Darolutamide (odm-201), A Better Topical Than Enzalutamide?

[IdealForehead]

@IdealForehead Would you be able to write a short post about your efforts to deal with the minoxidil damage? I suspect it's more of an issue for those in their 30s+ who are already losing collagen due to age.

The past year has been brutal on my skin... gradually getting old guy face with young guy hair (yeah the opposite of most people here). Lesson learned, watch how much minoxidil you're spreading outside of the scalp.

Yeah no problem. I actually did this already and made a thread about the issues here:

https://www.hairlosstalk.com/intera...ol-will-make-your-face-look-like-sh*t.109593/

Hope that helps. The discussion segued into a tangential one on antihistamines and other alternative therapies if I recall correctly, but I think that was interesting as well.

 

[kawnshawn]

Few weeks ago I started setipiprant and have been getting good results. I still have a LOT of enzalutamide I got for cheap that I have sitting around. I had it tested by a certified lab in the U.S. and came back clean. It's a super strong androgen, not as strong as daro but with the right dose it can come close. might sell ot if anybody is interested

 

[Georgie]

Few weeks ago I started setipiprant and have been getting good results. I still have a LOT of enzalutamide I got for cheap that I have sitting around. I had it tested by a certified lab in the U.S. and came back clean. It's a super strong androgen, not as strong as daro but with the right dose it can come close. might sell ot if anybody is interested

What do you mean by “good results”?

 

[kawnshawn]

What do you mean by “good results”?

As in no itch and no shedding. Wouldn't expect regrowth this early in.

 

[Georgie]

I thought we established that even 0.5mm would stimulate some growth factors, though not nearly as much as 1.5mm+. Do I have that wrong?

Yes you are quite correct, it does promote the stimulation of growth factors, but it's not wounding. For the most part, it assist in collagen formation and skin elasticity.

 

[Georgie]

As in no itch and no shedding. Wouldn't expect regrowth this early in.

And how much were you shedding prior to seti? If you say 30 hairs or less i'm not going to take you seriously.

 

[kawnshawn]

And how much were you shedding prior to seti? If you say 30 hairs or less i'm not going to take you seriously.

Then you don't need to take me seriously regardless, but to answer your question I would say everyday after taking a shower and brushing my hair, easily 40-60.

 

[IdealForehead]

You raise some valid points, but I am a big fan of both Occam's Razor and the process of elimination as problem solving tools.

What I mean is, when faced with an unknown question and inadequate evidence or knowledge to make a clear assessment, I find it useful to work through systematically by starting with the simplest or most common explanations, exhausting solutions for each one at a time, and then moving on to the most experimental and esoteric approaches only once all the basics have been exhausted.

In actual fact, I think you have done this very well up to this point. In brief:

- Biopsies have ruled out an auto-immune cause with fair certainty.
- Iron infusions and extensive bloodwork has ruled out a nutritional cause or other general medical condition.
- Most recently, the use of daro+duta+cypro has ruled out with fair certainty (in my opinion) that this is a primarily androgenic issue, or that antiandrogens can likely solve your problem.

In my opinion, that workflow logically leads next into a deeper evaluation of your female hormones and how well the balance of them could be affecting your hair.

It is certainly possible that there is a far more esoteric cause such as the cortisol issues you describe. However, I do not think you have remotely enough data or trials to first rule out the contribution of estrogens to the problem. I also don't think you have run nearly sufficient trials to be able to say you've evaluated the female hormone issues with the same thoroughness you have evaluated the other preceding possibilities listed above.

The fact that you have experienced dramatic sheds of hair when switching estrogens/progesterones actually provides some strong evidence that this is where your problems are coming from. If the female hormones were not a major factor, they wouldn't have such a powerful effect on your hair.

I don't think it's correct that excessive estrogen causes hair loss by converting to testosterone. "Although testosterone can be converted to estradiol, the reverse does not happen."

https://www.americanscientist.org/article/testosterone-in-women

Estrogen is very complicated when it comes to hair and the research we have is very poor. But in essence, from the information we do have, estrogen can be fairly considered to have a Goldilocks effect on hair - too much is bad and too little is bad as well. (Laser therapy for hair has been shown to exhibit a similar Goldilocks effect.)

Estrogen must also be considered with finesse in that each type of estrogen works differently from the others and these differences extend to how they also work in different parts of the body.

Estrogenic activity within a tissue is influenced by the type of estrogen and the subtype of estrogen receptor found within that tissue,[20]as well as by the distribution of cofactors and corepressors of the estrogen-receptor complex within the tissue.[21] With estradiol as the standard, binding affinity for both estrogen receptor (ER)-α and -ß is equal at 100.[20] Estrone has a binding affinity for ER-α of 60 and for ER-ß of 37. Estriol binds to ER-α with an affinity of 14 and to ERß with an affinity of 21. Therefore, estradiol has the strongest binding affinity for both ER-α and -ß.

https://www.medscape.com/viewarticle/571299_6​

This is where the greatest argument for bioidentical hormones comes from.

