). Which is another reason why the caffeine and 5a-DHP combo is so effective.

Which is also why 5a-DHP is so effective for PFS people and it converts directly into allopreg.

I would suggest re-reading through some of the logs here and you will see why DHEA has not been helpful really especially on its own. From my personal experience using DHEA has not been helpful, but worse since it can powerfully lower cortisol if metabolism isn't functioning right which is in 100% of PFS people.

In my case only a small amount with progesterone helps, but then again progesterone can antagonize DHEA so the exogenous DHEA added can be simply back filling the levels that were antagonized by the progesterone, not raising it further.

Testosterone levels in males are high, does that mean they are in a stressed state? No, actually quite the opposite due to the antagonism of cortisol.

Have you ever used finasteride before?

 

[sladerunner69]

Did you read the study? The only thing that seems to be low is DHP/allopreg really, which is actually kind of a relief somewhat.

Adding DHEA to PFS people makes them worse majority of us here have tried that and confirmed it too.

Adding something like DHEA when the body is already in a stress state can make it worse, Peat mentions this.

I think an interesting combo could be diamant and 5a-DHP and possibly T3.

I do remember one guy who claimed he fully recoverred from using topical dhea. He was using smaller doses less than 5mg through the day, so maybe that is part of the secret. It does work for well for some guys though, because I think that some guys have more of a problem with T/dht... Do you remember that study you posted with blood levels of various hormones in pfs patients? All 5-ar reduced steroids were low, including DHT. But allopreg seemed to be the most drastically low. I hope someday 5-ar enzyme will become available to take as a supplement.

 

[sladerunner69]

Do you really think pfs guys are floating with testosterone dhea pregnenolone... From studies frontal cortex is clearly damaged and frontal cortex is full of testosterone/dhea receptors and pregnenolone plays a stunning protective role in the frontal cortex...

Sometimes body elevates dhea and pregnenolone to fight back against stress

PTSD suffers have at times elevated dhea... But why 7-ketodehydroepiandrosterone is being studied as treatment for post traumatic stress disorder

Glycine is elevated in some stressful situations... And will you say that Glycine is bad to fight stress

How could soemthing like glycine become elevated? Can the body manufacture specific amino acids out of other amino acids?

Yes pfs have elevated pregnenelone and dhea, which is probably increased from stresss too, but the fact is obvious that it is backedup because it does not have enough 5-ar enzyme to convert these horomones downstream.