How Exactly And At Which Dose Does Finasterid Effect The Neurosteroids In The Brain?

Armando Jose

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"Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of Androgenetic Alopecia or BPH"

Precaution in the use.
 

couldntthinkofaname

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A growing body of research is offering clues about why finasteride might cause these symptoms in a subset of men. It suggests the enzyme that Propecia shuts down—5-alpha-reductase—does a lot more than convert testosterone to the hair-killing dihydrotestosterone (DHT). It also converts hormones like cortisol and progesterone into "neurosteroids" that play key roles in the brain.

"Blocking 5 alpha-reductase to any degree in the brain is a crapshoot," says Alan Jacobs, a New York–based neuroendocrinologist. "Theoretically, you are going to block the production of hormones that serve very important behavioral purposes."

Those brain changes themselves can exacerbate sexual problems, says Jacobs. But some research in animals suggest that, if taken long enough, the drug could also ultimately damage genital tissue, leaving penises fibrotic and scarred.

One recent study published in Neuroendocrinology found that after 20 days of finasteride exposure, male rats showed altered levels of a whole host of neurosteroids and receptors in their brains. Thirty days after going off the drug, the changes were more pronounced than when they were on the drug.

Studies in humans have only just begun, at Baylor, Boston University, and elsewhere, so it's way too early to draw firm conclusions. But the theory surrounding what some patients call "the crash" goes something like this: Cells in the brain and genitals are starved of important hormones while on the drug, so they grow more receptors to sop up all that they can get. Once the drug is discontinued, the hormones come flooding back with more than the cells can handle, which hurts or kills them. "Essentially, the cells get too much DHT, it puts them in overdrive and it burns them out," says Jacobs. So even if the body starts making all those missing compounds again, the tissue has trouble using them.


https://tonic.vice.com/en_us/articl...y-behind-americas-best-selling-hair-loss-drug
 

Armando Jose

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In 1974, 5 alphaa reductase was not well detailled in the differents forms, type 1, 2 and 3.

In a 1974 paper published in Science, Imperato-McGinley explained that the guevedoces lacked a key enzyme, 5-alpha reductase, which converts the male hormone testosterone into a far more potent hormone called dihydrotestosterone (DHT)
 

medSTATIC

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can someone give me a summary?

I don't know if I'm allowed to share it, but here is the full pdf paper: https://docdro.id/UgBKcPK

It's not really a study but an article about the current state of knowledge about 5α-R inhibitors. They tried to be exhaustive about possible side effects with more than 200 references.
IMO the paper brings up nothing new and sadly doesn't answer our legitimate questions about neuro-steroids. For example, is the response curve in the brain flat at 0.2mg/day ?
Moreover the article never differientates finasteride & dutasteride in their findings. Of course both are 5α-R inhibitors but we all know here the drugs are different enough that this approach is way too simplistic.
I will also pass on many of their assertions based on rodents or sheep in gestation. The "references" part is a melting pot of animal and human studies with 5α-R inhibitors. While I recognize the importance of animal models, I will always give more credits to a human-based study rather than obscure findings about penis tissue in rodents.

The neuro-steroid problem remains un-answered.
We need an appropriate study to see the impact of finasteride on neuro steroids & with different daily dosage. Ideally the study would also continue at least a year after withdrawal so that if there is a significant neuro steroid diminution, we could see if it persists or regenerates.
 

couldntthinkofaname

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what are these researchers even doing
 

Armando Jose

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In the article: "Based on the analysis of primary DNA sequences, the family
of 5α-Rs is currently thought to encompass five enzymes,
including the three main 5α-R isotypes (1, 2, and 3) and the
two trans-2,3 enoyl-CoA reductases (TECR and TECR-like)
[2, 3]."
Complex issue
 

Grasshüpfer

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Take it and find out. There, that's exactly how it affects you.
That's what it boils down to.
Try a lower dose maybe, 0,5 0,3 like you posted at the start of the thread.
 

tomJ

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"Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of Androgenetic Alopecia or BPH"

Precaution in the use.
That study will never happen. Costs money and Merck would not appreciate such a study. Merck=$
 

Obsessive

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"Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of Androgenetic Alopecia or BPH"

Precaution in the use.
Altering brain levels of allopregnenolone and derivatives is scary. Before starting finasteride, my lifestyle had been very pro-brain health. I had always been very discriminating about foods and supplements in an attempt to keep my mind as sharp as possible. I guess it still is with the exception of this damn pill I now take every day. Perhaps many people don't have cognitive side effects because the remaining 5AR in the brain (that which is not inhibited) has increased catalytic activity to compensate for the reduced levels of DHT, allopregnenolone, etc. Now if this were to happen in the scalp, 5ARI's would obviously not work for hair loss, but perhaps things are different in the brain?
 

