Whats this about DHT in our skin and Brain?

[mbehr22]

I was reading another thread and one poster said we (dutasteride users) are idiots for taking it simply due to the fact we need dutasteride for proper brain function and healthy skin.

I think he said impaired cognitive funtion and unsightly wrinkles were very real consequences of using dutasteride for an extended period of time.

Im not all that concerned since it seems this is an isolated poster - but thought it best to look into it.

Whats the good word?

 

[powersam]

go read abotu the blood/brain barrier and how hard it is to get things past it.

 

[Pondle]

I think these drugs do pass the blood/brain barrier, but my question is, does it matter? Please read extracts of the thread I started in the "side effects" forum. I don't have any answers, I'm just trying to think through the issues logically.

There has been some comment about the role of finasteride in regulating neurosteroids like allopregnanolone and potentially causing side effects such as something (?) called "brain fog".

Although there are studies on PubMed detailing experiments which reveal that finasteride can block the formation of certain neurosteroids, I assumed that any neurosteroidal changes attributable to 5-alpha-reductase inhibition would be due to an effect on 5ARI rather than 5ARII, since the former is found in the brain. We know that finasteride is selective for 5ARII, whereas dutasteride targets both 'flavours' of the enzyme.

However, I have seen various posts where people have claimed that very large amounts of finasteride can inhibit 5ARI as well as 5ARII. Bryan Shelton, for example, claims that large doses of finasteride taken at regular intervals each day could result in DHT inhibition approaching the levels achieved by dutasteride. Of course, finasteride has a fairly flat inhibition curve, but it's not totally flat - so this seems feasible.

So I surmise that the neurosteroidal changes induced by finasteride in various animal studies are due largely to the higher levels of inhibition achieved by massive doses of finasteride. I know some research was treating rats with as much as 50mg/kg, which is an enormous amount, equivalent to hundreds of milligrams daily in humans.

A secondary question is, even if finasteride at a low dose could modulate neurosteroids - which dutasteride certainly does - does it matter? After all, apart from physical developmental defects, no other clinical abnormalities have been observed for the intersexuals with a natural deficiency of 5ARII, even though I assume they should have a neurosteroidal profile similar to finasteride or dutasteride users. Equally, women have much lower levels of both 5ARI and 5ARII compared to men (frontal hair follicles in women had 3 and 3.5 times less 5- reductase type I and II, respectively, than frontal hair follicles in men) and there seems to be no medical 'penalty' attached to this.

I'm certainly no physician or biochemist, just an Ordinary Joe trying to interpret the literature. Any comments welcome.

 

[Bryan]

I think these drugs do pass the blood/brain barrier, but my question is, does it matter?

They do pass the BBB. To what degree that matters is up for debate!

However, I have seen various posts where people have claimed that very large amounts of finasteride can inhibit 5ARI as well as 5ARII. Bryan Shelton, for example, claims that large doses of finasteride taken at regular intervals each day could result in DHT inhibition approaching the levels achieved by dutasteride. Of course, finasteride has a fairly flat inhibition curve, but it's not totally flat - so this seems feasible.

When I wrote that, I was specifically referring ONLY to the inhibition of the type II enzyme, not type I. I had said (or at least I meant to imply) that 5 mg of finasteride taken at least four times a day (spread evenly throughout the day) should begin to approach the level of type II inhibition that dutasteride has. Sorry if I assumed incorrectly that everybody would know what I meant.

Gisleskog et al estimate in their finasteride/dutasteride studies that it would take about 270 mg/day of finasteride to inhibit the type I enzyme by 50%, which is an even larger dose than I had in mind above. So to achieve true dutasteride-like performance at reducing total DHT would require really large amounts of finasteride indeed.

So I surmise that the neurosteroidal changes induced by finasteride in various animal studies are due largely to the higher levels of inhibition achieved by massive doses of finasteride. I know some research was treating rats with as much as 50mg/kg, which is an enormous amount, equivalent to hundreds of milligrams daily in humans.

It's even more than that. Since I weigh about 100 kg, that would be the equivalent of my taking 5 GRAMS per day of finasteride! :freaked:

A secondary question is, even if finasteride at a low dose could modulate neurosteroids - which dutasteride certainly does - does it matter? After all, apart from physical developmental defects, no other clinical abnormalities have been observed for the intersexuals with a natural deficiency of 5ARII, even though I assume they should have a neurosteroidal profile similar to finasteride or dutasteride users.

As you pointed out before, they'd be closer to finasteride users than dutasteride users. A crucial difference would be that dutasteride users have a significant inhibition of the type 1 enzyme, whereas finasteride users and the pseudohermaphrodites don't.

 

[Pondle]

As you pointed out before, they'd be closer to finasteride users than dutasteride users. A crucial difference would be that dutasteride users have a significant inhibition of the type 1 enzyme, whereas finasteride users and the pseudohermaphrodites don't.

Bryan, is your feeling that the inhibition of 5ARI and consequent neurosteroidal changes matter? I'm guessing that they don't, given that women have less 5AR than men anyway, and seem to suffer no health penalties as a result.

 

[Bryan]

My guess is that the level of 5ARI inhibition that you get with the approved dose of Avodart is acceptable, and shouldn't cause any serious problems for the great majority of users. But dutasteride enthusiasts who go a lot higher than that approved dose are on their own, obviously.

 

[Sir_LagaLot]

everybody is different. i'm on a 0.5 mg dose of dutasteride every other day with 1 mg finasteride on the off days and my God! the brainfog i simply cant describe, it couples with a little bit of memory loss too and is quite scary. The feeling is like waking up in the morning after just 2 hours of sleep..just totally in a daze throughout..but thats how i feel THROUGHOUT the day..

i'm nearing a month on dutasteride, if this doesnt go away in another month i'll ditch it and the finasteride.

 

[CCS]

everybody is different. i'm on a 0.5 mg dose of dutasteride every other day with 1 mg finasteride on the off days and my God! the brainfog i simply cant describe, it couples with a little bit of memory loss too and is quite scary. The feeling is like waking up in the morning after just 2 hours of sleep..just totally in a daze throughout..but thats how i feel THROUGHOUT the day..

i'm nearing a month on dutasteride, if this doesnt go away in another month i'll ditch it and the finasteride.

I've taken dutas every day with grapefruit juice for a month, with finasteride EOD at the same time, and had no brain fog at all. Jayman did the same with prescribed avodart, and no finasteride, and for longer than I did. No brain issues. You must be one of the very unlucky ones.

 

[Pondle]

These phenomena were never recorded in the clinical trials for finasteride or dutasteride, as far as I'm aware. I believe the Avodart phase II hair loss trials mentioned 'headaches' as an infrequent adverse reaction but that's as far as it went.