Finasteride and Neurosteroides (DHT metabolites) - Potential Problem?

[Admin]

The problem is that the focus is on adverse events either way.

I sometimes wonder if guys from that "other site" come here just to scare people away from Propecia. These individuals are always brand new registrants. They appear out of nowhere and have nothing to say other than talking about Propecia health dangers.

Like for example, you just signed up this month and only have 13 posts.

 

[to the lost]

no man.. i'm not from another site, nor am I saing that propecia causes neurological damage. I have NEVER claimed that that is a real side effect. It is just my fear (and obviously not just my). I am not a neurologist/endocrinologist, so my correlations could be wrong, and probably it is (just I would like somebody to prove it with a scinentific study). I am not selling anything nor saying to get off propecia. I am just considering all possibilities

I am (still am) considering going on propecia, but i came across some studies and i thought that there would be a good argument to why they are wrong (in sense that finasteride does not cause neurological damage). I though that you guys came across these studys way before me, so i have expected help. so far the "forum" comunity has not been helpful. and as long as i don't find any evidence, i will not go on finasteride (my personal oppinion, i am not sugesting anything to anybody else). I am paranoid guy.

for the other things. I have slight hair loss from september (went to 3 dermatologist meanwile, and took a blood test, plus waiting for my endcrinologist appointment), so ofc i didn't register before (I didnt have to). and if you look at my first post (on general hair loss discusion, page 2 i think), you will see the real reason I have registered. If i had not have so strange results in my blood test, i probably would never registered. Only last week i found the first study (in the thread) and since then i have busted my *** to find more. I spent like 2-3 h per day for those (read everything and all). and than you come and discredit me like that

but i am not angry or anything. if i were you i would also be suspicious. you are right, this si my like 15 post so there is no real reason to trust me. I have allways encouraged people to share studies of their own or at least to explain why am I wrong (it would make my life easier too - i could get on finasteride)

and then you put this thread in the "dealing with sides", like I am claiming that this is a real side.

now back on topic, i would like to know what do you think about this.

 

[abcdefg]

As kind of an off topic thing I think the future of drug development and research is going to be robots and AI because robots can do studies and long experiments without ever stopping at all hours. Its impossible for humans to test all these different things it needs to be automated as best we can

 

[Fanjeera]

Isn't it stated on the info sheet that this drug can cause neurological side effects? You're not discovering anything new here. And of course, allopregnanolone depletion has an importancy here and it's probably very well known also. You just don't want to drown people into all the details and information when selling the drug.

 

[to the lost]

no, i mean.. it is said that it can cause depression and anxeity (yeah the neurological side effect from - look at the study on page 2, my first comment - depleted allopregnanolone and maybe androstenediol). but i was wondering - because neurosetroids play an important role, especialy alloprenanolone - what are the long term neurological side effects (if any). Low allopregnanolone was foud in some of the neurological disorder (and eventhough correlation does NOT mean causation, i was still wondering "what if"). so any study or anybody who knows more on this topic would be greatly welcome to share his thoughts

so for me the problem is not the small "side effects" like depression (OT: it would be also useful if somebody could prove that those are the only side effcts from low allo) but potentical big ones. but i am not claiming, that low alloprenanolo is main cause of neurological disorders like alzheimers (in truth science does not know, what is the cause). but it is said, that allopregnanolo is kind of "defender" (OT: also it could be usefule is there were a study on how low allopregnanolo is still "normal" so we can compare with how much finasteride is lowering it - i and Fanjeera have poste study on that on page 2).

but my intention is NOT to cause panic, or to say, that finasteride is the cause of anything. but i would like to be sure.

 

[Fanjeera]

I think it's not a very well known molecule and so isn't 5ar2, so it's best not to risk. What seems sure is that its high levels are good for you.

 

[to the lost]

well ideally (if you have hair loss ofc) it would be, to do whatever to 5AR, just to take something to keep your levels of neurosteroids "normal" (and how much is that?)

but this thread is depressing. like 600+ people look at it, and it has 25 replies.. has no one got anythig to contribute on the "defence" of finasteride (that it does not do anythig to neurosteroids that could be harmful?)

or is the subject too complex (or people don't care). I don't understand. even admin is ignoring me :thumbsdown:

like you guys, who have been on finasteride for long, you probably saw this study. maybe you have some material on this topic, you can share (and i haven't found it). or at least an opinion...

 

[Fanjeera]

There are many people who don't get depression while on finasteride and they'll probably find this topic soon too. But those two studies showing that finasteride decreases allopregnanolone is all -- that's the edge of science right now. We just have to wait. Oh, and there are probably some case reports and a few cohort and case-control studies that also say that they enountered depression as a side effect.

