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

[John Difool]

Based on this patent, I am looking at oral or topical administration of Equol. What would be similar dosages on human by mouth or on the scalp?

https://patents.google.com/patent/US20140135387A1/en

 

[Androgenic Alpaca]

Based on this patent, I am looking at oral or topical administration of Equol. What would be similar dosages on human by mouth or on the scalp?

https://patents.google.com/patent/US20140135387A1/en

I am also very interested in Equol. Not only does it seem to bind to DHT, but S-Equol is also a selective agonist of the ERβ receptor which should have positive effects on hair growth and overall skin health. It also seems to be an antioxidant, too.

Like you, I also have questions about Equol, though. I don't know what the best dosage is. I don't know whether a racemic mixture of equol would be good or if enantiopure (S)-Equol is needed. I don't know the best place to cheaply source it, and I don't know whether topical or oral is best method of administration.

If anyone has more data on equol, I'd love to see it.

This seems kinda far-fetched, but I'm even willing to try a soy-based diet and mega-dose on soy isoflavones to see if that'll metabolize into S-Equol. Apparently most westerners lack the needed bacteria to metabolize the soy isoflavones into equol, however. And its not entirely clear how to develop the proper gut flora to do this.

 

[Androgenic Alpaca]

Also, while I'm in this thread, to continue the earlier conversation about alfatradiol:

The fact that alfatradiol has a greater affinity for the ERα receptor should actually be a good thing, right? Because it has a much lower estrogenic activity than estradiol, it'd be a partial agonist of the ERα receptor so it'll block the receptor from stronger agonists like E2, right? Essentially the same mechanism that steroidal anti-androgens work on - partial agonism of the (in the case of AAs) androgen receptor.

This is just speculation on my part, would love to hear other opinions.

 

[whatevr]

Speculation indeed. Even if you could completely block estrogen receptor alpha and agonize beta, the damage still comes via AR. It's pretty clear experimentally that even serious ER agonism via estradiol can't outcompete DHT's harmful effect. Now you could argue that estradiol agonizes both receptors and hence isn't a good example, but alfatradiol isn't going to be much better in practice - it just doesn't do a whole lot. You can get it over the counter, it's probably one of the first things most people try (in Germany and places where it's easily available), and really, for the price (it's quite expensive) I'd much rather use minoxidil or even fluridil.

 

[Androgenic Alpaca]

Speculation indeed. Even if you could completely block estrogen receptor alpha and agonize beta, the damage still comes via AR. It's pretty clear experimentally that even serious ER agonism via estradiol can't outcompete DHT's harmful effect. Now you could argue that estradiol agonizes both receptors and hence isn't a good example, but alfatradiol isn't going to be much better in practice - it just doesn't do a whole lot. You can get it over the counter, it's probably one of the first things most people try (in Germany and places where it's easily available), and really, for the price (it's quite expensive) I'd much rather use minoxidil or even fluridil.

My understanding is that the main mechanism of action of Alfatradiol is that it is a 5ar inhibitor. Any effects on the estrogen receptors would be secondary and minor. I was responding to earlier comments about whether the ERα agonism of alfatradiol would have negative effects which outweigh the positive effects of its 5ar inhibition.

In any case, I think ER agonism could provide a very effective treatment for hair loss reversal - but only if a 5ar inhibitor (or an antiandrogen) is used in addition.

Regardless, I agree with you about alfatradiol not being worth the cost. I don't use it myself because its high price and difficulty in sourcing in the USA and because its effects seem to be minor, especially compared to a more effective 5ari like finasteride.

 

[whatevr]

My understanding is that the main mechanism of action of Alfatradiol is that it is a 5ar inhibitor. Any effects on the estrogen receptors would be secondary and minor. I was responding to earlier comments about whether the ERα agonism of alfatradiol would have negative effects which outweigh the positive effects of its 5ar inhibition.

