How Different Types Of Estrogen Promote (and Hinder) Hair Growth

[IdealForehead]

Man, I saw they sold one on amazon but not anymore!
That's very interesting, I will try to look into it as well. I see you can buy it as a powder here:
http://www.lotioncrafter.com/genistein.html

I'm a little sketched out at using estriol, and I refuse to use finasteride since I play sports.

Yeah I just added the lotioncrafter link too while you were replying. I have bought many things from them.

Keep in mind that whether it is human estrogen (eg. Estriol) or soy phytoestrogen (genistein) it does not matter to the body. All that matters is how much it binds your estrogen receptors.

If they bind equally you will get the same feminizing effect.

I'll have to do more research but according to this, genistein may be too weak to be very effective. They list it as 400-600 times less potent than estradiol.

https://www.ncbi.nlm.nih.gov/m/pubmed/17266178/

Also you should absolutely be sketched out at using estrogen. The idea of using estrogen BEFORE you've even tried finasteride is not logical. Estrogen is a desperate measure for a man. Most of us in this thread have tried just about everything before getting to estrogen treatments. It's not the first step and likely never should be, unless you're a woman.

 

[IdealForehead]

Found a good comparison of phytoestrogen strengths:

Considering the potency of body’s endogenous estrogen (17β-estradiol) as 100, in the Ishikawa assay the relative estrogenic potency of these compounds were found to be genistein (0.11), genistin (0.06), daidzein (0.08) and daidzin (0.07). In the yeast cell assay, the relative estrogenic potencies were genistein (0.1), genistin (0.01), daidzein (0.02) and daidzin (0.002). Estrogenic potency of equol was
almost equal (0.18 & 0.16) in both Ishikawa and yeast cell assays, respectively.

http://www.indjst.org/index.php/indjst/article/view/29849​

So it would appear genistein is maybe 2/3 as strong as estriol. S-Equol would be comparable in strength to estriol but its more obscure and not as available in common cream form unless someone can provide a link.

Overall then estriol should still be the best bang for the buck topical estrogen for hair. But genistein might still not be bad given one can easily buy a powder and for example add a bit to any usual topical solution. I might still try that.

 

[whatevr]

Keep in mind that whether it is human estrogen (eg. Estriol) or soy phytoestrogen (genistein) it does not matter to the body. All that matters is how much it binds your estrogen receptors.

Let me just point out one thing.

The difference between ESTRADIOL and ESTRIOL is not only in their binding affinity.

You seem to suggest that if ESTRIOL has a 100x weaker binding affinity, then using 100x as much ESTRIOL will give you the same effect as ESTRADIOL, implying that they have the same biological effect.

This is very false. If that were the case, then anti-androgens like RU would exert the same effect as DHT once bound to the androgen receptor, the whole idea of agonists and antagonists would fall apart.

Estriol besides having a weaker binding affinity will also exert much less estrogenic effects once bound to the receptor. They will be weaker, and probably in a narrower spectrum than estradiol. You can not simply compare them on the basis of binding affinity and assume that if you just use compensate for that, the effect will be the same. It doesn't work like that.

Consequently, if genistein binds to the estrogen receptor, it's very debatable how much and what kind of estrogenic activity it will actually produce in the end. I'd like to see data on that. It's not really even clear what they mean by 'estrogenic potency' in this regard. Are they talking about the spectrum of effects, or their strength ? I suppose they are not talking about binding affinity. It's rather confusing.

 

[Arrade]

Yeah I just added the lotioncrafter link too while you were replying. I have bought many things from them.

Keep in mind that whether it is human estrogen (eg. Estriol) or soy phytoestrogen (genistein) it does not matter to the body. All that matters is how much it binds your estrogen receptors.

If they bind equally you will get the same feminizing effect.

I'll have to do more research but according to this, genistein may be too weak to be very effective. They list it as 400-600 times less potent than estradiol.

https://www.ncbi.nlm.nih.gov/m/pubmed/17266178/

Also you should absolutely be sketched out at using estrogen. The idea of using estrogen BEFORE you've even tried finasteride is not logical. Estrogen is a desperate measure for a man. Most of us in this thread have tried just about everything before getting to estrogen treatments. It's not the first step and likely never should be, unless you're a woman.

