Here's one of the topical finasteride studies!

[Bryan]

but Bryan the lack of consistency in the studies would mean that its topical effect is still unknown rather than useless. if you could find out why that that study showed local effect with no systemic effect then it could turn into a great treatment. the potential would seem to be there, just needs more research and fine tuning.

Yeah, just like there's a potential that we could have peace in the Middle East.

If anybody manages to figure out how to make topical finasteride work reliably and consistently, I'm sure we'll all hear about it. I'll be the first one to offer them a tip of the hat. But until then, I'm not holding my breath while waiting for that to happen.

Bryan

 

[Old Baldy]

Bryan wrote:

Oh, I dunno. I find that abstract to be mildly interesting, but it's still a far cry from applying liposomal finasteride in vivo and testing for local versus systemic effects on hair follicles. I would have told those guys, ok, that's a good first step, now get back to us when you've completed the next ones!

Bryan: Bear with me on this one.

My thoughts are: (1) if the finasteride. or dutasteride. absorbs at 2.3 percent in liposomes, and 0.76 percent with hydroalcohol, into the pilosebaceous unit, isn't that pretty good compared to what would be delivered with your typical oral dose?, (2) is the amount of finasteride. or dutasteride. reaching the PU via the bloodstream more beneficial than reaching it via topical administration?

I mean, does it matter whether the medication reaches the PU via the bloodstream vs. topical administration? Is there some metabolization involved here that I don't know about?

 

[CCS]

2.3% is much better than the oral amount. Even 0.76 percent is better. The problem is although that much enters the skin and does so through the pores, it does not stay there. Sure the hair gets first crack at it, but I don't know if it passes by the hair long enough for the follicle to get saturated. Most of it likely goes into the blood stream. Finally, once the blood rinses most of the finasteride away, the blood concentration of finasteride outside the follicle is very low, which causes osmotic forces that may draw some of the finasteride back out of the follicle into the blood. With an oral dose, the blood is loaded with finasteride, so that even if some slips back out of the follicle, more finasteride also diffuses through into the follicle in an equlibrium. There is no difference in the metabolism. I would like to see a close up of the micro anatomy of the follicle and verify that the flow of finasteride does wash over the root and its arteries before dumping into the the larger veins.

I've seen graphs of DHT concentration vs time after various oral doses of finasteride, and I'm sure Bryan knows which ones I'm talking about. unfortunately, they showed 28 days, and it was hard to see what happens minute by minute in the first few hours after an oral dose. Once most of the 5ar2 is shut down, it would not matter if the finasteride diffused out of the follicles. I'm sure that blood finasteride slows 5ar2 re-build up more, but the process is slow enough that you just have to knock it out once every day or two and you should keep DHT levels low. Old Baldy, if you want maybe you can search through Bryan's old posts and see if you find some grafts that show the hour by hour serum or scalp DHT levels after a dose of finasteride, and also find a good picture of a follicle and sebum gland and sweat gland with enough detail that we can see the path that a drug might take into the skin and to the blood vessels.

we need a vehicle that will deliver a good percent over time (at least half a percent total) but will do it slowly, like over a 2 hour period. this is better than all the drug going into the skin and dumping into the blood and the follicle not having time to absorb and keep some of the finasteride long enough for all the 5ar2 to react. second, in some finasteride tests, the finasteride group did worse than the minoxidil placebo group, indicating that the vehicle probably caused hair loose. we need to avoid such vehicles. an oil based one should not cause hair loss, but i don't know what the absorption rate would be. the minoxidil solution does not cause hair loss, but I don't know if the absorption rate (vs time, not percent) is too fast to give the follicle a steady supply.

minoxidil goes into blood vessel walls, which are stationary. finasteride is mobile and attaches to blood plasma proteins. so dumping minoxidil into the skin is not as big a problem as dumping finasteride into the skin.

 

[Bryan]

Bryan: Bear with me on this one.

My thoughts are: (1) if the finasteride. or dutasteride. absorbs at 2.3 percent in liposomes, and 0.76 percent with hydroalcohol, into the pilosebaceous unit, isn't that pretty good compared to what would be delivered with your typical oral dose?

I'm not sure. A critical issue is what happens to that finasteride or dutasteride AFTER it reaches the vicinity of the pilosebaceous unit. Does it actually get absorbed into the hair follicle cells themselves, or does a lot of it get into the bloostream right away?