Ethinyl estradiol does not work the same as natural estrogens. Ethinyl estradiol is a primary ER-alpha agonist, and it triggers very different tissue responses from the natural estrogens which have a much more balanced function:

Differential effect of estrogen receptor alpha and beta agonists on the receptor

In the current investigation, we examined the effect of three estrogens with different potency for specific estrogen receptors (ER) on RAGE expression in human microvascular endothelial cells (HMEC-1). Of the three estrogens tested, ethinyl estradiol (EE), an estrogen receptor alpha (ERα) agonist, was the strongest inducer of RAGE expression in HMEC-1. By comparison, 17-epiestriol, an estrogen receptor beta (ERβ) agonist and 17-β-E2, an ER agonist that is almost equally potent for ERα and ERβ were less effective in stimulating RAGE expression

https://www.sciencedirect.com/science/article/pii/S0167488905000467
​

There is a simple study which proves incontrovertibly that ethinyl estradiol does not work the same on body tissues as natural estrogens do. Also we can note that estriol, which is the most famous estrogen for hairg growth in pregnancy has a predominantly ER-beta affinity, while ethinyl estradiol has the exact opposite (high ER-alpha affinity)

If your primary estrogen (ethinyl estradiol) is so dramatically unbalanced and unnatural in its binding and tissue stimulation, how can you expect a natural response?

It is absolute fact that ethinyl estradiol is very different in the body compared to natural estradiol/estriol/estrone.

This provides a very clear and easy explanation for a lot of the problems you are having with good basic scientific principles behind it.

If you wish to test this hypothesis (which I think should be the next most logical step in your workflow), and you wish to avoid cycling hormones, then again an approach of Triest (estradiol/estriol/estrone) with a low dose progesterone IUD plus some topical and/or oral antiandrogens for insurance would objectively make the most sense.

Until you have tried a solution that involves a more balanced and natural stimulation of your estrogen receptors, it is not possible to say to what extent this is the issue. If the problem is the disproportionately high ER-alpha stimulation by ethinyl estradiol, then you will not adequately resolve that problem until you remove ethinyl estradiol from your body and replace it with something that provides a better balance of ER-alpha and ER-beta stimulation (eg. Triest).

That may be a difficult thing to conceive of doing, given the uterine pain and bleeding as well as shock losses you've suffered from prior shifts in estrogen in the past. But I think it's an absolutely necessary step to take at some point in this process, and I think it is the step with the highest probability of success given the facts discussed above.

In the big scheme of things (overlooking temporary pains and discomforts if we can), one of two things may happen if you do this: (1) the problem will be solved, or (2) you will have added imbalanced estrogen as yet another cause of your problem to have been ruled out.

In my opinion, only then would it make sense to start experimenting with your adrenal axis which is a much funnier system to manipulate and less likely to be the culprit in the context of the above.

Again this is all your choice. Whatever you do, don't stand still. Keep working logically through the system, as you are making progress whether you feel it or not sometimes. The process of elimination is a powerful problem solving tool of used correctlu. I recommend this approach next because I think there is the greatest evidence and highest probability that if you pursue it, it may be the last experiment you will need to run.

I think I just found further proof of my theory that brings it all together into a final package:

Hair cycle control by estrogens: catagen induction via estrogen receptor (ER)-alpha is checked by ER beta signaling

Although 17beta-estradiol (E2) is recognized as a potent hair growth modulator, our knowledge of estrogen function, signaling, and target genes in hair biology is still very limited. Here we show that ER alpha, ER beta, and ER beta ins are all expressed throughout the murine hair cycle, both at the protein and RNA level, but show distinct expression patterns. We confirm that topical E2 arrests murine pelage hair follicles in telogen and demonstrate that E2 is a potent inducer of premature catagen development. The ER antagonist ICI 182.780 does not induce anagen prematurely but accelerates anagen development and wave spreading in female mice. ER beta knockout mice display accelerated catagen development along with an increase in the number of apoptotic hair follicle keratinocytes. This suggests that, contrary to previous concepts, ER beta does indeed play a significant role in murine hair growth control: whereas the catagen-promoting properties of E2 are mediated via ER alpha, ER beta mainly may function as a silencer of ER alpha action in hair biology. These findings illustrate the complexity of hair growth modulation by estrogens and suggest that one key to more effective hair growth manipulation with ER ligands lies in the use of selective ER alpha or -beta antagonists/agonists. Our study also underscores that the hair cycling response to estrogens offers an ideal model for studying the controls and dynamics of wave propagation in biological systems.

https://www.ncbi.nlm.nih.gov/pubmed/15591132
​

In other words:

• ER-alpha stimulates catagen (stopping hair growth dead).
• ER-beta blocks the ER-alpha pathway (causing hair growth).

