Exploring The Hormonal Route. Hair=life.

[MrOscar]

The gel is meant to go systemic, but that does not mean it does not work locally. Because of the extremely high (E2 is extremely potent since it circulates in picomolar concentrations) concentrations of the gel, it is not suitable to be used by "guys who wish to stay guys". In a previous post of mine I demonstrated that using E2 topically in concentrations of around 1mcg/mL (micrograms per mL) saturates the receptors. Any more than that cannot bind to receptors in the scalp, and so it will either be bound by albumin, SHBG or diffuse into the bloodstream. For people on HRT that is of course desirable to achieve the necessary serum concentrations. However, for males experimenting with topical E2 trying to eliminate sides this is not a good thing. That is also why certain vehicles are "better": they promote localization by limiting diffusion into the bloodstream, which reduces the needed concentration of E2. And that is a good thing, because with increasing concentrations the probability of systemic effects will increase as well (as more will enter the bloodstream). In fact, any medication is able to work locally, provided it is not a prodrug, (preferably) has not an extremely high molecular weight and the skin/scalp contains the particular receptors associated with the medication. Reducing systemic effects is then all about minimizing the concentration (and application area, but that does not really apply for male pattern baldness) and selecting a vehicle that limits diffusion while still providing passage through the stratum corneum. I hope this clarifies things a bit.

High local concentration of beta-estradiol might actually hurt, as in vitro estradiol optimal working range is in the nanomolar range (often tested in vitro at 10 nanoM and not more than 100 nanoM).
A 0.05%, 2 ml, full head topical is going to deliver estradiol at dermis in the order of 10 microM. Unfortunately there are no references for some "hair-specific" test of estradiol at microM. Found a dose-respinse test on eye lens epithelial cells, showing cell proliferation stimulation at nanoM, vs loss o viability and induction of apoptosis at 10 microM.

Effects of 17β-estradiol on proliferation, cell viability and intracellular redox status in native human lens epithelial cells

The purpose of this study was to examine the effects of 17β-estradiol on proliferation, cell death and redox status in cultured human lens epithelial cells (HLECs).HLECs were exposed to 17β-estradiol after which cell viability was measured ...

www.ncbi.nlm.nih.gov

Attached a graph showing the concentration response of hair growth model of estradiol.
Optimal concentration was 10 nanoM...and not 100 nanoM

 

[Swarleyd]

Thx. Nearly 3 years on hrt. And yeah I'm def way more into guys
View attachment 168084

Just an odd question, can you still erect and have “normal” sex functions ?

 

[Experimentality]

High local concentration of beta-estradiol might actually hurt, as in vitro estradiol optimal working range is in the nanomolar range (often tested in vitro at 10 nanoM and not more than 100 nanoM).
A 0.05%, 2 ml, full head topical is going to deliver estradiol at dermis in the order of 10 microM. Unfortunately there are no references for some "hair-specific" test of estradiol at microM. Found a dose-respinse test on eye lens epithelial cells, showing cell proliferation stimulation at nanoM, vs loss o viability and induction of apoptosis at 10 microM.

Effects of 17β-estradiol on proliferation, cell viability and intracellular redox status in native human lens epithelial cells

The purpose of this study was to examine the effects of 17β-estradiol on proliferation, cell death and redox status in cultured human lens epithelial cells (HLECs).HLECs were exposed to 17β-estradiol after which cell viability was measured ...

www.ncbi.nlm.nih.gov

Attached a graph showing the concentration response of hair growth model of estradiol.
Optimal concentration was 10 nanoM...and not 100 nanoM

Estrogen does not cause hair loss in humans and is hair protective. The study you linked is on epithelal lens cells, which have entirely different morphology than hair follicles. For example, estrogen causes proliferation in mammary cells but causes apoptosis in prostate cells. I have yet to read the first study that demonstrates a catagenic effect of E2 in human hair follicles. There have been reports of the anagen promoting effect of E2 being dependent on the scalp region in absence of androgens. In presence of androgens, E2 induces AR downregulation and thus makes androgens less "effective" (this is actually becoming a big problem for males with all traces of birth control pills floating around in tap water).

 

[MrOscar]

Estrogen does not cause hair loss in humans and is hair protective. The study you linked is on epithelal lens cells, which have entirely different morphology than hair follicles. For example, estrogen causes proliferation in mammary cells but causes apoptosis in prostate cells. I have yet to read the first study that demonstrates a catagenic effect of E2 in human hair follicles. There have been reports of the anagen promoting effect of E2 being dependent on the scalp region in absence of androgens. In presence of androgens, E2 induces AR downregulation and thus makes androgens less "effective" (this is actually becoming a big problem for males with all traces of birth control pills floating around in tap water).

