How Finasteride Works

[AntonKazz]

Something really puzzles me about how finasteride works. From what I understand it inhibits the production of the alpha 5 redutase enzyme so that it doesn't bind with the testosterone so we have less DHT. Now what I don't understand is why when you stop taking the drug you go to baseline as if you had never been taking it. Why does this happen? surley once DHT levels return to normal the rate of hair loss would just resume as normal? Also how does reducing DHT cause regrowth?

 

[Bryan]

Something really puzzles me about how finasteride works. From what I understand it inhibits the production of the alpha 5 redutase enzyme so that it doesn't bind with the testosterone so we have less DHT.

Finasteride _may_ have an effect on the production of the 5a-reductase enzyme, but that possible effect hasn't been documented or discussed very much. Finasteride's main effect is just to bind to that enzyme irreversibly, preventing it from producing DHT.

Now what I don't understand is why when you stop taking the drug you go to baseline as if you had never been taking it. Why does this happen? surley once DHT levels return to normal the rate of hair loss would just resume as normal?

The exact rate at which balding resumes after you stop taking finasteride is a controversial subject. Let's not open-up THAT can of worms!

Also how does reducing DHT cause regrowth?

Androgens cause scalp hair follicles to secrete various substances that inhibit the growth of the follicle. Removing enough of those androgens allows them to resume that normal growth.

 

[Mew]

Finasteride _may_ have an effect on the production of the 5a-reductase enzyme, but that possible effect hasn't been documented or discussed very much

Bryan, when you say "Finasteride _may_ have an effect on the production of 5AR enzyme", are you referring to a patient's SYNTHESIS of NEW (uninhibited) 5AR2, AFTER discontinuation of the drug?

If so, do you have any documents or discussions you could point us to?

Thanks.

 

[Bryan]

Bryan, when you say "Finasteride _may_ have an effect on the production of 5AR enzyme", are you referring to a patient's SYNTHESIS of NEW (uninhibited) 5AR2, AFTER discontinuation of the drug?

I don't really understand the point of your question, so I'm just going to answer it in as simple and direct a manner as I can: no, I'm talking about the synthesis of 5a-reductase ALL the time, not just after discontinuing finasteride. I have a study by Happle & Hoffmann which found that giving testosterone to cultured human scalp hair follicles caused them to make more of the type II enzyme (interestingly, the type I enzyme was relatively unaffected), so the cellular synthesis of that type II reductase enzyme is apparently sensitive to androgenic stimulation.

 

[abcdefg]

What about lots of people claiming finasteride loses effectiveness after 5-10 years? What would change that would cause that after 5 years of steady use of the same dose? Theres still so many unanswered questions with finasteride and how it works exactly why bother using it? its not really the long term cure its claimed to be. We need a more effective more understood treatment.

 

[Bryan]

What about lots of people claiming finasteride loses effectiveness after 5-10 years? What would change that would cause that after 5 years of steady use of the same dose?

A gradual increase in the fundamental balding process. Specifically, a gradually increased sensitivity of the scalp hair follicles to androgens.

 

[Mew]

I don't really understand the point of your question...

...no, I'm talking about the synthesis of 5a-reductase ALL the time, not just after discontinuing finasteride

Ok well let me clarify.

You stated: "Finasteride _may_ have an effect on the production of the 5a-reductase enzyme"

In other words, it sounds like you are saying Finasteride may have an effect on the patient's synthesis of 5AR2 -- either while on the drug, or after (ie, ALL the time).

I'm simply trying to clarify this point: what research have you come across that states Finasteride may have an effect on the PRODUCTION of 5AR2 enzyme?

Just to be clear -- we know it binds to and irreversibly inhibits 5AR2 once the enzyme has been PRODUCED/SYNTHESIZED by the patient, but that is a seperate point from this discussion. I'm more interested in understanding your statement that Finasteride may have effect on the actual production/synthesis of the enzyme itself (not inhibition, which takes place after synthesis).

Hope that makes it clearer. Any research links you can provide would be great, thanks.

 

[Bryan]

Ok well let me clarify.

You stated: "Finasteride _may_ have an effect on the production of the 5a-reductase enzyme"

In other words, it sounds like you are saying Finasteride may have an effect on the patient's synthesis of 5AR2 -- either while on the drug, or after (ie, ALL the time).

Yes, that's what I'm saying. The effect would wear-off, of course, after you stop taking finasteride.

