Let's Talk About Andogen Receptor Upregulation

[GoldenMane]

Androgen receptor upregulation is a significant cause for concern for me, and I'm sure for many of you too. Obviously, having more androgen receptors means that androgens, even at lower levels, may cause continuous Androgenetic Alopecia. As a result, even if we continue to take finasteride/dutasteride, we might expect that at some point, AR upregulation would mean hair loss starts again.

Now I had held off on starting dutasteride for this reason, I wanted more DHT suppression, but I've read many comments stating that stronger DHT inhibitors would lead to increased AR upregulation, thus you should only switch to dutasteride after finasteride has lost its effectiveness.

Now here comes my hypothesis: Inhibiting DHT does NOT cause AR upregulation. finasteride and dutasteride don't lower overall androgens, they just result in less Testosterone from being converted to DHT, and as such, overall andogens should remain the same, just more testosterone, which also binds with AR receptors and less DHT, which causes male pattern baldness.

So any thoughts on this idea? Anyone with greater knowledge of physiology/biochemistry/cell biology have any insights?

Also, if DHT inhibitors don't cause AR upregulation, why is it that many men notice an increase in hair loss 6-8 years into DHT treatment? I've considered that it could still be AR upregulation, but due to the progressive reduction in testosterone that occurs as we age,,, I've also considered that it could be a cumulative effect of even low levels of DHT over the years, in which case we should use the strongest DHT inhibitors available as early as possible.

So any thoughts/insight anyone?

 

[Samson123]

Well, all i have to offer is my own experience with finasteride. I wish I had never touched the stuff. finasteride did something to greatly worsen my hairloss, like in every way, massive shed, hairloss in places I was completely thick, and every single hair is at least a third of fourth of the thickness of my original hair. Some are almost invisible. I'm a diffuse thinner and have these dead zones all over my scalp now where no hair will ever grow again. I was on 1.25 mg for around 15 months and dropped the dosage to .5 mg. things were more or less stable for awhile and then a month ago I decided to drop it down to .25 mg over a couple weeks. I've only been on .25 mg for ten days. I buzzed my head with a two guard and things had gone rapidly downhill. Given that I didn't ever stop taking finasteride, how could things happen so fast? What happened to the 'flat dose response'? finasteride made my hair follicles super sensitive to androgens. That's the only answer. How does it do that? It has to be AR upregulation which is, for all intents and purposes, might as well be permanent. i would go bald waiting to see if the AR downregulated in response to normal (for me) levels of DHT. I know this really doesn't contribute to your original discussion but I really believe that guys that are losing hair with low DHT should stay away from finasteride or take it in very small doses.

 

[g.i joey]

Lol what. No the only answer is you toying with the dosage. finasteride at .25 won't be 5% worse than it at 1mg or whatever the negligible diff is. Maybe for someone .25 will work if they have hariloss over the span of 20 years but for aggressive hariloss sufferers like me .25 did nothing

 

[buckthorn]

Androgen receptor upregulation is a significant cause for concern for me, and I'm sure for many of you too. Obviously, having more androgen receptors means that androgens, even at lower levels, may cause continuous Androgenetic Alopecia. As a result, even if we continue to take finasteride/dutasteride, we might expect that at some point, AR upregulation would mean hair loss starts again.

Now I had held off on starting dutasteride for this reason, I wanted more DHT suppression, but I've read many comments stating that stronger DHT inhibitors would lead to increased AR upregulation, thus you should only switch to dutasteride after finasteride has lost its effectiveness.

Now here comes my hypothesis: Inhibiting DHT does NOT cause AR upregulation. finasteride and dutasteride don't lower overall androgens, they just result in less Testosterone from being converted to DHT, and as such, overall andogens should remain the same, just more testosterone, which also binds with AR receptors and less DHT, which causes male pattern baldness.

So any thoughts on this idea? Anyone with greater knowledge of physiology/biochemistry/cell biology have any insights?

