Exploring The Hormonal Route. Hair=life.

[Experimentality]

I am pretty certain that HRT can restore a head of hair but since I have multiple treatments, I am not much of a data point and here I am referring to microneedling which can at times, it appears, vastly improve a person's hair and in some cases, produce spectacular growth. I use generally 2.0mg and 2.5 mg needles. Since Bridge didn't microneedle, he is a better source.

I use finasteride and duta together and never a single side but no regrowth either but these are more so maintenance drugs. Like me, Bridge added oral minoxidil later in the game but he had already had substantial success by then and that's how my situation with oral min is. I absolutely think that it helps and is probably, after HRT and perhaps microneedling, the number one treatment for hair growth.

I have looked at those articles, at least a couple of them and eh, I just didn't find any of it convincing. There's a one person study from 2016 involving an MtF who was almost bald then regrowing her hair substantially just from E2 and spironolactone. I think that a lot of XY's want to believe that HRT won't work for hair, subconsciously, so that they don't have to try it since "it's not guaranteed to work". People have difference life preferences. One type of person that I find exceedingly ridiculous are the MtF's who think that using HRT only for hair is some sort of sacrilege by infringing on their territory.

I absolutely agree. HRT can definitely regrow hair everywhere on the head as proven countless times. However, we do not know the exact mechanism behind it - is it due to actual transcriptional activity at the ER or just AR suppression? Studies actually point to the latter, hence I am more and more leaning towards AR suppression, which E2 is extremely effective at, as the main driver behind regrowth. Castrates generally do not regrow any hair, but they do not have the AR suppression that E2 may provide. Backdoor and adrenal androgens are still abundant in castractes and local synthesis of DHT can still happen at a rate high enough to make regrowth impossible (5AR is highly expressed in the skin, making even minute amounts of residual testosterone dangerous for hair). Theoretically, a highly effective regimen for regrowth would consist of an antiandrogen to prevent AR binding, E2 to prevent AR upregulation as a response, and a 5ARI to remove highly potent androgens (DHT). Using an AA would probably be superfluous for people on HRT already, but it would not hurt either. I also postulate that such a regimen would be highly effective when used topically as well, which is the only viable option for males (even then, it is risky and should not be done without sufficient background knowledge).

 

[JaneyElizabeth]

I absolutely agree. HRT can definitely regrow hair everywhere on the head as proven countless times. However, we do not know the exact mechanism behind it - is it due to actual transcriptional activity at the ER or just AR suppression? Studies actually point to the latter, hence I am more and more leaning towards AR suppression, which E2 is extremely effective at, as the main driver behind regrowth. Castrates generally do not regrow any hair, but they do not have the AR suppression that E2 may provide. Backdoor and adrenal androgens are still abundant in castractes and local synthesis of DHT can still happen at a rate high enough to make regrowth impossible (5AR is highly expressed in the skin, making even minute amounts of residual testosterone dangerous for hair). Theoretically, a highly effective regimen for regrowth would consist of an antiandrogen to prevent AR binding, E2 to prevent AR upregulation as a response, and a 5ARI to remove highly potent androgens (DHT). Using an AA would probably be superfluous for people on HRT already, but it would not hurt either. I also postulate that such a regimen would be highly effective when used topically as well, which is the only viable option for males (even then, it is risky and should not be done without sufficient background knowledge).

That's one of the best comments that I have seen and it reflects what many MtF's tell me and even gals in their 20's might not get regrowth. But why, Goddess-Damit why? A lot of this stuff is all but circular so that makes it difficult to determine. I know less about receptor activity than I do about all female HRT meds.

You touch on one of my ideations which is that beard growth and scalp hair growth are just two different places to be hairy and yes, beards go bald too. It might be that laser hair-removal might help restart hair growth. HRT did nothing or my dermatitis on my face; yep, beard removal cured that too. Yes, it wasn't that long ago that people were gaslighting MtF's who stated that they re-masculinized after castration. Rob English seems to think that both elimination of DHT plus estrogen might result in full or almost full restoration but shh. I don't want to jinx it. I have been under 10pg/ml my last two tests with the lab but I also have hit some extremely high numbers.

