Exploring The Hormonal Route. Hair=life.

Swarleyd

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The fact is that some people are putting so much energy in order to restore their hair while they will still be ugly with or without hair lmao
 

Analogies

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Chiming in here. Not only ER-beta selectivity is important, but also the Relative Transactivational Capacity or Intrinsic Activity (IA) of your ligand. This seems to be forgotten quite often. I strongly encourage everyone interested in ER-beta ligands to read this paper (hyperlink removed). It contains all information that is currently available for known ER-beta agonists.

In short, the IA determines how many genes will be transcribed upon ligand binding with the receptor. Estradiol (E2) has an IA of 100 for both ER-alpha and ER-beta, which is the reference ligand for all other ligands. An IA higher than 100 means that the transcription will be broader than E2, while an IA lower than 100 means the transcription will be narrower than E2. This means that Estriol (E3), with an IA of 11% at ER-alpha and 17% at ER-beta [R], will not activate a very meaningful degree of transcription upon binding. Hence, there are many users that deem E3 as rather weak.

Back to the selective ER-beta ligands. If you want exclusive ER-beta activation, you need a ligand that is very selective for ER-beta (i.e. a high ERa/ERb RBA ratio), a high IA and a high binding affinity. My attention was initially drawn to 8b-vinylestradiol as well, since it has an exceptionally good selectivity (180-fold, functionally 46-fold [R]). However, when investigating the IA, it was only 45.8 relative to E2 [R]. I have not been able to find anything about WAY-200070, but I would be sceptical. There are not many ligands with a very high IA and simultaneously good selectivity for ER-beta.

The best option would be Erteberel, which has a functional selectivity of 32 for ER-beta, and is a full agonist of both receptors with an IA of 101 at ER-beta and 94 at ER-alpha [R]. Futhermore, Erteberel does not inhibit the HTPA axis as per [R] up until 25mg daily orally, and shows low bioavailability [R]. This makes it theoretically a great choice to effectively use topically in very low dosages. The downside if you want to test this is that it will cost you roughly $1500 per gram (untested from China).

However, personally I am sceptical about selective ER-beta activation. I think there is too little evidence that points exclusively in the direction of ER-beta. Yes, in murine models ER-alpha arrests hair growth [R], but this does not necessarily translate to human hair follicles. In murine models, E2 induces catagen [R], but in human hair follicles, E2 prolongs anagen in male frontotemporal HF's [R]. Not only does this indicate a completely different mechanism between men and women, it also indicates that there are regional differences in the scalp where E2 can be highly effective or detrimental. Obviously, estrogens are still extremely complex, but I do not think ER-alpha (which is the larger estrogen receptor by far) can be excluded at all.

Apologies for the lengthy reply. I hope some may find it useful.

Edit: I noticed that links to research that I included (the [R]'s) have been removed because of new member restrictions. If anyone wants to check a source, feel free to ask.
Ask and you shall receive:
Link to WAY-2000070 ligand binding affinity
 

tato123

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Good night everyone, I've been a little lost, but I'm back with good news.

I've never been so hairy, eyebrows come together with vertices, and I start to grow hairs on the forehead, near the eyebrows going up towards the forehead, a lot of hair.

In 90 days I reach the 1 year mark cycling e2.


My T today is lower around 550-600 dg/ml and my is E2 60-115dg/mL

My testicles are smaller too.

But perfect erection, perfect ejaculation, desire to have very good sex, I don't have any side effects in that sense, my ejaculation is not thin, it's milky thick or normal.


I added minoxidil again at some point in the treatment, sublingually. (5 mg max).


if you go back a few pages then you will see some pictures of me and believe me when I say that I'm with a lot more volume now, but I want to protect myself from always posting pictures.

My tip for you, insist with the treatment! is so slow, so f*****g slow man.

in end of the day I think I created an ideal environment

I dropped my physiological level of T, which was around 900, with the increase in chronic E2, I influenced regrowth with dermarroler and minoxidil, boosted it during the cycle with CPA and bicalutamide, and that's it, I had regrowth+volume, even knowing the risks I would do it all over again.

When I stopped the CPA, I switched to bicalutamide and removed it, I'm holding ground and gaining, I replace it with finasteride, and it's great


My liver is weaker after that, I had increased transaminases and it showed when I was drunk these days ago I felt pain in the right hypochondrium, I never felt it, but I drank too many days in a row so it could be an association, I just said that so you know that has that risk.


Other than that I'm fine.

I keep cycling the E2 and will probably do this for a long time.
 

Norwoody

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Good night everyone, I've been a little lost, but I'm back with good news.

