Attn: Bryan, regarding topical flutamide.

[diffuse propecia]

Do you know if a topical application of flutamide has any effect on hairloss that is caused by a local effect or are all results using topical fluta due to its systemic absorption?

 

[Bryan]

Do you know if a topical application of flutamide has any effect on hairloss that is caused by a local effect or are all results using topical fluta due to its systemic absorption?

I know of only three studies which examined that question scientifically, and they were all done with rodents (rats, mice, and guinea pigs). The early study that was done around the time flutamide was first released as a drug showed a mostly systemic route of absorption (there was a little stronger effect where the drug was actually applied to the animals, but only a little). The more recent Chen et al study showed an ENTIRELY systemic route of absorption in rodents (results were exactly the same at both the site of application, and the opposite side where it wasn't applied).

The recent Sintov et al study is the only one which claimed to find a "local" effect of topical flutamide in rats. However, I'm suspicious of the way they conducted the experiment. I don't fully trust their results.

 

[yvakin]

I found this but it looks like the study is fro 1979.

 

[Bryan]

topically applied medications are only systematically absorbed in minute quantities, a good example of this is topical minoxidil, topical minoxidil has a localized effect on the hair follicles, with very little systematic absorption, this is why most people do not experiance many side effects from topical minoxidil...

Years ago when I first got interested in hair loss, I was very interested in the question of to what degree (if any) that topical minoxidil was effective due to systemic absorption. Obviously, the only way to prove that fairly conclusively (one way or the other) would be to apply the minoxidil to only part of a balding scalp, while leaving another part of that same balding scalp alone as a control. While that rather obvious experiment doesn't appear ever to have been performed for common balding (androgenetic alopecia), I _have_ found a study that used that method to test its effect in alopecia areata. And guess what: it _did_ appear to show that at least PART of the beneficial effect for that condition was due to systemic absorption! While there was a little stronger effect where the drug was physically applied, it _did_ extend (at least a little) to the opposite side of the scalp where it wasn't applied.

My gut feeling is that topical minoxidil probably is benefical from a combination of BOTH those effects: some "local" effect, and some systemic effect.

however, those who take it orally have a much higher occurence of side effects because the systematic absorption is much higher, hence topical flutamide has a localized effect much like minoxidil.

Nope. See my post above about the animal experiments: topical flutamide clearly had a MAJOR systemic effect in those first two animal experiments. The Chen et al study in particular was OVERWHELMINGLY systemic.

 

[pproctor]

topically applied medications are only systematically absorbed in minute quantities, a good example of this is topical minoxidil, topical minoxidil has a localized effect on the hair follicles, with very little systematic absorption, this is why most people do not experiance many side effects from topical minoxidil, however, those who take it orally have a much higher occurence of side effects because the systematic absorption is much higher, hence topical flutamide has a localized effect much like minoxidil.

If memory serves, about 2-3 mg of minoxidil is absorbed from a typical topical application. This is not a lot compared to the 25-50 mg starter dose used for treatment of high blood pressure.

There is still some question about how much systemic absorbtion contributes to the hair-grow-inducing action of minoxidil. Again if memory serves, there are reports of patients taking as little as 5 mg per day of minoxidil getting some hair growth. So ya never know. In any case, the issue is probably moot since the level is well-below what will cause side effects. BTW, with proper cardiovascular support, people have survived taking multi-gram amounts of minoxidil in suicide attempts.

As for topical finasteride, flutamide, etc. the concensus these days is that most of their action is due to systematically-absorbed drug. This is not true of topical spironolactone, whose action seems purely local.

BTW, a common screen for systematic as opposed to purely topical action is the hamster. These animals have pairer androgen-dependent "flank organs" on each side. If a topical antiandrogen applied to only one side affects only that side, then it its action is though to be purely local. If it affects both sides, then its action is due to systemic absorbtion.

Peter H Proctor, PhD,MD

 

[Bryan]

I found this but it looks like the study is fro 1979.

Yep. But that study isn't particularly useful for our purpose, because it doesn't really test whether topical flutamide's main effect is "local" or "systemic". All it does is show that there is _some_ systemic absorption, without specifying how important that absorption is.

