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

IdealForehead

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Estrogen is known to have complex effects on hair. It can both promote and inhibit hair growth depending on the type of estrogen used.

The primary factor that seems to determine the outcome of estrogen on your hair is which type of estrogen receptor you are stimulating with that type of estrogen.

Types of Estrogen Receptors
The body has two types of estrogen receptors. These two estrogen receptors have dramatically different effects on hair growth.

1) ER-alpha
ER-alpha is the type of estrogen receptor you DON'T want to stimulate.

With hair, ER-alpha stimulation promotes catagen. Catagen is the cessation of hair growth. ie. The end of anagen (growth phase). After catagen comes telogen (hair shed). Any estrogen which stimulates ER-alpha predominantly will therefore stall hair growth and lead to hair shedding. (ref)

ER-alpha stimulation also may lead to osteoarthritis and osteoporosis. (ref)

2) ER-beta
ER-beta by contrast is the estrogen receptor you DO want to stimulate.

ER-beta signalling works by silencing the ER-alpha catagen signalling pathway. By blocking this catagen signalling, hair follicles can grow longer and spend more time in anagen. This leads to longer and healthier hair. (ref)

Types of Estrogen
To evaluate the usefulness of any type of estrogen, we therefore need to know to what extent they stimulate ER-alpha vs. ER-beta receptors.

1) 17 beta-Estradiol (E2)
The primary estrogen of the natural human body is 17 beta-estradiol. Estradiol binds equally well to ER-alpha and ER-beta. (ref)

Estradiol binds most strongly to the estrogen receptors of the natural estrogens. (ref) We can therefore use estradiol as a standard to compare other estrogen binding strengths, and rate estradiol as "100" binding strength for both receptors.

Because estradiol binds equally to ER-alpha and ER-beta, I would postulate that overall this may likely be considered a "good" estrogenic agent for promoting hair growth, but not the best as we will soon see.

2) Estrone (E1)
Estrone is the primary estrogen of menopause. It has been described as the "ugly estrogen". (ref)

Estrone has a binding affinity for ER-α of 60 and for ER-ß of 37 (relative to estradiol). (ref) This means it is primarily an ER-alpha stimulator, and thus can be considered absolutely undesirable for hair growth.

Estrone will lead to premature catagen of hair follicles. It is likely the reason postmenopausal women lose hair all over their heads and bodies.

3) Estriol (E3)
Estriol binds to ER-α with an affinity of 14 and to ER-ß with an affinity of 21. (ref)

This means it is the only natural estrogen with a greater ER-beta affinity than ER-alpha.

Estriol is therefore the primary estrogen we DO want to use for hair growth.

Estriol is most famous for shooting up dramatically after about 12 weeks pregnancy (ref), and it is credited in part for the fantastic glowing skin and long thick hair that pregnant women experience from this point of pregnancy onward.

Estriol has a half life of 6-9 hours with vaginal application, which may be similar to skin application. (ref) Twice a day application thus makes the most sense. It has a low affinity relative to the other estrogens (it is the weakest to bind), so larger amounts must be used if its effects are desired.

4) Ethinyl Estradiol (EE)
This is the primary estrogen used in birth control pills. Unfortunately, EE is a mostly ER-alpha stimulator. (ref) This likely makes it less useful for hair growth promotion (unless you are using it orally for chemical castration, which will help stop male pattern hair loss by shutting down all your androgen production).

Normal women can likely get away with EE usage in birth control pills because even on high dose contraception, they will still have their natural estrogens (E1, E2, E3) to provide ER-beta stimulation and help counteract EE's ER-alpha effect. (ref, ref)

However, EE will not provide benefits for hair in this context, and should likely be minimized or avoided compared to other estrogens if hair growth is the desired outcome.

Manipulating Estrogen Receptor Expression
As @Georgie pointed out in another thread, dexamethasone (a steroid) has been shown to decrease ER-alpha receptor expression by up to 38%, while having no effect on ER-beta receptor expression. (ref)

This means that topical steroids could in theory be used to downregulate ER-alpha receptors in the scalp and promote a more ER-beta predominant effect.