Once I used an entire tube of Estrogel in a day and I was regularly around pregnancy levels for E2 which correlated with hair regrowth but I have been using estrogen of USP quality so I might argue that it took all 7 of those transition years and my hair just got better and better but it feels much more like I induced this recently and I still think that extremely high E2 levels might be worth trying along with oral min for folks who are not seeing hair improvement. Mine is getting longer and less disruly but I still look better in my wig because hair length makes a huge difference in terms of passing as does, sigh, breast growth.

 

[Almas]

Effective Testosterone Suppression for Prostate Cancer: Is There a Best Castration Therapy?

Achieving and maintaining effective suppression of serum testosterone levels in men treated with androgen ablation is one of the essential strategies in the management of prostate cancer. Historically, a serum testosterone below 50 ng/dL was considered ...

www.ncbi.nlm.nih.gov

Hair growth is provided by a decrease in the T level to the castration level and an increase in the E level
T levels below 50 ng / dl are normal, but the ideal level is less than 20 ng / dl, this corresponds to castration levels and affects prostate cancer outcomes. Thus, we need to reduce T as much as possible. To do this, our E levels must be at least 250-300 ng / dL
It is not advisable to raise estradiol levels above 700 pg / ml, because in this case SHBG will go crazy, the level of free estradiol will decrease. This reduces the effectiveness of HRT. Therefore, "one cannot be mistaken in the big direction" is not quite a true statement. Ideal E levels are in the 300-700 pg / ml range, SHBG levels below 115. But because the main thing is to lower the T level to the castration level, then the error in the big direction is not as critical as in the lower one, and you will still get the result

If you do injections of Enanthate every 2 weeks with a minimum of 300 pg / ml on the last day, then according to my calculations, the peak level is around 1500 pg / ml, which is a lot. If injections are done once a week, then the peak level at the same minimum does not exceed 700 ng / dl. Therefore, I will consider giving injections once a week.

The Ikarus T level was above 100 ng / dl and the E level was 195 pg / ml. These are poor numbers and this could be one of the reasons why he was unable to restore the hairline.


View attachment 165180

Injections are ideal for T suppression because they are easiest to reach 250 + pg / ml estradiol, which will give you castration T levels below 20 ng / dL. Castration levels of T + estradiol give the best chance of success
My level is now 35 pg / ml, which is not bad either.

 

[JaneyElizabeth]

I am under 10 units of DHT on my last two tests. I think that under ten is castrate-level, no?

Injections are ideal for T suppression because they are easiest to reach 250 + pg / ml estradiol, which will give you castration T levels below 20 ng / dL. Castration levels of T + estradiol give the best chance of success
My level is now 35 pg / ml, which is not bad either.

 

[Experimentality]

That's one of the best comments that I have seen and it reflects what many MtF's tell me and even gals in their 20's might not get regrowth. But why, Goddess-Damit why? A lot of this stuff is all but circular so that makes it difficult to determine. I know less about receptor activity than I do about all female HRT meds.

You touch on one of my ideations which is that beard growth and scalp hair growth are just two different places to be hairy and yes, beards go bald too. It might be that laser hair-removal might help restart hair growth. HRT did nothing or my dermatitis on my face; yep, beard removal cured that too. Yes, it wasn't that long ago that people were gaslighting MtF's who stated that they re-masculinized after castration. Rob English seems to think that both elimination of DHT plus estrogen might result in full or almost full restoration but shh. I don't want to jinx it. I have been under 10pg/ml my last two tests with the lab but I also have hit some extremely high numbers.

Once I used an entire tube of Estrogel in a day and I was regularly around pregnancy levels for E2 which correlated with hair regrowth but I have been using estrogen of USP quality so I might argue that it took all 7 of those transition years and my hair just got better and better but it feels much more like I induced this recently and I still think that extremely high E2 levels might be worth trying along with oral min for folks who are not seeing hair improvement. Mine is getting longer and less disruly but I still look better in my wig because hair length makes a huge difference in terms of passing as does, sigh, breast growth.

I am not entirely sure about the theory, but I am definitely leaning in the direction of AR suppression as E2's main mechanism in HRT people. Another thing that I am unsure about is testosterone as a driver behind Androgenetic Alopecia. We know that individuals lacking 5AR are devoid of Androgenetic Alopecia, which is a bit surprising when we assume the testosterone-theory to be true. Hypotheses postulating that testosterone causes miniaturization because individuals on dutasteride still experience Androgenetic Alopecia are completely false. Local concentrations of 5AR are high enough to resist dutasteride, reflected by the fact that dutasteride only decreases scalp DHT by about 50% while decreasing serum DHT by more than 95% at the same time [source needed]. Interestingly, this may be addressed by a topical formulation of a 5ARI which achieves much higher local concentrations than oral formulations. There may be a cascade effect (I believe once mentioned by bridgeburn, albeit without any scientific support provided) where DHT "lights the fire" and T "burns down the house". Although certainly interesting, scientific data on all these statements is profoundly lacking, which makes it very difficult to make any confident claims.