My first hope would be that topical estrogen does not metabolize very strongly, if I remember correctly there was an oral S-equol marketed for hairloss, but it was so weak systemically that it definitely no effect on hair (Folexen). And I believe the argument for Brotzu's lotion is that S-equol doesn't have very profound effect in the body.

And I'm wondering, I don't know if it was your post or not but something in the daromulatide thread about daro vs RU58441 not behaving strongly in the body. That daro doesn't pass the blood brain barrier? I couldn't find the page again, but what I got out of it was that topically it could be stronger but systemically weaker or no affect.

 

[Arrade]

The thing for me as well @IdealForehead, is that I thought I remembered that DHT and estrogen often compete for the same receptors. I could be wrong, but in looking into steroids like anavar (synthetic DHT deriviative) and testoterone I thought I saw that it did. For example at the bones or in the brain they compete for the same receptors.

My optimistic theory is that adding estrogen would not be as bad as removing DHT, or that your circulating DHT would prevent added estrgoen from having bad side effects by out competing at the same receptor sites.
Thus, topical estrogen may work like RU54881 and not be very active in the body, while still have a strong affect on the hair follicles.
I'm on adderall right now so maybe I will get back to you on this, I'd like to see understand the dangers of topical estrogen to its full extent

 

[IdealForehead]

Let me just point out one thing.

The difference between ESTRADIOL and ESTRIOL is not only in their binding affinity.

You seem to suggest that if ESTRIOL has a 100x weaker binding affinity, then using 100x as much ESTRIOL will give you the same effect as ESTRADIOL, implying that they have the same biological effect.

This is very false. If that were the case, then anti-androgens like RU would exert the same effect as DHT once bound to the androgen receptor, the whole idea of agonists and antagonists would fall apart.

Estriol besides having a weaker binding affinity will also exert much less estrogenic effects once bound to the receptor. They will be weaker, and probably in a narrower spectrum than estradiol. You can not simply compare them on the basis of binding affinity and assume that if you just use compensate for that, the effect will be the same. It doesn't work like that.

Consequently, if genistein binds to the estrogen receptor, it's very debatable how much and what kind of estrogenic activity it will actually produce in the end. I'd like to see data on that. It's not really even clear what they mean by 'estrogenic potency' in this regard. Are they talking about the spectrum of effects, or their strength ? I suppose they are not talking about binding affinity. It's rather confusing.

Comparisons of strength for agonists ideally should start with EC50 data. This is what we want because it registers concentration required for a certain biological effect.

The EC50 is the concentration of a drug that gives half-maximal response
​

For androgen receptor antagonists we use IC50 data which i summarized here:

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

Dose response curves are not linearly related so you can't make a direct linear comparison.

Curves for different potency agonists will typically look like this:

In this random example I've pulled up, CCPA is a much stronger agonist here so it's ec50 will be much lower. But you can see with higher concentrations of the other agents almost equal maximal effect can be achieved. There is no linear relationship so you can't say exactly how much more of something is needed for equal effect without all the curve data for all agents. But in principle, yes, weaker agonism or antagonism can generally be compensated for up to a point by increasing concentration.

In the phytoestrogen strength comparison study I posted you can see they are measuring biological activity stimulated by binding as well. Not whether or not it binds. But the biological outcome of binding.

So long as your assay is assessing biological activity (EC50/IC50) or some other direct biological outcome of activation then it is useful info.

I think that is correct what you say that "affinity" by itself is not useful, as affinity is just its binding capacity, and it could bind as an antagonist or agonist for all you know just based on affinity alone.

 

[IdealForehead]

Just found the mother of all estrogen articles which I think explains the issue @whatevr raised well and provides comprehensive strength data on all the estrogens.