I've never been so hairy, eyebrows come together with vertices, and I start to grow hairs on the forehead, near the eyebrows going up towards the forehead, a lot of hair.

In 90 days I reach the 1 year mark cycling e2.


My T today is lower around 550-600 dg/ml and my is E2 60-115dg/mL

My testicles are smaller too.

But perfect erection, perfect ejaculation, desire to have very good sex, I don't have any side effects in that sense, my ejaculation is not thin, it's milky thick or normal.


I added minoxidil again at some point in the treatment, sublingually. (5 mg max).


if you go back a few pages then you will see some pictures of me and believe me when I say that I'm with a lot more volume now, but I want to protect myself from always posting pictures.

My tip for you, insist with the treatment! is so slow, so f*****g slow man.

in end of the day I think I created an ideal environment

I dropped my physiological level of T, which was around 900, with the increase in chronic E2, I influenced regrowth with dermarroler and minoxidil, boosted it during the cycle with CPA and bicalutamide, and that's it, I had regrowth+volume, even knowing the risks I would do it all over again.

When I stopped the CPA, I switched to bicalutamide and removed it, I'm holding ground and gaining, I replace it with finasteride, and it's great


My liver is weaker after that, I had increased transaminases and it showed when I was drunk these days ago I felt pain in the right hypochondrium, I never felt it, but I drank too many days in a row so it could be an association, I just said that so you know that has that risk.


Other than that I'm fine.

I keep cycling the E2 and will probably do this for a long time.
How is your strength in the gym?
 

Almas

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Good night everyone, I've been a little lost, but I'm back with good news.

I've never been so hairy, eyebrows come together with vertices, and I start to grow hairs on the forehead, near the eyebrows going up towards the forehead, a lot of hair.

In 90 days I reach the 1 year mark cycling e2.


My T today is lower around 550-600 dg/ml and my is E2 60-115dg/mL

My testicles are smaller too.

But perfect erection, perfect ejaculation, desire to have very good sex, I don't have any side effects in that sense, my ejaculation is not thin, it's milky thick or normal.


I added minoxidil again at some point in the treatment, sublingually. (5 mg max).


if you go back a few pages then you will see some pictures of me and believe me when I say that I'm with a lot more volume now, but I want to protect myself from always posting pictures.

My tip for you, insist with the treatment! is so slow, so f*****g slow man.

in end of the day I think I created an ideal environment

I dropped my physiological level of T, which was around 900, with the increase in chronic E2, I influenced regrowth with dermarroler and minoxidil, boosted it during the cycle with CPA and bicalutamide, and that's it, I had regrowth+volume, even knowing the risks I would do it all over again.

When I stopped the CPA, I switched to bicalutamide and removed it, I'm holding ground and gaining, I replace it with finasteride, and it's great


My liver is weaker after that, I had increased transaminases and it showed when I was drunk these days ago I felt pain in the right hypochondrium, I never felt it, but I drank too many days in a row so it could be an association, I just said that so you know that has that risk.


Other than that I'm fine.

I keep cycling the E2 and will probably do this for a long time.
This reminds me of what I wanted to try: 75-100mg of Bicalutamide + microdosing of Gel E to slightly lower the T level. But since even HRT does not always help, and I quickly lose my hair, I decided to go straight to the last option. Perhaps I will try microdosing E after HRT for support. But I have too aggressive baldness, so I decided to completely destroy T
Thank you for staying on the forum and keep us updated
 

tato123

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This reminds me of what I wanted to try: 75-100mg of Bicalutamide + microdosing of Gel E to slightly lower the T level. But since even HRT does not always help, and I quickly lose my hair, I decided to go straight to the last option. Perhaps I will try microdosing E after HRT for support. But I have too aggressive baldness, so I decided to completely destroy T
Thank you for staying on the forum and keep us updated
At first I thought it wasn't helping either, it's all very slow, but when I see pictures of me from 1 year ago it's shocking, I'm very different today almost 1 year later not only my hair, face, skin, eyelashes, eyebrows, I'm more brighter, whiter, with softer contours on the face.

But I only really started to see this after 8 months of treatment, of standing in front of the mirror and saying, I've changed.


8 f*****g months.

I didn't forget the treatment one day, I did the treatment every day, I changed drugs a few times.

But what I kept was perseverance.
 

Almas

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At first I thought it wasn't helping either, it's all very slow, but when I see pictures of me from 1 year ago it's shocking, I'm very different today almost 1 year later not only my hair, face, skin, eyelashes, eyebrows, I'm more brighter, whiter, with softer contours on the face.