Tommybommy1363

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Altering brain levels of allopregnenolone and derivatives is scary. Before starting finasteride, my lifestyle had been very pro-brain health. I had always been very discriminating about foods and supplements in an attempt to keep my mind as sharp as possible. I guess it still is with the exception of this damn pill I now take every day. Perhaps many people don't have cognitive side effects because the remaining 5AR in the brain (that which is not inhibited) has increased catalytic activity to compensate for the reduced levels of DHT, allopregnenolone, etc. Now if this were to happen in the scalp, 5ARI's would obviously not work for hair loss, but perhaps things are different in the brain?

I wouldn’t be surprised as the brain is a very plastic organ. We block much more significant neurotransmitters with things as simple as Zyrtec... ssris an extremely common medication will impact neurotransmitter balance much more significantly.

Will have little data on how propecia impacts long term brain health... one study showed no increased incidence of Alzheimer’s at 5 years, but say you take it for 20 years, what about then? As neurosteroids have shown to be neuroprotective there is a possibility of increasing your risk for dementia.

It’s all about risk benefit. Is saving your hair worth risking possibly having an increased risk for dementia? For me the answer is yes. My immediate cognition has not changed, so atleast I’m not dealing with brain fog
 

reyl

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Here's another one that page linked to which is freely accessible:

A second factor influencing mood is the impact on the production of neurosteroids (androstanediol, allopregnanolone, tetrahydrocortisol, tetrahdyrocortico-sterone, and tetrahydrodeoxycorticosterone). These neurosteroids modulate seizure susceptibility, anxiety, stress, and depression and require 5AR for synthesis.27 Finasteride administration decreases CSF and plasma neurosteroid levels and increases the amount of precursor steroids.28 The decrease of neurosteroid levels also as a consequence decreases dopamine levels, which theoretically could play a role in depressive thoughts and feelings.29,30GABAergic receptors are also modulated by 5AR and may possess antidepressant and anxiolytic effects.31In 2010, Romer32,33 published research on the effects of finasteride on mice and found that 5ARI administration decreased neurogenesis of the hippocampal region, which was associated with depression. Additionally the behavior changes in the mice were found to be reversible once treatment was discontinued. Other proposed mechanisms include 5AR acting in the amygdala as well as reduced metabolites of progesterone and deoxycorticosterone in the brain.

As of now, however, no direct link exists between 5ARI and depression, yet it is postulated that in some individuals, the link exists31 and there is concern for depressive symptoms arising in a small percentage of those treated with 5ARIs. However, further long-term studies would be helpful to better understand finasteride’s effects over the course of a lifetime. Further studies on the reversibility of psychiatric mood symptoms are also needed since the data on the matter is not conclusive.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023004/
I thought 5AR1 was responsible for the neurosteroids and not 5AR2? Which would put finasteride in the clear and dutasteride not.

I wouldn’t be surprised as the brain is a very plastic organ. We block much more significant neurotransmitters with things as simple as Zyrtec... ssris an extremely common medication will impact neurotransmitter balance much more significantly.

Will have little data on how propecia impacts long term brain health... one study showed no increased incidence of Alzheimer’s at 5 years, but say you take it for 20 years, what about then? As neurosteroids have shown to be neuroprotective there is a possibility of increasing your risk for dementia.

It’s all about risk benefit. Is saving your hair worth risking possibly having an increased risk for dementia? For me the answer is yes. My immediate cognition has not changed, so atleast I’m not dealing with brain fog
Does Zyrtec really affect neurosteroids? I read it was Benadryl that much more negatively affected the neurosteroids and actually increased risk of alzeimers.
 

stachu

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That's not what he's discussing.

A lot of the problems are definitely due to the effects of neurosteroids. For example,. it's now measured that people with PFS have no differences in their serum hormones, whereas they have significant differences in their cerebrospinal fluids.