Here is how they explain strength of an estrogen may be mediated:

Conceptually, the potency of an estrogen in activating a cellular response should reflect the affinities that characterize both steps involved in the assembly of the active ligand·receptor·coactivator complex. Thus, to better understand the molecular basis of estrogen potency, we developed a completely in vitro system (using radiometric and time-resolved FRET assays) to quantify independently three parameters: (a) the affinity of ligand binding to ER, (b) the affinity of coactivator binding to the ER·ligand complex, and (c) the potency of ligand recruitment of coactivator. We used this system to characterize the binding and potency of 12 estrogens with both ERα and ERβ. Some ligands showed good correlations between ligand binding affinity, coactivator binding affinity, and coactivator recruitment potency with both ERs, whereas others showed correlations with only one ER subtype or displayed discordant coactivator recruitment potencies. When ligands with low receptor binding affinity but high coactivator recruitment potencies to ERβ were evaluated in cell-based assays, elevation of cellular coactivator levels significantly and selectively improved their potency. Collectively, our results indicate that some low affinity estrogens may elicit greater cellular responses in those target cells that express higher levels of specific coactivators capable of binding to their ER complexes with high affinity.

We found that the relationship between ligand binding affinity and coactivator binding to ER·ligand complex is both ligand- and ER subtype-specific, and we found that the cellular potencies of estrogens correlated better with a combination of RCA and RRP than RLA. Thus, we demonstrate the importance of evaluating estrogen ligand potencies in the context of coactivators, and we also provide evidence that some weakly binding estrogens might be able to elicit considerable biological activity in target cells that express the proper combination of ER subtype and coactivator levels. In this regard, it is particularly notable that elevated levels of SRC3 can cause a preferential increase in the potency of certain ligands through ERβ.
​

Here is their primary data:

(RCA = relative co-activator binding affinity, RRE = relative recruitment efficacy)

It will take me more time to fully understand all this. Perhaps someone else can figure it out better than me. But from what I see, estriol (E3) does well on the ER-beta end of the spectrum compared with estradiol (E2). This is based on all three measures of EC50, RCA, and RRE. I think genistein did much more poorly based on its EC50 and RCA here.

The point is, I guess, it is very complicated to try to guess total power of a given estrogen and it will depend on variables like how much and what types of cofactors are present in the target tissue.

Ref:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075970/

 

[rclark]

I dont mind boobs, Id have them any day over hairloss. But them being asymmetrical bothers me lol. Did your fat years boobs not go away at all? Im pretty sure you'll lose them if you lose weight, I always thought fat man boobs and gyno boobs were different and the former can be removed by losing weight but I may be wrong on this.

That's the thing.

If man boobs stay for a period of time, they don't go away. Once so much time has passed, you
have to get the fat surgically removed.

 

[Jesse Navarro]

Prolactin levels are elevated by use of cyproterone? And is it necessarily bad for hair? Gonna monitor this.

 

[Arrade]

Just found the mother of all estrogen articles which I think explains the issue @whatevr raised well and provides comprehensive strength data on all the estrogens.

Here is how they explain strength of an estrogen may be mediated:

Conceptually, the potency of an estrogen in activating a cellular response should reflect the affinities that characterize both steps involved in the assembly of the active ligand·receptor·coactivator complex. Thus, to better understand the molecular basis of estrogen potency, we developed a completely in vitro system (using radiometric and time-resolved FRET assays) to quantify independently three parameters: (a) the affinity of ligand binding to ER, (b) the affinity of coactivator binding to the ER·ligand complex, and (c) the potency of ligand recruitment of coactivator. We used this system to characterize the binding and potency of 12 estrogens with both ERα and ERβ. Some ligands showed good correlations between ligand binding affinity, coactivator binding affinity, and coactivator recruitment potency with both ERs, whereas others showed correlations with only one ER subtype or displayed discordant coactivator recruitment potencies. When ligands with low receptor binding affinity but high coactivator recruitment potencies to ERβ were evaluated in cell-based assays, elevation of cellular coactivator levels significantly and selectively improved their potency. Collectively, our results indicate that some low affinity estrogens may elicit greater cellular responses in those target cells that express higher levels of specific coactivators capable of binding to their ER complexes with high affinity.