And to summarize from above:

• Ethinyl estradiol has "ERα selective agonistic potency" ie. only binds to ER-alpha (ref)
• 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)

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 (absolutely terrible) - exclusive alpha binding, will lead to premature catagen and cessation of hair growth

 

[Georgie]

Then you don't need to take me seriously regardless, but to answer your question I would say everyday after taking a shower and brushing my hair, easily 40-60.

Mmk. Where did you buy it?What dose and route of administration are you using, and when did you see the decrease in shedding? I’ll be getting my soon. Salivating.

 

[Georgie]

I think I just found further proof of my theory that brings it all together into a final package:

Hair cycle control by estrogens: catagen induction via estrogen receptor (ER)-alpha is checked by ER beta signaling

Although 17beta-estradiol (E2) is recognized as a potent hair growth modulator, our knowledge of estrogen function, signaling, and target genes in hair biology is still very limited. Here we show that ER alpha, ER beta, and ER beta ins are all expressed throughout the murine hair cycle, both at the protein and RNA level, but show distinct expression patterns. We confirm that topical E2 arrests murine pelage hair follicles in telogen and demonstrate that E2 is a potent inducer of premature catagen development. The ER antagonist ICI 182.780 does not induce anagen prematurely but accelerates anagen development and wave spreading in female mice. ER beta knockout mice display accelerated catagen development along with an increase in the number of apoptotic hair follicle keratinocytes. This suggests that, contrary to previous concepts, ER beta does indeed play a significant role in murine hair growth control: whereas the catagen-promoting properties of E2 are mediated via ER alpha, ER beta mainly may function as a silencer of ER alpha action in hair biology. These findings illustrate the complexity of hair growth modulation by estrogens and suggest that one key to more effective hair growth manipulation with ER ligands lies in the use of selective ER alpha or -beta antagonists/agonists. Our study also underscores that the hair cycling response to estrogens offers an ideal model for studying the controls and dynamics of wave propagation in biological systems.

https://www.ncbi.nlm.nih.gov/pubmed/15591132
​

In other words:

• ER-alpha stimulates catagen (stopping hair growth dead).
• ER-beta blocks the ER-alpha pathway (causing hair growth).

And to summarize from above:

• Ethinyl estradiol has "ERα selective agonistic potency" ie. only binds to ER-alpha (ref)
• 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)

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 (absolutely terrible) - exclusive alpha binding, will lead to premature catagen and cessation of hair growth

17-alpha, alfatradiol, is what is used in ell-cranell/Pantostin. It’s clinically proven to increase anagen hair counts. In fact, it’s bee used to treat male pattern baldness in women who have undergone aromatase inhibition for breast cancer. It isn’t bad for hair.

Estriol is the weakest bio available form of estrogen, and is a metabolite of estrogen. If estrogen is poor, estriol is even more so. Receptors have the highest affinity for 17b.

I agree and EE is not healthy and not normal. I also agree that it has a low affinity to estrogenic tissues because of its synthetic nature. I am willing to try a dose of 4mg 17b/100mg prometrium for a while but I’ll need to get the latter online.

 

[whatevr]

It’s clinically proven to increase anagen hair counts.

Yeah, so is saw palmetto. Pantostin is garbage, just very expensive water.

 

[Georgie]

Yeah, so is saw palmetto. Pantostin is garbage, just very expensive water.

Lol I agree, but I was just trying to say that it’s at the very least not BAD for hair.

 

[whatevr]

Lol I agree, but I was just trying to say that it’s at the very least not BAD for hair.

Right, but I'm not sure why you brought that up, because he is talking about estrogen receptor alpha and beta. Those are subunits of the estrogen receptor, and the 'alpha' and 'beta' nomenclature doesn't have any relation to the differences between 17-alpha estradiol (the weak isomer) and 17-beta estradiol ('real' estradiol).

 

[bridgeburn]

I'd just like to add one thing: Estradiol inhibits 5ar but Ethynl E doesn't

"Estradiol exhibited 40.8 +/- 14.2% inhibition at 10(-4) mol/L (P less than .01), whereas ethinyl estradiol at concentrations from 10(-8) to 10(-4) mol/L failed to inhibit 5 alpha-reductase activity. "

 

[kawnshawn]

Mmk. Where did you buy it?What dose and route of administration are you using, and when did you see the decrease in shedding? I’ll be getting my soon. Salivating.

