Propecia DOES NOT inhibit neurosteroids!

General Discussion
#1

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Propecia DOES NOT inhibit neurosteroids!

Only 5alpha-Reductase type 1 is found in the human brain and not 5alpha-Reductase type 2.

Therefore Finasteride does not inhibit neurosteroids.

This is an important and established FACT.[/size]

Has this been overlooked? It’s not mentioned clearly in most of the papers, probably because theyre normally rat studies and in rats finasteride inhibits both 1 &2.

Of course what Im saying here isn’t totally definitive. Finasteride can also inhibit type 1; but is 50 times less effective at doing so than Dutasteride. Also, 5alpha-reductase type 3 has been found in brain.

I think its worth creating a thread for this because it has important implications with regards to the variety of symptoms and how they may have come about.

#2

pmr.cuni.cz/Data/Files/PragueMedicalReport/pmr_110_2009_03/pmr2009a0025.pdf

Finasteride Treatment and Neuroactive Steroid Formation

Dušková M., Hill M., Hanuš M., Matoušková M., Stárka L.

Institute of Endocrinology, Prague, Czech Republic;

Urocenrum, Prague, Czech Republic

Abstract: Finasteride is the 5α-reductase inhibitor that received clinical approval
for the treatment of human benign prostate hyperplasia and androgenetic
alopecia. The 5α-reductase is enzyme responsible for the reduction of
testosterone to dihydrostestosterone, progesterone to dihydroprogesterone and
deoxycorticosterone to dihydrodeoxycorticosterone, steroids modulating the action
of γ-aminobutyric acid on GABA receptors. These neuroactive steroids possess
anticonvulsant, antidepressant and anxiolytic effects. The objective of the study
was to determine the effect of finasteride therapy on a broad steroid spectrum in
men with benign prostate hyperplasia. A group of 20 men with benign prostate
hyperplasia was involved in the present study. Finasteride in the daily dose
of 5 mg/day was administrated for 4 months. In all individuals, their hormonal
profile of steroid hormones was determined before and after 4 months lasting
finasteride treatment. Finasteride treatment resulted in a significant decrease
all α-reduced and increase of most 5β-reduced metabolites of testosterone and
progesterone as well as in an increase of 7α-hydoxyderivatives, which are known as
neuroactive steroids acting by modulation of GABAA and NMAD receptors in the
brain. In the course of finasteride treatment the decrease of the concentration of
circulating steroids with known inhibitory activity on GABA-ergic excitation in the
brain is very probably an important factors contributing to the development of the
symptoms of depression seen in some isolated cases of finasteride administration.

Oscar (Mew?) - would you mind pulling the original post? I think it will add confusion; I can pull up some more studies showing P effects on neurosteroid production if that would be helpful.

#3

studies?

#4

I find this very interesting. Perhaps there is much more to Alpha-Reductase type 3 ???

I recall reading a fascinating post by MEW which discussed AR type 3 at length, showing just how important it is, how finasteride inhibits it very potently, and also, how it has just been mentioned in medical literature in the past few years.

#5

Former, I have posted this study before. A large number of tissues can concievably contribute to circulating levels of these hormones, not just the brain (see here and here). So how does this study help us when we are trying to determine if what is happening in the brain is distinct and different from other areas of the body which do contain 5aR-type2? Simply, it doesnt. But there are other studies that do. Maybe levels of allopregnolone produced in other parts of the body do have an impact, so the title of this thread could be ‘Propecia DOES NOT inhibit neurosteroids! (in the brain)’.

Please do.

#6

Characterization of the 5a-Reductase-3a-Hydroxysteroid Dehydrogenase Complex in the Human Brain ncbi.nlm.nih.gov/pubmed/11238528

(This study involved used Finasteride on human brain tissue from 44 patients suffering from epilepsy.)


Expression of 5alpha-reductase in the human temporal lobe of children and adults. ncbi.nlm.nih.gov/pubmed/9768677




Topography and function of androgen-metabolizing enzymes in the central nervous system. ncbi.nlm.nih.gov/pubmed/15794125


Neurosteroids and Brain Function (2001) Text Book


#7

That’s something I’ve been questioning since Mew brought it up on HLT. It’s clear that finasteride affects neurohormones negatively somehow, but it’s NOT through the inhibition of 5AR Type 2.

#8

hairlosstalk.com/interact/viewtopic.php?p=593293#p593293

Here is a link to Mew’s post from Hairloss Talk which shows that allopregnenalone was significantly decreased due to finasteride use.

Oscar raises a good point that there is no theoretically sound reason this should be happening, as Propecia supposedly only inhibits 5-AR type 2 which should not effect neurosteroids, but the aforementioned link shows evidence that contradicts this notion.