(2) is the amount of finasteride. or dutasteride. reaching the PU via the bloodstream more beneficial than reaching it via topical administration?

I mean, does it matter whether the medication reaches the PU via the bloodstream vs. topical administration? Is there some metabolization involved here that I don't know about?

Not to my knowledge, but I think the important question is what I asked above.

Bryan

 

[CCS]

Someone find the blood flow rate to the scalp in mL/min.

I believe the problem with topical finasteride has two branches:

A: problems for people with finasteride side effects: 1. It leaves the scalp into the blood stream to fast. 2. Once it stops entering through the skin, and the blood has rinsed the excess into the main body and fresh blood is passing by, diffusion (always in the direction of higher concentration to lower concentration) causes finasteride to diffuse back out of the follicle and into the blood before it has bonded with most 5ar2 in the follicle.
B: problems for people who want a huge concentration in their scalp, but
don't want a huge concentration in their body: 1. Not a high enough percent of finasteride is absorbed through the skin, wasting most of it. 2. the same problems as in group B.

Goals:
To avoid side effects, most sensitive people need less than 0.04 mg entering their body, and probably as little as 0.01mg, based on graphs of DHT inhibition vs dose, and assuming DHT inhibition causes the side effects. However, they want the same concentration in their scalp that betweem 0.05 and 1mg orally would give.
Scalp megadosers would like to have the concentration in their scalp that 30mg orally would give, to REALLY inhibit DHT, but they'd prefer to pay for and subject their body to 1mg per day.

Both need it enter the scalp slowly and evenly over at about 3 hours. If it is all delivered at once, it just goes into circulation and then the follicle has none around unless the body is full enough for some to come back. It takes about 1-3 hours for most 5ar2 to bond to finasteride (Bryan, is that right?), so our vehicle must deliver the dose slowly over time, to keep the finasteride concentration in the micro arteries around the follicles high enough to balance the finasteride diffusing out of the follicles into the micro veins.

We can safely assume that all finasteride that enters the skin will go systemic eventually. Our goal should be to take advantage of the small volume of the scalp compared to the body and the flow rate of the drug into the scalp so that the concentration of drug in the small scalp is greater than the concentration in the body, even though there is more drug in the body than in the scalp.

Most of the drug enters through the pours. That is common pharmaceutical knowledge for most topicals. While a good diagram might tell us how much finasteride is likely to diffuse into the follicle directly instead of first into the blood, we know that if it has to leave the scalp eventually, it will leave through a micro vein. When the drug first enters, it will diffuse to the follicle and other structures, and it will diffuse down to the micro arteries and veins in equal amounts (50-50 chance of each). The half that enters micro veins is wasted, and the half that enters micro arteries will enter follicles and other structures so that the whole scalp is hit. Remember that veins go from the cells to the heart and arteries go from the heart to the cells.

I think the whole body has a volume of 75 L (for a 75kg person) and the blood has a volume of 11 L (please correct me on that).

For people with side effects, if everyone can handle 0.01mg per day, then that is the most we can have them absorb per day. We need a vehicle that will give them 0.01mg in 3 hours. So if our vehicle has a 0.5% penetration rate, then each dose of solution should have 2mg, which is affordable. We need a vehicle that is steady over 3 hours and has at least a 0.2% penetration rate, which is one proscar pill per day. This is very feasible.

Next, we have to know if this dose will be therapudic. In order for it to be therapudic, the finasteride in the blood in the micro arteries must be kept at at least the same concentration that 0.05mg/day orally would give. I'll say 0.2 mg/day orally, just to be safe, and will throw out the 60% absorption of the gut for further safety. We know that half our dose will be wasted since it will go straight into the micro veins. We need to know the blood flow rate of blood in the male pattern baldness part of the scalp. Someone needs to find the blood flow rate to the whole scalp, in mL per minute, which is probably in a reference somewhere.

We need to multiply the blood flow rate times 3 hours to know how much blood will flow through the follicles in 3 hours. Next, we divide 0.2mg by 75 liters, or make that 50 liters to be safe and account for bones, to get the finasteride concentration that is therapeudic. Next, we multiply this concentration by the 3 hour blood volume to get the mg finasteride that is needed to be therapudic. For the topical to work for people who are sensitive to finasteride, the number must me less than 0.01 mg.

