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

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hairloss expert
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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).
 

Ascendordie

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May 14, 2020
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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).

How was your DHT not being reduced at all and how did you figure this out? What did you replace finasteride with to combat baldness?
 
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