Dexamethasone is used in combination with 17 alpha-estradiol (alfatradiol) in a German product called Ell-Cranell Dexa. I am unsure of the ER-alpha vs. ER-beta stimulating balance of 17 alpha-estradiol, but presuming it is similar to 17 beta-estradiol, the mechanism of action for this product would make sense. The steroid will shift receptor balance towards ER-beta predominance, and estradiol will then bind to these increased ER-beta receptors, stimulating hair growth.

The problem with this approach is that topical steroids can lead to skin atrophy over time, so they are not a good long term treatment. Additionally, the same predominantly ER-beta stimulation can be accomplished much more simply by just using estriol cream instead.

So although it is interesting to conceptualize, I do not think the alfatradiol/dexamethasone combo is the most useful approach to manipulating estrogen pathways for hair growth.

Summary
In other words:
  • ER-alpha signalling stimulates catagen (stopping hair growth dead)
  • ER-beta signalling blocks the ER-alpha pathway (prolonging anagen and causing hair growth)
Evaluating the different types of estrogen:
  • Estradiol has a 1:1 alpha:beta binding ratio, estriol has a 3:2 beta:alpha binding ratio, and estrone has a 1.6:1 alpha:beta binding ratio (ref)
  • Ethinyl estradiol has "ERα selective agonistic potency" (ref)
Therefore we can conclude that if ER-alpha stimulation is a negative factor for hair, and ER-beta stimulation is a positive one, the value of each estrogen can be ranked as:
  • Estriol (best) - 3:2 beta:alpha
  • Estradiol (2nd best) - 1:1 beta:alpha
  • Estrone (poor) - 1.6:1 alpha:beta
  • Ethinyl estradiol (poor) - primarily alpha binding
Application
For both men and women, the most useful approach to estrogen therapy in the pursuit of hair growth will therefore likely be a topical estriol cream applied directly to the areas of the hairline where stimulation is desired.

Fortunately, estriol creams are freely available most places over the counter. I have been using this one myself:
https://www.amazon.com/Bioidentical-Supplements-Micronized-Bio-Identical-Menopause/dp/B004XJIDEO

I have read a higher concentration of 0.3% estriol can be used in compounded creams for acne. This can also have an anti-aging effect. If you are brave, you can use it on your face as well for these benefits. (ref)

Primary risks of estrogen therapy in general for men will likely be sexual dysfunction. I have noticed some mild erectile dysfunction when I am using large amounts of estriol cream, but it doesn't bother me at this stage. Other risks for all estrogens are of blood clots, increased risk of breast cancer, etc. (ref)

For my own part, I will continue to use estriol for both hair growth promotion and anti-aging effect on my skin as I have been using it for about two months now and it has appeared to be quite effective for both. Dosage can easily be adjusted by using more or less cream to minimize side effects.

No treatment for hair loss or skin care is perfect or well suited for everyone. Most men will probably want to avoid estrogen therapies even just in principle alone. However, if used correctly, estrogen is likely a powerful hair growth tool to consider for those who wish to utilize it to their benefit.
 
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whatevr

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I have not noticed any benefit of estriol in practice. And in theory, it seems like it would just compete for Estradiol for the same receptors. Given that it's weaker, I can see that actually hurting hair.
 

IdealForehead

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I have not noticed any benefit of estriol in practice. And in theory, it seems like it would just compete for Estradiol for the same receptors. Given that it's weaker, I can see that actually hurting hair.

That doesn't really make sense to me. Even just with my low concentration, over-the-counter estriol cream, I am easily able to get enough effect to have dose-limiting side effects. Ie. I have no need for greater estrogenic stimulation than the basic over the counter estriol is providing. If I had anything stronger the sexual side effects would be intolerable.

Estradiol has a less favorable ER-alpha/beta balance. The only advantage of estradiol is its greater affinity for the receptors and possibly a greater half life. But this is only a "benefit" if you are unable to get sufficient stimulation from estriol.

So if you are using a max potency estriol cream with no side effects and no benefits, then perhaps you are highly estrogen resistant, and in that case, an estradiol cream might make sense to consider instead.