Now 0.01 mg may be an underestimate. Some people may handle 0.05 or even 0.1 mg/day. Also, the assumption of 0.2 mg/day for therapudic needs is an overestimate, since 0.05 mg/day lowers DHT as much as 1mg/day, and any DHT inhibition is better than nothing, especially if it can be applied at the same time as minoxidil just by modifying minoxidil's vehicle.

Find me the blood flow rate through through the scalp (and I'll divide by 2 or 3 to just have the male pattern baldness area) and find a vehicle that has at least 0.2% penetration steadily over 3 hours, and I will tell you how much finasteride to put in it to give people with oral side effects the same benifits as everyone else, but without the side effects.

 

[Old Baldy]

Thanks for the info. Bryan and College. College I understand most your post but don't have the numbers you seek. Are you assuming all the finasteride./dutasteride. placed on the scalp makes its way beyond the strateum corneum (sp?)? I assume some does not make its way into the "scalp" and never gets absorbed?

Bryan wrote:

I'm not sure. A critical issue is what happens to that finasteride or dutasteride AFTER it reaches the vicinity of the pilosebaceous unit. Does it actually get absorbed into the hair follicle cells themselves, or does a lot of it get into the bloostream right away?

I understand, (agree 100 percent) and that's what I'd like to know.

Another question: Since I'm a layman I don't understand why finasteride. going into the bloodstream and back to the follicle would work, but finasteride. passing into the PU via topical application wouldn't work also.

The finasteride./dutasteride. delivered topically is "there" much like it would be "there" when it comes back via the bloodstream isn't it?

This is one area of metabolism I don't understand. Well, one that is relevent to what we're discussing. There's alot more about metabolism I don't understand!

I guess what I'm asking is why in the world would the cells absorb finasteride./dutasteride. coming via the bloodstream but not when they enter the follicles topically?

Maybe I need to look more closely at a diagram of the follicle? I assume you might be saying the PU isn't "close enough" to be 100 percent sure that what enters the PU will generally enter the follicle also (i.e., DP area)?

 

[Bryan]

Another question: Since I'm a layman I don't understand why finasteride. going into the bloodstream and back to the follicle would work, but finasteride. passing into the PU via topical application wouldn't work also.

The finasteride./dutasteride. delivered topically is "there" much like it would be "there" when it comes back via the bloodstream isn't it?

I don't have any a priori reason to expect it not to work; the only question is, DOES it in fact work? Or does it get absorbed into the bloodstream first, before the cells absorb it?

Maybe I need to look more closely at a diagram of the follicle? I assume you might be saying the PU isn't "close enough" to be 100 percent sure that what enters the PU will generally enter the follicle also (i.e., DP area)?

Yeah, something like that. What if it rapidly diffuses into the bloodstream before the cells themselves can grab it?

BTW, all this speculation reminds me of the unusual theory that Pearson & Shaw had about the ideal topical vehicle for use with steroids like androgens and estrogens (and, presumably, azasteroids like finasteride and dutasteride). They explained why they thought that DMSO was the ideal vehicle for the scalp! I don't want to go into it all here, but if you have a copy of "Life Extension", go read the chapter on male pattern baldness. They describe all their reasoning in there. If "College" reads it, he'll go nuts over it! :wink:

Bryan

 

[CCS]

I don't know what the stratum corneleum is. I assume it is the outer protective layer of skin that is the strongest barrier. You already gave me a study that said alcohol vehicles have 0.76% penetration through (we assume) the pours. I need a slower vehicle that has at least 0.2% penetration (just so people don't have to buy more than one proscar pill per day).

I'm not counting on the follicle being close enough for finasteride to diffuse to it. I was counting on finasteride diffusing up to the walls of blood vessels and entering them through the walls. Since half are arteries and half are veins, I figured half would enter arties that lead to some follicles, and that since the arteries are small, the concentration would still be high.

My plan has a big flaw that I am now aware of. What if the finasteride does not reach the blood vessels first. What if it enters the sweat glands and sebum glands, etc, and once inside, goes to the blood vessels. It won't go up stream into an artery, so it will instead go down stream into a vein. Then away it goes, never reaching the follicles.