It is also the case that people with PFS don't recover when taking treatments such as extra testosterone, clomid, etc. The one treatment that has helped people with mental slides is that of prolonged fasting, which is known to have a significant positive effect on the brain. You can go to any PFS help forum. Fasting helps them. Steroids do not help them. That refutes the position that it's due to testosterone and estrogen.

It may be that some of the sides that people report while taking finasteride (different from PFS) are due to testosterone and estrogen. However those sides have a simple solution -- stop taking finasteride. It's only the persistent sides that people need worry about.


"I think people dive to deep into it, your neurosteroids are directly effect, there really is no need to look further."

Come on man.

Deep down, most of this forum understands that inhibiting 5ar is a bad idea. That will be proven within a year or two, people will mostly drop finasteride for treatments such as Brotzu and CB0301 if they become available and are confirmed to be efficient.


I can't read the paper that @Armando Jose posted. I'm at home and they want me to pay $39.95. No thank you.

As far as I know, we only know the dosage response curve of finasteride in the serum and in the scalp. That suggests that ~0.10 mg/day is the minimal effective dose, though it might be as high as 0.20 mg/day. Above that, the curve saturates. The person popping 1 mg/day doesn't keep more hair than the person popping 0.20 mg/day.

We have no idea what the response curve is in the brain, the liver, etc. If it flatters at a higher point, that suggests that going to ~0.20 mg/day would be beneficial, as you'd have every single benefit for hair, but none of the damage to the brain. However, we don't have measurements, and the anecdotes are few and far between as well as unreliable.


Great Post, but i cannot agree with you in one point. People who popping 1mg of finasteride keep more hair than people with 0.2mg dose. I was on vary doses of finasteride within 3 years and i have the best results with quartering proscar pill for 1.25mg each than quartering propecia 1mg pill for 0.25mg dose. Greets.
 

reyl

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Great Post, but i cannot agree with you in one point. People who popping 1mg of finasteride keep more hair than people with 0.2mg dose. I was on vary doses of finasteride within 3 years and i have the best results with quartering proscar pill for 1.25mg each than quartering propecia 1mg pill for 0.25mg dose. Greets.
According to this Japanese study, 0.20mg was shown to be as 94-98%~ as effective as 1mg, although we can assume this study was conducted on Japanese males which could be a factor. http://www.ncbi.nlm.nih.gov/pubmed/15319158

I would take an approximate maximum of 10% less effectiveness if that meant it was much less likely to cause side effects.
 

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stachu

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According to this Japanese study, 0.20mg was shown to be as 94-98%~ as effective as 1mg, although we can assume this study was conducted on Japanese males which could be a factor. http://www.ncbi.nlm.nih.gov/pubmed/15319158

I would take an approximate maximum of 10% less effectiveness if that meant it was much less likely to cause side effects.

Thats why i never believe studies.

I Lost all gains being on 0,25mg for half year + reeceded and diffused
I get my gains back on 1,25 mg within 3 months


So thats it. Maybe its effective lowering DHT with similar percentage but i dont know, maybe its about suspended time between DHT rising again or so, whatsoever.

Try it on yourself, then we can discuss.
 

reyl

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Thats why i never believe studies.

I Lost all gains being on 0,25mg for half year + reeceded and diffused
I get my gains back on 1,25 mg within 3 months


So thats it. Maybe its effective lowering DHT with similar percentage but i dont know, maybe its about suspended time between DHT rising again or so, whatsoever.

Try it on yourself, then we can discuss.
Was it the same brand? Sometimes people can get a bad batch from a generic. I agree that it's likely more to do with how long the drug stays in your system.
 

stachu

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Was it the same brand? Sometimes people can get a bad batch from a generic. I agree that it's likely more to do with how long the drug stays in your system.

Proscar - 5mg
Propecia - 1mg

I use/used only these.
 

Tommybommy1363

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I thought 5AR1 was responsible for the neurosteroids and not 5AR2? Which would put finasteride in the clear and dutasteride not.


Does Zyrtec really affect neurosteroids? I read it was Benadryl that much more negatively affected the neurosteroids and actually increased risk of alzeimers.

No Zyrtec affects acetylcholine and neuron histamine. It does cross the blood brain barrier to some extent and has been shown to increase the risk of dementia if used chronically (not as much as Benadryl). Claritin is a better alternative
 
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