Why You Likely Don't Have To Worry About Androgen Receptor Upregulation

IdealForehead

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I have read many times people suggesting that if they use finasteride/dutasteride/RU/etc. they are concerned their hair will "upregulate androgen receptors" which will thus lead to them overcoming the medication or developing "reflex hypersensitivity".

It is true that androgen deprivation/blockade will likely lead to upregulation of androgen receptors. But the only studies I've seen on it suggest it's a transient and weak process.

How Prostate Androgen Receptors Respond to Castration
As an example, this was an animal study of how castration (both physical - cutting off the nuts, and chemical with the androgen receptor antagonist flutamide, etc.) affected androgen receptor expression in the prostates of rats.

Here was their primary finding on physical castration, which matched what they saw with chemical castration:

mrna-castration-androgen-receptor-png.png


In other words, there was a temporary increase in androgen receptor expression after the castration, but it went back to normal levels within a week.

Here is what they had to say about it:

discussion-1-png.png

discussion-2-png.png


In other words, they suggest both their study and a previous study by "Prins" showed only a temporary small effect of androgen receptor upregulation induced by androgen deprivation.

There is likely no plausible mechanism by which your hair will therefore infinitely or massively increase its number of androgen receptors in response to any degree of anti-androgen treatment, and this is likely nothing to worry about.

It's not perfect evidence to prove the point, but unless someone has something to the contrary, I think it's pretty good.

How Hair Responds to Androgen Deprivation
Another way of looking at the concept of androgen receptor upregulation and whether it should be a realistic concern, more directly as it relates to hair, is to simply observe what we see from the best studied anti-androgenic hair loss treatments.

Finasteride has the best studies overall, and works by reducing scalp DHT by around 60%. If androgen-receptor upregulation was a common or expected response to androgen deprivation, we should see hair counts drop off rapidly once this upregulation effect "kicks in". In actual fact, what we've seen in the studies is that hair counts stay very stable over long periods of finasteride use.

060406_propeciachart.jpg


People that respond initially continue to respond long term. People who don't respond initially are either so androgen sensitive the partial DHT reduction is not sufficient to block further damage, or their DHT is not being reduced at all (which was my case).
 
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hanginginthewire

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Interesting.

But it begs the question (for me) of why propecia isn’t doing jack sh*t for my hair. Or why so many report their hair or hairline is destroyed on antiandrogens.
 

IdealForehead

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Interesting.

But it begs the question (for me) of why propecia isn’t doing jack sh*t for my hair. Or why so many report their hair or hairline is destroyed on antiandrogens.

Finasteride only reduces scalp DHT by around 60-70% (ref).

So you still have 30-40% of your scalp DHT left in tact while on finasteride, plus ALL your testosterone.

Testesterone binds to the androgen receptor 3-5x less strongly than DHT, but it still binds and will damage your hair.

The only practical solution to an indadequate effect on finasteride/dutasteride is then to add a topical (or oral) androgen receptor antagonist which can "clean up" and block the rest of this mess still left behind even after finasteride/dutasteride have done their best work.
 
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IdealForehead

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Any idea why as @hanginginthewire has said that anti-androgens for some people (dutasteride, finasteride, RU..etc) have made their hair worse ?

I can only answer with what I said above regarding finasteride/dutasteride. As they only partially reduce DHT, and may in fact induce increases in testosterone, it is possible to get worsening at the frontal hairline which is most androgen sensitive.

I cannot come up with any explanation for how something like RU or another androgen receptor antagonist could make someone's hair "worse". I would guess those people are most likely just continuing to bald naturally and not responding to the treatment due to too low a dose, then blaming the treatment for their natural continued worsening.

Published hair loss studies for finasteride/dutasteride/RU have never shown the "treatment group" to do worse than the "placebo group" as a whole. Some people probably just have aggressive hair loss and may not end up responding to conventional treatments.
 

bridgeburn

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I have read many times people suggesting that if they use finasteride/dutasteride/RU/etc. they are concerned their hair will "upregulate androgen receptors" which will thus lead to them overcoming the medication or developing "reflex hypersensitivity".

I posted this as a reply buried in another thread here, but it's such a common concern, I thought it deserves its own thread.

It is true that androgen deprivation/blockade will likely lead to upregulation of androgen receptors. But the only studies I've seen on it suggest it's a transient and weak process.

As an example, this was an animal study of how castration (both physical - cutting off the nuts, and chemical with the androgen receptor antagonist flutamide, etc.) affected androgen receptor expression in the prostates of rats.

Here was their primary finding on physical castration, which matched what they saw with chemical castration:

View attachment 71294

In other words, there was a temporary increase in androgen receptor expression after the castration, but it went back to normal levels within a week.

Here is what they had to say about it:

View attachment 71295
View attachment 71296

In other words, they suggest both their study and a previous study by "Prins" showed only a temporary small effect of androgen receptor upregulation induced by androgen deprivation.

There is likely no plausible mechanism by which your hair will therefore infinitely or massively increase its number of androgen receptors in response to any degree of anti-androgen treatment, and this is likely nothing to worry about.