But I only really started to see this after 8 months of treatment, of standing in front of the mirror and saying, I've changed.


8 f*****g months.

I didn't forget the treatment one day, I did the treatment every day, I changed drugs a few times.

But what I kept was perseverance.
Some have accused me of not being persistent enough. But in fact, if you continue to go bald during treatment, it means that the scheme does not work. After 1,2,3,4 and 5 months on Bicalutamide I saw a deterioration, so there was no doubt that it was not helping me. Now I am on HRT and I will be evaluating the first results in 3 months.

There is a myth that you need to give treatment for at least half a year in order to conclude whether it helps. Sometimes these periods are extended to a year or two, which is even more absurd when we have to rush to treatment. In fact, more often than not, three months are enough. You should have had an improvement in hair quality and an increase in hair diameter before new ones began to grow.
 

Experimentality

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Ask and you shall receive:
Very good find, although I am not completely sure how to interpret these results (or actually I am, I think the results are incomplete the way they are presented here). Of course, we have the binding affinities on the left, indicating good selectivity of WAY-2000070 for ER-beta. On the right, we have the transactivation of the receptor, however, it is not specified to what extent the receptors are activated. For example, the compound 7-alpha-hydroxy-DHEA (7-HD) only has an EC50 of 20 uM, but is able to activate ER-beta with 60-70% potency of E2*. So, we see that the EC50 for transactivation of WAY-2000070 for ER-beta is 31nM, but it does not specify the transcriptional activity of the receptor at that concentration. This is a really important difference, since you might end up with a compound that can only activate a small part of ER-beta associated genes.

As a side note, the more I read about estrogens and their relation to hair growth, the more I am starting to doubt E2's real global efficacy (and the more I realise estrogens are very poorly understood, with many pathways other than ligand-binding that influence tissue genetic expression). In my previous post I mentioned that E2 lengthens anagen in frontotemporal male follicles (FMF), but induces catagen in the same female follicles (FFF)**. The authors of the associated paper conclude that E2 may have vastly different local effects depending on the scalp region. To complicate things even further, E2 is also known to strongly decrease AR density***, which may or may not account for some if not all of its positive effects on FMFs. If we were to replace E2 with a selective ER-beta ligand, we might not get any positive effects or maybe even induce catagen, like in the FFFs. To me, it is not clear enough whether ER-beta truly is the holy grail for hair growth. There has been only one study to my knowledge on these positive effects, and that one was executed on mice****. Since male and female human follicles already behave differently, these results are absolutely not transferable to human (male) follicles.

Personally, I think that E2 can definitely be useful. However, based on the current knowledge it should preferably be used locally, only on the frontotemporal region (for males, that is). Whether the positive effects are coming from direct estrogen-related gene transcription or AR supression is still unknown, unfortunately (at least to me). Also, anyone wanting to experiment with E2 (or any hormone for that matter) should be aware of all its direct and downstream effects, some of which are especially detrimental to males. Of course I am always open for discussion on this topic, as we can all learn from each other.

Source list (again, no hyperlinks, still restricted on my account):

*Estrogen Receptor b Ligands: Recent Advances and Biomedical Applications
**Estrogens and the hair follicle
***The hair follicle as estrogen target and source (really nice, complete article with tons of information)
****Hair cycle control by estrogens: catagen induction via estrogen receptor (ER)-alpha is checked by ER beta signaling

 
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Analogies

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At first I thought it wasn't helping either, it's all very slow, but when I see pictures of me from 1 year ago it's shocking, I'm very different today almost 1 year later not only my hair, face, skin, eyelashes, eyebrows, I'm more brighter, whiter, with softer contours on the face.

But I only really started to see this after 8 months of treatment, of standing in front of the mirror and saying, I've changed.


8 f*****g months.

I didn't forget the treatment one day, I did the treatment every day, I changed drugs a few times.

But what I kept was perseverance.
I say prove it. A picture of your hair then and now isn't going to expose you. Most of us are looking for a glimmer of hope to continue or even embark on this path. Your contributions are no exception. Talk is cheap...
 

KNemo

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I say prove it. A picture of your hair then and now isn't going to expose you. Most of us are looking for a glimmer of hope to continue or even embark on this path. Your contributions are no exception. Talk is cheap...
It's not like those effects and timeframes aren't well documented already, why would he need to prove something?
 

Analogies

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It's not like those effects and timeframes aren't well documented already, why would he need to prove something?
To the extent of keeping your manhood (Libido, gym strength) and regrow hair while on E2? I haven't seen anyone make these claims.
 

