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Topic Title: Finasteride and Neurological Damage
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Created On: 07/15/2009 06:03 AM
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 07/15/2009 06:03 AM
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alex.miller
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Hi,

My name is Alex Miller and I am studying biology -> specialization track: neurology and neurological sciences. I have been referred to this website by a good friend of mine who was using Propecia (Finasteride 1 mg) for 9 years. He never had any sexual side effects or other problems during this time. But about two month ago, he started having problems with cognitive function, forgetfulness, slurring of speech and depression. He went to several doctors and in the end a neurologist told him, that these effects come from the propecia. He then stopped using it and told me that if I have some time left, I should look into the matter. He started researching too and found this forum, where he said people named this side effect "brain fog". Unfortunately, I just don't have the time to read through this forum.

Before starting the research, I already knew that 5-alpha-reductase (5AR) has important functions in the central nervous system (CNS). So inhibiting it (by finasteride) might induce some side effects there. I will not address the possible sexual side effects but only the neurological ones. I will explain to you all what I have come up with so far. And guys: this is not looking good at all.

First of all, 5AR exists in two different isozymes: 5AR type 1 (5AR1) and 5AR type 2 (5AR2). 5AR1 is present mainly in the brain, muscle, liver and in sebaceous glands. 5AR2 is referred to as the "peripheral 5AR" since it is present mainly in the prostate, seminal vesicles, liver and hair follicles. Finasteride is a specific type 2 inhibitor and doesn't inhibit 5AR1 in significant amounts. But here comes something that not many people know: 5AR type 2 is also expressed in very significant amounts in spinal chord motor neurons, actually in similar amounts found in the prostate (Poletti et al. 2003) and could have (damn it!: WILL have) an effect there. What kind of effect this is, will be explained soon.

Something else, that many people don't know: Both isozymes of 5AR have more functions than just Testosterone (T) -> Dihydrotestosterone (DHT) conversion. They do the following conversions:

1. Testosterone -> Dihydrotestosterone
2. Progesterone -> Dihydroprogesterone
3. Deoxycorticosterone -> Dihydrodeoxycorticosterone

The latter two conversions are also inhibited by finasteride and so the production of neuroactive steroids is inhibited, since their metabolic pathway continues like this:

Dihydroprogesterone -> Tetrahydroprogesterone or also called Allopregnanolone.
Dihydrodeoxycorticosterone -> tetrahydrodeoxycorticosterone

These converions are catalyzed by an enzyme called 3-alpha hydroxysteroid dehydrogenase (3-alpha HSD).

You can read about these neuroactive steroids on wikipedia in order to get a rough idea about them:

Tetrahydrodeoxycorticosterone
Allopregnanolone

Altough it states there, that Tetrahydrodeoxycorticosterone is synthesized by 5AR1 in the brain, this is only partially true since, as explained above 5AR2 is also present in the CNS namely in the motor neurons of the spinal chord.

Now we come to the REAL concern: The inhibition of Allpregnanolone production. Altough Allopregnanolone can be produced in the brain by 5AR1, the CNS is also dependent on peripheral 5AR2. I quote from "Implications of neuroimaging for the treatment of epilepsy":

"Allopregnanolone formed in peripheral tissues readily enters the brain where it acts to enhance activation of GABA. A receptors" (William H. Theodore, MD; Clinical Epilepsy Section NIH Bethesda, MD).

Now to repeat again: Finasteride definitely inhibits allopregnanolone production in spinal chord motor neurons where mainly 5AR2 is present and also reduces allopregnanolone levels in the brain and other parts of the CNS since these parts are dependent on peripheral 5AR2 conversion of progesterone to dihydroprogesterone which is then converted to allopregnanolone by 3-alpha HSD.