Right. However, that gets me thinking, we could technically do that with the androgen receptor as well. For example, using a weaker androgen in large amounts essentially becomes an anti-androgen, preferably one that cannot be metabolized into DHT, as in high enough dose, will displace stronger androgens from the AR. There are even such crazy ideas out there:

 

[Androgenic Alpaca]

Right. However, that gets me thinking, we could technically do that with the androgen receptor as well. For example, using a weaker androgen in large amounts essentially becomes an anti-androgen, preferably one that cannot be metabolized into DHT, as in high enough dose, will displace stronger androgens from the AR. There are even such crazy ideas out there:

Yeah I think that if there is ever a "magic cure" for androgenic alopecia, it'll be some combination of a SERM + SARM. The problem would be to design a proper SARM that is anti-androgenic in scalp tissue without effecting other tissues (and not down regulating endogenous testosterone production) and a SERM that is a ERβ agonist in scalp tissue with anti-estrogenic effects in other tissues. I'm not a biochemist, though, so I won't be making those any time soon.

In reference to that first video you posted, isn't bicalutamide already a therapy that prevents androgenic effects of androgens while maintaining their anabolic effects? Bicalutamide obviously blocks androgen receptors, but it actually upregulates endogenous testosterone production, so wouldn't this lead to high testosterone levels and the testosterone would maintain its anabolic effects, correct? Any side effects would come from endogenous testosterone aromatizing to estrogen (which is why bicalutamide has high rates of gyno) but this could be prevented with an aromatase inhibitor or SERM, right?



Anyway, back on topic for this thread: I've recently started topical application of an estriol cream that I bought on amazon. It supposedly contains 5mg estriol per pump. I'm using two pumps on my scalp and one pump on my face (hopefully for increased collagen production, anti-acne, and anti-aging) twice a day, or 30mg total. Will this be a high enough dose? Will it have any positive effects?

 

[Sanchez1234]

Yeah I think that if there is ever a "magic cure" for androgenic alopecia, it'll be some combination of a SERM + SARM. The problem would be to design a proper SARM that is anti-androgenic in scalp tissue without effecting other tissues (and not down regulating endogenous testosterone production) and a SERM that is a ERβ agonist in scalp tissue with anti-estrogenic effects in other tissues. I'm not a biochemist, though, so I won't be making those any time soon.

In reference to that first video you posted, isn't bicalutamide already a therapy that prevents androgenic effects of androgens while maintaining their anabolic effects? Bicalutamide obviously blocks androgen receptors, but it actually upregulates endogenous testosterone production, so wouldn't this lead to high testosterone levels and the testosterone would maintain its anabolic effects, correct? Any side effects would come from endogenous testosterone aromatizing to estrogen (which is why bicalutamide has high rates of gyno) but this could be prevented with an aromatase inhibitor or SERM, right?



Anyway, back on topic for this thread: I've recently started topical application of an estriol cream that I bought on amazon. It supposedly contains 5mg estriol per pump. I'm using two pumps on my scalp and one pump on my face (hopefully for increased collagen production, anti-acne, and anti-aging) twice a day, or 30mg total. Will this be a high enough dose? Will it have any positive effects?

I trialed estriol recently. 80mg in total. Gave me gyno. But im prone to it. Pegasus and obsessive are doing 2ml x 20mg and think it had benefit.

 

[Canuto]

In reference to that first video you posted, isn't bicalutamide already a therapy that prevents androgenic effects of androgens while maintaining their anabolic effects? Bicalutamide obviously blocks androgen receptors, but it actually upregulates endogenous testosterone production, so wouldn't this lead to high testosterone levels and the testosterone would maintain its anabolic effects, correct? Any side effects would come from endogenous testosterone aromatizing to estrogen (which is why bicalutamide has high rates of gyno) but this could be prevented with an aromatase inhibitor or SERM, right?

It doesn't work like that. A high enough dose of bicalutamide will displace all androgens from the AR, making it impossible for them to express their androgenic effects. You can have a 2000 ng/dL total T level in serum, but if it doesn't reach the AR, it can't do its job.

