Topical Finasteride - Concentration Or Total Dose?

[Paulito9x9]

Hi guys,

having stalked the forum for a long time I finally decided to post something myself. I have recently undergone a hair transplant which fixed around the frontal 40% of my scalp. However, this made a very clearly visible line of transplanted hair and the thinned out hair at the back. This convinced me to give topical finasteride a second try. This time I followed a tutorial and whipped up a 0.025% solution using Essengen-F and Stemoxydine. I only apply ~0.47ml of it a day which comes to about 0.12mg of finasteride.

The problem is, I'm getting side-effects even from this tiny dose. I tried 0.2% topical finasteride and Alfatradiol in the past and the side-effects are pretty much the same thing. It started with testicular pain (which has nearly subsided now) dizziness...and believe it or not...face pain. Or maybe jaw pain. It's hard to tell exactly. But I had the same thing on Alfatradiol. It moves between my jaw bone, jaw muscles and my cheeks.

Anyway, this brings me to my question...0.025% has been proven to be a good trade-off between scalp and serum DHT reduction (http://europepmc.org/article/med/26636418). But I'm wondering - Is it really the concentration or the total dosage that matters more? If it really were just the concentration I could potentially cover my non-HTed scalp areas with less than 0.47ml. But if it's the total dosage that matters then I doubt it'd be effective as I'm already using just half of what the lowest concentration from that study is (0.2275mg).

Any thoughts on this?

 

[corkmeister]

You are misunderstanding the study you cited. 0.025% may be a good trade-off between scalp and serum dht - but you have to understand that this is only at a single point in time. A week is not enough to account for accumulation. The results at the 1 week mark are essentially only the starting point of a long trend downwards, which will eventually result in near oral levels of systemic dht inhibition.

I would say it's the total dosage that matters. How long does it take until you notice side-effects? 0.12mg is most likely too high if you want to avoid significant systemic inhibition of dht.

 

[Paulito9x9]

You are misunderstanding the study you cited. 0.025% may be a good trade-off between scalp and serum dht - but you have to understand that this is only at a single point in time. A week is not enough to account for accumulation. The results at the 1 week mark are essentially only the starting point of a long trend downwards, which will eventually result in near oral levels of systemic dht inhibition.

I would say it's the total dosage that matters. How long does it take until you notice side-effects? 0.12mg is most likely too high if you want to avoid significant systemic inhibition of dht.

Damn, good to know :-/ I'm glad I asked. Are you aware of any studies that looked into long-term topical finateride usage?
Apart from that, which dosage would you recommend?

 

[corkmeister]

Damn, good to know :-/ I'm glad I asked. Are you aware of any studies that looked into long-term topical finateride usage?
Apart from that, which dosage would you recommend?

There is very little data on it. There's the study by Mazzarella from 1998 or 1999. He used 0.01% (0.005%*2), so 0.1mg daily, and saw no effect on serum dht in his subjects. I should say that a lot of people have tried to replicate his results, but a significant portion were unsuccessful. I personally don't believe his results or flawed or forged, but I think 0.1mg per day is close to the upper limit of what you can use daily without effects on serum dht. Once you go over a certain threshold, it starts snowballing (accumulating) over time. Arriving at an end-point of 25% systemic vs. 50% scalp reduction is theoretically possible, I think, but would be almost impossible in practice. You'd need to get the dosage just right.

If you want to use topical finasteride without any effect on serum dht, I would recommend you start low, lower than 0.1mg, and then slowly work your way up, monitoring your dht-levels through bloodtests. It can be done, but you will obviously sacrifice effectiveness at doses this low.

 

[Paulito9x9]

Thanks. I'll adjust the dosage and report back after a while.
Not sure about the blood-tests though. I haven't measured my baseline and they can get pretty pricey.

 

[Paulito9x9]

One more thing came to mind as I was reading through some studies: For example this one https://pubmed.ncbi.nlm.nih.gov/10037433/ says

The effect of prolonged treatment with this time-dependent irreversible inhibitor on the recently described prostatic type I 5alpha-reductase, however, is not clear

What do they mean by irreversible? I'm not familiar with chemistry lingo but it I was under the assumption that finasteride should eventually be flushed out of the system when discontinued.