The question is what the result of long-term allopregnanolone depletion is. Before you have to understand what the myelin-sheath of neurons is. The axon of neurones (both, peripheral neurons and neurons in the CNS) are surrounded by an electrically insulating layer: the myelin sheath. This is vital for fast and efficient impulse propagation on the neurons. I don't want to go into details here. Fact is: Allopregnanolone has vital function in the myelination of neurons as seen in the following studies:

When you read these, you'll see that the metabolic pathway of progesterone (inhibited by finasteride...) is vital for myelination and other functions in the CNS. In fact there are dozens of studies about the effects of progesterone metabolism and allopregnanolone on myelination.

1. Progestins and antiprogestins: mechanisms of action, neuroprotection and myelination (Link)

2. Progesterone: Therapeutic opportunities for neuroprotection and myelin repair (Link)

Quote: "Progesterone and its metabolites promote the viability of neurons in the brain and spinal cord. ".

Oh damn it! Didn't we say just before, that the motor neurons of the spinal chord expresses mainly 5AR type 2 (inhibited by finasteride)? So there will be a negative effect of myelination there for sure!

2. Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of niemann-pick C mice (Link)

3. There is also a study of Goumari et al. (didn't find it on the net) that shows the function of allorpegnanolone in myelination. Quote: "... allopregnanolone accelerated myelination ..." (Ghoumari et al. 2003b)

Alright. Let's see what the effects of demyelination are: Read Myelin . The most worrying effect is again demyelination of the motor neurons of the spinal chord which will be the effect of long term finasteride use:

"Sub-acute combined degeneration of the spinal cord secondary to pernicious anaemia can lead to anything from slight peripheral nerve damage to severe damage to the central nervous system affecting speech, balance and cognitive awareness. When myelin degrades, conduction of signals along the nerve can be impaired or lost and the nerve eventually withers."

Do you see those symptoms? Speech is affected, balance and cognitive awareness. This is exactly what you call brain fog here. The question is wheter this effect is reversable if you take finasteride for years. I certainly hope so for my friend altough, you know, neurogegeneration can really be irreversible.

It has to be said, that these effects are of LONG-TERM use but probably WILL eventually happen after years of finasteride use.

Now, I don't want to scare any one of you. I just want to give my input as a student of neurological sciences. Is it worth for you hair? My friend definitely regrets taking it.

Please ask if you have any questions but I don't know if I have the time to answer them.

Have a nice day.
 07/15/2009 06:26 AM
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Twister
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I cant wait for Bryan and Moximus to sink their teeth into this one !

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 07/15/2009 06:38 AM
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Balance
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Interesting post. It should be noted however that Fin etc don't completely inhibit 5ar but rather just a percentage of it.
 07/15/2009 06:47 AM
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majorsixth
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Originally posted by: Twister

I cant wait for Bryan and Moximus to sink their teeth into this one !




Now Now! Would that be professor Bryan you refer to, from the hair loss forum university.com? Lol.

Edited: 07/15/2009 at 06:58 AM by majorsixth
 07/15/2009 07:05 AM
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Twister
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Originally posted by: majorsixth

Originally posted by: Twister



I cant wait for Bryan and Moximus to sink their teeth into this one !








Now Now! Would that be professor Bryan you refer to, from the hair loss forum university.com? Lol.




LOL major

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 07/15/2009 07:40 AM
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Smitty109
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finally! something that matches my speculations. ..there have
been studies going on as of recent about the effects of fin and the neurological system..check this out

scroll to the bottom

http://www.propeciahelp.com/fo...ostorder=asc&start=20

even in italy apparently


Oh yeah and btw..a little supression of 5AR2 doesnt mean "hey man im gonna be ok" since no one really knows how much damage any type of 5AR2 inhibition
is causing. Notice the guy in the example had been taking it for years with no sexual side effects? what does that tell us? most likely he still had a fair amount of DHT in his body? maybe his estrogen levels were in balance? these things need to be investigated more

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 07/15/2009 10:16 AM
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Hanger
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Originally posted by: majorsixth

Originally posted by: Twister



I cant wait for Bryan and Moximus to sink their teeth into this one !








