AR3?

[gh05]

Can someone tell me about this AR3 which finasteride supposedly inhibits, lowering protection to the nervous system etc?

What are these 'other' effects which people claim that finasteride has which were previously unknown at the time of the FDA studies?

Thanks

 

[brian liles]

finasteride only inhibits AR2

 

[gh05]

I'm not really sure what I'm asking for - I read a thread here the other day where a few people chiming in about the long term unknown risks because finasteride causes other changes in the brain and therefore less protection to the nervous system. Someone mentioned AR3

 

[Wuffer]

Not much is known about AR3, but apparently finasteride does inhibit it. I'm not sure how much it is inhibited or what it's function is, but I think there are some studies on Propeciahelp that show a bit more about this.

Some people theorize that since finasteride inhibits 5AR, that it could affect neurosteroids that those enzymes are also responsible for creating. Some believe that affecting these neurosteroids could cause problems such as Alzheimer’s, seizures, motor control problems, and so on… This could in fact be the case, but it’s important to note that pseudohermaphrodites are born without any 5AR whatsoever. They exhibit ambiguous sexual characteristics during developmental stages in the womb and during puberty, as is to be expected, but do not show additional conditions such as the ones mentioned above.

It’s always possible to find an association if you are actively searching for it, but people have been taking finasteride for over 20 years and I haven’t heard of any ‘other’ symptoms popping up in these people.

It's all theory and speculation right now, and most of this is coming from people who are looking day and night to TRY to find some sort of association. It's great to come up with a hypothesis, but everyone is skipping the most important step in the scientific method which is to TEST and to VERIFY. Sure it 'makes sense' right now, but until it's actually been verified, it's not fact, it's just an interesting idea.

 

[gh05]

Not much is known about AR3, but apparently finasteride does inhibit it. I'm not sure how much it is inhibited or what it's function is, but I think there are some studies on Propeciahelp that show a bit more about this.

Some people theorize that since finasteride inhibits 5AR, that it could affect neurosteroids that those enzymes are also responsible for creating. Some believe that affecting these neurosteroids could cause problems such as Alzheimer’s, seizures, motor control problems, and so on… This could in fact be the case, but it’s important to note that pseudohermaphrodites are born without any 5AR whatsoever. They exhibit ambiguous sexual characteristics during developmental stages in the womb and during puberty, as is to be expected, but do not show additional conditions such as the ones mentioned above.

It’s always possible to find an association if you are actively searching for it, but people have been taking finasteride for over 20 years and I haven’t heard of any ‘other’ symptoms popping up in these people.

It's all theory and speculation right now, and most of this is coming from people who are looking day and night to TRY to find some sort of association. It's great to come up with a hypothesis, but everyone is skipping the most important step in the scientific method which is to TEST and to VERIFY. Sure it 'makes sense' right now, but until it's actually been verified, it's not fact, it's just an interesting idea.

Thanks. That's interesting.

I guess that if these people born without any AR enzymes don't have other serious health problems down the line then things should be ok...

I know I'm really overthinking this but I don't want to damage my health and regret it in 30 years time.

Hell i was even reading up on having my sperm frozen earlier because I'd be gutted if i ever damaged my fertility for vanity.

 

[Wuffer]

A few case reports have indicated that finasteride can affect sperm fertility, but it has always been shown to reverse after discontinuing treatment. No need to freeze your sperm, but it might be a good idea to get a good baseline test done before you start treatment.

 

[gh05]

A few case reports have indicated that finasteride can affect sperm fertility, but it has always been shown to reverse after discontinuing treatment. No need to freeze your sperm, but it might be a good idea to get a good baseline test done before you start treatment.

But with a lot of these reversible effects, isn't it true that they don''t say how long it took to reverse?

Why get a baseline test?

Can I ask what your situation is wuffer? You been taking finasteride/sides/hair?

 

[Wuffer]

Here is a case report examining 3 occurrences of infertility, believed to have resulted from finasteride treatment:

http://www.scielo.br/pdf/rhc/v59n4/21389.pdf

I didn't read the entire thing, but the discussion indicates that after discontinuation of finasteride treatment, sperm returned to normal. I have not seen a single case report that indicates finasteride might cause permanent infertility.

Keep in mind that two of these men had a varicocele, and one was obese, both which could affect sperm quality. They may have already been prone to this issue, and its possible finasteride exacerbated these symptoms.

If you are concerned about your fertility, just to be safe it is a good idea to get baseline sperm quality tested. If you already have borderline fertility issues, finasteride may potentially make it worse. If after some time of using finasteride you have issues conceiving and see that your sperm quality is down, you know more or less for certain finasteride caused it and it wasn’t pre-existing. It also helps you track if you recover while discontinuing finasteride.

Sure, I’ve been on for 1.5 years. I had a few minor issues for the first couple weeks (libido, testicle ache) but that all stabilized after the first month and I haven’t had any sides since. I started as a NW3V, and resulted in a strong NW2 after about 6 months of use. A year later, results have held steady and my hair continues to thicken. All in all, I had a great experience and very strongly recommend it as a treatment.