Same wording here:
https://www.ncbi.nlm.nih.gov/pmc/ar...s a 5α-reductase,levels of neurosteroids [39].

Finasteride, an irreversible inhibitor of 5α-reductase, blocks the synthesis of all 5α-reduced neurosteroids, including testosterone-derived androstanediol [24] and deoxycorticosterone-derived allotetrahydrodeoxycorticosterone (THDOC) [25] and thereby may affect epileptogenesis.

 

[corkmeister]

Irreversible, as far as I know, refers to the fact finasteride binds irreversibly with 5-alpha-reductase enzymes. That just means the enzyme is useless until it's gone from the body. The body constantly produces new 5-alpha-reductase enzymes though. So yes, finasteride is eventually flushed out of the system (rather quickly actually), although it'll take longer to fully replenish functioning 5-alpha-reductase enzymes, depending on the dose.

 

[Paulito9x9]

Gotcha. Thanks for the explanation. I've read that the Mean Accumulation Ratio of Finasteride is 90%. Having a rough understanding of it, taking into account how fast 5-alpha-reductase replenishes, there must be a dosage interval which would prevent accumulation. Any idea how to calculate it?

Btw the Mazzarella study seems to be behind a paywall. Any idea where to access it for free?

 

[corkmeister]

Gotcha. Thanks for the explanation. I've read that the Mean Accumulation Ratio of Finasteride is 90%. Having a rough understanding of it, taking into account how fast 5-alpha-reductase replenishes, there must be a dosage interval which would prevent accumulation. Any idea how to calculate it?

Btw the Mazzarella study seems to be behind a paywall. Any idea where to access it for free?

I'm not sure I understand the question (and I don't really know what mean accumulation ratio means either). When you say you want to calculate an interval to prevent accumulation, you mean interval in terms of frequency? I.e. how often you're applying it?

I would be more concerned with the actual dosage rather than frequency in terms of preventing accumulation. For topical finasteride I personally believe something close to 0.1mg is the upper limit. The most basic way to look at it is like this: every time you apply finasteride, functional 5ar in the scalp and the rest of body decreases. If 5ar is not fully replenished by the time of your next dosage, then it will gradually trend downwards, although it does eventually even out. Ideally, you want to create a situation where 5ar in the scalp is unable to replenish by the time of your next application, whereas the rest of the body (which receives a different amount of the drug, i.e. the amount that goes systemic) is recovered or nearly recovered. Because there is a higher localized effect with topical finasteride, there's a certain margin that theoretically allows you to achieve this. I do not know how much inhibition on the scalp you can achieve with this, but I believe it could be significant enough to have an effect.

As to how to calculate it, I honestly have no idea. Almost all of the available information is on oral finasteride/dutasteride. So while there are some models available, you'd also have to know how much of your topical finasteride is going systemic. And even then I doubt you could accurately calculate it. There are just so many variables to account for. I still don't quite understand how/how quickly the body produces new 5ar, for example. In part due to conflicting information from studies and the information given by Merck.

That's why I suggested starting low (Mazzarrela's dosage is essentialy the only data-point we have for topical finasteride over a long period of time) and monitoring with bloodtests, because that's the only alternative as opposed to calculating it. The mistake made by many people is that they simply start at Mazzarella's dosage exactly and try to replicate his results. It's quite clear by now that this is a hit or miss approach. If you cross a certain threshold and the body can't keep up with the amount of finasteride you're introducing to it every day, it will simply spiral out of control. That's why you need to start lower.

You can find Mazzarrella's study here: https://sci-hub.se/https://www.tandfonline.com/doi/abs/10.3109/09546639709160517

If you're interested in the workings of finasteride, dutasteride and their effect on 5ar/dht, I would advise you to read these studies:
https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/20460827/
https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/9871428/

 

[Paulito9x9]

I'm not sure I understand the question (and I don't really know what mean accumulation ratio means either). When you say you want to calculate an interval to prevent accumulation, you mean interval in terms of frequency? I.e. how often you're applying it?

