Could It Be That Topical finasteride Only Works Due To Systemic Absorption?

[Michael1986]

This is something that I've wondered about. Is it known to what extent topical finasteride is absorbed directly through the skin and into the hair follicles? Could it be that its main mode of action is through being absorbed systemically in the first place and then making its way from the bloodstream to the hair follicles, rather than through being absorbed directly through the skin into the hair follicles? Anyone know of any research done on this?

This is obviously an important question, because if topical finasteride only works by means of systemic absorption, this defeats the entire purpose of using it as an alternative to oral finasteride in the first place.

 

[TomRiddle]

From what i have read and documented about, yes, it does not work if it's not absorbed into the bloodstream. But, putting it directly on the head it should go right where it's needed minimizing systemic absorption to somewhat 25% or something like that. When you take the pill it has a different "roadtrip" until it reaches the follicle, besides the fact that everything in the pill is absorbed by your body... I saw recently an interesting article or study about it but can't remember where, if i find it i will post it here...

 

[INT]

We don't really know it yet. The two biggest researches on this had results that completely contradict each other. One showed less systemtic DHT reduction but better results for topical and the other showed similar systemic DHT results but inferior results for the topical version.

 

[Ausgebombt]

This is something that I've wondered about. Is it known to what extent topical finasteride is absorbed directly through the skin and into the hair follicles? Could it be that its main mode of action is through being absorbed systemically in the first place and then making its way from the bloodstream to the hair follicles, rather than through being absorbed directly through the skin into the hair follicles? Anyone know of any research done on this?

This is obviously an important question, because if topical finasteride only works by means of systemic absorption, this defeats the entire purpose of using it as an alternative to oral finasteride in the first place.

In my opinion, yes finasteride must go systemic in order to work. Think about it: 1) The hair follicle is exposed to serum DHT levels because each follicle is exposed to the blood stream. So all this talk about scalp vs. serum DHT levels is largely irrelevant because there is no reason to believe that the DHT in your scalp skin has anything to do with the hair miniaturization. and 2) finasteride works by inhibiting the production of DHT, however most serum DHT is not produced at the scalp but at internal organs such as the liver and balls. From there, it spreads throughout your body. For this reason, it would be very difficult to locally inhibit DHT.

As an interesting side note, there is a good argument to be made that the only reason topical minoxidil works, is because it goes systemic as well. Oral doses of minoxidil as low as 1mg have been shown to work very well for hair loss. The standard dose of minoxidil is 100 mg/day applied topically and topical minoxidil has been shown to have about a 1-4% systemic absorption rate. That means 1 to 4 mg is going systemic. This also explains why people pretty frequently report hair growth on other parts of their body while using minoxidil topically on their scalp. Keep in mind that the vasodilator theory for minoxidil is just a theory and that science still does not fully understand the reason why minoxidil grows hair. It actually hasn't been proven at all that vasodilation results in hair growth, because other much stronger vasodilating drugs have no effect on hair growth whatsoever. So I strongly suspect minoxidil grows hair by some other mechanism that we have not identified.

 

[INT]

In my opinion, yes finasteride must go systemic in order to work. Think about it: 1) The hair follicle is exposed to serum DHT levels because each follicle is exposed to the blood stream. So all this talk about scalp vs. serum DHT levels is largely irrelevant because there is no reason to believe that the DHT in your scalp skin has anything to do with the hair miniaturization. and 2) finasteride works by inhibiting the production of DHT, however most serum DHT is not produced at the scalp but at internal organs such as the liver and balls. From there, it spreads throughout your body. For this reason, it would be very difficult to locally inhibit DHT.

