Finasteride Does Reduce Allopregnanolone

[alex1307]

So, I realize this topic about 5-ARIs and neurosteroids has been beaten to death on this forum, but I couldn't find any thread on this article:

https://pdfs.semanticscholar.org/cfbb/6e441d2f878a71ba13a2ecaf70c4b7a43394.pdf

I refer to table 4, where they compare the compare the control group to those who have been on finasteride 5mg/day for 4 months. They have statistically significant reduction in several neurosteroids, including allopregnanolone.

It goes on further in the discussion:
"In recent study [17] it was found that plasma concentrations of free, non-conjugated neuroactive steroids pregnenolone and dehydroepiandrosterone correlate with those in the brain. According to present study the changes in plasma concentrations of androstane and pregnane derivatives are profoundly changed after finasteride treatment."
And:
"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 [20].
The more detailed knowledge of the potential neuroactive steroids seems to be useful, as the action of individual metabolites differs not only according to their chemical structure but also whether they act on GABAA or NMAD receptors."

Now, I know, some of you will undoubtably say its 5 mg/day so its not comparable, but its the same drug mechanism so it is reasonable to assume you will still get a pretty decent reduction from 1 mg/day (but I can't find any real research on it)
I also expect to hear the usual argument of "finasteride doesn't inhibit 5-AR1, in the brain", but from what I have read allopregnanolone is able to cross the blood brain barrier anyway. This (unrelated) article about allopregnanolone states: "Like other neurosteroids, allopregnanolone is highly lipophilic and easily crosses the blood brain barrier. After intramuscular injection in mice, levels of allopregnanolone was much higher in the brain than in the plasma"

http://mr.ucdavis.edu/uploads/1/1/7...perrefractory-se-neurologyreviews-dec2016.pdf
https://www.mdedge.com/neurologyrev...pregnanolone-may-treat-superrefractory-status

So a reduced blood level would be significant. Or could be. The truth is no one really understands or knows what the long term effects of a reduction in your neurosteroids will be. All we know is that this neurosteroid seems to be important for neurogenesis. And that it is even showing promise as a treatment in Alzheimers, Parkinsons and epilepsy.


Im 28 years old and balding. Which really sucks. I got a prescription for Propecia but I reconsidered after some more reading. Of course from clinical trials you might say oh its only less than 2% who get side effects like depression, ED, infertility, and then you can just stop. Its been used since the 90s, and is approved by the FDA.
But either way you toss and turn it, the fact is that if you are using finasteride, you are artificially lowering your neurosteroids for years on end. Who knows what clinically silent effects this can have on your brain?
No one does.

Any counter arguments are welcome.

Peace

 

[abcdefg]

I do think this is probably the biggest negative long term risk with finasteride. Lowering neurosteroids long term could end up being a bad thing. Id gladly take sexual sides over something more serious involving the brain. It might not end up doing anything in practical terms though.

BACKGROUND

Allopregnanolone is a neurosteroid metabolite of progesterone. It is an allosteric modulator of inhibitory γ-aminobutyric acid (GABA-A) receptors on neural stem cells and other cell types in the brain (Luchetti et al., 2011). Allopregnanolone levels have been reported to be reduced in the temporal cortices of people with Alzheimer's disease (Naylor et al., 2010).

In transgenic Alzheimer's mouse models, allopregnanolone has been reported to increase neurogenesis, reduce amyloid deposition, and improve performance of learning and memory tests (e.g. Wang et al., 2010; Chen et al., 2011; Zhang et al., 2015). In mouse models of the lipid storage disease Niemann-Pick Type C, restoring low allopregnanolone levels lengthened survival. This neuroprotective effect is thought to be mediated by the pregnane X steroid receptor (Sep 2006 news).

The rationale behind evaluating allopregnanolone in Alzheimer's disease is that a combined regenerative and neuroprotective effect will counteract the ongoing neuronal cell loss in this neurodegenerative disease (Irwin et al., 2014). However, other studies have reported that allopregnanolone can impair learning function in two different AD mouse strains (e.g. Bengtsson et al., 2013).

FINDINGS