Here's one of the topical finasteride studies!

[Bryan]

For all those of you who are fascinated by the prospect of applying finasteride or dutasteride topically (you know who you are! ), I thought I'd reproduce most of the contents of one of those (in)famous topical finasteride studies which have already been done in the past. After reading this particular one, you'll probably understand why I have such a rather blasé attitude toward the whole idea myself.

This one is "Topical 0.05% finasteride significantly reduced serum DHT concentration, but had no effect in preventing the expression of genetic hair loss in men", Rushton et al, from the book "Hair Research for the Next Millenium", 1996. I'm going to skip typing out the whole Introduction section, and get right to the meat of the matter by starting with the Materials and Methods section (I'm not leaving anything out here, so there's no use asking for additional information...this is all there is about what they did):

---------------------------
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)

Discussion

[....] In this study we employed a topical formulation of 0.05% finasteride in view of its presence in seminal fluid in subjects receiving oral therapy. Despite achieving serum DHT levels 40% lower than baseline, no hair regrowth occurred. Additional data from 10 males showed no further loss of hair in two subjects while on treatment; however the remaining eight withdrew after 12 months due to lack of efficacy (unpublished data).

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.
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There you have the meat of the study. I included that very last paragraph of the Discussion, mainly for laughs!! It shows how much we've learned about hairloss in the last several years! :wink:

Bryan

 

[CCS]

Thanks for the study, Bryan.

While it provides some info, it does not refute the use of topical finasteride.

To all my other comrades:

When bryan said that the end showed how much we've learned since the study, he was refering to the fact that the researchers wanted a drug that inhibits the type 1 5ar, and we now know that only the type 2 in the follicle is responsible for hair loss. (well, the type 1 may be responsible for 1-5% of the DHT that causes hair loss).

They also concluded that some of the men who did not respond well must not have much 5ar activity going on in their follicles, and did not respond because something else is causing their baldness. we now know that once the snow ball is rolling, we need minoxidil and copper peptides and other stuff to break the cycle from other angles. I also found it interesting that my 3/4 inch vellus hair is classified as vellus hair by them, since it is less than 30mm.

But back to the meat of this, before I bore anyone. In one year, 10% of non-vellus hairs fell out, and 3% of vellus hairs fell out, in a 1cm2 area. Since they had 174 hairs to start, that is pretty close to full average density. I looked at the propecia placebo group, and they lost 12.5 hairs over about 4 times that area, so they loss 1/4th as much. This suggests the carrier vehicle caused hair loss, unlike the minoxidil carier vehicle.

Bryan, did the study say what part of the head was measured? Propecia was on the top center.

Next, 40% is, not large by itself, but it could show that the scalp did not absorb much. Some graphs I saw said that 0.01mg/day reduced serum levels by 5%, and 0.05mg/day finasteride reduced serum levels by about 70% or so, more than propecia. So I assume that if 40% were reduced, this means that between 0.01 and 0.05mg/day was absorbed. Since the solution was 0.05%, and 4mL were applied per day, that means 200mg were applied per day. This shows an etremely low absorption rate. While the scalp could be saturated after the first dose, it still shows that at most 0.04g made it through.

I wonder what the vehicle was, but I also wonder if it matters. If the systemic dose is between 0.01 and 0.04mg/day, then my assumption that (200-400)/4 times that much getting absorbed by the follicle may not be accurate. Perhaps it is rensed away in the blood faster than the follicle can absorb it. Or perhaps something in the vehicle made the finasteride useless at the point of entry.

I could argue that maybe a 40% reduction has no effect, but that has no help since the main point here is that I thought the follicles should get a greater concentration dose than the rest of the body. Perhaps the finasteride did enter the follicles, but once the scalp blood concentration dropped, the finasteride in the follicles diffused back out into the blood. Perhaps a constant concentration is needed to keep it in the follicles. I'm still wondering if the vehicle caused hair loss. Some other vehicles had 0.76% absorption, so if 0.035mg were absorbed with them, they would need 4.6mg on the scalp. I think unless the 200mg vehicle was very bad, the low absorption was due to fast evaporation or to saturation of the scalp. Though saturation of the scalp would mean the follicles should get all they need if they even can absorb it topically. So that just leads to the time for absorption, the blood circulation speed, and maybe some inactive ingredients suppressing something.