As an interesting side note, there is a good argument to be made that the only reason topical minoxidil works, is because it goes systemic as well. Oral doses of minoxidil as low as 1mg have been shown to work very well for hair loss. The standard dose of minoxidil is 100 mg/day applied topically and topical minoxidil has been shown to have about a 1-4% systemic absorption rate. That means 1 to 4 mg is going systemic. This also explains why people pretty frequently report hair growth on other parts of their body while using minoxidil topically on their scalp. Keep in mind that the vasodilator theory for minoxidil is just a theory and that science still does not fully understand the reason why minoxidil grows hair. It actually hasn't been proven at all that vasodilation results in hair growth, because other much stronger vasodilating drugs have no effect on hair growth whatsoever. So I strongly suspect minoxidil grows hair by some other mechanism that we have not identified.

Had a rough night with only 1,5 hrs of sleep so I already apologize if this post will be incoherent and written like a 5 year old.

Still, I think the point where finasteride enters your system might be important. If it enters via your scalp this is where most of the finasteride will latch onto the tissue in this area and do 'its work' there. Not all of it though and some of this will go to the other bodies as well. On top of that your total serum DHT levels will still be lower because it gets less DHT from one of its main contributors, being the scalp.

Like you said with the topical minoxidil example. It is not uncommon to see hair growth elsewhere but usually most of the growth happens closest to the area where it gets applied.

 

[Ausgebombt]

Had a rough night with only 1,5 hrs of sleep so I already apologize if this post will be incoherent and written like a 5 year old.

Still, I think the point where finasteride enters your system might be important. If it enters via your scalp this is where most of the finasteride will latch onto the tissue in this area and do 'its work' there. Not all of it though and some of this will go to the other bodies as well. On top of that your total serum DHT levels will still be lower because it gets less DHT from one of its main contributors, being the scalp.

Like you said with the topical minoxidil example. It is not uncommon to see hair growth elsewhere but usually most of the growth happens closest to the area where it gets applied.

Haha. Same here. I'm surprised you were able to understand my last post.

Is the scalp a main contributor of serum DHT? I've never heard that before.

I really wish there were more studies on topical finateride vs. Serum DHT levels. The only studies I am aware of were the studies from the company that was looking into P-3074. Unfortunately, their phase II dose ranging study only allowed for like 7 days or something between the start of topical administration and the tests to determine how serum DHT levels were affected. 7 days is not long enough for the body to reach steady-state in terms of DHT levels when talking about the administration of low doses (<.5 mg) of finateride daily. So really their results are totally meaningless... Just another "scientific" study that was purposefully skewed to get investors... oh well.

In their phase III study, they neglected to measure serum DHT altogether. Reading between the lines, it seems to me that even low doses of topical finasteride gradually accrue in the system until eventually the level of systemic DHT inhibition is equal to that obtained by oral administration of finasteride. Thus making the entire topical endeavor useless unless it is somehow more effective due to the possible localized effects you described.

 

[INT]

Haha. Same here. I'm surprised you were able to understand my last post.

Is the scalp a main contributor of serum DHT? I've never heard that before.

Oh take that comment with a grain of salt. It is one of the sites that contributes to serum dht, no idea if it is a major one. Just the one that (for obvious reasons) gets mentioned the most.

 

[TomRiddle]

The balding scalp has a lot more 5AR density and little aromatase, at least every study found this. As for the most contributor of serum DHT, from what i have read it's the prostate and liver or something like that but the main hair miniaturization contributor is the actual local tissue that is producing the DHT locally, there is no correlation between serum DHT and balding, there are tons of people who are full of DHT and with a full head of hair, it's all about the susceptibility...

 

[INT]

The balding scalp has a lot more 5AR density and little aromatase, at least every study found this. As for the most contributor of serum DHT, from what i have read it's the prostate and liver or something like that but the main hair miniaturization contributor is the actual local tissue that is producing the DHT locally, there is no correlation between serum DHT and balding, there are tons of people who are full of DHT and with a full head of hair, it's all about the susceptibility...

Do you maybe got some sources for that? I am quite curious.

 

[badhabiz]

Most likely there is a minimal accumulation rate.
How much and how this affect the therapy and the hormonal panel is something we'll never know. Would take at least 3 years of somministration of minimal dosage

 

[TomRiddle]

Do you maybe got some sources for that? I am quite curious.

Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia.
Sawaya ME1, Price VH.
Author information

Abstract
In this study, 12 women and 12 men, ages 18-33 y, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The androgen receptor, type I and II 5alpha-reductase, cytochrome P-450-aromatase enzyme were measured and analyzed in hair follicles from these scalp biopsies. Findings revealed that both women and men have higher levels of receptors and 5alpha-reductase type I and II in frontal hair follices than in occipital follicles, whereas higher levels of aromatase were found in their occipital follicles. There are marked quantitative differences in levels of androgen receptors and the three enzymes, which we find to be primarily in the outer root sheath of the hair follicles in the two genders. Androgen receptor content in female frontal hair follicles was approximately 40% lower than in male frontal hair follicle. Cytochrome P-450-aromatase content in women's frontal hair follicles was six times greater than in frontal hair follicles in men. Frontal hair follicles in women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively, than frontal hair follicles in men. These differences in levels of androgen receptor and steroid-converting enzymes may account for the different clinical presentations of androgenetic alopecia in women and men.

https://www.ncbi.nlm.nih.gov/pubmed/9284093

Very hard to find because unfortunately i don't bookmark everything i read and i miss some important things because of this, but it's too much information especially in this domain.... And i read something somewhere but can't remember that SERUM DHT could actually have an impact if it's too much of it because the body produces it in tissues prostate liver and so on, they don't even know all the places where it's produced, so it seems that even with all the studies, it's possible that SERUM also could have an impact, but only if it's very high and your hair is sensitive anyways to it...

"DHT is thought to attach to androgen receptors on hair follicles and, through an unknown mechanism, genetically trigger the receptors to begin miniaturizing.

As evidence for this, researchers have found that both plucked follicles and skin from a balding scalp contain higher levels of DHT than those from a non-balding scalp.

Some scientists believe that male pattern baldness in any specific individual is caused by a genetically transmitted susceptibility to otherwise normal levels of circulating androgens, particularly DHT.

Science is yet to understand fully why DHT’s effects are greater in some individuals, but there are a number of possible mechanisms at work:

Increased DHT receptors at the follicle
Increased local DHT production
Increased androgen receptor sensitivity
Increased DHT being produced elsewhere in the body and arriving through circulation, perhaps via the prostate
Increased circulating " class="glossaryLink " style="box-sizing: border-box; touch-action: manipulation; color: rgb(85, 85, 85); border-bottom: 1px dotted;">testosterone that acts as a precursor for DHT
It is known that DHT binds to follicle receptors five times more avidly than " class="glossaryLink " style="box-sizing: border-box; touch-action: manipulation; color: rgb(85, 85, 85); border-bottom: 1px dotted;">testosterone. However, the amount of DHT in the scalp is tiny compared with the levels in the prostate. How levels are controlled and why they change are not yet understood."

 

[Michael1986]

Thanks for all your responses guys. It does seem that we don't know for sure whether or not topical finasteride primarily works by going systemic, but I would wager that it most likely does. I wonder if there are people on this forum who got sides on oral finasteride, then switched to topical and maintained their results while experiencing milder or no sides? If so, this would provide useful anecdotal evidence that topical finasteride does, at least in part, have a localized effect rather than necessarily working by going systemic.

 

[TomRiddle]

Thanks for all your responses guys. It does seem that we don't know for sure whether or not topical finasteride primarily works by going systemic, but I would wager that it most likely does. I wonder if there are people on this forum who got sides on oral finasteride, then switched to topical and maintained their results while experiencing milder or no sides? If so, this would provide useful anecdotal evidence that topical finasteride does, at least in part, have a localized effect rather than necessarily working by going systemic.

In my own personal experience, i saw a lot of reports on many forums of people who used oral finasteride and got sides and after switched to topical and minimized or got no sides on it. But i also saw a lot of reports from people who said they experience the same sides on oral and topical. What topical were they using? What recipe, how much they applied? How much was placebo and how much wasn't? Without proper studies anecdotal experiences are just anecdotal experiences, you could react totally different and in an unknown factor and that's why your own experience is what matters for you only...