Also, if DHT inhibitors don't cause AR upregulation, why is it that many men notice an increase in hair loss 6-8 years into DHT treatment? I've considered that it could still be AR upregulation, but due to the progressive reduction in testosterone that occurs as we age,,, I've also considered that it could be a cumulative effect of even low levels of DHT over the years, in which case we should use the strongest DHT inhibitors available as early as possible.

So any thoughts/insight anyone?

I am completely convinced that this is what happened to me. It has to be. 3 months into finasteride, I started losing an insane amount of hair. At the same time, I started getting this burning, itchy crawling sensation all over my scalp. 12 months into finasteride, my hair was just shredded. It literally looked like I had gone through chemo or something. 6 months after dropping it, and the scalp sensations are still there, although they are becoming more minimal.

This is a f&cked up scenario because if upregulation really is occurring, then what the hell happens after you drop finasteride?? Do the receptors continue to be this active and expressed? If so, you are f^cked on two levels now. Your DHT levels will rise to normal and now you have more receptors for them to bind. THIS is why this medication is SO messed up in my opinion.

 

[Afro_Vacancy]

Lol what. No the only answer is you toying with the dosage. finasteride at .25 won't be 5% worse than it at 1mg or whatever the negligible diff is. Maybe for someone .25 will work if they have hariloss over the span of 20 years but for aggressive hariloss sufferers like me .25 did nothing

The difference between 0.25mg and 1.00 mg in fighting hair loss has been shown by multiple studies to be very, very small.

You have a weird passion for high dosages of finasteride. There's no empirical backing for those high dosages.

 

[GoldenMane]

So some people do experience accelerated hair loss after taking DHT inhibitors, but why do you think this is? Like I said, how can androgen receptors become upregulated if overall androgen levels stay the same. Are we to believe that androgen receptors specifically upregulate in response to lowered DHT even though overall androgen levels stay the same?

 

[Fullhead1day]

Oral + Topical AA = Fullhead 4 life

 

[Afro_Vacancy]

So some people do experience accelerated hair loss after taking DHT inhibitors, but why do you think this is? Like I said, how can androgen receptors become upregulated if overall androgen levels stay the same. Are we to believe that androgen receptors specifically upregulate in response to lowered DHT even though overall androgen levels stay the same?

Overall androgen levels don't stay the same. A molecule of testosterone is not the same as a molecule of DHT.

 

[GoldenMane]

Overall androgen levels don't stay the same. A molecule of testosterone is not the same as a molecule of DHT.

DHT is more potent for sure, but androgen levels should remain the same and just as much androgens should bind with androgen receptors, just more testosterone and less DHT. Testosterone does have a lower affinity for androgen receptors than DHT though.

 

[Afro_Vacancy]

DHT is more potent for sure, but androgen levels should remain the same and just as much androgens should bind with androgen receptors, just more testosterone and less DHT. Testosterone does have a lower affinity for androgen receptors than DHT though.

No such precise thing as "androgen levels", every receptor and every androgen is it's own thing.

The only way to define an "androgen level" is to sum over all the distinct androgens and assign each of them an arbitrary weight.

 

[WangMQ]

DHT is more potent for sure, but androgen levels should remain the same and just as much androgens should bind with androgen receptors, just more testosterone and less DHT. Testosterone does have a lower affinity for androgen receptors than DHT though.

Your body upregulates ARs when it feels there's not enough androgens doing its job.

Does your body determine that by the amount of available yet unbound androgen in your system, or the amount of binded androgen who are really doing their job?

 

[buckthorn]

Oral + Topical AA = Fullhead 4 life

nope, not true at all, sorry. oral + topical AA = fullhead for life OR losing all your hair within a year like a chemo patient. role the dice. If you lose it on this combo, rest assured it will never grow back.

 

[GoldenMane]

Okay good points David and Wang, but still, as far as I'm aware testosterone binds to the same androgen receptors as DHT does so shouldn't higher testosterone counteract the lower DHT when on DHT inhibitors? Or is it the lower affinity of testosterone for ARs that results in upregulation?

 

[g.i joey]

The difference between 0.25mg and 1.00 mg in fighting hair loss has been shown by multiple studies to be very, very small.