We found that the relationship between ligand binding affinity and coactivator binding to ER·ligand complex is both ligand- and ER subtype-specific, and we found that the cellular potencies of estrogens correlated better with a combination of RCA and RRP than RLA. Thus, we demonstrate the importance of evaluating estrogen ligand potencies in the context of coactivators, and we also provide evidence that some weakly binding estrogens might be able to elicit considerable biological activity in target cells that express the proper combination of ER subtype and coactivator levels. In this regard, it is particularly notable that elevated levels of SRC3 can cause a preferential increase in the potency of certain ligands through ERβ.
​

Here is their primary data:

View attachment 83529
(RCA = relative co-activator binding affinity, RRE = relative recruitment efficacy)

It will take me more time to fully understand all this. Perhaps someone else can figure it out better than me. But from what I see, estriol (E3) does well on the ER-beta end of the spectrum compared with estradiol (E2). This is based on all three measures of EC50, RCA, and RRE. I think genistein did much more poorly based on its EC50 and RCA here.

The point is, I guess, it is very complicated to try to guess total power of a given estrogen and it will depend on variables like how much and what types of cofactors are present in the target tissue.

Ref:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075970/

i’ll look Again but I’m pretty sure Genistein had a much higher RRP, which is receptor potency. It was like 200 times more potent than estradiol for activating estrogen beta in Table 3.
The table you provided also seemed to show a better estrogen beta/estrogen alpha ratio (4?) than Estriol

 

[rclark]

Than you shouldnt be afraid of getting on HRT considering you already have tits lol

Why are you afraid about "UNEVEN BOOBS"?

Are you a male or female?

 

[IdealForehead]

Well I can't completely sort this out without putting more mental energy into it that I don't have to give right now so I just decided on the basis of (1) genistein having a dramatic ER-beta binding preference, (2) genistein being easy to get cheap powder of, to try buying some.

Ordered 25 grams from lotioncrafter. I'm gonna start adding it to my topical scalp solution (with daro, niacinamide, and desloratadine).

I'll keep using estriol cream on my face and hairline. That plus the genistein in my solution should give me a pretty good and favorable estrogenic stimulation in the places I want it.

We'll see.

 

[whatevr]

Well I can't completely sort this out without putting more mental energy into it that I don't have to give right now so I just decided on the basis of (1) genistein having a dramatic ER-beta binding preference, (2) genistein being easy to get cheap powder of, to try buying some.

Ordered 25 grams from lotioncrafter. I'm gonna start adding it to my topical scalp solution (with daro, niacinamide, and desloratadine).

I'll keep using estriol cream on my face and hairline. That plus the genistein in my solution should give me a pretty good and favorable estrogenic stimulation in the places I want it.

We'll see.

Good experiment, somehow I still don't think that these plant estrogens come anywhere close to estradiol (potency-wise). I'd love to be proven wrong though.

 

[IdealForehead]

More evidence that ER-beta is the target we want to trigger for the positives of estrogen therapy:

The distribution of estrogen receptor beta is distinct to that of estrogen receptor alpha and the androgen receptor in human skin and the pilosebaceous unit.

Both estrogens and androgens play important parts in skin and hair physiology, although studies of estrogen action in human skin have been rather limited. Recently, a second estrogen receptor (beta) has been identified in many nonclassical target tissues, including androgen-dependent tissues. Therefore, we have revisited the role of estrogens in human skin and hair by comparing the pattern of expression by immunohistochemistry for both estrogen receptors (alpha and beta) and the androgen receptor. Immunolocalization of androgen receptors was only seen in hair follicle dermal papilla cells and the basal cells of the sebaceous gland. Little specific staining of estrogen receptor alpha was seen anywhere except the sebaceous gland. In contrast estrogen receptor beta was highly expressed in epidermis, blood vessels, and dermal fibroblasts, whereas in the hair follicle it was localized to nuclei of the outer root sheath, epithelial matrix, and dermal papilla cells. Serial sections also showed strong nuclear expression of estrogen receptor beta in the cells of the bulge, whereas neither estrogen receptor alpha or androgen receptor was expressed. In the sebaceous gland, estrogen receptor beta was expressed in both basal and partially differentiated sebocytes in a similar pattern to estrogen receptor alpha. There was no obvious difference in the expression of either estrogen receptor in male or female nonbalding scalp skin. The results of this immunohistochemical study propose that estrogen receptor beta and not estrogen receptor alpha is the main mediator of estrogen action in human skin and the hair follicle. Further studies with androgen-dependent skin are required to determine whether estrogen receptor beta has a regulatory role on androgen receptor expression in the hair follicle in parallel with its role in other androgen-dependent tissues.

https://www.ncbi.nlm.nih.gov/m/pubmed/12895004/
​

I still have to put some more work into understanding that estrogen strength article so I can calculate likely dose equivalences. But I think genistein is looking better and better.