Now Now! Would that be professor Bryan you refer to, from the hair loss forum university.com? Lol.



No, the Bryan that works for Dr. Proctor out of Houston!! lol

 07/15/2009 11:06 AM
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madclown
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Alex,

It would be very much appreciated if you could share your expertise with the men such as myself suffering from long-term neurological damage from Finasteride usage. There is a forum dedicated to these men at: http://www.propeciahelp.com

... in particular, feel free to post in a copy of the thread you made here on hairlosshelp, in the "Mental Side Effects" section -- http://www.propeciahelp.com/forum/viewtopic.php?t=2577

-------

Also FYI, here are some additional threads about Finasteride's use as a neurosteroid inhibitor which corroborate your findings:

http://www.propeciahelp.com/forum/viewtopic.php?t=1387
http://www.propeciahelp.com/forum/viewtopic.php?t=668
http://www.propeciahelp.com/forum/viewtopic.php?t=128
http://www.propeciahelp.com/forum/viewtopic.php?t=837


Thanks for shedding some light on the other 5AR pathways inhibited by Finasteride which many are not aware of.
 07/15/2009 11:34 AM
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Smitty109
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madclown how long have you been off propecia?

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 07/15/2009 12:41 PM
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alex.miller
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Alright guys. I had a quick look at the propeciahelp.com website. This site is a hell of a forum and I'll need to read through the whole forum before making comments there. For this, I need a lot of time, which I, unfortunately, do not have right now. But I plan to do it soon when time allows.

But: I will write a brief comment on the condition of the guys experiencing permanent sides from finasteride:

I think, not only the mental side effects but also the sexual side effects are a result of the neurological damage from finasteride. Namely, demyelination of the motor neurons in the spinal chord. These neurons need to work otherwise you do experience sexual dysfunction. Your sexual dysfunction condition (I read comments like "there is no connection between the brain and the penis") seems to be similar to the sexual dysfunction of multiple sclerosis.

Read multiple sclerosis on wikipedia. I quote the most important points:

"Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune disease in which the body's immune response attacks a person's central nervous system (brain and spinal cord), leading to demyelination.."

Your demyelination just happend because of a lack of allopregnanolone which is synthesized by 5AR2 (yes, type 2 and only type 2!!) in the spinal chord and not because of an immune response. But the condition is the same.

Multiple sclerosis is a kind of Spinal Cord Injury. (see link)

I quote from there:

"Sexual function is also associated with the sacral region, and is often affected. Men normally have two types of erections. The brain is the source of psychogenic erections. The process begins with sexual thoughts or seeing or hearing something stimulating or arousing. Signals from the brain are then sent through the nerves of the spinal cord down to the T10-L2 levels. The signals are then relayed to the penis and trigger an erection. A reflex erection occurs with direct physical contact to the penis or other erotic areas such as the ears, nipples or neck. A reflex erection is involuntary and can occur without sexually stimulating thoughts. The nerves that control a man's ability to have a reflex erection are located in the sacral nerves (S2-S4) of the spinal cord."

So here you go: Sexual dysfunction. I don't think that an hormonal imbalance after finasteride use is the reason for the sexual dysfunction but rather the demyelination of the spinal chord which prevents impulses from the brain to reach the genitals. This fits perfectly to the description of "no connection to brain and penis" which isn't like "normal" sexual dysfunction. If you have sexual dysfunction but nomal Testosterone levels after using finasteride, your damage is neurological for sure.

@Balance: Finasteride is a very potent inhibitor of 5AR2. Its inhibition is strong enough to stop hair loss (by a significant DHT reduction). So it certainly inhibits progesterone metabolism significantly too.

@Smitty109: I meant in the first post, that during all these years my friend didn't experience sexual sides. But in the end he experienced them. They started at the same time as the mental ones. I didn't write it clearly, sorry. It seems that both are an effect of motor neuron damage in the spinal chord.