Otherwise, estriol will provide a much better ER-alpha/beta stimulation balance and in my experience, it is plenty strong enough.

One should note @whatevr that you have noted no benefit from many treatments in practice, and thus perhaps unfortunately your experiences may not be too generalizable. Some people (like myself) don't respond to finasteride/dutasteride, but that does not mean they are not useful potential therapies for most.
 

whatevr

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That doesn't really make sense to me. Even just with my low concentration, over-the-counter estriol cream, I am easily able to get enough effect to have dose-limiting side effects. Ie. I have no need for greater estrogenic stimulation than the basic over the counter estriol is providing. If I had anything stronger the sexual side effects would be intolerable.

Estradiol has a less favorable ER-alpha/beta balance. The only advantage of estradiol is its greater affinity for the receptors and possibly a greater half life. But this is only a "benefit" if you are unable to get sufficient stimulation from estriol.

So if you are using a max potency estriol cream with no side effects and no benefits, then perhaps you are highly estrogen resistant, and in that case, an estradiol cream might make sense to consider instead.

Otherwise, estriol will provide a much better ER-alpha/beta stimulation balance and in my experience, it is plenty strong enough.

One should note @whatevr that you have noted no benefit from many treatments in practice, and thus perhaps unfortunately your experiences may not be too generalizable. Some people (like myself) don't respond to finasteride/dutasteride, but that does not mean they are not useful potential therapies for most.

I have experienced the best results from everything I tried so far with topical estradiol. It seriously thickened up my hair and reversed some miniaturization. No such luck with estriol, but perhaps I did not use it long enough.

BTW if what you say about ethinyl estradiol is true, then explain this guy's results:


He was on ethinyl estradiol among other things.
 
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IdealForehead

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I have experienced the best results from everything I tried so far with topical estradiol. It seriously thickened up my hair and reversed some miniaturization. No such luck with estriol, but perhaps I did not use it long enough.

BTW if what you say about ethinyl estradiol is true, then explain this guy's results:


He was on ethinyl estradiol among other things.

Estrogen of any type when added to men in large amounts heavily suppresses androgen production. This is how estrogen is used in transgender therapy. For example, as discussed here:
https://www.medpagetoday.com/meetingcoverage/endo/46497

I would presume the primary benefit a guy like that would get from EE would be the neutering anti-androgen effect. This is in effect chemical castration, which will definitely help androgenic hair loss.

Ie. In this case the positive of chemical castration has outweighed the negative of ER-alpha stimulation.

Ideally an ER-beta predominant agent should still be better. But anything you take orally to chemically castrate yourself will probably stop male pattern baldness. Thats a fair thing to clarify so I added it to the EE section above.
 
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Georgie

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Estrogen of any type when added to men in large amounts heavily suppresses androgen production. This is how estrogen is used in transgender therapy. For example, as discussed here:
https://www.medpagetoday.com/meetingcoverage/endo/46497

I would presume the primary benefit a guy like that would get from EE would be the neutering anti-androgen effect. This is in effect chemical castration, which will definitely help androgenic hair loss.

Ideally an ER-beta predominant agent should still be better. But anything you take orally to chemically castrate yourself will probably stop male pattern baldness.
I think of it this way:

Men may still have better hair growth on certain types of estrogen, but any estrogen is still going to be amazing for male hair. It has been shown time and time again that when men use estrogen, whether it's ethyl E, transdermal estradiol, oral estradiol, estriol, combined bioidentical estrogen's - it will be helpful. It's a different story for women. We see women losing their hair on combined oral contraceptives, bioidentical hormone treatment, and even when women have an excess of their own natural estrogen. The mechanisms behind this are not well understood, but men and women simply cannot apply the same formula to the same problem here. through my own reading, i have come to understand that women must have a very fine balance of natural estrogens. When this is thrown off, sh*t goes haywire. Women must have optimum activation of 17b oestrogen receptors. Men can just take pretty much any estrogen and it's going to be useful apart from the fact that that it turns them into a partial woman.
 