- I can dissolve probably around 1% into my usual topical (estriol creams are compounded at 0.3% strength for acne).
- Even if we assume genistein is 1/3 as strong as estriol, this should still give plenty of biological effect.
- Genistein is cheap as dirt and almost purely an ER-beta agonist.

I'll update when my powder arrives.

 

[Arrade]

More evidence that ER-beta is the target we want to trigger for the positives of estrogen therapy:

The distribution of estrogen receptor beta is distinct to that of estrogen receptor alpha and the androgen receptor in human skin and the pilosebaceous unit.

Both estrogens and androgens play important parts in skin and hair physiology, although studies of estrogen action in human skin have been rather limited. Recently, a second estrogen receptor (beta) has been identified in many nonclassical target tissues, including androgen-dependent tissues. Therefore, we have revisited the role of estrogens in human skin and hair by comparing the pattern of expression by immunohistochemistry for both estrogen receptors (alpha and beta) and the androgen receptor. Immunolocalization of androgen receptors was only seen in hair follicle dermal papilla cells and the basal cells of the sebaceous gland. Little specific staining of estrogen receptor alpha was seen anywhere except the sebaceous gland. In contrast estrogen receptor beta was highly expressed in epidermis, blood vessels, and dermal fibroblasts, whereas in the hair follicle it was localized to nuclei of the outer root sheath, epithelial matrix, and dermal papilla cells. Serial sections also showed strong nuclear expression of estrogen receptor beta in the cells of the bulge, whereas neither estrogen receptor alpha or androgen receptor was expressed. In the sebaceous gland, estrogen receptor beta was expressed in both basal and partially differentiated sebocytes in a similar pattern to estrogen receptor alpha. There was no obvious difference in the expression of either estrogen receptor in male or female nonbalding scalp skin. The results of this immunohistochemical study propose that estrogen receptor beta and not estrogen receptor alpha is the main mediator of estrogen action in human skin and the hair follicle. Further studies with androgen-dependent skin are required to determine whether estrogen receptor beta has a regulatory role on androgen receptor expression in the hair follicle in parallel with its role in other androgen-dependent tissues.

https://www.ncbi.nlm.nih.gov/m/pubmed/12895004/
​

I still have to put some more work into understanding that estrogen strength article so I can calculate likely dose equivalences. But I think genistein is looking better and better.

- I can dissolve probably around 1% into my usual topical (estriol creams are compounded at 0.3% strength for acne).
- Even if we assume genistein is 1/3 as strong as estriol, this should still give plenty of biological effect.
- Genistein is cheap as dirt and almost purely an ER-beta agonist.

I'll update when my powder arrives.

I'm interested in your research. Yes from what I read, the soy isoflavones such as genistein or equol have the best affinity for the beta receptors. I don't know if taking estriol and genistein at the same time if they would compete for the same receptors. In your experimentation it might prove useful to try solely genistein, at least for a period.
"even more preferably S- equol, at a concentration comprised between 0.1% and 2% and preferably between 0.3% and 1% of the phospholipid amount used" - this is in the patent for the Brotzu potion, so it seems your predicted concentration is similar to their use.
Wikipedia shows: Genistein – phytoestrogen; 16-fold selectivity for ER-β over ERα > 13-fold selectivity of S-equol
I Know genistein is different from equol; it's interesting to see that it may be more potent, even though you can find it much cheaper.

 

[bridgeburn]

According to wikipedia on ethynl estradiol?
"It binds to and activates both isoforms of the estrogen receptor, ERα and ERβ.[34] In one study, EE was found to have 233% and 38% of the affinity of estradiol for the ERα and ERβ, respectively.[35] In another study, it was found to possess 194% and 151% of the affinity of estradiol for the ERα and ERβ, respectively.[36]"

 

[IdealForehead]

Some stuff on genistein vs s equol and the risks of genistein:

It has been suggested that equol has greater affinity for the estrogen receptor than its parent precursor daidzein, and has similar potency to genistein.