It's not perfect evidence to prove the point, but unless someone has something to the contrary, I think it's pretty good.
... rats
 

IdealForehead

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On the German forum people usually actually use the ket cream, they mix it with minoxidil and have good results. Ket cream is actually a much bigger part of their regimes.
As we discussed once before here with a study that showed it, ketoconazole is actually a very potent antiandrogen. It is just limited in usefulness because oral administration leads to liver toxicity, and it has horrible solubility, so must be used topically in creams.

I bought some keto powder from Alibaba and was going to use it in my topicals but then I realized it doesn't really dissolve in any useful liquids well.
 

IdealForehead

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I asked there and they gave me this link for 2% topical ket cream intended for athletes foot, etc.

https://www.alldaychemist.com/nizral.html

It wouldn't be a bad option for you since you want to avoid more experimental therapies but might benefit from some added local antiandrogenic activity. Also you probably wouldn't mind the cream format too much I'm guessing with how your hair is.

Give it a shot.
 

countjulian

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It wouldn't be a bad option for you since you want to avoid more experimental therapies but might benefit from some added local antiandrogenic activity. Also you probably wouldn't mind the cream format too much I'm guessing with how your hair is.

Give it a shot.

I am, as soon as I get home from this trip I am ordering it.
 

abcdefg

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Finasteride only reduces scalp DHT by around 60-70% (ref).

So you still have 30-40% of your scalp DHT left in tact while on finasteride, plus ALL your testosterone.

Testesterone binds to the androgen receptor 3-5x less strongly than DHT, but it still binds and will damage your hair.

The only practical solution to an indadequate effect on finasteride/dutasteride is then to add a topical (or oral) androgen receptor antagonist which can "clean up" and block the rest of this mess still left behind even after finasteride/dutasteride have done their best work.

Right. I agree with your saying about receptors too. Also hamilton found that older men injected with androgens lose their hair faster then younger men. IMO as you get older sensitivity continues to increase. We dont understand sensitivity to androgens in the first place so its hard to know why this is, but it seems to happen
The magic bullet for maintance we are all missing is the CB or commercial topical that is cheap and readily available like minoxidil but to attack male pattern baldness from the AR angle. If we had CB a safe effective topical plus you take dutasteride or finasteride I think that might do the trick for preventing male pattern baldness for a very long time for most men. Prevention though is the best it gets with any AA no matter how powerful
The statistics for success with AAs though still makes me believe all the envirnmental factors mentioned in the twin study is not a major factor in male pattern baldness. If they were any major influence that AAs simply wouldnt work as well as they do without addressing the underlying factors at play
 

Quineapig

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Im using spiro200mg ED and dut0,5mg ED. they worked perfectly for 2 years and now they are starting to fail. Im pretty sure that my androgen receptors have upregulated or I have built tolerance to spironolactone.
 

IdealForehead

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Im using spiro200mg ED and dut0,5mg ED. they worked perfectly for 2 years and now they are starting to fail. Im pretty sure that my androgen receptors have upregulated or I have built tolerance to spironolactone.

Keep in mind that even finasteride/dutasteride show a gradual hair decline after the first year or two.

Spironolactone is also a very complex agent. It is a SARM, meaning it has some androgen stimulatory behaviors. It cannot be used in prostate cancer for this reason as it can stimulate some prostate cancers into overdrive. So spironolactone is not a pure antiandrogen and it may exhibit mixed behavior in real life for hair as well.

That is a very aggressive regimen nonetheless. I am blown away you can handle it unless you are trans. You could try changing the spironolactone to cypro 50-100 if you have it in your country. This is a more pure antiandrogen than spironolactone.
 

Quineapig

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Keep in mind that even finasteride/dutasteride show a gradual hair decline after the first year or two.

Spironolactone is also a very complex agent. It is a SARM, meaning it has some androgen stimulatory behaviors. It cannot be used in prostate cancer for this reason as it can stimulate some prostate cancers into overdrive. So spironolactone is not a pure antiandrogen and it may exhibit mixed behavior in real life for hair as well.

That is a very aggressive regimen nonetheless. I am blown away you can handle it unless you are trans. You could try changing the spironolactone to cypro 50-100 if you have it in your country. This is a more pure antiandrogen than spironolactone.


Im full straight guy. I dont have sides from it.
I've asked for cypro from my Doctor but she wont give it to me because of hepatoxicity. And I guess it would be too strong even for me :)
 

IdealForehead

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Im full straight guy. I dont have sides from it.
I've asked for cypro from my Doctor but she wont give it to me because of hepatoxicity. And I guess it would be too strong even for me :)

That's amazing you can handle it. spironolactone was exhausting for me with all the pissing and drinking all day.

Cypro killed my dick dead within two weeks. Definitely stronger than spironolactone.

Alternatively you could try adding a tropical antiandrogen like ru.
 

Quineapig

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That's amazing you can handle it. spironolactone was exhausting for me with all the pissing and drinking all day.

Cypro killed my dick dead within two weeks. Definitely stronger than spironolactone.

Alternatively you could try adding a tropical antiandrogen like ru.

My dick is still fully working and pissing and drinking arent bad when your body adapts to the drug.
Topicals are too pricy for me and too hard to get. Not practical long term.
 

countjulian

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My dick is still fully working and pissing and drinking arent bad when your body adapts to the drug.
Topicals are too pricy for me and too hard to get. Not practical long term.

Do you work out, take DIM, or otherwise try to keep your T high and estrogen low?
 
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