IdealForehead

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I think of it this way:

Men may still have better hair growth on certain types of estrogen, but any estrogen is still going to be amazing for male hair. It has been shown time and time again that when men use estrogen, whether it's ethyl E, transdermal estradiol, oral estradiol, estriol, combined bioidentical estrogen's - it will be helpful. It's a different story for women. We see women losing their hair on combined oral contraceptives, bioidentical hormone treatment, and even when women have an excess of their own natural estrogen. The mechanisms behind this are not well understood, but men and women simply cannot apply the same formula to the same problem here. through my own reading, i have come to understand that women must have a very fine balance of natural estrogens. When this is thrown off, sh*t goes haywire. Women must have optimum activation of 17b oestrogen receptors. Men can just take pretty much any estrogen and it's going to be useful apart from the fact that that it turns them into a partial woman.

I think this could be explainable in the context of the feminization effect from estrogen in men.

As stated, any significant circulating estrogen in men will cause androgen levels to drop dramatically. For men, 99% of our hair problems are androgen-mediated.

So any significant amount of any type of estrogen will go a long way to shutting down our androgens and thus the primary cause of our hair loss.

But this is only if you are using sufficient estrogen as a man to have systemic absorption/circulation and throw off your whole hormone balance.

If the goal as a man is to use a very small amount topically for a primarily local effect, then you will want the estrogen with the most favorable hair growth profile and ideally also the lowest serum half life. This seems clearly to me to be estriol.

For women, yes estrogen is more complicated, because you need and have estrogen in much higher levels at baseline. It does seem to become a delicate balance between the various types of estrogens and their overall levels.
 

Georgie

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Do you know what regime she was on cause I cant find it anywhere?
That's actually a man, not a trans woman. It says at the end of the video what he used. If i can remember correctly, he began using finasteride and minoxidil which didn't work very well for him, then he started taking oestrogen with finasteride, added cypro then switched to diane35. Ended up only on diane35 and spironolactone i believe. Pretty frustrating since that very same combination plus oral and topical minoxidil did jack sh*t for me.
 
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Georgie

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Thanks for the help, I still cant find the regime anywhere lol maybe Im just thick. Wonder why he switched from cypro to spironolactone, I recently reduced my cypro dose from 50 to 25 cause I was afraid prolactin would lead to hairloss, hopefully the high dose of Estrogen Im taking is enough to get my T as close as possible to 0.

Anyways, do you do bloodtests? Is your T and Prolactin at a good level? Do you know your E levels? If you take very high dosages of Estrogen you ought to get results. If I remember correctly you're only on 1 diane 35 pill a day which is a very low dose. Did you ever try any other form of estrogen or other routes of administration?
It's at the end of the video. It only flashes up quickly so maybe you missed it.

I have had blood tests, yes. My T has gone up slightly since taking avodart, as has my DHT for some fucked up reason. I can't test my oestrogen because i'm on the pill. My prolactin is within normal range.

Diane35 is infact THE highest form of oestrogen. It contains ethinyl estradiol which is 10 x stronger than estradiol. So i am intact on an incredibly high dose of synthetic estrogen. The reason this guy would have dropped cypro is because diane contains 2mg of cypro, so to compliment it he probably decided that spironolactone was best.

It's not as simple for women as taking oestrogen and having great hair like it is for men, but i'm not surprised that this guy had amazing regrowth and also grew boobs.
 

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Georgie

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I have not noticed any benefit of estriol in practice. And in theory, it seems like it would just compete for Estradiol for the same receptors. Given that it's weaker, I can see that actually hurting hair.
Not harmful, but less effective, definitely. Estriol is the weakest form of the three oestrogen's and has the lowest affinity for receptors. If you look at it from the perspective of side effects, its the best for men because it will have the least feminising effects. I think irrefutably however, 17b estradiol is the best option for male hair, which has time and time again been shown in studies.
 