 

[gh05]

Here is a case report examining 3 occurrences of infertility, believed to have resulted from finasteride treatment:

http://www.scielo.br/pdf/rhc/v59n4/21389.pdf

I didn't read the entire thing, but the discussion indicates that after discontinuation of finasteride treatment, sperm returned to normal. I have not seen a single case report that indicates finasteride might cause permanent infertility.

Keep in mind that two of these men had a varicocele, and one was obese, both which could affect sperm quality. They may have already been prone to this issue, and its possible finasteride exacerbated these symptoms.

If you are concerned about your fertility, just to be safe it is a good idea to get baseline sperm quality tested. If you already have borderline fertility issues, finasteride may potentially make it worse. If after some time of using finasteride you have issues conceiving and see that your sperm quality is down, you know more or less for certain finasteride caused it and it wasn’t pre-existing. It also helps you track if you recover while discontinuing finasteride.

Sure, I’ve been on for 1.5 years. I had a few minor issues for the first couple weeks (libido, testicle ache) but that all stabilized after the first month and I haven’t had any sides since. I started as a NW3V, and resulted in a strong NW2 after about 6 months of use. A year later, results have held steady and my hair continues to thicken. All in all, I had a great experience and very strongly recommend it as a treatment.

Thanks for such a helpful post.

Couple of other questions if you don't mind...you say your libido stabilised...do you mean that it just went back to how it was before? Have you got the 'watery semen' which I see everyone seem to mention? Lastly, did you get any blood tests or anything else done beforehand...if i go on finasteride then i want to get these done but need to be sure what I am doing.

Thanks.

 

[Mestys]

I'm pretty sure the the pseudohermaphrodites have a 5AR type 2 deficiency only. Their Type 1 5AR is fully functional, I'm not sure about Type 3 though but I'd imagine that is also functional.

 

[gh05]

I'm pretty sure the the pseudohermaphrodites have a 5AR type 2 deficiency only. Their Type 1 5AR is fully functional, I'm not sure about Type 3 though but I'd imagine that is also functional.

Hmmm...Anyone got any other info on this?

 

[Mestys]

Just done a bit of googling, seems Bryan also pointed this out:
viewtopic.php?f=61&t=74309

Also:

http://emedicine.medscape.com/article/924291-overview

 

[gh05]

Just done a bit of googling, seems Bryan also pointed this out:
viewtopic.php?f=61&t=74309

Also:

http://emedicine.medscape.com/article/924291-overview

so, what does this mean to us? (sorry im getting confused after so much reading tonight)..

is it basically that DHT is not necessarily what causes the sexual development but the DHT that comes from the AR2 type enzyme?

Suppose no info exists on the AR3 in these people...?

cheers

 

[Mestys]

It all depends where the 5AR is located in the body, I believe Type 2 is found in the hair follicle, liver, prostate and genital skin etc. 5AR 1 is found in the brain, non genital skin, prostate and the liver. They're still unsure what exactly Type 1 5AR is for, apart from in the brain where it converts Progesterone into Dihydroprogesterone. DHP is then converted into Allopregnanolone via some other enzyme, which apparently is an important neurosteroid.

Finasteride is a Type 2 5AR inhibitor, although it can also inhibit Type 1 but has a very weak affect in contrast to Dutasteride which is 100x more potent than Finasteride at inhibiting Type 1.

Theoretically finasteride should not reduce levels of Allopregnanolone, but I remember seeing a study posted on this forum showing that Finasteride did indeed reduce levels of this neurosteroid.

Anyway, comparing the effects of Finasteride to 5 Alpha-reductaste Type 2 deficiency (pseudohermaphrodites) is unwise, they have normal levels of 5AR1, therefore produce normal levels of Alloporegnanonlone. As the deficiency is Type 2 only, they will also have normal levels of 5AR3 which Finasteride inhibits.

 

[gh05]

It all depends where the 5AR is located in the body, I believe Type 2 is found in the hair follicle, liver, prostate and genital skin etc. 5AR 1 is found in the brain, non genital skin, prostate and the liver. They're still unsure what exactly Type 1 5AR is for, apart from in the brain where it converts Progesterone into Dihydroprogesterone. DHP is then converted into Allopregnanolone via some other enzyme, which apparently is an important neurosteroid.

Finasteride is a Type 2 5AR inhibitor, although it can also inhibit Type 1 but has a very weak affect in contrast to Dutasteride which is 100x more potent than Finasteride at inhibiting Type 1.

Theoretically finasteride should not reduce levels of Allopregnanolone, but I remember seeing a study posted on this forum showing that Finasteride did indeed reduce levels of this neurosteroid.

Anyway, comparing the effects of Finasteride to 5 Alpha-reductaste Type 2 deficiency (pseudohermaphrodites) is unwise, they have normal levels of 5AR1, therefore produce normal levels of Alloporegnanonlone. As the deficiency is Type 2 only, they will also have normal levels of 5AR3 which Finasteride inhibits.

Thanks.