In my post I said there are no data of estradiol effect at microM concentration in vitro, so mentioned the closest possible study testing a dose response from nanoM to microM. MicroM estradiol doesn't happen in nature on hair follicle, but can happen by putting at 0.05% topical on the scalp.
If the scope is to make working best estradiol on hair follicle, then I assume the target concentration has to be nanoM, as microM is orders of magnitude above the physiological concentration. I think you are the only one that is testing estradiol a very low dosage, on 5ARi and topical AA and I believe your test is very interesting, as I couldn't find a true microdosing test for topical estradiol.

 

[MrOscar]

Estrogen does not cause hair loss in humans and is hair protective. The study you linked is on epithelal lens cells, which have entirely different morphology than hair follicles. For example, estrogen causes proliferation in mammary cells but causes apoptosis in prostate cells. I have yet to read the first study that demonstrates a catagenic effect of E2 in human hair follicles. There have been reports of the anagen promoting effect of E2 being dependent on the scalp region in absence of androgens. In presence of androgens, E2 induces AR downregulation and thus makes androgens less "effective" (this is actually becoming a big problem for males with all traces of birth control pills floating around in tap water).

Here an old study:

Sex hormones and antiandrogens influence in vitro growth of dermal papilla cells and outer root sheath keratinocytes of human hair follicles - PubMed

Anagen hair bulb papillae, interfollicular dermal fibroblasts, and interfollicular keratinocytes isolated from fronto-parietal scalp biopsies as well as outer root sheath keratinocytes from plucked anagen hairs were separately grown in subculture for 14 d. The effect of different concentrations...

pubmed.ncbi.nlm.nih.gov

In the study (also) estradiol effect was tested on hair cell lines, within a concentration range.
For DP cells the minimum concentration causing increased cell growth was 180 nM (about 50 ug/l).
Concentration above 1.8 uM (3.6 uM) decreased the metabolic activity.
Reference 27 used cell cultures derived from balding scalp, but unfortunately for this one, full text is not available.

In vitro effects of testosterone, dihydrotestosterone and estradiol on cell growth of human hair bulb papilla cells and hair root sheath fibroblasts - PubMed

The influence of testosterone, dihydrotestosterone (each 10 ng/ml up to 300 ng/ml) and estradiol (0.2 ng/ml up to 10 ng/ml) on the growth behaviour (cell count, [3H]thymidine uptake, cell doubling time) of subcultured human hair bulb papilla cells and hair root sheath fibroblasts was studied...

pubmed.ncbi.nlm.nih.gov

Says that up to 10 ng/ml (10 ug/l or about 36 nM) of E2 the effect on cells growth was not detectable, but increased significantly above this concentration.

What's the concentration at DP you are targeting?

 

[keepcoolmybabies]

Just an odd question, can you still erect and have “normal” sex functions ?

If I wanted to I could, but my libido is very low and it would require some physical stimulation. I never get random erections or "morning wood" or anything like that.

 

[Solxama]

I was looking up good places to apply Estrogel beside arms/thighs and I found a very interesting article. Apparently applying even small amounts of transdermal E2 to the scrotum raises Estradiol levels high, into the 200-400pg/ml range. I'm not sure I want to try this method yet, but I might If I find myself running low on gel, or my future Estradiol blood test results are too low for my liking.

Also I don't think it's a good idea for people who want to keep their masculinity and/or libido and dick working. For me it's not a problem, but for others, proceed with caution. Oh, and apparently according to people on reddit, armpits are also a good place to put the gel, I got mine shaved so I might try it for my evening dose.

Redirecting…

 

[JaneyElizabeth]

Well I already got gel, so for now I'm going with that. I also don't want much breast growth so definitely avioding pills lol.

About the local effects, some people like Bridge used it with success on their head, so I'm not so sure with the not having local effects thing. And besides Estrogen is Estrogen so it should do the job regardless where I put it.

To wrap things up, I will be probably going with injections in the future, as I will most likely be staying on HRT for life. But for now to start off I'm going the Bridge route, that is Gel+AAs.

Estradiol might be addictive. In many ways, it might be similar to SSRI's in terms of the calming effects and the reduction in sexual input.

 

[JaneyElizabeth]

Thank you! And HRT really did wonders for your hair, it looks great

And to @JaneyElizabeth , thank you for your words of encouragement, I hope you are right and no shedding will happen for me. To be honest when I signed up here a month ago, I already knew what has to be done to save my hair, but I was still scared of some potential effects of HRT, mainly breast growth. But thanks to your kindness and words, and of all the others who interacted with me, I overcame these fears and have taken the plunge into what I hope will be a better life, with a head full of hair and a body that feels more in tune with my soul.