Georgie

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EthinylEstradiol is more potent yes but you're still on a low dose. On the NHS guidelines it recommends 50-150mcg per day, so two 35mcg daily ie 2 Diane 35 pills for feminization. And thats only a starting dose, the recommended dose is 3 pills and thats still not a very high dose. You can read up on it here if youre interested https://www.bcapformulary.nhs.uk/in...in-Transwomen-Male-to-Female-Transsexuals.pdf

Not all girls are euqally sensitve to Estrogen so you may need higher doses. If I was you Id seriously increase my Estrogen dose. Why dont you try IM estradiol and patches? You could use a diane 35 as a bonus dose like I plan to do. Is there a reason you dont want to try high doses of Estrogen?
Haha ok no, so not all synthetic estrogens are created equally. 50mcg in microgynon is actually the lowest dose, because it's a different kind of ethyl E. 150mcg in that same kind would be equivalent to 35mcg of the type that's in diane. It's complicated but not all oestrogen's in contraceptives are the same. Diane is the highest dose of synthetic oestrogen, and because it is, it's actually banned in some countries because it's caused strokes and venous embolisms in some women. You don't add more estrogen to diane because it's asking for a blood clot or cancer.
 

IdealForehead

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EthinylEstradiol is more potent yes but you're still on a low dose. On the NHS guidelines it recommends 50-150mcg per day, so two 35mcg daily ie 2 Diane 35 pills for feminization. And thats only a starting dose, the recommended dose is 3 pills and thats still not a very high dose. You can read up on it here if youre interested https://www.bcapformulary.nhs.uk/in...in-Transwomen-Male-to-Female-Transsexuals.pdf

Not all girls are euqally sensitve to Estrogen so you may need higher doses. If I was you Id seriously increase my Estrogen dose. Why dont you try IM estradiol and patches? You could use a diane 35 as a bonus dose like I plan to do. Is there a reason you dont want to try high doses of Estrogen?

The much more rational approach for a girl with premature ovarian failure is to switch to bioidentical hormone replacement with estradiol and estriol.

Dose and balance between these two can be adjusted to within a wide range and levels can be monitored to ensure they are within normal female levels on bloodwork.

These two hormones will provide natural estrogenic stimulation with an ER-beta predominance.
 

Georgie

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There are trans girls on 2 or 3 diane 35 pills. 1 Diane 35 pill is equivalent to 5mg of Progynova so its not a high dose. Youre right though it is dangerous thats why I dont know why you dont just take high doses of Estradiol Hemihydrate or Valerate instead. I think you'll get better levels and results on IM estradiol or taking high doses of Progynova. 1 dose of Diane 35 is not enough, yes its more potent but I know no trans girl who just takes 1 diane 35 for feminization
These are men, i am a woman. I am talking about what is appropriate for a woman with ovaries. If i were to take 3 diane pills a day i would bleed non stop and get caner.
 
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Georgie

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@Georgie If I were you I would just get on something like this and attempt to balance out my hormones first and foremost:

https://www.amazon.com/Life-Flo-98586-Biestro-care-4-Ounce/dp/B003LYDBCG

That would at least make up for what you're deficient in. I've used it as a guy and it worked (for better or worse). And drop the Diane.
Thing is because i'm so young, doctors fist line of treament is the combined contraceptive because A: It's contraceptive, B: It's easier to prescribe someone a single pill and send them on their way, C: it's a high dose.
It's incredibly rare that any woman as young as me is prescribed bioidentical hormones, but there can be exceptions to everything. I know that the immediate and event one year fallout could be excruciatingly painful, it's likely i will lose far more hair, and i may become more depressed, but i'm running out of options and it's something i haven't yet ruled out. I briefly tried a "natural" pill called Qlaira and i was not functional because of the severe pain and bleeding, but i feel if i buy the hormones separately i can tweak them to find a sweet spot. Hopefully.
 

Georgie

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Ah ok that makes sense. So 1 diane 35 is as high as you could go. Damn that sucks Im sorry to hear that :(
Yes. In fact, the recommended dose of bio hormones are 100-200mg progesterone and 2mg estradiol, because of the huge risk of cancer. Without ovaries, sure, it's less of an issue. With ovaries, you have very little wiggle room. I plane to take 4-6mg estradiol with 100mg prometrium, but this is incredibly risky.
 