Or it could be that a mega dose to the follicles 2 hours of the day followed by no finasteride in the blood is not the way to go. And a correction to my previous calculation of 0.01-0.04mg entering. That is how much entered systemically. Maybe some stayed in the follicles, though the hair loss results seem to indicate that it all diffused back out of the follicles. Maybe the hour or two of contact was not enough to get rid of sufficient 5AR.

 

[Bryan]

Bryan, did the study say what part of the head was measured?

Nope. I've already included every detail about the physical part of their experiment in what I've already posted.

Next, 40% is, not large by itself, but it could show that the scalp did not absorb much. Some graphs I saw said that 0.01mg/day reduced serum levels by 5%, and 0.05mg/day finasteride reduced serum levels by about 70% or so, more than propecia. So I assume that if 40% were reduced, this means that between 0.01 and 0.05mg/day was absorbed. Since the solution was 0.05%, and 4mL were applied per day, that means 200mg were applied per day.

You mean 2 mg, not 200 mg. 1 mL of a 0.05% finasteride solution would contain half a milligram of the drug.

Bryan

 

[Old Baldy]

Bryan, did the study say what part of the head was measured?

Nope. I've already included every detail about the physical part of their experiment in what I've already posted.

Next, 40% is, not large by itself, but it could show that the scalp did not absorb much. Some graphs I saw said that 0.01mg/day reduced serum levels by 5%, and 0.05mg/day finasteride reduced serum levels by about 70% or so, more than propecia. So I assume that if 40% were reduced, this means that between 0.01 and 0.05mg/day was absorbed. Since the solution was 0.05%, and 4mL were applied per day, that means 200mg were applied per day.

You mean 2 mg, not 200 mg. 1 mL of a 0.05% finasteride solution would contain half a milligram of the drug.

Bryan

I've seen that study you posted earlier. I read it from an alt.baldspot post you made.

It's like this for me Bryan: Topical finasteride/dutasteride appears to be so variable in result that it's a crap shoot as to how an individual will respond.

Some might respond favorably, some might respond negatively and some might not respond. My wild guess is most will respond favorably. Due to internal effects only? Don't know, it might have an effect locally also.

I simply can't say more than that Bryan.

I don't think it's as "dangerous" when applied topically vs. taken orally IMHO. That's where I make my "quantum leap" (i.e., systemic absorption is minimized and topical metabolization occurs).

 

[powersam]

I being something of an optimist would like to see the study that actually worked.

 

[CCS]

me too. i want to see a study where hair growth occured and serum DHT levels were only moderately lowered.

i feel so lame right now. I look at all the threads, and they all have my username as the last person to post. it just shows I have no life.

 

[Old Baldy]

I being something of an optimist would like to see the study that actually worked.

Power, I'll repost the favorable study:

The instructions from that study were as follows:


"Fifteen tablets of finasteride (5 mg each) were triturated
(ground into a fine powder) and then wetted with 2 mL of
propylene glycol. The mixture was incorporated into Dermabase
(Paddock Laboratories, Inc.) by levigation (that is, mixed evenly
by high-speed mixer and gradually incorporated). The final
cream contained 0.25% finasteride."


And here's the abstract:


Endocr Pract 2001 Jan-Feb;7(1):5-10
Finasteride cream in hirsutism.
Lucas KJ.


OBJECTIVE: To determine, in a preliminary study, whether women
with hirsutism attributable to various causes would benefit from
treatment with finasteride cream. METHODS: Finasteride cream
(0.25%) and placebo cream were administered to eight women
with various degrees of facial hirsutism. The two creams were
used on opposite sides of the face in an area of excessive hair
growth. The side chosen for the finasteride cream versus placebo
was randomized and blinded. In a 1 cm2 area on each side of
the face, hair counts were done every 2 months throughout the
6-month study period. Hair thickness was also measured.
RESULTS: Hair follicles respond to testosterone by the conversion
of this androgen to dihydrotestosterone through the action of
5a-reductase. Finasteride partially blocks this enzyme. Because
of the easy solubility of this medication through the skin, a cream
applied to the area of hair growth would be expected to decrease
hirsutism locally. After a 6-month period, mean hair counts
decreased significantly from 27.5 to 15.5 (P<0.05) in the
finasteride-treated sites but showed no significant change
from baseline in the placebo-applied sites. Moreover, the mean
thickness of the measured hairs (in hundredths of millimeters)
was significantly different between the placebo and finasteride-
treated sites (4.33 versus 3.11, respectively; P<0.001).
CONCLUSION: In this study of women with facial hirsutism,
topically applied finasteride significantly decreased hair growth
and thickness, and no adverse effects were noted.