I think you will recover quickly especially with religious adherence to once a week microneedling.

 

[JaneyElizabeth]

I was looking up good places to apply Estrogel beside arms/thighs and I found a very interesting article. Apparently applying even small amounts of transdermal E2 to the scrotum raises Estradiol levels high, into the 200-400pg/ml range. I'm not sure I want to try this method yet, but I might If I find myself running low on gel, or my future Estradiol blood test results are too low for my liking.

Also I don't think it's a good idea for people who want to keep their masculinity and/or libido and dick working. For me it's not a problem, but for others, proceed with caution. Oh, and apparently according to people on reddit, armpits are also a good place to put the gel, I got mine shaved so I might try it for my evening dose.

Redirecting…

Yep. That article has been on transfemscience for a while. If minoxidil has localized effects, why can't Estrogel? On the scalp, couldn't it diminish DHT even if Estradiol itself needs to go systemic? We know that Estrogel has at least temporary local effects if used on breast tissue but the question is whether it lasts as a tool in developing breast tissue but this shouldn't change the local effects issue. I believe if used on the testicles, it's clear that it has localized effects temporarily.

I continue to think that if estradiol works for a person, they need to hit above 100pg/ml for a sustained period and I think 300pg/ml is a better target but we are all just feeling around in the dark. Estriol is just not strong enough and I don't know of evidence showing that estriol is associated with less breast growth. This is just conjecture anyway and conjecture is rarely worth considering in hormonal solutions similar to prostaglandins. There's no excitement about them any longer. It just didn't work. Microneedling might be more effective than estrogen but I have little way of telling since I have used microneedling concurrently with oral min and estradiol. Anagen is key here and most fail to understand that hair counts seem to be a consequence of anagen, not the other way around. So I predict any male solutions apart from hormones will involve greatly increasing anagen.

I have been monitoring the hair coming out in my brush and virtually all of them are short or malformed. Many, many of them are kinked to the point that it almost looks like the hair knotted itself. No bulbs on any hairs coming out. Virtually any hairs with color mismatch are malformed which is interesting because being gray doesn't usually decrease hair quality. I am plucking any that are not light brown or blondish because in my view, they are just sucking up resources. The closer they are in distance, the better that plucking might improve cross-talk among follicles. Why is this important? I think that kids who say cut their heads under their hair might not have any lack of density because the follicles on the rest of the head might increase a little in terms of diameter and anagen.

Shedding might be the best thing for anyone on HRT because the mass dump allows for much closer synchronization of all follicles up to 85 percent together. If all follicles are at widely varying anagen stages that might contribute to the noticeability. Looks for hair counts to increase last in terms of being visible. That's just now apparent for me and I have never seen actual regrowth before, ever from any med. I will try to post follicle pics. I am continuing to lower oral min dosage down to maybe 3mg since females need much less apparently and I am seeing substantial peripheral hair increases. Microneedling once a week with min and using it once a day topically might attenuate oral min's side effects. I continue with retin-A everywhere above the neck and that plus lowering oral min dosage has eliminated the "alien" eyes effect.

What we do not know is if much lower doses of estradiol might work but just take much longer but since even this way with microneedling took me two years to almost reach female lengths that are all but fully restored, it might be unrealistic for non-MtF's to rejigger any of the hair effects without hitting female targets. The search is probably now to see if middling or half and half E2/T environments are associated with hair restoration.

Janey

 

[JaneyElizabeth]

Estrogen does not cause hair loss in humans and is hair protective. The study you linked is on epithelal lens cells, which have entirely different morphology than hair follicles. For example, estrogen causes proliferation in mammary cells but causes apoptosis in prostate cells. I have yet to read the first study that demonstrates a catagenic effect of E2 in human hair follicles. There have been reports of the anagen promoting effect of E2 being dependent on the scalp region in absence of androgens. In presence of androgens, E2 induces AR downregulation and thus makes androgens less "effective" (this is actually becoming a big problem for males with all traces of birth control pills floating around in tap water).

There have been reports of the anagen promoting effect of E2 being dependent on the scalp region in absence of androgens

Can you discuss this a bit more in terms of hair restoration expectations using estradiol?

Thanks,
Janey

 

[Almas_NW0]

Almost 2.5 months on HRT. I think there is more fluff on my temples, and it slowly returns, and the vellus hair is lengthened. But I'm not sure about that, maybe I'm wishful thinking. The next two months will show better

In any case, the results from HRT are very slow. It takes a long time even to restore Norwood 1. There is also a problem with the quality of the hair: you need not only to fill the bald patches with hair, but also to achieve the desired thickness and shine. Judging by Gergely, it takes at least 9 months to improve the quality of hair. Considering all these factors, my fear of worsening and the rate of baldness, I began to question the viability of the idea of HRT cycles. But we will find out about this next year.