Regardless, I believe that E2 in presence of androgens will always yield a net positive effect. Extrapolating on the data from my previous posts, that effect may be enhanced in the frontotemporal region, at least in males.

Microneedling releases a plethora of growth factors and should always be included in every hair loss regimen, period.

 

[Pls_NW-1]

My adrenal gland is currently blasting androgens cuz it can't create cortisol and has to set it off, as well as the left overs of the prior-stage-cortisols, by creating adrenal androgens NON-STOP!

rip

Pls_NW-1 2021-2021

 

[JaneyElizabeth]

Well great is your knowledge but I am high as a kite, so, eh. I am very confused about circulating and local effects or both.

I am not entirely sure about the theory, but I am definitely leaning in the direction of AR suppression as E2's main mechanism in HRT people. Another thing that I am unsure about is testosterone as a driver behind Androgenetic Alopecia. We know that individuals lacking 5AR are devoid of Androgenetic Alopecia, which is a bit surprising when we assume the testosterone-theory to be true. Hypotheses postulating that testosterone causes miniaturization because individuals on dutasteride still experience Androgenetic Alopecia are completely false. Local concentrations of 5AR are high enough to resist dutasteride, reflected by the fact that dutasteride only decreases scalp DHT by about 50% while decreasing serum DHT by more than 95% at the same time [source needed]. Interestingly, this may be addressed by a topical formulation of a 5ARI which achieves much higher local concentrations than oral formulations. There may be a cascade effect (I believe once mentioned by bridgeburn, albeit without any scientific support provided) where DHT "lights the fire" and T "burns down the house". Although certainly interesting, scientific data on all these statements is profoundly lacking, which makes it very difficult to make any confident claims.

Regardless, I believe that E2 in presence of androgens will always yield a net positive effect. Extrapolating on the data from my previous posts, that effect may be enhanced in the frontotemporal region, at least in male

 

[JaneyElizabeth]

I absolutely agree. HRT can definitely regrow hair everywhere on the head as proven countless times. However, we do not know the exact mechanism behind it - is it due to actual transcriptional activity at the ER or just AR suppression? Studies actually point to the latter, hence I am more and more leaning towards AR suppression, which E2 is extremely effective at, as the main driver behind regrowth. Castrates generally do not regrow any hair, but they do not have the AR suppression that E2 may provide. Backdoor and adrenal androgens are still abundant in castractes and local synthesis of DHT can still happen at a rate high enough to make regrowth impossible (5AR is highly expressed in the skin, making even minute amounts of residual testosterone dangerous for hair). Theoretically, a highly effective regimen for regrowth would consist of an antiandrogen to prevent AR binding, E2 to prevent AR upregulation as a response, and a 5ARI to remove highly potent androgens (DHT). Using an AA would probably be superfluous for people on HRT already, but it would not hurt either. I also postulate that such a regimen would be highly effective when used topically as well, which is the only viable option for males (even then, it is risky and should not be done without sufficient background knowledge).

I agree with all of this. You know your literature. But I will aways stay on duta and finasteride both most likely so bicalutamide probably would be overkill. Remember Jurassic Park: Nature found a way. Here it is DHT somehow found its way. You can't kill DHT off because it circulates all through facial hair. Only beard removal resolved my serious dermatitis issues. I had moderate acne in high school, iand early incipient baldness all DHT artifacts.I can hold a lot more pee now, that's useful.

 

[Experimentality]

I agree with all of this. You know your literature. But I will aways stay on duta and finasteride both most likely so bicalutamide probably would be overkill. Remember Jurassic Park: Nature found a way. Here it is DHT somehow found its way. You can't kill DHT off because it circulates all through facial hair. Only beard removal resolved my serious dermatitis issues. I had moderate acne in high school, iand early incipient baldness all DHT artifacts.I can hold a lot more pee now, that's useful.