Yeah, how often and how much. But you're right. There's just way too many variables.

Thanks for the great insights and sources. I appreciate it and will make sure to read them.
I suppose I'll wait for a while for my 5-alpha levels to replenish, get a bloodtest and try again with something like 0.05mg or maybe even lower. Then see if I get sides and get another bloodtest done.

 

[corkmeister]

Yeah, how often and how much. But you're right. There's just way too many variables.

Thanks for the great insights and sources. I appreciate it and will make sure to read them.
I suppose I'll wait for a while for my 5-alpha levels to replenish, get a bloodtest and try again with something like 0.05mg or maybe even lower. Then see if I get sides and get another bloodtest done.

Glad to help. Good luck with your experiment. If you've only used finasteride, your 5ar levels should be back to normal in 2-3 weeks.

 

[jazz1]

I been using Topical Finasteride over 10 years now at 0.1% over time from different compound pharmacies.

Check my thread:

https://www.hairlosstalk.com/intera...oxidil-finasteride-mixture-check-here.126633/

 

[Paulito9x9]

I been using Topical Finasteride over 10 years now at 0.1% over time from different compound pharmacies.

Check my thread:

https://www.hairlosstalk.com/intera...oxidil-finasteride-mixture-check-here.126633/

Considering what 0.12mg did to me I'm guessing 0.1% at a large enough volume would probably kill me

That being said, do you think there could really be a difference between the same concentration from let's say Minoxidilmax+Stemox and something componded at a lab? I guess the vehicle could matter...

 

[jazz1]

Considering what 0.12mg did to me I'm guessing 0.1% at a large enough volume would probably kill me

That being said, do you think there could really be a difference between the same concentration from let's say Minoxidilmax+Stemox and something componded at a lab? I guess the vehicle could matter...

0.12mg sounds high lol, 0.1% is the recommended dosage which is 1mg, I use mine in lotion form and not liquid so maybe that keeps things localised compared to liquid formula. Stemox even work? Cheap but is it effective........

 

[Paulito9x9]

0.12mg sounds high lol, 0.1% is the recommended dosage which is 1mg, I use mine in lotion form and not liquid so maybe that keeps things localised compared to liquid formula. Stemox even work? Cheap but is it effective........

Lucky you that you can tolerate 0.1% concentration.
I don't know about stemox. It's just something to dilute it with. It's a cosmetical compound so it should be harmless.

 

[jazz1]

Lucky you that you can tolerate 0.1% concentration.
I don't know about stemox. It's just something to dilute it with. It's a cosmetical compound so it should be harmless.

So why not have it compounded to a lower dosage for you like half? 0.050%.

 

[Paulito9x9]

So why not have it compounded to a lower dosage for you like half? 0.050%.

Like I said, I whipped up 0.025% myself. I'm planning on diluting it down even further. I'd only consider having it compounded by a pharmacy if somebody insisted that they can do it better. As in use a better quality vehicle or something.

 

[Paulito9x9]

Reading through the Japanese study @corkmeister posted above I came across something I don't quite get. Looking at this graph

and quoting this part:
Repeated oral administrations of 0.01 or 0.05 mg
finasteride decreased serum DHT by only 10 and 30%,
respectively (Fig. 7). In contrast, repeated oral administrations
of 0.2 or 5 mg finasteride to decreased serum
DHT concentration by about 60% (Fig. 7).

They then go on to say this:
In a clinical study, serum DHT
was reduced by 49.5% after administration of finasteride
at 0.05 mg/day for 42 days, and by about 70% after 0.2–5
mg/day.17) These clinical observations are consistent with
our simulation results.

Those 49.5% don't quite match the graph above. Could someone shen some light on it? Am I reading it wrong?
In any case, a dose of let's say 0.02mg per day seems pretty safe. Even more so if it's used topically.

 

[jazz1]

Like I said, I whipped up 0.025% myself. I'm planning on diluting it down even further. I'd only consider having it compounded by a pharmacy if somebody insisted that they can do it better. As in use a better quality vehicle or something.

Ah ok, check the compound pharmacy I use and see what vehicle options they might be able to provide you.....