IdealForehead

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Wouldnt she see results on high dose Estradiol Hemihydrate or Valerate? Shouldnt that give high levels of Estradiol which would be sufficient? Or is the balance between Estradiol and Estriol important?I though Estriol was useless, at least for trans girls

For a woman with premature ovarian failure the goal should not be high dose or low dose, but rather the correct dose to get her back into the ideal normal zone.

The caveat to that is "normal" estrogen levels cover a wide range for women depending on where they are in their period cycle. This means there is a lot of flexibility for dosing. Since a woman in menopause does not need to cycle, she can try to find the optimal zone for her to maintain ideal growth patterns.

Estriol is absolutely important in women if you want the benefits it offers.

The two primary starting approaches to natural estrogen replacement in women are:

1) BiEst - 80% estriol, 20% estradiol
2) TriEst - 80% estriol, 10% estradiol, 10% estrone

Dosing is reviewed here:
https://www.womensinternational.com/dosing/

The reason these products are so heavily weighted to estriol is that estriol only has a small fraction of the binding strength as estradiol and it also has a much shorter half life.

This means as I commented previously that if you want a good "estriol effect" (and most women do), you need to use a lot of it.

Based on the ER-alpha predominant activity of estrone, I think it likely deserves its title as the "ugly estrogen" and thus ideal hormone replacement for a female should be done with only estriol and estradiol (eg. The BiEst approach).

Georgie in particular has said she already has some estradiol valerate, which converts into 17 beta-estradiol in the body. If she can get some estriol tablets in addition and take the added estriol twice daily, it is my strong belief she should be able to produce a very favorable and natural estrogen balance in her body to promote hair growth and better general health as well.

Prometrium is needed for women to keep the uterine lining thin. Otherwise it will build up from the estrogen. Progesterone has a bit of an androgenic effect from what I understand so the goal is to minimize this. Progesterone binding to the androgen receptor is described here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740213/

The alternative for women in menopause is to get a low dose progesterone IUD which will accomplish the same goal of keeping the uterus thin with less circulating progesterone. My sister has one of these IUDs for contraception and is very happy with it. I would probably go that route myself if I was a woman in menopause going on HRT.
 
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IdealForehead

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Thank you for the reply that was a really interesting read. I didnt know that its so different for women than trans girls. For trans girls you never really hear about Estriol as it so weak its kinda useless.

I dont get how this balance would promote hair growth though. By having a higher ratio of weak Estriol than Estradiol wouldn't that lead to having diminished effects leading to less hair growth as the Estriol is significantly weaker?

Estriol is only "weaker" in that it has a shorter half life and a lower binding affinity. This means only that higher concentrations administered at more regular intervals are necessary to get a similar amount of binding effect.

Affinity to my understanding dictates how long a compound binds to a receptor, how tightly it binds, and how competitively it binds. Low affinity can always be compensated for by increasing the concentration, until you reach a maximum practical level.

Increasing the levels will give the compound more opportunities to bind and rebind over time.

While it is bound, it will activate the receptor just fine. Estriol is not going to bind and then do nothing. Once it binds it will create strong ER-beta stimulation which will promote a prolonged anagen, which is absolutely favorable.

If it was not a favorable approach this wouldn't be the standard method for bioidentical hormone replacement.
 

IdealForehead

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I should also just say that reflecting upon this, likely the issue of ER-alpha induced catagen stimulation is variable from person to person.

We all know that androgens can bind to some men's hair (eg. Guys like Clooney) and nothing happens, while they can bond to other men's hair and create rapid dramatic hairloss. This depends on genetic responses to the binding which vary from person to person.

Probably the same applies with estrogen receptors. Some people are probably less or more sensitive to the negative effects of ER-alpha stimulation (eg. From estrone or ethinyl estradiol).

For example, it is my opinion that Georgie's main problem at this stage is that due to overly aggressive ER-alpha sensitivity and having only EE as her estrogen, she is being put into catagen from head to toe. This explains her whole body hair loss, which is not typical in androgenic loss. Another woman with the same hormonal situation might not have such a dramatic catagen response.

Just like all the variables we must keep in mind hair growth and loss can be multifactorial, and everyone will respond to different treatments to differently based on our genetic sensitivities.
 
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