 

[Bryan]

from my understanding,The structure of the human skin prevents that drugs or cosmetics can penetrate the stratum corneum, the uppermost layer of the epidermis, not more then 0.01% of a hydrophilic (water and/or alcohol) formulated solution can be absorbed by the skin or substantially excreted into the bloodstream.

That may be true, but you have to keep in mind that it doesn't take very much absorbed finasteride or dutasteride to have a significant systemic effect!

If systematic absorption was high through the stratum corneum , it would preclude that topical finasteride or duasteride would be an effective alternative to oral adminastration,however studies have been conducted on topical adminastration of finasteride, and they showed less effective.

The results of topical finasteride studies have been all over the map: sometimes it seems to work a little, sometimes it doesn't seem to work at all, sometimes there's significant systemic absorption, sometimes there isn't any systemic absorption at all. It's all rather inconsistent and unpredictable.

 

[Bryan]

You are correct in stating that it does not take very much, however, it does take more than 0.01% to have significant systematic absorption.

The proof of the pudding is in actual experimental results. Do you want me to dig out some studies from my Study Stack which showed reductions in serum DHT and other systemic effects from topical finasteride, in both humans and animals?

 

[Bryan]

As I stated earlier many of these ''studies'' were not conducted using the proper scientific methodology. If a study had been conducted by the fda or another highly reputable source, that would be persuasive.

I see that you're a newbie here, so learn this right away: I don't base my opinions on the results of flimsy or disreputable studies! :smack:

 

[Bryan]

Below is the main graph from the Chen et al study. The nifty thing is that they tested BOTH flutamide and finasteride topically on hamsters at various doses, and BOTH drugs showed total systemic absorption.

 

[Bryan]

If memory serves, about 2-3 mg of minoxidil is absorbed from a typical topical application. This is not a lot compared to the 25-50 mg starter dose used for treatment of high blood pressure.

Dr. P, you may recall that I posted back on alt.baldspot several years ago about the study (see below) which found a statistically significant increase in cardiac LV mass and other parameters with the normal use of topical minoxidil. What concerns me is that the sudy lasted for only six months! An obvious question is, what happens with YEARS of continuous topical minoxidil use? Does the LV mass reach a "steady-state" after a relatively short period of time, or does it continue to slowly increase year after year after year? This unanswered question makes me nervous, and makes me want to avoid topical minoxidil altogether.

Br J Clin Pharmacol. 1988 Oct;26(4):481-5.
"Topical minoxidil: cardiac effects in bald man." Leenen FH, Smith DL, Unger WP.
Department of Medicine, Toronto Western Hospital, Ontario, Canada.

Systemic cardiovascular effects during chronic treatment with topical minoxidil vs placebo were evaluated using a double-blind, randomized design for two parallel groups (n = 20 for minoxidil, n = 15 for placebo). During 6 months of follow-up, blood pressure did not change, whereas minoxidil increased heart rate by 3-5 beats min-1. Compared with placebo, topical minoxidil caused significant increases in LV end-diastolic volume, in cardiac output (by 0.751 min-1) and in LV mass (by 5 g m-2). We conclude that in healthy subjects short-term use of topical minoxidil is likely not to be detrimental. However, safety needs to be established regarding ischaemic symptoms in patients with coronary artery disease as well as for the possible development of LV hypertrophy in healthy subjects during years of therapy.

 

[Bryan]

Bryan stated-''The results of topical finasteride studies have been all over the map: sometimes it seems to work a little, sometimes it doesn't seem to work at all, sometimes there's significant systemic absorption, sometimes there isn't any systemic absorption at all. It's all rather inconsistent and unpredictable''

These studies that you are refering to hardly sound reputable, ''inconsitent and unpredictable'' these are usually not attributes of accurate scientific studies, how can you draw a conclusion about finasterides systematic absorption, with these inconsistancies, consistant results are always an earmark of proper scientific methodology.

But I'm NOT drawing any conclusion about it, for that very reason: the results are too inconsistent to draw any firm conclusions.

