Finasteride vs Castration - Model of effects on androgens

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#1

Excellent graphs and models illustrating the effects of castration vs Finasteride on Prostatic Androgens and hormone levels. The file is from the US Environmental Protection Agency.

epa.gov/comptox/bosc_review/ … Barton.pdf

Also note the following observations:

"5a-reductase isoforms

Type 1: Located throughout the body, high in liver, low in prostate.
Finasteride competes competitively with T for 5a-reductase type 1.
Reversible enzyme inhibition.

Type 2: High concentrations in prostate, low in most other tissues.
Finasteride exhibits time-dependent inhibition of 5a-reductase type 2.
Very slow off rate (~30 d). Virtually irreversible enzyme inhibition."

#2

What does the about 30 days off rate mean??

#3

Likely the slow rate at which those 5AR2 enzymes which were bound by Finasteride completely dissasociate from Finasteride… it is such a slow process the inhibition is virtually irreversible.

Screenshots from below Patent, for more info:

google.com/patents?id=x_MXAA … ng#PPA5,M1



#4

So I’m trying to figure out if it matters how long one takes finasteride that determines the half life of one month. Let’s take my situation since I was on finasteride for 8 weeks (not a few days and not years either). If the half life is one month, after one month half of the finasteride will still be bound to the 5AR enzymes. After two months, one fourth of it will be. After three months, 1/8 of it will be. After four months, 1/16 of it will be. After five months, 1/32. And after six months, 1/64 of the enzymes will still be bound to finasteride. So essentially, the binding gets weaker but it takes some time.

Am I following this right?

#5

My understanding is it does not matter how long you took it for… it is from the last dose that the clock starts ticking for the “one month” process to begin… since if you continue taking it, you will simply be delaying the process of enzyme-inhibitor disassociation with each dose.

In other worsd, it would only be after your last dose that 5AR2 begins to slowly be re-synthesized (although nobody has tested for 5AR2 yet to confirm this does in fact happen for those with permanent issues)… while at the same time, it takes 30 days for the previously bound 5AR2+Fin complexes from your last dose to decompose.

#6

What does it mean when the study says dihydro-3-oxide-4-azasteroid is the only product recovered? Recovered from the urine or something? And isn’t this in and of itself proof of some sort of testing?

#7

Going off that real quick, if I’ve been off of Propecia for 11 weeks and change, 1 out of 8 enzymes should still be bound, which does not seem like very many. But I’m still having speech problems. What’s up with that?For example, yesterday I told a girl “Thank you for letting you borrow my car”, even though it was supposed to be “Thank you for letting me borrow your car.” That’s not slurring per se but stems from the same problem I’m sure.

I also notice that when I come to work at 9 AM I have no anxiety to speak of, but it’s only after I start talking to people that I realize my slurred speech is still here, and that’s when the anxiety to speak kicks in.

#8

I’ve been trying to think about this logically. If Propecia was supposed to block about 70% of our 5ARII, after about 30 days, about 35% of 5AR would still be bound to finasteride, after two months about 17.5%, after three months 8.75%, after about four months 4.3525%, etc.

Perhaps new 5ARII are not resynthesized until the old ones are finally unbounded from the finasteride. And the half life of about 30 days is after one dose, and contrary to some opinion, it seems logical that many doses make the half life exponentially longer.