One of the endocrinologists I have visited stated that he believes there is some neurosteroid-linked mechanism at play that has not yet come to light. However, whatever the mechanism may be is entirely beyond my scope of biological knowledge.

#9

viewtopic.php?f=5&t=5748

#10

Frustrated, that is the study me and Former discussed. That study is about circulating hormones, no offence to our Czech friends but Allopregnolone can also be produced from other parts of the body, as a I also mentioned above. No study regarding finasteride contradicts the notion that it will not inhibit neurosteroids in the brains of humans.

Well, tell him that 5aR2 is not found in the brain. Tell him that 5aR1 is in the human brain and should not be inhibited by Finasteride. This may be a very important clue. We are effected more like the rats in the studies.

#11

Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis. ncbi.nlm.nih.gov/pmc/articles/PMC1600006/


#12

@OSCAR,

Do you think it has something to do with Alpha-Reductase type 3?

Mew made a most interesting post on this a while back and if I recall it is expressed heavily in the brain, as well as inhibited potently by Finasteride.

#13

Dont know, you have as much information available as I do. The paper does say “Type-3 could be the main enzyme for 5a-reductase activity”. (see viewtopic.php?f=8&t=5168), so maybe its involved with neurosteroid formation.

It could also be that we metabolised Finasteride slowly so that it inhibited type-1 (although it would require a x50 dose?) or that we have a mutation of the 5a-Reductase genes. This paper talks about the genetic differences between rats and human 5a-Reductases and even mentions that mutations may exist, although it doesnt mention that human 5aR1 may sometimes be more sensitive to Finasteride.

Four-amino acid segment in steroid 5 alpha-reductase 1 confers sensitivity to finasteride, a competitive inhibitor
ncbi.nlm.nih.gov/pubmed/1314830


#14

Finasteride induced depression: a prospective study. ncbi.nlm.nih.gov/pubmed/17026771

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#15

Oscar you know of the table that shows finasteride inhibits allopregnanalone by 300% after 4 months of treatment.

Where else in the body is allopregnanalone made in the body to reduce circulating levels by this much?

#16

Sorry to bother you oscar, this answers it.

Several of these steroids accumulate in the brain after local synthesis or after metabolism of adrenal steroids or gonadal steroids, especially testosterone. Neurosteroids are synthesized in the central and peripheral nervous system, especially in myelinating glial cells, from cholesterol or steroidal precursors imported from peripheral sources.[7][8] They include 3β-hydroxy-Δ5 derivatives, such as pregnenolone (PREG) and dehydroepiandrosterone (DHEA), their sulfates, and reduced metabolites such as the tetrahydroderivative of progesterone 3α-hydroxy-5α-pregnane-20-one (3α,5α-THPROG).

en.wikipedia.org/wiki/Neuroactive_steroid

#17

Yes Tim, that table is from this study; ‘The influence of low dose finasteride, a type II 5a-reductase inhibitor, on circulating neuroactive steroids’, this study is mentioned at he beginning of this thread. Here is a clearer graph from the study;

The problem with this study is this;

There is no (or almost no) 5a-R2 in the brain and serum levels of allopreg comes from other sources than the brain (see below).

So its possible the study does not tell us whats happening in he brain at all, only whats happening with ‘circulating levels’ that are produced by 5a-R2 elsewhere in the body.

viewtopic.php?f=1&t=5960&p=48613#p48613

‘CLINICAL IMPLICATIONS OF CIRCULATING NEUROSTEROIDS, A.R. GENAZZANI et al.’

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‘Neurosteroids and Brain Function By Giovanni Biggio’

#18

The thought i was thinking about was perhaps yeah there is no 5ar2 in the brain, but perhaps the brain and CNS rely on allopregnanolone (and other steroids for that matter) coming from other parts of the body. Re. this statement…

#19

Maybe, or maybe Fin has effected 5a-R1. I do think it has effected the brain somehow and possibly in a different way than normal, which is important. Also, that table you metioned is from a different study than the one i was thinking of! I was thinking of a later study by the same people, they have done an earlier study over 4 months with 5mg/day Proscar.

Here are the results of that study on neuroactive steroids with 1mg/day Finasteride.

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#20

Well its been seen to cross the bbb so there could be damage there, we could be the few.
When i crashed, i crashed hard, had vertigo, hand shakes, muscle twitches all the time, vision problems, it felt like a brain, central nervous system injury, still does.

The study i would like to see, obviously its not available would be pre fin treatment, during fin treatment, which we have and 2 months off fin, someone who has pfs, this could potentially tell us everything.

It wouldn’t matter if the pre and on were the ones that we have via the table we have, we need to know what has come back and in what amount after being off the drug post crash.