 

[to the lost]

yeah, I mean there is a study that said exactly wich hormones are affected (and consenquently some neurosteroids, allopregnanolone being only one of them). but on the other side there are a lot of guys who don't have sides. But are they safe (like if you don't get sides right away, does that mean that you dont have low neurosteroid or just that you don't have ED and such. Do neurosteroid get lower over time on finasteride? and do they cause neurological damage if they are low - well that probably no one can answer yet, because the cause of some nuro-deseases are not known)

so I was wondering:
1. probably allopregnanolone was high in those guys to start with (or it did not fell, which is less likely). what are the the normal levels (or at least reference range) for the neuorsteroids? and what are the posible actions to "artificially" increase neurosteroids (user boobyinspector said one way that he increases alloprenanolone - if i understood corectlly from suplements)?
2. the 5 AR 1 (which is found in brain) is just mildly affected by finasteride (so mildly that authors say that finasteride blocks only 5 AR 2). So how can there be low allopregnanolone? first i thought that those who have sides are unlucky ones and get the 5 AR 1 blocked too. but then that czech study said - if i understand corectly - that those 20 pations had decrese in following (NOTE: study did not say that they complained on sides, so i assume that they did not have them):

"A significant
(at the level p<0.05) decrease was seen in most of the 5α-reduced metabolites
(5α-dihydrotestosterone, androsterone, epiandrosterone, allopregnanolone)
and in most of the 5-ene steroids and their 7α- and 16α-hydroxy-derivatives
(dehydroepiandrosterone, 7α-hydroxy-dehydroepiandrosterone,
16α-hydroxy-dehydroepiandrosterone), whereas significant increase occurred
in one of the 5β-reduced metabolites, epietiocholanolone"

"Here we demonstrate that it concerns a broad
spectrum of testosterone and progesterone metabolites as products of
oxido-reduction metabolic pathways. Finasteride treatment exerted also effect
on the concentration of hydroxy-metabolites, which seem to be important for
the brain function as e.g. 7-hydroxyderivatives of DHEA or pregnenolone"

but it should be noted the age of the patients (they all were above 50)
so they got blocked the AR1 too? or what?

3.) there should be a long term study on brain neurosteroids and effect of finasteride.

4.) can't udestand one more thing. there was a study, on long term safty of proecia (5 and 10 year study i think). which said that sides do NOT occur over prolonged use (if you have them, they come right away). but there are some guys who got sides after like 4 years or 10 years on finasteride (it should be notet that i read those stories on forum - not sure which - so it is not a scientific evidence). but could the decreased neurosteroids be to blame? or the sides could occor spontaniusly over time (so without long ter "small" damage)..

those are like just some of the questions..

 

[Fanjeera]

5ar2 is also in the brain. Like I told, the molecule is not that well known yet and it may be in much more cells than we imagine.

 

[to the lost]

Hi, me again.

Found some important study. But don't have access to whole, but just abstract.

It says, that neurosteroid can be sythesized not only in body (through hormones) but also in brain. So that could mean, that finasteride does really block only 5AR2 (that could lead to decrease of neurosteroid production in body but not in brain). For cholesterol i am not sure, but i am sure that decrease is seen in neurosteroid from progesterone (finasteride blocks that one).

Endogenous neurosteroids such as allopregnanolone, allotetrahydrodeoxycorticosterone, and androstanediol are synthesized either de novo in the brain from cholesterol or are generated from the local metabolism of peripherally derived progesterone or corticosterone.

but the abstract does end in rather worrying way.

Considering the large charge transfer generated by these persistently open channels, even subtle changes in neurosteroid concentrations can have a major impact on neuronal excitability. Consequently, aberrant levels of neurosteroids have been implicated in numerous disorders, including, but not limited to, anxiety, neurodegenerative diseases, alcohol abuse, epilepsy, and depression.

link: http://www.degruyter.com/view/j/bmc.2013.4.issue-1/bmc-2012-0033/bmc-2012-0033.xml

2. found this too, but my poor undestanding of the subject (what is D2, D1), did not help. maybe it will be useful to somebody else. http://www.sciencedirect.com/science/article/pii/S0306453012002661

3. here is another rat study on the 5Ar2 in brain http://www.sciencedirect.com/science/article/pii/S0306453012002235

These findings show that, in the adult brain, 5αR2 is distributed in critical regions for behavioral regulation, suggesting that the functional role of this isoform is present throughout the entire lifespan of the individual

