Hasson & Wong Update on Topical Finasteride

[Swooping]

Completely agree.

What do you think about CB's potential considering it acts on that level? Am I right in assuming CB could be used in a much higher concentration to almost completely block androgen receptors without causing side effects, or am I missing something?

Yeah you could be right. I actually hope that CB proves to be very potent and have a good side effect profile. Perhaps CB could be used indeed at a high concentration to almost shield of all DHT from the androgen receptors + test. I guess we will have to wait on the study results to see how CB really behaves. Hopefully they will release much information after the clinical trial completion.

[robodoc]

First do an internet search. Someone here should know the concentration recommended.

Having said that consider this: if you have Finasteride 1% soln then that means you hav 1000mg/100ml or 10mg/ml. The question now is how much is systemically absorbed? I don't know but if I was making a solution and want to use 2 X 1ml I might make 0.1% solution. You do the math, 1.0mg/ml with the assumption there was somewhere around a 70% absorption. This is all theory so don't go make a 0.5% and use because it may be too much.
I just want you to know concentrations, absorption considerations and I would dissolve in Minoxidil soln, perfect hydro-alc-peg solvent

If you make your own and don't want the powder fillers in your solution, make up 30-60ml solution dissolved in Minox or other and pass it thru a coffee filter. Wet the filter first with Isopropyl Alc 70% so no drug sticks to the filter. I highly recommend 100ml graduate cylinder to do your prepping bought on line or your local INDEPENDENT pharmacy will get you one. Does this help anyone?

[efedrez]

I understand that DHT carried through the blood will still eat at the hair follicle; but I don't mind experimenting to see if eliminating the DHT locally can at least help to slow down the loss until something better comes out. I am going through the recession process and I want to try applying some creamy fin on my hairline before bed rather than going all out with the pill; I don't need help in the crown or any other area.

Having said that; my hair responded really well to .25mg of oral fin everyday. What concentration and vehicle should I ask for at the compounding pharmacy to attain an equivalent effect with the topical? Is anyone here knowledgeable enough about this or should I just ask the pharmacist?

Thanks guys

A few post/days ago, Desmond, who is knowledgeable enough mentioned he would informed about a reasonable formulation to take to the pharmacist

Desmond, are you still there? Buddy we could use some help now!

[robodoc]

Isnt DHT in the scalp or converted to DHT in the scalp? I don't know the mechanism. You are saying systemically Finasteride blocks the conversion of Testosterone to DHT in the blood? I thought this occurs in different organs of the body, ie, testicles, skin. Can you help me out?

[robodoc]

Can you send the formula? I know how to get it done. Thanks much.

[nohawk]

I understand that DHT carried through the blood will still eat at the hair follicle; but I don't mind experimenting to see if eliminating the DHT locally can at least help to slow down the loss until something better comes out. I am going through the recession process and I want to try applying some creamy fin on my hairline before bed rather than going all out with the pill; I don't need help in the crown or any other area.

Having said that; my hair responded really well to .25mg of oral fin everyday. What concentration and vehicle should I ask for at the compounding pharmacy to attain an equivalent effect with the topical? Is anyone here knowledgeable enough about this or should I just ask the pharmacist?

Thanks guys

[FearTheLoss]

It's not 5AR2, it's DHT. Oral medications like finasteride and dutasteride work that well because they actually decrease serum DHT. I don't exactly understand what you mean by "spillover"?

if you are going to only inhibit 5AR2 at scalp level you ain't going to get far because sufficient DHT will still be produced at other sites in the body. This will go into circulation and will attach to the DP AR through the blood. I think your heart pumps your blood around not ?

We can actually also understand this as on the scalp 5AR1 expression is way more prevalent and expressed in the scalp;



As you know finasteride has no effect on 5AR1. Furthermore highly contradicting studies are found about 5AR2 in terms of the micro environment of the hair follicle. Some older studies say that 5AR2 expression is found in the dermal papilla but some later studies show that 5AR2 expression is minimal there to non existent. For instance a recent one;



Anyway if "local" activity was such a predominant factor then why does finasteride work in most people while 5AR1 is by far the most active enzyme in the scalp? Can you explain? Considering that finasteride has no impact on 5AR1?

Also on a genetical level there is really nothing in terms of the 5-reductases in terms of the pathology of androgenetic alopecia. The androgen receptor is.

Local androgen receptor blocking would be enough, local 5-reductase blocking would be not. Simply because DHT is still being produced at other local sites, and the DHT will still find it's way to the dermal papilla. If you block the androgen receptor however DHT will never bind to the hair follicle.

That is why topical AR antagonists with a good safety profile are so much more exciting than finasteride.

Anyway topical finasteride will go systemic, there is no other way around and there are no magical vehicles. The dose response curve as mentioned here by FTL is a factor and metabolism of the compound can't occur quickly enough before going systemic.

Completely agree.

What do you think about CB's potential considering it acts on that level? Am I right in assuming CB could be used in a much higher concentration to almost completely block androgen receptors without causing side effects, or am I missing something?