Great point on the DHT produced by beard follicles, although I doubt it would impact Androgenetic Alopecia significantly (especially on dutasteride). Local DHT concentrations (that is, locally produced DHT) are magnitudes higher than any serum DHT arriving at the follicular site. Local DHT (maybe T, not clear) and AR receptor density (or transcriptional sensitivity) are the most significant problems when dealing with Androgenetic Alopecia. This is why AR degraders hold such big promise: they remove the most significant contributor to Androgenetic Alopecia entirely (only non-genomic/ligand-binding effects would remain, which contribute weakly at best). This would also allow to test the true mechanism of E2: if it would only work through AR suppression, it would not be doing anything once those AR's are degraded (or may even be harmful).

 

[JaneyElizabeth]

Great point on the DHT produced by beard follicles, although I doubt it would impact Androgenetic Alopecia significantly (especially on dutasteride). Local DHT concentrations (that is, locally produced DHT) are magnitudes higher than any serum DHT arriving at the follicular site. Local DHT (maybe T, not clear) and AR receptor density (or transcriptional sensitivity) are the most significant problems when dealing with Androgenetic Alopecia. This is why AR degraders hold such big promise: they remove the most significant contributor to Androgenetic Alopecia entirely (only non-genomic/ligand-binding effects would remain, which contribute weakly at best). This would also allow to test the true mechanism of E2: if it would only work through AR suppression, it would not be doing anything once those AR's are degraded (or may even be harmful).

The reason why I think whatever is because my dermatitis took two largely untreatable areas and sort of overlapped. Excess sebum might carry T or be correlated with high T levels. I am also fairly certain that mountain men with great beards often had little or no scalp hair. That could happen in Western-type pictures.

 

[JaneyElizabeth]

The reason why I think whatever is because my dermatitis took two largely untreatable areas and sort of overlapped. Excess sebum might carry T or be correlated with high T levels. I am also fairly certain that mountain men with great beards often had little or no scalp hair. That could happen in Western-type pictures.

I usually answer before I read the question.

 

[JaneyElizabeth]

The reason why I think whatever is because my dermatitis took two largely untreatable areas and sort of overlapped. Excess sebum might carry T or be correlated with high T levels. I am also fairly certain that mountain men with great beards often had little or no scalp hair. That could happen in Western-type pictures.

Again, you really know your stuff and you understand what is likely to work and the normal curve effects of pretty much any treatment. But you mention local DHT. Does that mean that Estrogel on the scalp works marginally better than pills say;it seems under that logic. I don't know and I keep going back and forth in my beliefs. Estrogel probably works at least marginally to pump up things for a while.

 

[JaneyElizabeth]

I absolutely agree. HRT can definitely regrow hair everywhere on the head as proven countless times. However, we do not know the exact mechanism behind it - is it due to actual transcriptional activity at the ER or just AR suppression? Studies actually point to the latter, hence I am more and more leaning towards AR suppression, which E2 is extremely effective at, as the main driver behind regrowth. Castrates generally do not regrow any hair, but they do not have the AR suppression that E2 may provide. Backdoor and adrenal androgens are still abundant in castractes and local synthesis of DHT can still happen at a rate high enough to make regrowth impossible (5AR is highly expressed in the skin, making even minute amounts of residual testosterone dangerous for hair). Theoretically, a highly effective regimen for regrowth would consist of an antiandrogen to prevent AR binding, E2 to prevent AR upregulation as a response, and a 5ARI to remove highly potent androgens (DHT). Using an AA would probably be superfluous for people on HRT already, but it would not hurt either. I also postulate that such a regimen would be highly effective when used topically as well, which is the only viable option for males (even then, it is risky and should not be done without sufficient background knowledge).

One guess of mine is that it might take both to "turn hair growth" back on, meaning very high E2 levels with close to zero HRT. I think that is the case for both Bridge and me but I am all but completely feminized below the neck so one reason I post pics is to dissuade people from getting into this in case literally, estradiol works like a drug that you get hooked on it. And to mention that the boob growth which is usually permanent comes before the good hair part of things. You might end up looking like Buddha on blissful estrogen but with no hair! Yikes.

