S-equol (or Similar) Will Likely Be Better Than Ru. Poor Performance Of Ar Antagonists Explained

whatevr

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These past few days I was trying to figure out why compounds such as RU58841 typically do not result in regrowth if the androgenic activity is largely stopped - RU after all is a powerful AR antagonist, and if the AR is knocked out of commission that should effectively allow estrogen to dominate and cause regrowth. However, this typically doesn't happen.

After a while I made the conclusion that there must be more ways that DHT interacts with the hair follicle than merely through its own AR 'receptor'. If we further connect this thought with the well known fact that DHT is a strong estrogen antagonist, after a bit of searching, I discovered this study:

Thus, the antiestrogenic effect of androgen in mouse breast may be the result of effects of dihydrotestosterone on the estrogen receptor. If so, dihydrotestosterone performs one of its major actions independent of the androgen receptor.

It seems that not only does DHT kill your hair follicle by activating its androgen receptor, it also prevents estrogen from healing the follicle by modulating estrogen's receptor. When you block the AR with a compound like RU58841, you are at best only negating a part of DHT's destructive effect on the hair follicle. It will still largely inhibit the effect of estrogen by acting on the estrogen receptor thus preventing regrowth and reversal of miniaturization.

That is why, for the most part, RU58841 and other AR 'receptor' antagonists you can at best only expect maintenance.

A molecule such as S-Equol sounds like it would theoretically be superior to RU in every way.
The ideal solution is not just to block the AR, but to prevent DHT from interacting with anything in the scalp, and the best way to do that is to bind the DHT molecule like SHBG or S-Equol would do. If we achieve high enough concentration of S-Equol it will likely mop up the majority of DHT in the scalp, and you can enjoy watching your hair grow out stronger and thicker with every passing cycle.

The flipside of this question is then, why don't finasteride or dutasteride cause regrowth if they prevent the DHT from being made in the first place. I think the answer to this question is simply a matter of androgen/estrogen ratio, perhaps the problem is that both of these medications still leave a fair amount of DHT in the scalp, while removing it in the serum and other areas in far greater amounts. Perhaps the amount of estrogen a normal male has is still not enough to overcome the 30% or so of remaining scalp DHT even on Dutasteride. Certainly if we were able to disable >95% of the DHT in the scalp we would probably see regrowth in the majority of users, and maybe if that weren't enough a very low dose of estrogen to the scalp would probably be enough to tip almost everyone into regrowth territory.
 
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Afro_Vacancy

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Interesting that you brought up SHBG.

SHBG is the only blood parameter that is measured to correlate with baldness in a statistically significant way. The lower your SHBG, the stronger your baldness, it's not absolute but it's the strongest correlation that's been measured by an overwhelming margin.

In contrast, testosterone and DHT show little correlation with baldness.

I've managed to increase my SHBG in the past 1.5 years but I'm not sure it's enough to make a difference, as the science of that correlation is not understood.

By the way I think s-equol also tickles the estrogen receptor.
 

whatevr

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Interesting that you brought up SHBG.

SHBG is the only blood parameter that is measured to correlate with baldness in a statistically significant way. The lower your SHBG, the stronger your baldness, it's not absolute but it's the strongest correlation that's been measured by an overwhelming margin.

In contrast, testosterone and DHT show little correlation with baldness.

I've managed to increase my SHBG in the past 1.5 years but I'm not sure it's enough to make a difference, as the science of that correlation is not understood.

By the way I think s-equol also tickles the estrogen receptor.

Indeed, going by the school of thought that only 'free' hormones are biologically active (Free T, Free DHT...) it makes sense that the less SHBG, the more active and unbound hormones are around, the more baldness...

I believe Bryan Shelton who used to frequent HairLossTalk.com and HLH many times made the argument about DHT being an 'autocrine' rather than an 'endocrine' hormone - that meaning that it is primarily active on the site where it is made, rather than contributing via systemic circulation. That would explain serum DHT not meaning much in the global severity of baldness and it would also mean that inhibiting scalp DHT would be enough to help with baldness, without the need for crushing it systemically like Finasteride or Dutasteride do. I don't believe there is conclusive evidence for this yet but it wouldn't surprise me if this were the case. I believe finasteride and dutasteride leave around 50% and 30% of scalp DHT intact, respectively, and for some people even that is not enough to stop hair loss completely (all the while nuking serum levels 70+%).
 

Afro_Vacancy

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Indeed, going by the school of thought that only 'free' hormones are biologically active (Free T, Free DHT...) it makes sense that the less SHBG, the more active and unbound hormones are around, the more baldness...

I believe Bryan Shelton who used to frequent HairLossTalk.com and HLH many times made the argument about DHT being an 'autocrine' rather than an 'endocrine' hormone - that meaning that it is primarily active on the site where it is made, rather than contributing via systemic circulation. That would explain serum DHT not meaning much in the global severity of baldness and it would also mean that inhibiting scalp DHT would be enough to help with baldness, without the need for crushing it systemically like Finasteride or Dutasteride do. I don't believe there is conclusive evidence for this yet but it wouldn't surprise me if this were the case. I believe finasteride and dutasteride leave around 50% and 30% of scalp DHT intact, respectively, and for some people even that is not enough to stop hair loss completely (all the while nuking serum levels 70+%).