 

[Michael1986]

In my own personal experience, i saw a lot of reports on many forums of people who used oral finasteride and got sides and after switched to topical and minimized or got no sides on it. But i also saw a lot of reports from people who said they experience the same sides on oral and topical. What topical were they using? What recipe, how much they applied? How much was placebo and how much wasn't? Without proper studies anecdotal experiences are just anecdotal experiences, you could react totally different and in an unknown factor and that's why your own experience is what matters for you only...

Yes that's true. Self-reports are unreliable as there are many confounding factors such as the power of placebo etc. However, I guess that if a large number of people were to consistently report the same thing, a consensus could be built up, but not enough people have used topical finasteride and then reported consistent findings for us to be able to form a consensus. Its a shame there's been so little scientific research done on topical finasteride. I myself am using dutasteride (oral), and I would definitely switch to a topical version of it if I knew for sure that the topical worked and that its mode of action was primarily a localized one.

 

[Michael1986]

As an interesting side note, there is a good argument to be made that the only reason topical minoxidil works, is because it goes systemic as well. Oral doses of minoxidil as low as 1mg have been shown to work very well for hair loss. The standard dose of minoxidil is 100 mg/day applied topically and topical minoxidil has been shown to have about a 1-4% systemic absorption rate. That means 1 to 4 mg is going systemic. This also explains why people pretty frequently report hair growth on other parts of their body while using minoxidil topically on their scalp. Keep in mind that the vasodilator theory for minoxidil is just a theory and that science still does not fully understand the reason why minoxidil grows hair. It actually hasn't been proven at all that vasodilation results in hair growth, because other much stronger vasodilating drugs have no effect on hair growth whatsoever. So I strongly suspect minoxidil grows hair by some other mechanism that we have not identified.

Yes that's another thing I've wondered about. I use topical minoxidil and I've sometimes thought to myself that if it primarily works only by going systemic, there's nothing to gain by using topical instead of the convenience of taking it orally. However, I saw an old post on this forum by the late Bryan Shelton (some of you may remember him), who mentioned a study in which minoxidil was consistently applied over one half of each participant's scalp but not the other half, and the results were that the participants had regrowth over their whole scalps, but the half of their scalps where the minoxidil was applied had significantly more regrowth than the other half. This suggests that minoxidil works partly by going systemic, but that it also has a localized effect too. Bryan didn't provide a link to the study in his post, and I wasn't able to find the study when I searched for it online, but if anyone on here is able to provide a link to it, that would be great.

 

[Derelict]

Yes that's another thing I've wondered about. I use topical minoxidil and I've sometimes thought to myself that if it primarily works only by going systemic, there's nothing to gain by using topical instead of the convenience of taking it orally. However, I saw an old post on this forum by the late Bryan Shelton (some of you may remember him), who mentioned a study in which minoxidil was consistently applied over one half of the participants' scalps but not the other half, and the results were that the participants had regrowth over their whole scalps, but the half of their scalps where the minoxidil was applied had significantly more regrowth than the other half. This suggest that minoxidil works partly by going systemic, but that it also has a localized effect too. Bryan didn't provide a link to the study in his post, and I wasn't able to find the study when I searched for it online, but if anyone on here is able to provide a link to it, that would be great.

Doesn't minoxidil when applied topically bypass the liver when going systematic though? so cant be converted? Maybe i have that wrong lol

 

[Ausgebombt]

Yes that's another thing I've wondered about. I use topical minoxidil and I've sometimes thought to myself that if it primarily works only by going systemic, there's nothing to gain by using topical instead of the convenience of taking it orally. However, I saw an old post on this forum by the late Bryan Shelton (some of you may remember him), who mentioned a study in which minoxidil was consistently applied over one half of each participant's scalp but not the other half, and the results were that the participants had regrowth over their whole scalps, but the half of their scalps where the minoxidil was applied had significantly more regrowth than the other half. This suggests that minoxidil works partly by going systemic, but that it also has a localized effect too. Bryan didn't provide a link to the study in his post, and I wasn't able to find the study when I searched for it online, but if anyone on here is able to provide a link to it, that would be great.