I'm simply trying to clarify this point: what research have you come across that states Finasteride may have an effect on the PRODUCTION of 5AR2 enzyme?

Do you have access to a medical library? If you do, I'll dig-up that study again, and give you the full citation. I didn't find it in a medical journal, it was a chapter in a medical book.

Just to be clear -- we know it binds to and irreversibly inhibits 5AR2 once the enzyme has been PRODUCED/SYNTHESIZED by the patient, but that is a seperate point from this discussion. I'm more interested in understanding your statement that Finasteride may have effect on the actual production/synthesis of the enzyme itself (not inhibition, which takes place after synthesis).

So why did you ask me if I was referring to a patient's synthesis of new enzyme, after discontinuation of finasteride? What does THAT have to do with anything?

 

[Mew]

Do you have access to a medical library? If you do, I'll dig-up that study again, and give you the full citation. I didn't find it in a medical journal, it was a chapter in a medical book.

Great, please do post the citation. I have some contacts who do have access to a medical library, yes.

So why did you ask me if I was referring to a patient's synthesis of new enzyme, after discontinuation of finasteride? What does THAT have to do with anything?

It has to do with quite a lot. You state:

"Yes, that's what I'm saying. The effect would wear-off, of course, after you stop taking finasteride."

Yes, that is how things are supposed to work -- but what I'm more interested in is if the drug's possible effects on production of 5AR2 _could_ continue POST-Finasteride. This is in addition to understanding more about the mechanism by which finasteride could affect synthesis of 5AR2 only while on the drug (as you state).

Cheers.

 

[Bryan]

Great, please do post the citation. I have some contacts who do have access to a medical library, yes.

Here it is: the name of the chapter is "RNA-levels of 5a-reductase and androgen receptor in human skin, hair follicles and follicle-derived cells", pages 327-331, from the book Hair Research for the Next Millenium, copyright 1996. D.J.J. Van Neste and V.A. Randall (Eds).

So why did you ask me if I was referring to a patient's synthesis of new enzyme, after discontinuation of finasteride? What does THAT have to do with anything?

It has to do with quite a lot. You state:

"Yes, that's what I'm saying. The effect would wear-off, of course, after you stop taking finasteride."

Yes, that is how things are supposed to work -- but what I'm more interested in is if the drug's possible effects on production of 5AR2 _could_ continue POST-Finasteride.

I don't see how it could.

 

[Todd]

Bryan has got it right.

To supplement:

Finasteride is a competitive inhinitor, wich means it competes for the same site (usually called the A- site, or the active site in pharmacological terms) of the enzyme as testosterone. Finasteride, having a greater affinity (wich on a molecular level means having a structure that better fits the shape of the A- site than testosterone), binds irreversibly to the enzyme and keeps testosterone from binding to it.
Thus, the enzyme is "inhibited". It is not destroyed or removed from the body in any sense, it is simply inhibited from having an effect on testosterone, because finasteride is "taking up space".

EDIT: after a while, it is, of course removed, as every protein in the body is metabolized and new ones are produced. Reason should state that when the inhibited enzyme is degraded, and a new one is transcibed, the new enzyme is NOT inhibited.
That is, unless, you keep taking finasteride.

One could speculate if finasteride has an effect on RNA transcription, or even DNA expression, of the 5A- reductase enzyme, but I am not familliar with any research on this. A qualified guess would be "probably not"

 

[Bryan]

One could speculate if finasteride has an effect on RNA transcription, or even DNA expression, of the 5A- reductase enzyme, but I am not familliar with any research on this. A qualified guess would be "probably not"

See the reference in my post just above. They found that testosterone given to human scalp hair follicles in vitro increased mRNA levels of the 5a-reductase type II enzyme (but not the type I enzyme). That obviously strongly imples that the gene is influenced by androgenic stimulation, which means that finasteride probably does have an effect on it.

 

[Todd]

One could speculate if finasteride has an effect on RNA transcription, or even DNA expression, of the 5A- reductase enzyme, but I am not familliar with any research on this. A qualified guess would be "probably not"

See the reference in my post just above. They found that testosterone given to human scalp hair follicles in vitro increased mRNA levels of the 5a-reductase type II enzyme (but not the type I enzyme). That obviously strongly imples that the gene is influenced by androgenic stimulation, which means that finasteride probably does have an effect on it.

It would seem so, yeah...
Interesting.