To conclude: Finasteride has been tested by Merck before it got approved. It might be true that only 2% had side effects during that 5 year hair loss study. But neurodegeneration can happen over many years. And I bet they didn't check for demyelination. I think that most people taking finasteride over the years will experience neurological damage (demyelination) in the spinal chord. It's just that for some it happens in a shorter timeframe and for others it develops during several years. This is why Merk said, that no long term studies have been done, so that they don't need to take responsibility for this kind of damage. But they certainly know that it will happen.

Someone please copy this post to propeciahelp.com. I can't write everything on two different forums.
 07/15/2009 01:01 PM
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Smitty109
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Alex..this is by far probably the most interesting find I've come across.

Bryan should have some interesting things to say about this once he gets on.

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 07/15/2009 01:22 PM
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Farrel
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"Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune disease in which the body's immune response attacks a person's central nervous system (brain and spinal cord), leading to demyelination.."


Well if the cause is theoretically from the same thing, then logically the symptoms should be consistent with MS too.

However you appear to be saying it's related to sexual disfunction.

I don't see how neurological damage would affect one thing, but not another.

Why aren't these people reporting MS like symptoms too?

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Disclaimer - I am not a physician or an expert and my advice should not be considered medical/expert advice. - If you follow my opinions and/or advice you do so at your own risk.
 07/15/2009 01:34 PM
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Farrel
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Also, check this quote.

Erectile dysfunction is extremely common, with as many as 70 to 85 percent of men with MS experiencing problems with their erections. These typically are not the first MS symptoms that a man experiences, but happen some years after the onset of symptoms or diagnosis.


So while ED has some commonalities with MS, here are the differences.

ED is not part of the early onset of MS, it only happens much later after MS has been diagnosed. Which means long after the major neuromuscular symptoms of MS have manifested themselves.

Therefore, if motor neuron damage was being caused by finasteride, rather than ED being the first noticeable symptom, it should be one of the last, just like with MS.

How do you explain this?

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Disclaimer - I am not a physician or an expert and my advice should not be considered medical/expert advice. - If you follow my opinions and/or advice you do so at your own risk.
 07/15/2009 01:44 PM
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alex.miller
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@Farrel:

The explanation to this is really easy: Real Multiple Sclerosis affects the brain and spinal chord. Most symptoms come from neurodegeneration in the brain then ED follows when the neurones of the spinal chord get demyelinated. Obviously, you see the effect of the brain damage first.

But: The brain has 5AR1 but the spinal chord has mainly 5AR2. Finasteride only inhibits 5AR2. I said the CONDITION at the spinal chord is the same. It's not a real case of MS though since the brain is not as strongly affected of 5AR2 inhibition as the spinal chord. But I personally still think the brain is somewhat affected from peripheral neurosteroid inhibition although not as much as the spinal chord neurons.

This also explains why these neurological effects appear years after finasteride usage. It takes a longer period of time of allopregnanolone depletion for neurodegeneration to occur.

The symptoms of "brain fog" are definitely the same as demyelination of spinal chord motor neurons, as written in my first post.

Hope this answers your question.
 07/15/2009 01:55 PM
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Farrel
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I'm quoting you here because I still don't think my question has been answered.

So here you go: Sexual dysfunction. I don't think that an hormonal imbalance after finasteride use is the reason for the sexual dysfunction but rather the demyelination of the spinal chord which prevents impulses from the brain to reach the genitals.


If the sexual disfunction is a result of damage being done to the spinal cord, then why aren't there other physical symptoms being experienced as well?

It would seem to me that other physical effects, like the inability to walk, balance, exercise etc, would manifest themselves a lot sooner than brain fog would if there was physical damage that was being done to the spinal cord.

Surely if impulses are not being reached by the brain from the genitals, then the same would be true for impulses from your legs and arms.

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Disclaimer - I am not a physician or an expert and my advice should not be considered medical/expert advice. - If you follow my opinions and/or advice you do so at your own risk.
 07/15/2009 02:03 PM
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RichLocks
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Pretty scary stuff.