4. another study on alloprenanolone http://www.jneurosci.org/content/25/19/4706.short

5. another study on rats and 5AR http://www.fasebj.org/content/17/11/1428.short

Our results demonstrate that both isozymes of 5α-R are expressed in the cerebral cortex of adult rats. The gene expression of 5α-R type 2 is under the positive control of T and DHT. The gene that codes for 5α-R type 1 is not constitutive, because its expression is negatively regulated by T and DHT. These results open up a new research line that may lead to a better understanding of the role of 5α-R isozymes in the physiology of the central nervous system

- - - Updated - - -

5ar2 is also in the brain. Like I told, the molecule is not that well known yet and it may be in much more cells than we imagine.

i didn't know that. yeah i agree. there is virtualy imposibile to find scietific answers for question that I have. Probably thats why no one is responding.
that and the fact that this tread is like invisible (hidden with all the "paranoid" topics that deal with sides). mostly the new guy look at these (i think).

and this thread is probably scaring them ****less lol. I am not happy taking the role of paranoid "anti-propecia" guy, but i really didn't find any studies which could prove something different. but for the defence of finasteride, neither have i found anythig that correlates finasteride to neurological damage, nor that low alloprenanolone is the main cause in degenerative neurological deseases (just a speculation).

 

[Fanjeera]

Don't delve too deep into the rat studies. You can't conclude everything based on them. Firstly, finasteride inhibits both 5ar-s in rats. And secondly, especially in the isoenzymal distribution there can be big differences between species. They are both still enzymes with the same goal, so I think it's pretty random or just too complicated how it could be developed.
Though, if you see a very disturbing side-effect in rats, you don't risk the drug on humans usually. For me this is enough, because it can be permanent and certainly progresses with the time of usage: http://www.asiaandro.com/archive/1008-682X/5/33.htm
I think this study should be shown to everyone thinking about finasteride. Still, many people say they feel no change in their penises after taking it, but some still do. But we shouldn't start this penis discussion here, as I've started many topics on it already.

 

[to the lost]

well the human studies are scarce. but i do agree we can not conclude everything from rat studies (but if rat has both enzimes 5AR1 and 2 in cerebral cortex, than it could mean that humans have it too - just tha 5AR2 gets blocked and not both). so that is why it is essential, that there be some human studies. like NOW.

there are people complaining at sides, but no one is doing a proper study (not that i know of). but for me, neurosteroid levels are far more important than penis problems (agree those could be devestating too, but medical priority should be neurosteroids)

 

[WhereDaHair]

I'm quitting the SSRI soon - if it's a choice between antidepressants and Propecia, I'd go with finasteride any day. No amount of Prozac would be able to counter the depression caused by balding

Hey man, about quitting the SSRI... have you? What about this I came across in another thread:

SSRIs (antidepressants like Zoloft) have been shown to upregulate levels of progesterone and allopregnanolone (THP) [PMID 12957330] as well as neurogenesis [PMID 14872203, 15001810, 14512209]. In animal models it¹s the hippocampal neurogenesis that accounts for the behavioral effects of SSRIs [PMID 12907793]. Conversely, inescapable stress which reduces hippocampal neurogenesis also causes depression [PMID 12838272].

I mean correct me if i'm wrong. But both this thread (and the other finasteride and neurological problems thread on HLH) focus on the the lower synthesis of allopregnanalone because this action is inhibited by finasteride just the same as T -> DHT because it's also 5AR.

So having lower levels of allopregnanalone is bad, and SSRI's upregulate levels of allopregnanalone, then wouldn't it be advantageous to take an SSRI (never though I would say that) if you are also taking finasteride?

Also says this here:

People have commented on supplementing with the following;
SSRI's
5-HTP
Glutamine
Theanine
Fish Oil

All of these supplements are agonists for uptake of GABA in some shape or form. It seems too coincidental to me that many people have reported these as being positive for hard flaccid, for it to be unrelated to GABA. People talk about their anti-inflammatory affects, but it's specifically the mode of action through GABA that creates the bigger change.

See, I dropped 1mg Propecia AND 100mg Zoloft same day! Cold Turkey! I'm now realizing that may have been a bad idea... But, at least as far as the neurological problems go, actually taking Zoloft may help... right?