So yes, estrogens were discovered in the 20's and 30's so after one hundred years, we know that you probably will know that the price of the very best hair is extreme feminization of everything unless one masters cycling perhaps. For this to work best, for many reasons MtF's have advantages that are not available to cis-males regarding mainly the duration of the state of baldness and the continuous ingestion of estrogen over a period of many years. Some seem to get great regrowth right away but hair takes a lot of time in terms of months and years to reach cis-female or Asian female type hair with all of the sheen. No hair is better; I just want to have my locks back and if looking androgynous is part of that then I am fine with not being able to pass as male anymore especially with my new voice that is completely androgynous. I am still strictly chicky so that butches me up some.

 

[Experimentality]

Again, you really know your stuff and you understand what is likely to work and the normal curve effects of pretty much any treatment. But you mention local DHT. Does that mean that Estrogel on the scalp works marginally better than pills say;it seems under that logic. I don't know and I keep going back and forth in my beliefs. Estrogel probably works at least marginally to pump up things for a while.

Well, we know that HRT in the sense of exogenous E2 can yield positive results. The degree in which this happens seems to depend on multiple factors like androgen sensitivity, time of dormancy, fibrosis etc. This is why results are unpredictable and HRT is by no means a cure for everyone. In theory, hairloss is completely local. That means, as soon as the local environment is devoid of androgens, hair will not miniaturize under the influence of systemic androgens. We are not considering age-related decline in hair quality hair, or decline due to any other factors (pure Androgenetic Alopecia). Thus, we are striving to obtain a local environment devoid of androgenic activity. Drugs are entirely possible to be effective only locally, and so is E2. So, I would go even further with your statement and say E2 is significantly more effective topically as long as it is kept locally (since it achieves a concentration that is magnitudes higher than the systemic concentration). The crux here is obviously to keep the drug locally (a dermal delivery) as opposed to Estrogel, which delivers E2 transdermally. Hence, Estrogel is a terrible choice for dermal E2, as it was designed to deliver E2 transdermally. So actually you are right, Estrogel is marginally more effective if not indifferent to systemic E2.

There are some ways to achieve a dermal delivery, although they are not abundant. The best way is through nanoparticles. Nanoparticle assembly is very difficult and should be attempted in a lab. Furthermore, the stability of nanoparticles is variable. Currently I am experimenting with E2 loaded on a Azone/Laurocapram-based vehicle. Azone is currently probably the best agent for dermal delivery that is easily incorporated. There are many studies on Azone, but one specifically for E2 is listed below. Of course, as mentioned, one also needs an AA and 5ARI for this to have any chance of succeeding.

However, all of this is theoretically. We do not know if systemic androgens still influence follicles despite having an optimal local environment. Possible ways in which this may happen are non ligand-binding or non-genomic effects, which do not rely on receptor binding of the ligand but on the mere presence of it. Collectively, these effects are sometimes called androgen receptor signaling (for androgens). Contrary to my username I am a theorist, but experimentation is necessary in order to gauge what works and what does not work, at least for me individually.

Source: Enhanced buccal and mucosal retention and reduced buccal permeability of estradiol in the presence of padimate O and Azone: a mechanistic study.

 

[JaneyElizabeth]

Well, we know that HRT in the sense of exogenous E2 can yield positive results. The degree in which this happens seems to depend on multiple factors like androgen sensitivity, time of dormancy, fibrosis etc. This is why results are unpredictable and HRT is by no means a cure for everyone. In theory, hairloss is completely local. That means, as soon as the local environment is devoid of androgens, hair will not miniaturize under the influence of systemic androgens. We are not considering age-related decline in hair quality hair, or decline due to any other factors (pure Androgenetic Alopecia). Thus, we are striving to obtain a local environment devoid of androgenic activity. Drugs are entirely possible to be effective only locally, and so is E2. So, I would go even further with your statement and say E2 is significantly more effective topically as long as it is kept locally (since it achieves a concentration that is magnitudes higher than the systemic concentration). The crux here is obviously to keep the drug locally (a dermal delivery) as opposed to Estrogel, which delivers E2 transdermally. Hence, Estrogel is a terrible choice for dermal E2, as it was designed to deliver E2 transdermally. So actually you are right, Estrogel is marginally more effective if not indifferent to systemic E2.

There are some ways to achieve a dermal delivery, although they are not abundant. The best way is through nanoparticles. Nanoparticle assembly is very difficult and should be attempted in a lab. Furthermore, the stability of nanoparticles is variable. Currently I am experimenting with E2 loaded on a Azone/Laurocapram-based vehicle. Azone is currently probably the best agent for dermal delivery that is easily incorporated. There are many studies on Azone, but one specifically for E2 is listed below. Of course, as mentioned, one also needs an AA and 5ARI for this to have any chance of succeeding.