I myself think that I've had brain fog, but i just shrug it off.

If this is not reversible, that's a big problem. I know a few long time users here who had the brain fog after 8+ years of usage said things got back to normal after several months. I suppose it varies from individual to individual.
 07/15/2009 02:06 PM
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Twister
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Ive quit Fin today due to sides

Someone said not to go cold turkey as I will F myself

Does anyone have an opinion on stoppin Fin, as in stop completly or taper off ?

Cheers guys

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 07/15/2009 02:12 PM
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Mabe
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Twister, no one really knows for sure if tapering off will make much of a difference, but the general consensus is that you should taper off the drug just in case. Better safe than sorry. If I were you, I'd slowly ween off the drug rather than just quit cold turkey.
 07/15/2009 02:16 PM
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Twister
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Ok dude

Thanx for ure reply

I was just gonna quit, but will taper off just to be safe (r)

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 07/15/2009 02:29 PM
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alex.miller
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Originally posted by: Farrel

I'm quoting you here because I still don't think my question has been answered.



So here you go: Sexual dysfunction. I don't think that an hormonal imbalance after finasteride use is the reason for the sexual dysfunction but rather the demyelination of the spinal chord which prevents impulses from the brain to reach the genitals.




If the sexual disfunction is a result of damage being done to the spinal cord, then why aren't there other physical symptoms being experienced as well?



It would seem to me that other physical effects, like the inability to walk, balance, exercise etc, would manifest themselves a lot sooner than brain fog would if there was physical damage that was being done to the spinal cord.



Surely if impulses are not being reached by the brain from the genitals, then the same would be true for impulses from your legs and arms.


lol, do you think the spinal chord is just like an electrical cable? It is a highly complex structure. Within the spinal chord, you have specific regions, each has its function. 5AR2 is expressed in ANDROGEN SPECIFIC parts of the spinal chord.

Maybe this (Link) helps:

Quote:

"Spinal cord motoneurones express high levels of androgen receptor. However, in responsive tissue, the effects of testosterone is often mediated by the more potent androgenic derivative 5-alpha-dihydrotestosterone (DHT). This compound is formed in androgen target cells by the enzyme 5-alpha-reductase. Two isoforms of the 5-alpha-reductase, with limited degree of homology, have been cloned, type 1 and type 2. The low affinity-constitutive type 1 isoenzyme is widely distributed in the body; the high affinity-androgen regulated 5-alpha-reductase type 2 is confined to androgen-dependent structures and shows a peculiar pH optimum at acidic values. We have previously shown that high levels of 5-alpha-reductase activity are detectable in rat spinal cord. Here, using reverse transcriptase-polymerase chain reaction, we show that both isoforms are expressed in the whole spinal cord of the rat. The enzymatic pH optimum measured in immortalized spinal cord motoneurones (NSC34) is typical of the type 2 isoenzyme. Using in situ hybridization technique, we found that 5-alpha-reductase type 2 is confined to the motoneuronal cells of the anterior horns of the rat spinal cord, the cells that also are known to express high levels of androgen receptor. Because of the close association of androgen receptor and 5-alpha alpha-reductase type 2, motoneuronal cells should be considered as target cells for androgens."

I understand this is a rat study. But from the study of polletti at al. 2003b I know that the human spinal chord has similar androgen dependent structures.

And again: The brain fog symtoms are the same as the ones of spinal chord motor neuron degeneration. Is that so hard to understand? It even makes sense as cognitive function / speech behaviour are regulated by androgens too, so there will be an effect when the androgen dependent part of the spinal chord undergoes neurosteroid inhibition. Obviously, the strongest effect will be on sexual function as without impulse propagation through the androgen dependent structures of the spinal chord it won't function properly. It's not like you inhibit neurosteroid production and then you can't walk anymore lol. I still think this theory is correct and people suffering these effects had demyelination going on in their (androgen dependent structures of the) spinal chord.

I hope this is clear now.
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