I think I can get or estimate those flow rates myself. We do need a diagram though to get some idea of how much might diffuse to the follicle and how much will enter other cells that lead to veins (which go to the hear and not other cells) and how much might just diffuse randomly up to some blood vessels (which may be veins or arteries) and split 50-50, with some of the finasteride from the micro arteries travelling micro meters to a follicle or other skin structure. I'm not planing on benefiting from finasteride that enters a vein, goes to the heart, gets diluted, and comes back to the follicle. By then it should be diluted, and if it is not too diluted to be therapudic, then that means the body got a high enough concentration to get side effects. That is why I'm not counting the finasteride that enters micro veins in the scalp. I'm counting on finasteride diffusing through the scalp from the pore structure and entering blood vessels randomly, and the half that enters the micro arteries travelling just milimeters before entering more cells and then maybe going back into veins and away.

If the finasteride stays in the sebacious pore structure, and exits into a vein, then my plan will not work.

Finasteride has to leave or else it will build up or saturate the scalp so that no more can enter.

When I take 1mg/day, all the blood has a therapudic concentration of finasteride. Molecules enter and leave the cell randomly and in steady state all the time. For every molecule that leaves, another enters, until the finasteride is metabolised by the liver in several hours. When the blood concentration drops, finasteride keeps diffusing out as normal, but much less enters than what is exiting. This is finasteride as long as finasteride has had 1-3 hours to bind with all the 5ar2. The finasteride entering the cells enters through the micro arteries around the cells. Even if an alcohol vehicle gets finasteride to the cell arteries, it does not keep it there the needed 3 hours. In 30 minutes, maybe only 1/3 of the 5ar2 is bonded. Then the cell goes empty of finasteride. I'm thinking though that perhaps the finasteride does not even enter the arteries, and goes straight into the veins and comes back diluted.

If this is the case, a good penetration enhancer may be needed, one that will let finasteride diffuse through cells to the blood vessel walls, instead of following the path of least resistance all the way through the pore to the vein. But if we can see a diagram that not only shows the structure, but the blood vessels and pathways in the structure, we can make more educated guesses.

 

[CCS]

blood flow

I found out that each beat of a heart at 72 beats per minute has about 70mL, so that is about 5000mL per minute. I could do an approximation that the scalp gets an amount proportional to its volume, but I heard that the brain gets the most, that balding scalp has worse circulation (though fixing that does not remove baldness) and I'm sure the muscles get a disproportionate amount. I could still use 1/4 their volume shair as lower limit, but since slower blood flow would help our drug, I think assuming volume proportionate blood flow would be sufficiently strick. So the area we are treating is 200mL and the body is 80L, then 1/400 x 5000 mL/min = 12.5 mL/min, x 3 hours x 60min/1hour = 2.250 L of blood in 3 hours as an upper estimate, and 5.1 L as a lower estimate.

Since an oral dose is absorbed by all cells and not just the body, the volume we are working with is 50 L (a lower estimate to be safe), which is less than 80 L for the whole body. So if we want 0.2mg/50L = 0.004mg/L finasteride flowing past the follicles. This is 0.004mg/L x 2.25 L = 0.009 mg in the arteries. Suppose 1/4 of the amount in the scalp enters the arteries or diffuses to the follicle, and the rest goes directly into veins. Then 0.009 mg x 4 = 0.036 mg enters the body. This figure is from strict over and under estimates aimed at finding the maximum likely amount that would enter the body in 3 hours to get the dose to the follicles we want.

I saw a graft that showed that 0.05 mg orally, which is 0.03 mg absorbed, inhibits as much DHT as 1mg orally per day. But 0.01 mg inhibits only 5% of DHT. So if we aim to give the follicle the same effect that 0.06 mg orally would have, then the body would have 6/20 x 0.036mg = about 0.01mg per day, which should not give anyone side effects because it only lowers systemic DHT 5%.

It seems like according to my estimates, a topical dose can give the scalp 6 x the systemic concentration for 3 hours, and maybe as much as 12 times the concentration. 0.06 mg/day in the scalp is like 0.1 mg orally because only 60% is absorbed orally. If a slow vehicle as 0.3% penetration, then we would need 2 mg per dose on the skin, once per day. This is feasible. We just need to know if the finasteride as the chance of penetrating a blood vessel wall such as an artery, which is thicker than a vein wall.