A classic example of that is a SERM like clomid. While it raises E2 in serum, it can give some low E2 symptoms in some tissues, the most common being the eyes, due to the fact that it binds to the estrogen receptor and makes it impossible for the estrogens to express their activity.

Regarding the estrogens topic, they have been prescribed and used topically by thricologists since more than 20 years in Italy. The most common being 17-a estradiol and estrone (both in its sulfate or bio identical version). Thricograms have shown more than often an improvement in hair density and diameter, but obviously won't do much as a monotherapy, like almost everything.
Estriol doesn't really get prescribed often, due to its weakness compared to the other estrogens.

 

[Canuto]

Based on this patent, I am looking at oral or topical administration of Equol. What would be similar dosages on human by mouth or on the scalp?

The patent looks a bit confused. First of all it's not clear how equol would "bind to DHT". What it can do is binding to the AR receptors or play the role of SHBG and bind to DHT, avoiding a bigger amount of free DHT to express its androgenic activity, along with freeing more SHBG that it's then available to bind to total T and E2. The result would be a lower free T, lower free E2 and lower free DHT.

What the study seems to ignore is that DHT gets produced locally in tissues, so the serum levels are irrelevant anyway and it's not what they should target.

In practical application several people tried topical s-equol in Italy after the Trinov's marketing campaign at dosages of 10mg per ml. No one ever reported any result whatsoever.

 

[Androgenic Alpaca]

It doesn't work like that. A high enough dose of bicalutamide will displace all androgens from the AR, making it impossible for them to express their androgenic effects. You can have a 2000 ng/dL total T level in serum, but if it doesn't reach the AR, it can't do its job.

A classic example of that is a SERM like clomid. While it raises E2 in serum, it can give some low E2 symptoms in some tissues, the most common being the eyes, due to the fact that it binds to the estrogen receptor and makes it impossible for the estrogens to express their activity.

Regarding the estrogens topic, they have been prescribed and used topically by thricologists since more than 20 years in Italy. The most common being 17-a estradiol and estrone (both in its sulfate or bio identical version). Thricograms have shown more than often an improvement in hair density and diameter, but obviously won't do much as a monotherapy, like almost everything.
Estriol doesn't really get prescribed often, due to its weakness compared to the other estrogens.

I wasn't referring to the androgenic effects of testosterone, which obviously would be blocked by bicalutamide. I was referring to the anabolic effects. I don't know much about hormonal biochemistry admittedly. Are the anabolic effects of androgens mediated by the ARs or do they occur through a different pathway? I would think it would be the latter since different anabolic steroids have different ratios of anabolic to androgenic effects. But again, I am not well educated on this topic.

 

[Canuto]

I wasn't referring to the androgenic effects of testosterone, which obviously would be blocked by bicalutamide. I was referring to the anabolic effects. I don't know much about hormonal biochemistry admittedly. Are the anabolic effects of androgens mediated by the ARs or do they occur through a different pathway? I would think it would be the latter since different anabolic steroids have different ratios of anabolic to androgenic effects. But again, I am not well educated on this topic.

No, each androgen molecule come with its own anabolic to androgenic ratio. Once it binds to the AR, it then express its androgenic AND anabolic effect. So the perfect compound would be fully anabolic, with no androgenic activity and with a higher binding affinity than DHT. It hasn't been found yet, despite the potential treatment ability of some SARMS.

Topical nandrolone is not a viable option, since it's highly suppressive of the HPTA and a little bit will get systemic like everything applied topical. It also comes with its own side effects profile. In theory it would bind to 5-ar in tissues, decreasing the amount of 5-ar that generate DHT, it would be 5-ar reduced to DHN which is several folds less androgenic, but on the other hand it has a weak AR affinity, so you will still get testosterone and DHT getting to the AR.

 

[Androgenic Alpaca]

The patent looks a bit confused. First of all it's not clear how equol would "bind to DHT". What it can do is binding to the AR receptors or play the role of SHBG and bind to DHT, avoiding a bigger amount of free DHT to express its androgenic activity, along with freeing more SHBG that it's then available to bind to total T and E2. The result would be a lower free T, lower free E2 and lower free DHT.