BTW, here's an example of a couple of studies with "proper scientific methodology" which got differing results as to whether or not topical finasteride is systemically absorbed:

1) "Topical 0.05% finasteride significantly reduced serum DHT concentrations, but had no effect in preventing the expression of genetic hair loss in men", D.H. Rushton, M.J. Norris, and I.D. Ramsay; Hair Research for the Next Milllenium, 1996. Topical finasteride reduced serum DHT by about 40% in this study.

2) "Lack of effect of topical finasteride suggests an endocrine role for dihydrotestosterone", Price et al, Division of Reproductive Endocrinology and Infertility, Greenville Hospital System, Greenville, South Carolina. Despite the application of strong 0.25% - 0.5% alcoholic solutions of finasteride, there was no effect on serum DHT in these patients.

In addition, the study that you provided was not from a human model, it would be premature to make such claims about systematic absorbtion from an animal study alone.

Are you referring to the graph above from the Chen et al study? Once again, I am NOT drawing firm conclusions from any one animal study alone. I'm looking at the WHOLE of the available evidence, which includes both animal and human experiments. Rodent studies are pretty clear about the danger of systemic absorption from both finasteride and flutamide when applied topically; and human experiments with topical finasteride are an inconsistent, mixed bag. If you want to go ahead and use it despite those inconsistencies, go right ahead! Be my guest!

Additionally, I provided you with a human study(on topical finasteride) and as I explalined earlier it had many flaws, if you are so confident about your views certainly you could provide me with a human study conducted under proper scientific methadology with a control group and at minimum a year study.

But I am NOT "confident" about my views on topical finasteride, because the available evidence is so conflicting.

 

[pproctor]

Dr. P, you may recall that I posted back on alt.baldspot several years ago about the study (see below) which found a statistically significant increase in cardiac LV mass and other parameters with the normal use of topical minoxidil. What concerns me is that the sudy lasted for only six months! An obvious question is, what happens with YEARS of continuous topical minoxidil use? Does the LV mass reach a "steady-state" after a relatively short period of time, or does it continue to slowly increase year after year after year? This unanswered question makes me nervous, and makes me want to avoid topical minoxidil altogether.

Good point. I have also wondered about the issue of increased left ventricular mass, etc.. E.g., in theory at least, a little bit of minoxidil could cause (say) blood vessel dialatation that is not reflected as a perceptible decrease in blood pressure.

This might could cause (e.g.) a slight increase in effective circulatory volume, among other compensatory processes. One response to this might be an increase in the left vertricle, by any number of mechanisms.

One greatly-oversymplified way to look at this is the heart has more blood to pump, so it gets a little larger. Virtual exercise hypertrophy as opposed to the kind of hypertrophy that happens in (say) heart failure.

As you note and seems to be the case (since in over 20 years nobody has reported anything different), this seems to reach an equilibrium pretty quickly. IIRC, other investigators did not see it longer term. One way to reconcile these results is that it may be a specific change that is associated with starting treatment and goes away long term as other compensitory mechanisms (e.g., tolerance) come into play. All of these are wild guesses, naturally.

Peter H. Proctor, PhD,MD

 

[diffuse propecia]

Thanks for reply bryan (and everybody else), and dr.proctor your input was very much appreciated. I am guessing you do not find the heart effects of minoxidil worrisome as it is present in proxiphen? when I first read a reference to that research I immediately thought it must have been done on oral minoxidil but to find out it was topical minoxidil blew me away.

 

[pproctor]

Thanks for reply bryan (and everybody else), and dr.proctor your input was very much appreciated. I am guessing you do not find the heart effects of minoxidil worrisome as it is present in proxiphen? when I first read a reference to that research I immediately thought it must have been done on oral minoxidil but to find out it was topical minoxidil blew me away.

I have used Minoxidil in Proxiphen personally and on patients for roughly 25 years. I have yet to see any problems with systemic absorbtion. What gives me some confidence is that people have survived suicide attempts after taking gram amounts of this drug.

Moreover, they were mostly-unscathed after recovery. The hitch is that they had to spend months in the ICU under cardiorespiratory support, vasoconstrictors, etc., because their vessels were big-time dialated. But once that effect wore-off, everything seems to have been fine. Go figure...

Peter H. Proctor, PhD,MD