As for people who do not have side effects, and want to use high doses of dutasteride perhaps, the 6:1 ratio could mean that 15 capsules per month gives their scalp the dutasteride concentration that 2.5 mg per day would give, while their body only gets the concentration that 0.83 mg per day orally would give, and their pocket book pays for only 15 capsules per month. dutasteride absorption rates may be different from finasteride though.

I'm really skeptical though about the finasteride entering an artery instead of a vein.

 

[Old Baldy]

College the pilo sebaceous unit is pictured in the link below:

http://www.lucid-tech.com/vivaScope/

It is my opinion that the researchers in the study (i.e., where they concluded 0.76 percent of the finasteride. in the hydroalcohol vehicle penetrated into the PU) meant it was there for use by EITHER the seb. glands and/or follicle.

Bryan's not so sure that it is absorbed into the follicle. Maybe it isn't but the researchers must have thought that this is assumed. I assume that medical professionals take this for granted (i.e., if a chemical makes its way into the PU it can effect follicle and seb. gland growth, etc.)?

That's why I got excited when I saw the good penetration results for liposomes and hydroalcohol vehicles.

Look at the picture and remember professionals view the PU as the entire hair growing "apparatus". It isn't a quantum leap in logic to think if something gets into the PU it will have an effect on the follicle and seb. gland (i.e., if the chemical has any potential in the first place).

It should be absorbed IMHO. Will it just pass through like a race car on a race track? I doubt it but can't prove it. The way I see it is the 0.76 percent they were talking about did not "race through". :wink:

The finasteride. was there to be used by the entire PU? Otherwise, what's the point of the study in the first place?

Now, maybe another portion of the finasteride. "raced" through other tissues? :shock:

 

[Bryan]

It is my opinion that the researchers in the study (i.e., where they concluded 0.76 percent of the finasteride. in the hydroalcohol vehicle penetrated into the PU) meant it was there for use by EITHER the seb. glands and/or follicle.

Bryan's not so sure that it is absorbed into the follicle. Maybe it isn't but the researchers must have thought that this is assumed. I assume that medical professionals take this for granted (i.e., if a chemical makes its way into the PU it can effect follicle and seb. gland growth, etc.)?

I want everybody to be clear about where I'm coming from on all this. I don't doubt that at least SOME topically-applied finasteride makes it into the hair follicle and is utilized there, I'm simply questioning the relative percentages involved. Is it a significant or insignificant amount? We already know from the study I posted at the start of this thread that a significant amount of topical finasteride is NOT absorbed directly by hair follicles, because of the systemic effects that were observed (serum DHT was lowered by ~40% or so).

But if it eventually turns out that only a few molecules of finasteride here and there go straight to hair follicle cells after topical application and do their job there, while the rest of them get into the bloodstream and have the usual systemic effects, then what's the point of messing with it?

That's why I got excited when I saw the good penetration results for liposomes and hydroalcohol vehicles.

Before _I_ can get excited about it, I'll have to see evidence that it's having the desired effect that we all want: more "local" effect, and less systemic effect. Just the simple fact that the penetration into the vicinity of the pilosebaceous unit is better doesn't really prove that.

Bryan

 

[guybrush]

Did anyone notice that in the study with serum DHT supression subjects used 2ml of solution instead of the standard 1ml? That means a lot of water, which I believe can increase systemic absorption and reduce the time the drug stays in the skin. That could make the difference between the successfull italian study and this unsuccessfull one...

By the way there's another study finding transcutol P to enhance the transdermal absortion of finasteride...

 

[Ende]

Bump.

 

[John979]

Missing the forest for the trees:

"These findings suggest that in individuals in whom hair follicles have little or no type-II 5a-reductase activity, topically applied inhibitors like finasteride are unlikely to be effective. Oral Proscar (5 mg finasteride) is also unlikely to be effective unless metabolites with different specificity to 5a-reductase isozymes are produced. We therefore eagerly await the arrival of a type-I or mixed 5a-reductase inhibitor."

We therefore eagerly await the arrival of a type-I or mixed 5a-reductase inhibitor.

This is Dutasteride.

And it works topically.

 

[couldntthinkofaname]

Materials and Methods

Initial dosing studies were designed to establish the most effective topical concentration of finasteride with respect to serum DHT 5mg Proscar tablets were crushed to prepare the appropriate concentration suitable for topical dosing studies.