 

[Keaphare]

Has anyone had insomnia on finasteride? that's because allopregnenolone which is a substance finasteride prevents the body making is necessary for sleep. It's also interesting whether DHT is a neurotransmitter. I've had depression before commencing finasteride so I can't really blame it on the finasteride, however, I've always found it difficult (impossible) to get off antidepressants.
Now here is a bold statement and I appologize up front for those who really defend finasteride. But...what if finasteride shortens the human life span as they discover more about it? There are side effects for all meds, but taking a med for cosmetic reasons is different for taking an anti-rejection drug for a heart transplant (no, I didn't say a "hair transplant" ..kidding).
Having said this, I still take finasteride because my hair is important to me. Why? Let's face it, are we vain? do we find it more appealing to women? Have we attached our very own "identity" to the hair. I recall one guy saying if he lost his hair he'd throw himself of a bridge, obviously he is young and has a lot of growing up to do.

 

[to the lost]

"So having lower levels of allopregnanalone is bad, and SSRI's upregulate levels of allopregnanalone, then wouldn't it be advantageous to take an SSRI (never though I would say that) if you are also taking finasteride?"

that can be logical conclusion, but I don't know the mechanism of SSRI's (how do they elevate allopregnanolone). But yeah in theory it would be posible. But remember, the SSRI's have FAR greater precentage of reported sides on ED (like 60% i think, some permanent). So i don't know.

Keaphare @ well i don't know about insomnia. I am not sure neither how much does finasteride "inhibits" allopregnenolone (i think i read that there are 2 sourcen to allo, cholesterole and 5 alpha reductaze from DHProgesterone, not sure though).

Depresion is a side effect of finasteride, and low allopregnanolone is likley the cause. But as you said, you can have low allo either way (not taking finasteride). so does that mean that depression is corelated with neurological damage?
but i have poor understanding of SSRI's (just wikipedia), it would be usefule to look at that too. Because if the SSRI really elevate allopregnanolone, than it would be useful. see, an idea that's why i like to get more comments

 

[Quadzilla99]

Lol medical advice from the bros at hairlosstalk.com

 

[to the lost]

no one here is giving medical advice. we are just debating and sharing studies.

 

[ham373]

You should do a slow taper (slower than almost everyone considers doing). This has a very good chance of reducing the chance of post-finasteridesyndrome. Apart from requiring patience there is no down side.


The short summary:


1. Very small doses of finasteride(like 0.04mg) inhibits DHT quite a lot.
2. A single dose of finasterideinhibits DHT for 4-7 days for a tiny dose (like 0.04mg to 0.2mg) andeven longer for a 1mg dose.
3. The post-finasteride syndrome has alot of the hallmarks of a hormonal axis shut down, likely due to thesurge in DHT following stopping the drug.
4. Like in other hormonal shutdownsthis risk can be minimised by a very slow tapering regime.
5. I will explain at length therationale below but one point worth making- there is no downside totapering. If you have been on the drug for x years then three months(or so) tapering cannot add a lot of risk and it may be highlybeneficial.
6.A slow tapering regime forfinasteride involves the following in broad outline:
a.going to about 0.25mg a day straightaway (this inhibits DHT the same as 1mg/day),
b.then going to 0.25mg every secondday, third day and then fourth day.
c.At this point you should reduce thedose, while dosing every fourth day. An eight of a tablet is 0.125mg.
d.Ideally you would get down to about0.04mg every fourth day which might be done by very careful cuttingup of eights of a tablet.
e.From every fourth day on 0.04mg,space this out to 5, 6, 7, 10 and 14 days.
f.There is even rationale to go toeven more smaller doses - like 0.02mg and 0.01mg at these intervals.
g. Timing: step a. can be donestraight away. step b. can be done over a couple of weeks. steps c.to f. should be done as slowly as you can stand. It is very likelythat when you get to 0.125 mg every fourth day you will notice animprovement in your side effects and you might also be able todiscern a time line of worse symptoms about 24-36 hours after a dosethat improves over the next 2-3 days. This is not the time to quitcold turkey! This is the time to go slow. This period should removeany doubt in your mind where the side effects have come from. But youneed to wean off slowly to give a chance to safely land your hormonalsystem. It is tough to put a drug into your mouth that you realise isdoing you harm, but it is far tougher to risk the prolonged sideeffects that might come from stopping quickly.

 

[Wolf Pack]

I think finasteride will increase the risk of depression/anxiety in those prone to it due to the imbalance of neurosteroids. But some people will feel better despite this affect due to more hair. However, if you feel it's affecting your mood, stop taking it. It's reversible. Simple! The link to Alzheimer's is nitpicking at best, if you look hard enough in anything, you will find something bad. Goes for medication and non medication.

Example : Running can cause arthritis. Shall we stop running?

Benefits V Risks e.t.c.