I would be interested to see that study.

I used minoxidil topically on my beard area and it definitely grew hair on other parts of my body such as my earlobes, arms, and knuckles. It’s possible that the relative effects on these parts of my body were low compared to what would have happened if I was applying it at those locations, but without dedicated experimentation, it’s hard to say.

 

[topicalthunder]

Finasteride has a similar chemical structure to testosterone. 5AR will take finasteride instead of test and then be disabled until it is reproduced by the body.

The reason why it works topically is because the molecule size is small and can penetrate the scalp. DHT is made locally, therefore when finasteride gets to the follicle, 5ar will absorb finasteride (rather than test) and be disabled until it is renewed.

 

[Michael1986]

Doesn't minoxidil when applied topically bypass the liver when going systematic though? so cant be converted? Maybe i have that wrong lol

Not as far as I know. I'm fairly sure that the portion of it that goes systemic still gets metabolised, which is why some people report side-effects from topical minoxidil.

I would be interested to see that study.

I used minoxidil topically on my beard area and it definitely grew hair on other parts of my body such as my earlobes, arms, and knuckles. It’s possible that the relative effects on these parts of my body were low compared to what would have happened if I was applying it at those locations, but without dedicated experimentation, it’s hard to say.

I found the study. Here's the link to it, but unfortunately only the abstract is available unless you pay for the full study: https://www.ncbi.nlm.nih.gov/pubmed/3549809. Bryan made the following post in an old thread quoting some interesting information from the study that is not available in the abstract: https://www.gourmetstylewellness.com/interact/threads/radius-of-minoxidil-absorption.28549/#post-782205. Basically, the findings of the study support the idea that minoxidil works best on the areas of the scalp where it is directly applied.

 

[scientist_0005]

In my opinion, yes finasteride must go systemic in order to work. Think about it: 1) The hair follicle is exposed to serum DHT levels because each follicle is exposed to the blood stream. So all this talk about scalp vs. serum DHT levels is largely irrelevant because there is no reason to believe that the DHT in your scalp skin has anything to do with the hair miniaturization. and 2) finasteride works by inhibiting the production of DHT, however most serum DHT is not produced at the scalp but at internal organs such as the liver and balls. From there, it spreads throughout your body. For this reason, it would be very difficult to locally inhibit DHT.

As an interesting side note, there is a good argument to be made that the only reason topical minoxidil works, is because it goes systemic as well. Oral doses of minoxidil as low as 1mg have been shown to work very well for hair loss. The standard dose of minoxidil is 100 mg/day applied topically and topical minoxidil has been shown to have about a 1-4% systemic absorption rate. That means 1 to 4 mg is going systemic. This also explains why people pretty frequently report hair growth on other parts of their body while using minoxidil topically on their scalp. Keep in mind that the vasodilator theory for minoxidil is just a theory and that science still does not fully understand the reason why minoxidil grows hair. It actually hasn't been proven at all that vasodilation results in hair growth, because other much stronger vasodilating drugs have no effect on hair growth whatsoever. So I strongly suspect minoxidil grows hair by some other mechanism that we have not identified.

this is painfully wrong. dht is a paracrine hormone, it is not a classical hormone and in fact 5AR is highly expressed in the skin, comparable to its expression in the prostate. if you look at a balding vs non balding scalp, it is obvious that there is higher 5AR expression. the dht from the prostate alone does not suffice to ruin your hair. soyes, there is ALL reason to believe that the dht in your skin is related to minaturization. its part of the fubdamental theory of why we go bald. serum levels do not matter. 2) is just wrong.. most of the dht produced in the prostate is used in that tissue. most of the dht minaturizing hair gets produced in the scalp skin