Alibaba. The "companies" on there that sell chemicals are merely middlemen that buy their product from the same manufacturer. Oral 1.5g a day split morning and night. About two weeks ago saw decrease. Don't take it before bed, makes falling asleep difficult.

 

[infinitepain]

No we don’t have photos.

People respond differently to medications. Rolling with 0.5mm isn’t wounding. It might just increase absorption of topicals.

Do some research before you believe everything you see and read.

Actually, he is using 1.5mm daily which is insane:

How red and sore does your scalp get before you stop rolling and apply the minoxidil?
- Just slightly red, no bleeding. I use roller very lightly, size I have been using is 1.5 mm since 2013. I tried for few months 0,5 mm, but felt I got better results from 1.5 mm

Anyone is growing hair on darolutamide or not? I only remember Ideal saying he was growing his hairline back but he's using a fuckton of things at once.

 

[infinitepain]

Few weeks ago I started setipiprant and have been getting good results. I still have a LOT of enzalutamide I got for cheap that I have sitting around. I had it tested by a certified lab in the U.S. and came back clean. It's a super strong androgen, not as strong as daro but with the right dose it can come close. might sell ot if anybody is interested

What do you mean good results? weeks is nothing to evaluate results.

I think I just found further proof of my theory that brings it all together into a final package:

Hair cycle control by estrogens: catagen induction via estrogen receptor (ER)-alpha is checked by ER beta signaling

Although 17beta-estradiol (E2) is recognized as a potent hair growth modulator, our knowledge of estrogen function, signaling, and target genes in hair biology is still very limited. Here we show that ER alpha, ER beta, and ER beta ins are all expressed throughout the murine hair cycle, both at the protein and RNA level, but show distinct expression patterns. We confirm that topical E2 arrests murine pelage hair follicles in telogen and demonstrate that E2 is a potent inducer of premature catagen development. The ER antagonist ICI 182.780 does not induce anagen prematurely but accelerates anagen development and wave spreading in female mice. ER beta knockout mice display accelerated catagen development along with an increase in the number of apoptotic hair follicle keratinocytes. This suggests that, contrary to previous concepts, ER beta does indeed play a significant role in murine hair growth control: whereas the catagen-promoting properties of E2 are mediated via ER alpha, ER beta mainly may function as a silencer of ER alpha action in hair biology. These findings illustrate the complexity of hair growth modulation by estrogens and suggest that one key to more effective hair growth manipulation with ER ligands lies in the use of selective ER alpha or -beta antagonists/agonists. Our study also underscores that the hair cycling response to estrogens offers an ideal model for studying the controls and dynamics of wave propagation in biological systems.

https://www.ncbi.nlm.nih.gov/pubmed/15591132
​

In other words:

• ER-alpha stimulates catagen (stopping hair growth dead).
• ER-beta blocks the ER-alpha pathway (causing hair growth).

And to summarize from above:

• Ethinyl estradiol has "ERα selective agonistic potency" ie. only binds to ER-alpha (ref)
• 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)

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 (absolutely terrible) - exclusive alpha binding, will lead to premature catagen and cessation of hair growth

Go ER.

 

[kawnshawn]

What do you mean good results? weeks is nothing to evaluate results.



Go ER.

lol when you have done propecia, minoxidil oral/topical, ketoconazole, LLLT, RU, enza, spironolactone, and wounding for over a period of three years and none of them stopped shedding at all and then a few weeks on seti completely stops all shedding I would say that is good results so far.

 

[infinitepain]

lol when you have done propecia, minoxidil oral/topical, ketoconazole, LLLT, RU, enza, spironolactone, and wounding for over a period of three years and none of them stopped shedding at all and then a few weeks on seti completely stops all shedding I would say that is good results so far.

Well a lot of people say shedding is normal in the begining of a working treatment, specially minoxidil since it resets growth cycles, but if further hairloss has stopped I guess that sounds good?

Where did you get the seti from, is topic or oral, and what doses? what's the vehicle like for the topical? did you have scalp itch or some sort of sensation in your scalp?

 

[kawnshawn]

Well a lot of people say shedding is normal in the begining of a working treatment, specially minoxidil since it resets growth cycles, but if further hairloss has stopped I guess that sounds good?

Where did you get the seti from, is topic or oral, and what doses? what's the vehicle like for the topical? did you have scalp itch or some sort of sensation in your scalp?

I'm aware of shedding in the beginning but I did all of those for long periods of time and never had stoppage of shedding or any regrowth. I already said above were I got it, dose, and how I take it a few post up. Used to have very bad itch but hardly ever have it now.