Mike

It doesn't provide DHT in serum numbers but the side of the face where the placebo was applied had no effect(s).

That could mean there wasn't much systemic absorption.

 

[CCS]

yeah, and the funny part is they did not discard the powder. I wish I knew what was in that cream, but I think a time released effect is key. 0.25%. I wonder how many grams was applied. All we know is that there was some PPG. The hyroalcohol solution in the other study with 0.76% absorption did not mention PPG, and the failed study bryan quated did not mention the vehicle either. This is why it is hard to know what works. The research has been done, but they are not reporting it.

We can still use people who get systemic side effects. Instead of just asking what dose gives them side effects, we need to recruit volunteers to try different vehicles for 2 weeks on and two off, or however long it takes for sides to come and go, and tell us which one gives side effects with the lowest topical dose. Actually even that does not solve the problem. I'll have to think about this some more. We need to measure the time release rate. If it takes days to get the side effects, then we don't know if it all entered their system in minutes or if it was released over hours. So the volunteers might not help us there. They can just tell us wether anything is being absorbed and what percent. In fact, we can have them take small doses of oral finasteride and record what sides they get at each dose, and then tell us which side effects they get with each topical dose, and then we can guess how much finasteride was absorbed systemically. It is cheaper than us getting DHT serum tests after every topical application. The time release may be important because I don't know how soon finasteride enters cells it would diffuse back out if there is not more finasteride outside the cell diffusing in. I think that since most DHT is destroyed within hours of 5ar being shut down, it shows that finasteride would fall out soon. However, if it can shut down all 5ar in a few hours of application, we would not need finasteride absorption the remaining 22 hours, so it would not matter if the finasteride left the cells. we just need to know how long it takes for finasteride to react with most 5ar, and build a vehicle that will deliver finasteride for at least that amount of time, which I think is 2-3 hours.

 

[CCS]

I doubt a purely water and alcohol vehicle would last 2 hours. It would probably last 30 minutes to an hour tops. minoxidil has a burst for I'm guessing 40 minutes, and then slows way down by 2 hours, and lingers slightly up to 4 hours. I think we just need slow it down a little with something else. I'm not sure what.

 

[Old Baldy]

Bryan: I'd like to hear your take on Merck filing a patent a few years ago stating theraputic doses of finasteride. can be delivered topically to thwart systemic effects?

(Note: The Merck patent doesn't specifically say what I've "condensed" above but the entire patent is presented in a way that I can only conclude is meant to give methods of delivering smaller theraputic doses of finasteride., (i.e.,topically), so as to reduce systemic effects. In other words, IMHO, that's the ENTIRE point of the patent.)

http://www.hairlosstalk.com/newsletter/article167.htm

I'd also like to know why you have such a negative opinion of topical finasteride./dutasteride.? I ask this now that it is the year 2006.

 

[Old Baldy]

College: Read the Merck patent I linked above and let us know your thoughts.

 

[Felk]

I'd also like to know why you have such a negative opinion of topical finasteride./dutasteride.? I ask this now that it is the year 2006.

I'd love to hear an answer to this, as well

Also, I read this at hairsite as being new study about topical fina and liposomal penetration. Im not sure if it's actually new, but thought i'd post it.

http://www.hairsite4.com/dc/dcboard.php ... 5422&page=

"this study shows some interesting things:

- liposomes are able to target the pilosebaceous unit
- liposomes penetrate 300 % better than alcoholic solutions
- the idea of using finasteride as a topical becomes more popular
- finasteride can be brought directly to the pilosebaceous unit using the right size liposomes"

 

[CCS]

merk patent

The first part is just them outlining everything they patented, which is interesting because they tell use several other chemicals that would work like finasteride. The patent is good for hurituism and acne has a loop hole. If more than 5mg per day is used, another company may sell it. Perhaps that means 5mg/day is guaranteed to give side effects to those who get them from oral finasteride.