Males with genetic hair loss were selected on a named patient basis, and all gave their informed consent. Following a baseline blood test and medical examination, hair variables were assessed with the Unit Area Trichogram (a method with proven reproducibility) basely and, from the same sites, 12 months later. All blood tests were performed before 11 am following a 12 hr fast, with follow-up blood tests and medical examinations after 1, 4, and 12 months of therapy.

Results
Hormonal changes during dosing studies

The dosing study data are presented in Table 1 and Table 2. The results show that a twice daily application of 0.05% finasteride solution (2 x 2 ml) significantly lowers the serum DHT concentration, with only a marginal increase in DHT suppression being observed when the concentration was increased from 0.05% to 0.075% (data not presented).

Table 1.
Dosing data (mean, n=2) for topical 0.01% finasteride (2 x 2 ml daily) over a four week duration.

........................................ Week 0 ...... Week 1 ............. Week 4 ..... % Change
Testosterone (nmol/L) ..... 25.0 ........... 31.0 .................. 25.0 ............. 0%
DHT (nmol/L) ..................... 2.9 ............. 1.7 .................... 1.7 ............. -31%

Table 2.
Dosing data (mean +/- sd, n=9) for topical 0.05% finasteride (2 x 2 ml daily) over a 4 week duration

........................................ Week 0 ...... Week 4 ....... % Change ........ (paired t-test)
Testosterone (nmol/L) ...... 20.2 ......... 19.4 ............... -4% ................ NS
DHT (nmol/L) ..................... 1.8 ........... 1.1 ................ -39% ............... p<0.003

Hormonal and hair changes during topical 0.05% finasteride therapy
(Table 3)

During the treatment period significant suppression of the serum DHT was achieved in all individuals, with each remaining below the lower limit of normal (1.3 to 2.5 nmol/L) throughout treatment. In addition, no significant reduction in circulating serum testosterone or oestradiol concentration was found. The mean values obtained for total hair density (hair per cm^2) and non-vellus hair density are also presented. A vellus hair was defined as a hair less than or equal to 40 um in diameter, less than or equal to 30 mm in length.

Table 3.
Mean hair densities and hormonal values from 5 subjects treated with topical 0.05% finasteride for 12 months

Time (months) ........................ 0 ................. 12 ....... Significance ...... Normal Range
Total hair per cm^2 .............. 256 ............. 248 ............ NS ................ (256 - 359)
Non-vellus hair per cm^2 ..... 174 ............. 158 ............ NS ................ (232 - 325)
Testosterone (nmol/L) .......... 15.0 ............ 14.0 ........... NS ............... (10.0 - 35.0)
DHT (nmol/L) ......................... 1.42 ............ 0.85 ......... p<0.01 ........... (1.3 - 2.5)

i found this:

Objective: The effects on scalp and serum dihydrotestosterone (DHT) of different doses of a novel topical solution of 0.25% finasteride (P-3074), a type 2 5α-reductase, were investigated in men with androgenetic alopecia. Methods: Two randomized, parallel-group studies were conducted. Study I: 18 men received 1 mL (2.275 mg) P-3074, applied to the scalp once a day (o.d.) or twice a day (b.i.d), or 1 mg oral tablet o.d. for 1 week. Study II: 32 men received P-3074 at the dose of 100 (0.2275 mg), 200 (0.455 mg), 300 (0.6285 mg), or 400 (0.91 mg) μL or the vehicle o.d. for 1 week. Scalp and serum DHT and serum testosterone were evaluated at baseline and treatment end. Results: Change from baseline in scalp DHT was -70% for P-3074 o.d. and approx. -50% for P-3074 b.i.d. and the tablet. Serum DHT decreased by 60 - 70%. The doses of 100 and 200 μL P-3074 resulted in a -47/-52% scalp DHT reduction, similar to the 300 and 400 μL doses (i.e., -37/-54%). A -5.6% inhibition was observed for the vehicle. Serum DHT was reduced by only -24/-26% with 100 and 200 μL P-3074 and by -44/-48% with 300 and 400 μL P-3074. No relevant changes occurred for serum testosterone. Conclusions: The novel finasteride 0.25% solution applied o.d. at the doses of 100 and 200 μL results in an appropriate inhibition of scalp DHT potentially minimizing the untoward sexual side-effects linked to a systemic DHT reduction.



https://www.researchgate.net/public...one_in_healthy_men_with_androgenetic_alopecia