[Swooping]

I disagree, I don't think it's clear at all that 5AR2 in other tissues will affect hair follicles. The DHT that is in your bloodstream is a small amount that is spillover from target tissues and is tightly bound to SHGB...

It's not 5AR2, it's DHT. Oral medications like finasteride and dutasteride work that well because they actually decrease serum DHT. I don't exactly understand what you mean by "spillover"?

if you are going to only inhibit 5AR2 at scalp level you ain't going to get far because sufficient DHT will still be produced at other sites in the body. This will go into circulation and will attach to the DP AR through the blood. I think your heart pumps your blood around not ?

We can actually also understand this as on the scalp 5AR1 expression is way more prevalent and expressed in the scalp;

The predominant form of 5alpha-reductase (5aR) in human scalp is 5aR1.

As you know finasteride has no effect on 5AR1. Furthermore highly contradicting studies are found about 5AR2 in terms of the micro environment of the hair follicle. Some older studies say that 5AR2 expression is found in the dermal papilla but some later studies show that 5AR2 expression is minimal there to non existent. For instance a recent one;

Abstract: Androgens regulate hair growth, and 5alpha-reductase (5alphaR) plays a pivotal role in the action of androgens on target organs. To clarify the molecular mechanisms responsible for controlling hair growth, the present study presents evidence that the human follicular dermal papilla cells (DPCs) from either beard (bDPCs) or scalp hair (sDPCs) possess endogenous 5alphaR activity. Real-time RT-PCR revealed that the highest level of 5alphaR1 mRNA was found in bDPCs, followed by sDPCs, and a low but detectable level of 5alphaR1 mRNA was observed in fibroblasts. Minimally detectable levels of 5alphaR2 mRNA were found in all three cell types.

Anyway if "local" activity was such a predominant factor then why does finasteride work in most people while 5AR1 is by far the most active enzyme in the scalp? Can you explain? Considering that finasteride has no impact on 5AR1?

Also on a genetical level there is really nothing in terms of the 5-reductases in terms of the pathology of androgenetic alopecia. The androgen receptor is.

Local androgen receptor blocking would be enough, local 5-reductase blocking would be not. Simply because DHT is still being produced at other local sites, and the DHT will still find it's way to the dermal papilla. If you block the androgen receptor however DHT will never bind to the hair follicle.

That is why topical AR antagonists with a good safety profile are so much more exciting than finasteride.

Anyway topical finasteride will go systemic, there is no other way around and there are no magical vehicles. The dose response curve as mentioned here by FTL is a factor and metabolism of the compound can't occur quickly enough before going systemic.

[KO1]

5AR2 is located in many tissues and so is DHT is produced in many tissue. The 5AR2 located on the scalp is only a fraction of the 5AR2 that is located somewhere else in tissue.

This would still leave much of DHT that is located in the blood serum to bind to the dermal papilla.

It would probably be effective but far less when it's going systemic, which it is going to do anyway.

I disagree, I don't think it's clear at all that 5AR2 in other tissues will affect hair follicles. The DHT that is in your bloodstream is a small amount that is spillover from target tissues and is tightly bound to SHGB...

[GSD]

You don't need systemic presence of fin, however, you can't stop it from doing so. Even if a little amount enters the blood stream, the dose-response curve is such that it will cause side effects. That's why things like CB work, without sides.

+1

[Swooping]

That's the thing though, *my understanding* is that DHT is something that is locally active in the target tissue, while the DHT that is floating around is spillover from the target tissue and in smaller amounts. If that is true then I don't think we would need systemic presence of fin.

5AR2 is located in many tissues and so is DHT is produced in many tissue. The 5AR2 located on the scalp is only a fraction of the 5AR2 that is located somewhere else in tissue.

This would still leave much of DHT that is located in the blood serum to bind to the dermal papilla.

It would probably be effective but far less when it's going systemic, which it is going to do anyway.

[FearTheLoss]

You don't need systemic presence of fin, however, you can't stop it from doing so. Even if a little amount enters the blood stream, the dose-response curve is such that it will cause side effects. That's why things like CB work, without sides.

[KO1]

That's the thing though, *my understanding* is that DHT is something that is locally active in the target tissue, while the DHT that is floating around is spillover from the target tissue and in smaller amounts. If that is true then I don't think we would need systemic presence of fin.

[Swooping]

Why do you say it needs to go systemic to be effective? 5AR2 is present in the scalp, so if it knocks it out locally, I don't see why we would need systemic presence of fin for it to be effective?

Well let me re-phrase that. It will surely be a whole lot less effective if it only stays local (it doesn't though). Let's assume you knockout all 5AR2 on the scalp you still have much DHT coming through the blood which can bind to the AR in the dermal papilla. So ideally you want to block systemic 5ar2 not only local 5ar2.

[KO1]

Topical finasteride will and needs to go systemic to be effective.

Why do you say it needs to go systemic to be effective? 5AR2 is present in the scalp, so if it knocks it out locally, I don't see why we would need systemic presence of fin for it to be effective?