 

[Almas_NW0]

This is FTM transgender. On his example, you can see the differences between male and female hairline: a man without baldness has a sharper growth line, thick hair. Women have more fluff and a rounded growth line. This is an interesting example.

 

[JaneyElizabeth]

This is FTM transgender. On his example, you can see the differences between male and female hairline: a man without baldness has a sharper growth line, thick hair. Women have more fluff and a rounded growth line. This is an interesting example.

See if you can compare pics of three races with overlapping gene patterns: non-European Siberians, the Inuit and Native Americans and adding in say Easter Island and Hawaii is likely to be similar. These groups all seem to have oval hair lines regardless of gender.

 

[JaneyElizabeth]

This is FTM transgender. On his example, you can see the differences between male and female hairline: a man without baldness has a sharper growth line, thick hair. Women have more fluff and a rounded growth line. This is an interesting example.

Great pic. Now look at the side pattern in both. Men seem to often lose hair in front of the ears that leaves a partial jutting out area that is quite noticeable. This might be associated with better long-term baldness outcomes but certain temple hair loss outcomes.

 

[JaneyElizabeth]

Almost 2.5 months on HRT. I think there is more fluff on my temples, and it slowly returns, and the vellus hair is lengthened. But I'm not sure about that, maybe I'm wishful thinking. The next two months will show better

In any case, the results from HRT are very slow. It takes a long time even to restore Norwood 1. There is also a problem with the quality of the hair: you need not only to fill the bald patches with hair, but also to achieve the desired thickness and shine. Judging by Gergely, it takes at least 9 months to improve the quality of hair. Considering all these factors, my fear of worsening and the rate of baldness, I began to question the viability of the idea of HRT cycles. But we will find out about this next year.

What I predict that you won't see for many months is any frontal regrowth especially in the temples where it is most easily identified. First time in my life, I have ever seen an improvement in hair counts but microneedling seems to be an important facilitation tool but not necessary for MtF's. It probably greatly increases improvements in hair counts and appearance of new hair. Mine look like darker vellus hairs mixed with light hair maybe similar at first glance to beard hair.

 

[Almas_NW0]

If HRT helps me, then I think the temples will fill, but the hair on the temples and growth lines will be of poor quality, too thin. Ikarus quickly regained the growth line, but it remained thin

 

[JaneyElizabeth]

If HRT helps me, then I think the temples will fill, but the hair on the temples and growth lines will be of poor quality, too thin. Ikarus quickly regained the growth line, but it remained thin

He or she or they didn't microneedle though.

 

[Experimentality]

Here an old study:

Sex hormones and antiandrogens influence in vitro growth of dermal papilla cells and outer root sheath keratinocytes of human hair follicles - PubMed

Anagen hair bulb papillae, interfollicular dermal fibroblasts, and interfollicular keratinocytes isolated from fronto-parietal scalp biopsies as well as outer root sheath keratinocytes from plucked anagen hairs were separately grown in subculture for 14 d. The effect of different concentrations...

pubmed.ncbi.nlm.nih.gov

In the study (also) estradiol effect was tested on hair cell lines, within a concentration range.
For DP cells the minimum concentration causing increased cell growth was 180 mM (about 50 ug/l).
Concentration above 1.8 uM (3.6 uM) decreased the metabolic activity.
Reference 27 used cell cultures derived from balding scalp, but unfortunately for this one, full text is not available.

In vitro effects of testosterone, dihydrotestosterone and estradiol on cell growth of human hair bulb papilla cells and hair root sheath fibroblasts - PubMed

The influence of testosterone, dihydrotestosterone (each 10 ng/ml up to 300 ng/ml) and estradiol (0.2 ng/ml up to 10 ng/ml) on the growth behaviour (cell count, [3H]thymidine uptake, cell doubling time) of subcultured human hair bulb papilla cells and hair root sheath fibroblasts was studied...

pubmed.ncbi.nlm.nih.gov

Says that up to 10 ng/ml (10 ug/l or about 36 nM) of E2 the effect on cells growth was not detectable, but increased significantly above this concentration.

What's the concentration at DP you are targeting?