Did a bit of reading. It does seem a bit worrying if this neurosteroid is inhibited long term. Who knows what it could do to the brain. See the comments of this article http://www.baldingblog.com/2011/10/26/f ... gnanolone/ .

still confused about this AR3 and what that might do mind..

What's your dealings with finasteride been like? Success? any sides?

 

[abcdefg]

It all depends where the 5AR is located in the body, I believe Type 2 is found in the hair follicle, liver, prostate and genital skin etc. 5AR 1 is found in the brain, non genital skin, prostate and the liver. They're still unsure what exactly Type 1 5AR is for, apart from in the brain where it converts Progesterone into Dihydroprogesterone. DHP is then converted into Allopregnanolone via some other enzyme, which apparently is an important neurosteroid.

Finasteride is a Type 2 5AR inhibitor, although it can also inhibit Type 1 but has a very weak affect in contrast to Dutasteride which is 100x more potent than Finasteride at inhibiting Type 1.

Theoretically finasteride should not reduce levels of Allopregnanolone, but I remember seeing a study posted on this forum showing that Finasteride did indeed reduce levels of this neurosteroid.

Anyway, comparing the effects of Finasteride to 5 Alpha-reductaste Type 2 deficiency (pseudohermaphrodites) is unwise, they have normal levels of 5AR1, therefore produce normal levels of Alloporegnanonlone. As the deficiency is Type 2 only, they will also have normal levels of 5AR3 which Finasteride inhibits.

Finasteride though inhibits 5-ar 2 which you said is not found in the brain in high amounts. So how would finasteride change the levels of neurosteroids in the brain if the type 1 is the enzyme responsible for that?

 

[Mestys]

I stated that Finasteride also inhibits type 1, but has a relatively weak effect when compared to Dutasteride. This could be the reason, but it seems unlikely.

There needs to be more research on this.

 

[Wuffer]

It is my understanding that only 5AR type 1 is found in the brain, which is not inhibited by finasteride. 5AR Type 1 and 2 both exist in the body, and both produce allopregnanolone. There was a study posted here that showed significantly reduced allopregnanolone levels in individuals who take finasteride, but these levels were only measured in circulating blood serum, not from the brain.

I believe finasteride passes through the blood/brain barrier, meaning that it can become active in the brain. However, since it does not (or only extremely weakly) inhibits 5AR type 1, chances are it's not causing any direct problems. If we look at the drug dutasteride, it very strongly inhibits 5AR type 1, so we would expect to see way more people with problems on that drug, but actually the converse appears to be the case.

However, I also heard that 5AR type 2 exists in the spinal cord, which could potentially be responsible for feeding allopregnanolone to the brain.

There are a lot of theories out there about the effect finasteride has on the brain. Personally, I look to the known symptoms that are consistently reproduced in studies and based on those, don't believe that finasteride typically has a significant impact on neurosteroid production. However, it may have some detrimental effect, and individuals who are already predisposed to these types of conditions may end up with problems. This is the reason Depression was added to the side effect list for the drug.

Also keep in mind that millions of older men have been taking finasteride for the last 20 years for BPH. It's believed that significantly lowering allopregnanolone levels will lead to Alzheimer’s, but I have yet to see any evidence that this is actually happening to any increased frequency. The fact is, many people are actively searching for something that links finasteride to persistent symptoms. If you look hard enough, you will eventually be able to find something that appears to indicate causation. However, this is all conjecture until it is actually measured and put through the scientific method. Clearly, further research is needed.

I am not 100% at ease about the safety of finasteride, but I am still very confident that it is a safe drug. Go to pubmed, search 'finasteride' and read the hundreds of studies done on it. It actually has a remarkable safety profile, and you might even be surprised to see that there are studies done that show NO side effects whatsoever when tested in a controlled environment.

 

[Mestys]

5AR Type 1 and 2 both exist in the body, and both produce allopregnanolone.

5AR does not produce allopregnanolone. Allopregnanolone is produced from Dihydroprogesterone via 3?-hydroxysteroid oxidoreductase.

Also according to "wiki" Progesterone -> Dihydroprogesterone is done via 5AR Type 1. Not sure how true this is, can't find any more information on it.

Anyway I agree with a lot of what you said, I think Finasteride is a safe and well studied drug. But there are lot of things the scientific community are unsure of surrounding 5AR and the real effects 5AR inhibition can cause.

 

[Wuffer]

You're correct; I was more referring to the resulting mean levels of allopregnanolone resulting from 5AR inhibition. There is not much info out there about this type of stuff. What is known is not exactly conclusive, and often contradictory. Certainly, the full effects of finasteride on the body and brain are currently unknown, and there is a good chance it is affecting things that we don't even yet know about. However, this can also be said for any prescription medication out there.

If you picked any prescription medication at random, searched hard enough, you would eventually make some sort of link that indicates that it is more dangerous than previously thought. If you look hard enough, you can establish some sort of correlation between anything! No substances, especially prescription medications, are 100% safe. We can be 99.9% sure of their safety, but there is always a chance we are missing something. But just because there are unknowns, doesn't automatically make the drug unsafe.