However, all of this is theoretically. We do not know if systemic androgens still influence follicles despite having an optimal local environment. Possible ways in which this may happen are non ligand-binding or non-genomic effects, which do not rely on receptor binding of the ligand but on the mere presence of it. Collectively, these effects are sometimes called androgen receptor signaling (for androgens). Contrary to my username I am a theorist, but experimentation is necessary in order to gauge what works and what does not work, at least for me individually.

Source: Enhanced buccal and mucosal retention and reduced buccal permeability of estradiol in the presence of padimate O and Azone: a mechanistic study.

So yes, my biggest period of restorative growth came when I went from 2.5mg of Premarin to two Climara patches which are steady state and got me to levels on their own and then I added unlimited use of Estrogel on scalp and genital tissue. I have also done it on my breasts, "just to see". I am not sure about Estrogel but I have also read somewhere that it is absorbed by fat and released pretty slowly. Otherwise, I am trying to figure out what dermal versus transdermal means in terms of the patch.

 

[Norwoody]

Well, we know that HRT in the sense of exogenous E2 can yield positive results. The degree in which this happens seems to depend on multiple factors like androgen sensitivity, time of dormancy, fibrosis etc. This is why results are unpredictable and HRT is by no means a cure for everyone. In theory, hairloss is completely local. That means, as soon as the local environment is devoid of androgens, hair will not miniaturize under the influence of systemic androgens. We are not considering age-related decline in hair quality hair, or decline due to any other factors (pure Androgenetic Alopecia). Thus, we are striving to obtain a local environment devoid of androgenic activity. Drugs are entirely possible to be effective only locally, and so is E2. So, I would go even further with your statement and say E2 is significantly more effective topically as long as it is kept locally (since it achieves a concentration that is magnitudes higher than the systemic concentration). The crux here is obviously to keep the drug locally (a dermal delivery) as opposed to Estrogel, which delivers E2 transdermally. Hence, Estrogel is a terrible choice for dermal E2, as it was designed to deliver E2 transdermally. So actually you are right, Estrogel is marginally more effective if not indifferent to systemic E2.

There are some ways to achieve a dermal delivery, although they are not abundant. The best way is through nanoparticles. Nanoparticle assembly is very difficult and should be attempted in a lab. Furthermore, the stability of nanoparticles is variable. Currently I am experimenting with E2 loaded on a Azone/Laurocapram-based vehicle. Azone is currently probably the best agent for dermal delivery that is easily incorporated. There are many studies on Azone, but one specifically for E2 is listed below. Of course, as mentioned, one also needs an AA and 5ARI for this to have any chance of succeeding.

However, all of this is theoretically. We do not know if systemic androgens still influence follicles despite having an optimal local environment. Possible ways in which this may happen are non ligand-binding or non-genomic effects, which do not rely on receptor binding of the ligand but on the mere presence of it. Collectively, these effects are sometimes called androgen receptor signaling (for androgens). Contrary to my username I am a theorist, but experimentation is necessary in order to gauge what works and what does not work, at least for me individually.

Source: Enhanced buccal and mucosal retention and reduced buccal permeability of estradiol in the presence of padimate O and Azone: a mechanistic study.

Thoughts on bi-estro? Also, as an aside, I am curious about your views on RU.

 

[JaneyElizabeth]

Just wait till they find out that DHT is actually good for hair but just shy about being around in an estrogenic chemical environment. Thus, the DHT actually grows the hair but estrogen is needed to reduce inflammation first and nothing else works, literally, except estradiol. Whoa. That's pretty deep.

 

[Experimentality]

Thoughts on bi-estro? Also, as an aside, I am curious about your views on RU.

Bi-estro contains E2 and E3. E3 has very poor intrinsic activity at the ER (see one of my previous posts on this thread) and as I am sceptical anyway about the transcriptional effects being positive I do not see the merit of E3. Furthermore, to achieve a purely (or as pure as possible) dermal delivery you need a specialized vehicle. This may be the reason that many topicals are not effective: they may have effective actives but they do not have an effective vehicle. Bi-estro is no exception. Using a custom vehicle is extremely important, and I have mentioned a few ways how to proceed in my previous post.