In [0003], they are talking about how oral antiandrogens can cause feminization and make the testes produce more testosterone.
In [0004] they point out that finasteride does not cause the testes to produce mroe because it only has a local effect in target organs.
The patent sounds like it includes dutasteride, but becuase it only includes alkyl substitutioins, dutasteride is not included. Merk does not seem to think a dose below 0.01 mg/day topically would work. Actually, in [0011], it looks like they are patenting dutasteride for topical use. Can they do that?
The synthesis of finasteride is described in U.S. Pat. No. 4,760,071.
Merk is also patenting a potassium channel opener.
They cover every method from skin injections to shampoos to sprays. Very thurough.
Topical pharmaceutical compositions useful in the method of treatment of the present invention may include about 0.001% to 0.1% of the active compound in admixture with a pharmaceutically acceptable carrier.
The FT-IR spectrum shows bands at 3431, 3237, 1692, 1666, 1602 and 688 cm-1
The FT-IR spectrum shows bands at 3441, 3215, 1678, 1654, 1597, 1476 and 752 cm-1
Those last two lines are useful to me when check drugs for authenticity.
At the end they state how they isolate 5ar, unless I misread that. They also say how they count hairs on heads. I don't know why this info is in the patent and what legal implications it has.

 

[CCS]

looks like they were thurough, but I don't understand the patent reasons why they would mention all the delivery methods if they had already patented the drug. They only mentioned 1-4 applications per day. Does that mean there is a loophole for using it 5 times per day? If not, then why did they mention the 1-4 times per day? I tells me that they think 1 time per day might not be enough, but they don't think more than 4 times per day will be needed.

 

[Bryan]

Bryan: I'd like to hear your take on Merck filing a patent a few years ago stating theraputic doses of finasteride. can be delivered topically to thwart systemic effects?

I think they did that mainly as a pre-emptive strike to keep other parties from taking out a patent on it in the future. I doubt that they actually considered it to be a viable treatment.

I'd also like to know why you have such a negative opinion of topical finasteride./dutasteride.? I ask this now that it is the year 2006.

???

For the reasons I've been saying for years and years: it just doesn't appear to be a very good treatment. The results of topical finasteride studies have been all over the map. In one study it seemed to work as intended, but in others, it didn't seem to work at all. The lack of consistency is puzzling and disturbing.

Bryan

 

[Old Baldy]

Bryan wrote:

For the reasons I've been saying for years and years: it just doesn't appear to be a very good treatment. The results of topical finasteride studies have been all over the map. In one study it seemed to work as intended, but in others, it didn't seem to work at all. The lack of consistency is puzzling and disturbing.

I thought you might have changed your mind a little after considering the abstract Felk and I posted that was conducted in May of 2006? See Felk's link posted above.

As to the Merck patent, maybe you're correct, however, they did go a long way around the barn if that's all they were doing IMHO.

 

[powersam]

old baldy - thanks for posting that study.

For the reasons I've been saying for years and years: it just doesn't appear to be a very good treatment. The results of topical finasteride studies have been all over the map. In one study it seemed to work as intended, but in others, it didn't seem to work at all. The lack of consistency is puzzling and disturbing.

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.

 

[CCS]

merk thought there was enough of a possibility to warrant spending money on a patent.

 

[Felk]

merk thought there was enough of a possibility to warrant spending money on a patent.

Well at least that's what we hope...

Two things I still need to know about topical finasteride:

In the successful studies, was it applied once or twice a day?

Could spironolactone be added to a topical finasteride mix without the drugs reacting, or is this probably too risky?

 

[Bryan]

Bryan wrote:

For the reasons I've been saying for years and years: it just doesn't appear to be a very good treatment. The results of topical finasteride studies have been all over the map. In one study it seemed to work as intended, but in others, it didn't seem to work at all. The lack of consistency is puzzling and disturbing.

I thought you might have changed your mind a little after considering the abstract Felk and I posted that was conducted in May of 2006? See Felk's link posted above.

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! :wink:

As to the Merck patent, maybe you're correct, however, they did go a long way around the barn if that's all they were doing IMHO.

With the deep pockets that Merck had at that time, I think it was no big deal at all for them to do that, "just in case".

Bryan