The latest research in mice raises a disturbing question about the
safety of FDA approved 5AR inhibitors like finasteride
(Proscar/Propecia) and especially dutasteride (Avodart) when it comes to
managing long-term risk for neurodegenerative diseases like Alzheimer's.
This is because these drugs not only reduce levels of DHT but also wound
allopregnanolone production in the process.
To summarize the new findings on allopregnanolone (see attached below),
Niemann-Pick type C is a rare lysosomal storage disorder/childhood
neurodegenerative disease in which brain cells accumulate fat and die
due in part to severely disrupted neurosteroidogenesis. A mutant gene
for lysosomal acid sphingomyelinase disturbs cholesterol synthesis
throughout the body and results in the accumulation of sphingomyelin.
Progressive loss of neurosteroid synthesis may contribute to
neurodegeneration. Replacing lost allopregnanolone substantially
increases the survival of mice with this type of disease by mitigating
the damage and delaying the onset of symptoms. Results were best when
administered as early as possible in the animal¹s life.
Allopregnanolone may be effective with managing other neurodegenerative
disorders. Other important neurosteroids like pregnenolone are also
diminished in Niemann-Pick type C but what's interesting here is how
valuable allopregnanolone is by itself.
<http://www.sciencedaily.com/releases/2004/07/040713082347.htm>. NPC
model mice may have amyloid-beta accumulations similar to those in
Alzheimer's [PMID 14982851, 14982829] and may represent a good model for
studying general aspects of neurodegeneration.
5 alpha reductase (5AR) is an enzyme which comes in two forms, type I
and type II. It not only converts testosterone (T) to
dihydrotestosterone (DHT, a ketone), it also converts progesterone to
allopregnanolone and deoxycorticosterone (Doctor) to tetrahydroDOC (THDOC),
both allosteric enhancers of the GABA(a) receptor (e.g., they increase
the effectiveness of inhibition signals relayed along GABA channels in
nerves). The second stage of this conversion is performed by
3alpha-hydroxysteroid oxidoreductase.