You have a weird passion for high dosages of finasteride. There's no empirical backing for those high dosages.

No it's more like I spent almost a whole year using .25 till I realized it wasn't doing anything. Only when I moved from .5+ was when I was at the least maintaining. These forums tell people to use a small dosage and it will work.

If you're so convinced that .25 is as good as 1mg link me to 1 success story where a guy uses .25 and shows an actual visual benefit... I'll be waiting

Now don't get me wrong if someone noticed hariloss at 18 and then at 30 is a nw2 .25 may do something but in most cases it's a waste of time.

 

[Fullhead1day]

nope, not true at all, sorry. oral + topical AA = fullhead for life OR losing all your hair within a year like a chemo patient. role the dice. If you lose it on this combo, rest assured it will never grow back.

Wait, what? That doesn't make sense at all in theory. What else will be attacking your follicles then? lol

 

[buckthorn]

Wait, what? That doesn't make sense at all in theory. What else will be attacking your follicles then? lol

testosterone, upregulated androgen receptors... who knows man. there are many accounts of people on both RU58841 and dutasteride that continue to have aggressive hair loss. I have restarted both, so I will let you know.

 

[Fullhead1day]

testosterone, upregulated androgen receptors... who knows man. there are many accounts of people on both RU58841 and dutasteride that continue to have aggressive hair loss. I have restarted both, so I will let you know.

Yeah but topical AA should take care of that. For sure, I'm also on dutasteride + RU

 

[buckthorn]

Yeah but topical AA should take care of that. For sure, I'm also on dutasteride + RU

how long have you been on both of these? any results so far?

 

[Armando Jose]

Well, all i have to offer is my own experience with finasteride. I wish I had never touched the stuff. finasteride did something to greatly worsen my hairloss, like in every way, massive shed, hairloss in places I was completely thick, and every single hair is at least a third of fourth of the thickness of my original hair. Some are almost invisible. I'm a diffuse thinner and have these dead zones all over my scalp now where no hair will ever grow again. I was on 1.25 mg for around 15 months and dropped the dosage to .5 mg. things were more or less stable for awhile and then a month ago I decided to drop it down to .25 mg over a couple weeks. I've only been on .25 mg for ten days. I buzzed my head with a two guard and things had gone rapidly downhill. Given that I didn't ever stop taking finasteride, how could things happen so fast? What happened to the 'flat dose response'? finasteride made my hair follicles super sensitive to androgens. That's the only answer. How does it do that? It has to be AR upregulation which is, for all intents and purposes, might as well be permanent. i would go bald waiting to see if the AR downregulated in response to normal (for me) levels of DHT. I know this really doesn't contribute to your original discussion but I really believe that guys that are losing hair with low DHT should stay away from finasteride or take it in very small doses.

I dunno
"finasteride made my hair follicles super sensitive to androgens. That's the only answer. "

How do you know it?

 

[Samson123]

I know this because of what finasteride did to my hair. As I wrote in my previous post, the hair I still have has become very fine. That was the first red flag that I didn't heed a couple of months into finasteride. I noticed some shed hairs in the sink and was happy to see how think one end was compared to the other. I wasn't even looking at it closely to be able to see the difference. I picked one up to marvel at what great effect finasteride was having on my hair when I noticed that the thinner end was the root side! This was not the case before because I have always been obsessed with hairloss and would often analyze shed hairs and they were always of uniform thickness throughout. What else could cause a hair to visibly thin so fast? It has to be greater sensitivity to the androgens that cause this to happen via some mechanism. What other mechanism do we know of already that could cause this? Most likely AR upregulation. Maybe it could be that my receptors were uptaking other androgens that caused my hair to rapidly thin. I'm open to alternate ideas, but I'm going to punch the next person who say 'well, maybe it was your hairloss just following it's natural progression'. Also the fact that my unbelievably thick and dense donor area thinned out considerably. What else could cause thick donor hair to thin out both in density and hair shaft diameter but a greater sensitivity to androgens?