Pls_NW-1

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Hello, long time someone heard of me.


Well, I needed to get some more info, and...

I was correct with my asumption!

I have (severe) problems with androgens and other hormones.

My newest endocrinologist in the bigger clinics found out that I have either problems with my adrenal gland/gonads or some other hormone production structure/organ. And that it is some kind of a mutation being probably in the family. My sister has hyperandrogenism -> some form of PCOS.

I will probably leave this forum aka. get offline as nothing will help me, I am probably a genetic defect and have to live my life with it. I hope that this is not the case and I can correct that via meds or surgical operations... but as of now... I am not even allowed to take hormone altering drugs such as Finasteride.

Just a little reminder; am 17 years old.

Hope you all have a great day, and not having to live through this hell as I do! GG's!!

EDIT: Forgot to tell it, it's AGS.
 
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Almas

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Hello, long time someone heard of me.


Well, I needed to get some more info, and...

I was correct with my asumption!

I have (severe) problems with androgens and other hormones.

My newest endocrinologist in the bigger clinics found out that I have either problems with my adrenal gland/gonads or some other hormone production structure/organ. And that it is some kind of a mutation being probably in the family. My sister has hyperandrogenism -> some form of PCOS.

I will probably leave this forum aka. get offline as nothing will help me, I am probably a genetic defect and have to live my life with it. I hope that this is not the case and I can correct that via meds or surgical operations... but as of now... I am not even allowed to take hormone altering drugs such as Finasteride.

Just a little reminder; am 17 years old.

Hope you all have a great day, and not having to live through this hell as I do! GG's!!

EDIT: Forgot to tell it, it's AGS.
If I were you, I would follow Noah's example and try HRT cycles, all medicines can be bought at any age. This is the only medicine with a high chance of success, and short-term HRT does not interfere with looking like a guy, many do not even lose muscle thanks to Bicalutamide, the only problem is breasts that can be masked, removed surgically, and it also disappears by itself after stopping HRT. I understand how HRT can scare a guy, I was in your place. But as you know, now I am on HRT and am not afraid of anything, because I am well aware of the effects. Perhaps you will come to this in time
 
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Pls_NW-1

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If I were you, I would follow Noah's example and try HRT cycles, all medicines can be bought at any age. This is the only medicine with a high chance of success, and short-term HRT does not interfere with looking like a guy, many do not even lose muscle thanks to Bicalutamide, the only problem is breasts that can be masked, removed surgically, and it also disappears by itself after stopping HRT. I understand how HRT can scare a guy, I was in your place. But as you know, now I am on HRT and am not afraid of anything, because I am well aware of the effects. Perhaps you will come to this in time
Buddy, it´s a snydrome... a defect of your adrenal gland enzyms. You can´t stop this with HRT, in my case. I will probably have to start HRT as in, taking Cortisol. I will report when I get some news, but as of now I have to drop Finasteride due to hormonal problems. AGS gets autosomal recessively (very unlucky man I am) inherited in your family and is manifested into your genome. I hope this clarifies :/
 

Pls_NW-1

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How long will your treatment take and will it cause even further balding? Im sorry bro
I first have to get my genetic mutation fully diagnosed. If it is indeed the case, I will prob have to take Cortisol or smt other as HRT to compensate the defect of the certain enzym being responsible in the synthesis of Cortisol, for as long as I live lol. Uhm... It would put balding at a normal pace. Like... what I am experiencing is premature balding due to the adrenal androgens. I started losing hair at the age of 12/13.
 

Pls_NW-1

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So it will slow down your current balding, but your natural male pattern baldness will progress and you will be nw6 like your dad in mid 20s?
Possibly. It could also be that my dad had this pile of sh*t... I will probably wear a system or just shave it off. I am pretty sure that at some point, hair will be treatened like some refill appointment.

Btw. as of today, my dad has almost no hair, not even on the horseshoe pattern...
 

Pls_NW-1

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We would need hair cloning or some very strong growth stimulant. Im also in pretty bad situation, finasteride improved my hair on top, but retrograde became so bad I cant even do a small transplant anymore. Lest hope something will be done before 2030.
Yeah... really! As ofto today, I will have to stop using Finasteride. It´s said by the doctors who prescribed it to me and as well by those who suspect me to have that syndrome.

Funny though is that I haven´t noticed any kind of changes... no positive nor negative changes while on Finasteride. I was on it since the 02th February, so nearly six months. I felt like taking freakin candy, and I took the quartered 5mg pills! This once again proves that I have underlying issues manifested into... my-... myself.
 
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