@JaneyElizabeth. Higher systemic E2 will very likely increase local concentrations as well. However, I feel like I need to stress that this is not an option for males whatsoever. Even for transgenders I would advise to be hesitant about introducing large amount of hormones in systemic circulation. Hormones are extremely complex, and have countless downstream effects that are not well understood. With a purely dermal delivery local concentrations can be achieved that trump any systemic dose, without any of the systemic (side) effects. This goes not only for E2 but literally any drug that is not a prodrug and can be metabolized by the skin (you would have to check the presence of the particular cytochrome P450 enzyme for your drug in the skin). Estrogel and bi-estro are not suitable for such dermal delivery. I would place them under the umbrella of systemic E2.

@Norwoody. RU is actually a mediocre antiandrogen. IdealForehead once made a great thread (although not entirely scientifically sound) about the binding affinities of different AA's. Not only the binding affinities matter when looking at AA's. Receptor binding time is important as well, as is half-life (RU has a very short serum half-life which is extended somewhat in the skin) and diffusive ability (which should ideally as low as possible to keep things local). However, the most important variable is again the vehicle. A PG-based vehicle is poor and will not yield maximum results for everyone as it is not ideally dermal (or local). Personally I would never use a drug (RU) that is not clinically approved, which (for me) is the minimum threshold for anything to even consider experimenting with. Currently I am using Apalutamide as it has a decent half-life (which means it is not broken down in a matter of hours. When using a good vehicle that can keep things as local as possible the serum half-life should ideally be around a day or so), is clinically approved and is currently the most effective drug against prostate cancer, which is a good measure of antiandrogenic potency (Enzalutamide shares the same effectivity, but has a half-life too long for my liking). Darolutamide has a perfect half-life but is intrinsically inferior to Apalutamide. The lack of results reported in the past with Darolutamide and Enzalutamide can be attributed to use of very poor vehicles (I mean DMSO, come on...) or AR upregulation. Upregulation can be effectively prevented by E2 as mentioned. To further increase the efficiency finasteride or dutasteride can be added. Microneedling should be done in order to provide the necessary growth factors. Possibly add a PKCa/b inhibitor like BIM-I after wounding to stop epidermal differentiation à la pegasus2 as a bonus.

 

[Experimentality]

you have a vehicle that than penetrates and delivers therapeutic amounts of the active throughout the hair folicle & supporting structure, but selectively avoids penetrating blood vessels?

https://stemsontx.com/wp-content/uploads/2019/06/hair-follicle-biology-diagram1.jpg

What you propose is impossible. The key here is to limit diffusion into the subcutaneous layer, where most blood vessels reside. At the same time, the vehicle should be powerful enough to penetrate the stratum corneum. Some systemic absorption is inevitable, which is why I do not advise anyone to experiment unless they know exactly what they are doing. Run a quick search on nanoparticle vehicles and you will find that localized delivery is definitely within the realm of possibilities. I am still trying to assess whether such an assembly is feasible with the equipment at my disposal. For the time being, I am using a Azone-based vehicle. There are plenty of articles indicating that Azone does a great job in localized delivery. I have linked one already, another one can be found in this post.

What vehicle did you use? If you were using any of the conventional vehicles, it is no surprise you did not get any results. Furthermore, experiments should be run for at least 6 months to preferably one year to assess effectiveness. I completely agree with @JaneyElizabeth that it can sometimes takes years to fully reverse fibrosis and generate new growth. Any experiment run for a couple of weeks/months cannot be regarded as a valid data point.

Weekly microneedling is likely needed as well to get results. Using AA's and E2 alone will not release any growth factors whatsoever but merely create an ideal environment for hair growth to occur again. Again, this also depends on individual parameters that can impossibly be predicted a priori.

Source: In Vitro and in Vivo Evaluation of DMSO and Azone as Penetration Enhancers for Cutaneous Application of Celecoxib.

Localized delivery of celecoxib with Azone (vehicle #5, SC = stratum corneum, EP+D = epidermis + dermis (follicular site), permeated through skin = compound detection in subcutaneous layers).

 

[tato123]

The forum is having problems I can't post photos.


So there is their link.


MY PICS

Nova hosted at ImgBB

Image Nova hosted in ImgBB

ibb.co

New-2 hosted at ImgBB

Image New-2 hosted in ImgBB

ibb.co

The site itself is going to go out soon.



:*