I don't follow that argument at all. If DHT is an autocrine hormone, why would SHBG have any effect at all? SHBG affects circulating hormones.
 

whatevr

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I don't follow that argument at all. If DHT is an autocrine hormone, why would SHBG have any effect at all? SHBG affects circulating hormones.

It's a good question. I agree that a lot about this still isn't fully understood. For example this study seems to suggest that even SHBG-bound hormones can be taken up into the cell:

https://www.ncbi.nlm.nih.gov/pubmed/7529185

Ultimately I think the clue is to be found within the real-world results. We typically don't see regrowth from AR antagonists (which I believe is decently explained in the OP), and we don't really see it from 5-AR inhibitors either. We know they take out a good deal of serum DHT, but leave a moderate amount of scalp DHT still intact - to me that suggests the importance of the remaining scalp DHT in causing hair loss.
 

Afro_Vacancy

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Since you believe in this, consider getting your SHBG levels tested, and then making lifestyle changes to increase them if they're low.
 

whatevr

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Since you believe in this, consider getting your SHBG levels tested, and then making lifestyle changes to increase them if they're low.

I could get it tested. Interestingly enough when I used to do alternate-day fasting 2-3x a week, several years ago, I developed a serious case of hyperandrogenicity. Drastic surge in libido, painful cystic acne out of nowhere, oily face and scalp, hair loss started right about that time as well.
That would suggest lower SHBG i.e. much more free androgens. It took me some months of 'normal' eating for that to subside.
 

abcdefg

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The problem for years with s-equol is there is no magic s-equol store selling it formulated for male pattern baldness. The evidence it works is still flimsy, and people say its a pretty expensive thing to manufacture.
If it was easily accessible, and affordable more people would try it. There is enough talk about alternative DHT inhibitors to fill books. We still dont have one anyone agrees on that works.
 

rclark

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I've always thought that estrogen genetically made the hair stronger, and stay in the growth cycle for a longer
period of time than normal. Most women don't start losing their hair until after menopause, it's a known fact. After
menopause their ovaries still produce testosterone, although it is still much less than males. Men produce a small
amount of progesterone in their testes, which gets converted to testosterone.

Pregnant women don't lose their hair until around three to five months after child birth. That definitely states something.
That, and the fact that there bodies could be producing androgens if they are carrying a male child. Yet they still do
not lose their hair.

DHT provides more than just secondary male characteristics. It's very important in development, and probably influences
our neurology to some degree.
 

bridgeburn

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Strong antagonists with good half lives like darolutamide absolutely work and I'm getting good results/regrowth as we speak.
are there really no sides with this?
 

IdealForehead

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are there really no sides with this?
Well in theory you are at risks of all antiandrogenic sides which run the gamut from dry skin to infertility to osteoporosis etc.

I'm using 6 mg a day topically. Prostate cancer dose is 600 mg twice daily orally. So my dose is absolutely tiny.

I'm still getting a tiny bit of dry eyes on this dose but it's tolerable. I intend to drop it to 4-5 mg next and see if that resolves eventually. Otherwise it's been fine for me.
 

bridgeburn

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Well in theory you are at risks of all antiandrogenic sides which run the gamut from dry skin to infertility to osteoporosis etc.

I'm using 6 mg a day topically. Prostate cancer dose is 600 mg twice daily orally. So my dose is absolutely tiny.

I'm still getting a tiny bit of dry eyes on this dose but it's tolerable. I intend to drop it to 4-5 mg next and see if that resolves eventually. Otherwise it's been fine for me.
does it just block the receptor, or does it act on the HPG axis as well?
 

IdealForehead

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does it just block the receptor, or does it act on the HPG axis as well?

Read the thread. It doesn't cross the blood brain barrier, so there's negligible change in any circulating hormone levels induced by its use even at high levels.

As pure and clean a receptor antagonist as exists on this planet.
 

IdealForehead

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don't tell me what to do
cartman-i-do-what-i-want.jpg
 

BetaBoy

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I know this is a long time ago, but I just want to say while this thread is revived that the failure of RU in my opinion has to do with its short half life above all else:

https://www.hairlosstalk.com/intera...conversion-of-ru58841-to-darolutamide.109065/

Strong antagonists with good half lives like darolutamide absolutely work and I'm getting good results/regrowth as we speak.

If general consensus among those who are currently trialling ODM-201 remains positive I'll hopefully switch out the oral AA's I'm currently on for it sometime in early 2018.

From what you have written above are you implying S-equol has a half-life similar to RU? S-equol as far as I can tell should be quite an effective weapon against Androgenetic Alopecia, it binds to DHT, and is an agonist of the β-oestrogen receptor.
 
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