I like your input, thanks for posting. I was actually targeting E2's EC50 value, which has not been determined unambiguously but should be around 0.1nM for both receptors (see here for study links). Check this earlier post of mine. Actually, applying around 1ng of E2 on the temples is already sufficient to reach such concentrations (also taking fractional absorption into account). However, I agree that this may be a little short-sighted, because I did not consider the hair follicle as a structure (but just the test-tube estrogen receptors). What concentration would you suggest? 1mcg (on the temples) provides 1000 times the EC50 and should saturate every single receptor available. That is pretty huge, because it would allow us to employ a powerful way to maintain (and a slight possibility for regrowth) hair without the cost of usual sides (20% going systemic - 0.2mcg will not give anyone sides. For full scalp coverage, under 2mcg going systemic should be feasible). To clarify, this does not come even close to oral HRT in terms of effectiveness, but it could allow us to get some of the benefits without any of the side effects.

@JaneyElizabeth. I do not know. I think hairloss in most people is multi-faceted with actually a major inflammatory compound that does not originate from androgens. I would guess that the effectiveness of E2 would depend on the "degree of male pattern baldness" that someone has. For pure male pattern baldness, E2 would of course be a winner since it directly opposes androgens in many ways. Probability for regrowth then depends on factors like scalp calcification and probably age. You cannot really predict the severity of that a priori, but microneedling may help breaking up some fibrosis. Reducing systemic inflammation through dietary adjustments is absolutely underrated in my opinion. While it will not have any effect on male pattern baldness on its own, it should speed up (and increase) the effect of treatments. I would postulate that the lower the systemic inflammation, the higher the chances on regrowth on HRT.

The article on locally varying effects of E2 was in one of my previous posts. Since there is never really absence of androgens in vivo, I think the results cannot be translated to treatments. The study suggested that in hair follicles on the vertex, E2 was actually catagenic. I do believe, however, that E2 is especially effective in male frontotemporal follicles, since they lack aromatase compared to female frontotemporal follicles. In short, I believe that topical E2 definitely adds value to any regimen

 

[JaneyElizabeth]

I like your input, thanks for posting. I was actually targeting E2's EC50 value, which has not been determined unambiguously but should be around 0.1nM for both receptors (see here for study links). Check this earlier post of mine. Actually, applying around 1ng of E2 on the temples is already sufficient to reach such concentrations (also taking fractional absorption into account). However, I agree that this may be a little short-sighted, because I did not consider the hair follicle as a structure (but just the test-tube estrogen receptors). What concentration would you suggest? 1mcg (on the temples) provides 1000 times the EC50 and should saturate every single receptor available. That is pretty huge, because it would allow us to employ a powerful way to maintain (and a slight possibility for regrowth) hair without the cost of usual sides (20% going systemic - 0.2mcg will not give anyone sides. For full scalp coverage, under 2mcg going systemic should be feasible). To clarify, this does not come even close to oral HRT in terms of effectiveness, but it could allow us to get some of the benefits without any of the side effects.

@JaneyElizabeth. I do not know. I think hairloss in most people is multi-faceted with actually a major inflammatory compound that does not originate from androgens. I would guess that the effectiveness of E2 would depend on the "degree of male pattern baldness" that someone has. For pure male pattern baldness, E2 would of course be a winner since it directly opposes androgens in many ways. Probability for regrowth then depends on factors like scalp calcification and probably age. You cannot really predict the severity of that a priori, but microneedling may help breaking up some fibrosis. Reducing systemic inflammation through dietary adjustments is absolutely underrated in my opinion. While it will not have any effect on male pattern baldness on its own, it should speed up (and increase) the effect of treatments. I would postulate that the lower the systemic inflammation, the higher the chances on regrowth on HRT.

The article on locally varying effects of E2 was in one of my previous posts. Since there is never really absence of androgens in vivo, I think the results cannot be translated to treatments. The study suggested that in hair follicles on the vertex, E2 was actually catagenic. I do believe, however, that E2 is especially effective in male frontotemporal follicles, since they lack aromatase compared to female frontotemporal follicles. In short, I believe that topical E2 definitely adds value to any regimen

What about estradiol greatly increasing anagen instead of counts? That might be key or the related synchronizing of anagen among all scalp hair could be significant which sheds purportedly do. Together both would then increase hair counts on the scalp. The thing about E2 in the front makes no sense but I do hear or read that in various places. Again, theoretical might not happen because of a variety of unforeseen changes. What about seeing hair loss on the head as being in some sort of stasis equilibrium state? Thus people like Bridge who lost much of his beard it appeared would be metered for better scalp hair growth. Allegations about minoxidil beards and my own beard removal seem to me to make this at least partially likely meaning shut down only the pubertal beard growth but that's all although practically beard and body hair above the waist seem to be highly correlated as well. This might involve Sarms or Serms, my favorite ding-dong sort of parallel words in HRT.