What the study seems to ignore is that DHT gets produced locally in tissues, so the serum levels are irrelevant anyway and it's not what they should target.

In practical application several people tried topical s-equol in Italy after the Trinov's marketing campaign at dosages of 10mg per ml. No one ever reported any result whatsoever.

I'd think the primary mechanism of action for equol would be through the ERβ receptor. Regardless of the specifics of how it works, there's experimental evidence showing that Equol is very good for the skin and is strong antioxidant. See for some experimental results for skin health: https://sci-hub.se/https://doi.org/10.1111/ics.12408

Interestingly, that study uses 0.5% equol solution topically applied which is less than the 10mg/ml that you mention.

Seems to be less experimental evidence for hair regrowth, but it seems intuitive that it would help with hair regrowth by the same mechanism.

Besides, even if it doesn't help with hair growth, I'd like to get my hands on some for skincare...

 

[Canuto]

I'd think the primary mechanism of action for equol would be through the ERβ receptor.

If that's you target, just use any topical estrogens you want at reasonable percentages (apart from 17-b estradiol) and they will work way better.
They are bio-identical hormones and the body knows very well how you utilise them.

 

[pegasus2]

Yeah I think that if there is ever a "magic cure" for androgenic alopecia, it'll be some combination of a SERM + SARM. The problem would be to design a proper SARM that is anti-androgenic in scalp tissue without effecting other tissues (and not down regulating endogenous testosterone production) and a SERM that is a ERβ agonist in scalp tissue with anti-estrogenic effects in other tissues. I'm not a biochemist, though, so I won't be making those any time soon.

In reference to that first video you posted, isn't bicalutamide already a therapy that prevents androgenic effects of androgens while maintaining their anabolic effects? Bicalutamide obviously blocks androgen receptors, but it actually upregulates endogenous testosterone production, so wouldn't this lead to high testosterone levels and the testosterone would maintain its anabolic effects, correct? Any side effects would come from endogenous testosterone aromatizing to estrogen (which is why bicalutamide has high rates of gyno) but this could be prevented with an aromatase inhibitor or SERM, right?



Anyway, back on topic for this thread: I've recently started topical application of an estriol cream that I bought on amazon. It supposedly contains 5mg estriol per pump. I'm using two pumps on my scalp and one pump on my face (hopefully for increased collagen production, anti-acne, and anti-aging) twice a day, or 30mg total. Will this be a high enough dose? Will it have any positive effects?

5mg is a little low, but it should work. At that dose there is pretty much no risk of major side effects. Good luck.

 

[John Difool]

If that's you target, just use any topical estrogens you want at reasonable percentages (apart from 17-b estradiol) and they will work way better.
They are bio-identical hormones and the body knows very well how you utilise them.

Why apart from 17b estradiol?

 

[Canuto]

Why apart from 17b estradiol?

Because it's the most estrogenic and it will go systemic and silence the HPTA to a certain degree, through the usual negative feedback loop. Gyno is pretty much sure, due to offsetting the ratio between androgens and estrogens in the body.
Not an option for whoever wants to retain his masculinity.

 

[telogen]

At that dose there is pretty much no risk of major side effects.

What major side effects could Estriol produce when applyed to the skin/scalp?

 

[pegasus2]

What major side effects could Estriol produce when applyed to the skin/scalp?

At very high doses it has the potential to cause gyno, weight gain, and maybe some problems with libido. Just keep it at a reasonable dose. Work your way up, and if you notice any systemic effects dial it back.

 

[John Difool]

Because it's the most estrogenic and it will go systemic and silence the HPTA to a certain degree, through the usual negative feedback loop. Gyno is pretty much sure, due to offsetting the ratio between androgens and estrogens in the body.
Not an option for whoever wants to retain his masculinity.

That's exactly what I am looking for. Btw adding Progresterone topical at 10% boosted my hair appearance significantly