The results showed that genistein has a potent inhibitory effect on 3β-HSD activity, which is presumably linked to its ability to suppress androgen biosynthesis. In comparison with genistein, equol exerted a lesser inhibitory effect on human testis microsomes and had no effect on 17β-HSD3 activity in both the human and rat testis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739362/
​

So long high doses of genistein might suppress testosterone production. Still gonna try it. Of course the goal is to get as much local ER-beta stimulation by using it topically as possible while minimizing systemic effect. But that's never completely possible.

 

[IdealForehead]

According to wikipedia on ethynl estradiol?
"It binds to and activates both isoforms of the estrogen receptor, ERα and ERβ.[34] In one study, EE was found to have 233% and 38% of the affinity of estradiol for the ERα and ERβ, respectively.[35] In another study, it was found to possess 194% and 151% of the affinity of estradiol for the ERα and ERβ, respectively.[36]"

That's helpful and it is probably more correct than the references I cited in the first post of this thread.

According to their reference #35 though its still very heavily weighted towards ER-alpha. Even as per #36 its more heavily weighted to ER-alpha though not as dramatically.

At absolute best, this extra ER-alpha stimulation is likely neutral or useless. The skin biopsy study showed there werent a lot of ER-alpha receptors in human scalp. This may mean we are less vulnerable to the ER-alpha catagen induction issue than mice are, and ER-alpha stimulation may not be as immediately damaging.

But it also definitely seems to be the case that ER-beta is the receptor that we want to stimulate. And given that ER-alpha is associated with inflammatory conditions like arthritis and osteoporosis, no one should probably want more ER-alpha agonism than they truly need. For us, as men, I think we want as little ER-alpha as possible to get good hair growth and minimize side effects.

For women like Georgie it's probably more complicated because she will need a more balanced estrogen profile throughout her body for her uterus, etc. and some degree of ER-alpha stimulation will be necessary.

 

[bridgeburn]

For us, as men, I think we want as little ER-alpha as possible to get good hair growth and minimize side effects.

Surely alpha must be good for something! oh, Also on the EE wiki page it claims Estrogens have antigonadotropic effects through activation of the ERα.

For women like Georgie it's probably more complicated because she will need a more balanced estrogen profile throughout her body for her uterus, etc. and some degree of ER-alpha stimulation will be necessary.

From the pics she posts, her hair actually looks pretty good to me

 

[IdealForehead]

Surely alpha must be good for something! oh, Also on the EE wiki page it claims Estrogens have antigonadotropic effects through activation of the ERα.

From the pics she posts, her hair actually looks pretty good to me

I think we have to mentally subdivide estrogen therapy for male pattern hair loss into two categories:

1) High amounts of systemic estrogen with a goal of shutting down androgen production as well as possibly stimulating hair follicles. In this approach I dont think it matter which type of estrogen you use too much since any will chemically castrate you in sufficient amounts. Though still probably an ER-beta weighting is favorable.

2) Small amounts of topical estrogen with a goal of leaving systemic hormone levels unaffected and just stimulating hair growth locally at the follicles. In this approach (which is what I will be aiming for with genistein/estriol), you really only want ER-beta stimulation since that's what seems to be expressed in the follicles. ER-beta seems to be the receptor that triggers estrogen mediated anagen cycling. Any ER-alpha stimulation is likely neutral or unhelpful in this case.

As for @Georgie she still has great hair but there's no doubt if you see her hair a few years ago she's lost a fair amount. She definitely needs to get it under control and it's good she's trying in my opinion before she gets very thin. She has at this point stumped many specialists with her hair and hormones so its mostly speculation. But by process of elimination and based on the fact that she is losing hair head to toe (ie. Not a truly androgenic pattern), her biopsies and blood showed no other problems, and this diffuse full body hair loss pattern is common in menopausal women, my money is still on imbalanced and faulty estrogen signalling due to her ovarian failure and reliance on Diane 35 for hormone replacement as the primary cause.

Looks like she's starting the process of switching over to more natural estrogen therapy soon, so we will see.