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

Sanchez1234

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@IdealForehead Can't wait for you to try this. Haven't been this exicted in a while for a new treatment.
Do you have all the stuff to make a topical? If so, are you gonna start this week with treatment.

Lets hope you won't get any sides in the first weeks. Your friend LUO will have lots of new customers.
 

whatevr

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I have worked out an initial test composition for darolutamide solution. The background logic and data is presented here:
https://www.gourmetstylewellness.com/intera...vent-vehicle-composition.109259/#post-1565120

The end idea I have come to from that thread is as follows.

TEST COMPOSITION

Solvent:

  • 40% ethanol
  • 40% propylene glycol, dipropylene glycol, or propranediol
  • 10% water
  • 10% DMSO

Actives:
  • 0.3% Darolutamide (3 mg/mL)
  • 7.5% RU58841 (75 mg/mL)
  • 3.5-4% Minoxidil (35-40 mg/mL)
  • 5% Niacinamide (50 mg/mL)

Should have my first batch made by Saturday. We'll see what happens. I'll post back how it goes.


Epic. You have no idea how important this is what you are doing. This forum needs more people like you.

I will likely try MDV first and then hopefully the next time around, if your results prove this compound to be good, we can organize a group buy for Darolutamide instead.

Good luck, keep us posted.
 

Sanchez1234

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I have worked out an initial test composition for darolutamide solution. The background logic and data is presented here:
https://www.gourmetstylewellness.com/intera...vent-vehicle-composition.109259/#post-1565120

The end idea I have come to from that thread is as follows.

TEST COMPOSITION

Solvent:

  • 40% ethanol
  • 40% propylene glycol, dipropylene glycol, or propranediol
  • 10% water
  • 10% DMSO

Actives:
  • 0.3% Darolutamide (3 mg/mL)
  • 7.5% RU58841 (75 mg/mL)
  • 3.5-4% Minoxidil (35-40 mg/mL)
  • 5% Niacinamide (50 mg/mL)

Should have my first batch made by Saturday. We'll see what happens. I'll post back how it goes.

You're gonna use RU & Daro in 1 topical? Isn't that a bit like doing finas & duta at the same time?

How many ML will you apply and how many times a day?
 

Sanchez1234

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Epic. You have no idea how important this is what you are doing. This forum needs more people like you.

I will likely try MDV first and then hopefully the next time around, if your results prove this compound to be good, we can organize a group buy for Darolutamide instead.

Good luck, keep us posted.
Why try MDV first? Daro is superior in everyway and much more safe (in theory).
 

Sanchez1234

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I have no intention of stopping RU58841 and just using darolutamide. They're both short half life antiandrogens in the blood. But RU58841 has a shorter half life. So although it's much weaker, it's also likely to have even fewer side effects than darolutamide. Although RU58841 hasn't been a complete miracle to me, I'm fairly certain it's helped my hair over the past two years.

I would rather ADD darolutamide to RU58841 than replace it. They have slightly different mechanisms of action. But yes, they are both androgen receptor antagonists, so they overlap.

Probably I would be fine to replace RU58841 completely with darolutamide, but I have no intention of taking any risks with my hair. I want to take what I'm doing now and AMPLIFY it. You can't have too much blockage of your androgen receptors. No such thing. The more you can block in the scalp the better.

I am at this stage taking a very aggressive approach with my hairloss. I want the most powerful topical formulation I can create, and this is it.

I will apply 2-2.5 mL twice daily as I do now. I find this is a good amount to cover my top of head with a bit of redundancy so hopefully I'm not missing anywhere.

Thats 5mlx3mg= 15mg DARO per day. Correct me if i'm wrong but it will cost you $7.50 extra a day above your current regime? Expensive long term treatment.

Calculation: 500$ 1 gram. 1000/15 = 66,67 days. 500$ / 66,67 = $7.5 per day.
 

whatevr

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RU f^cking sucks though. So much effort to mix that stuff every few days and apply that greasy mess to your head every night. For what?
Hardly even maintains. Expensive, too. Pretty poor AA compared to these new antiandrogens. The only thing it has going for it is the very short half life. Doesn't block transcription, low affinity, probably activates the receptor somewhat on its own too. No wonder the results are so sh*t.
Enza and daro should kick the snot out of it, results-wise. But we'll see.


Why try MDV first? Daro is superior in everyway and much more safe (in theory).

Perhaps because of the insane price and the fact that almost no one knows about it and the fact that there are actually group buys for MDV happening right now and I need something right now and by the time I get public awareness about darolutamide going and enough people interested it's gonna be past Christmas and that's not even mentioning the fact that the only supplier on Alibaba (there is just 1 ) might be a complete scam. Whew, probably the longest sentence I ever wrote.
 

Sanchez1234

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1969-moon_2113935i.jpg


Well that's it. Just applied my first 2 mL.

Assuming it is what it was supposed to be, we just broke some new ground.
Can i have your TV if it al goes wrong?



Kiddin ;). You are officialy a pioneer!
 

Sanchez1234

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Yeah, this has gone surprisingly very smoothly and quickly for me too assuming everything checks out on confirmatory testing. If everything checks out I'll order 5 grams from Luo which in total should last me a full year. If for any reason it doesn't, I'll order a gram to test from Beryl Yang and we'll start keep going.

Either way the darolutamide train keeps running. :)

Just applied 2.5 mL. At 2-2.5 mL per application, that's 6-7.5 mg twice a day. Castration doses as we reviewed previously are 600 mg twice a day (due to the short half life), so even if it all goes systemic, this is still just a tiny fraction of that. If I could afford it, I'd use more. I'd love 1-2%. 1% would probably be amazingly powerful and still with likely fewer or the same side effects as finasteride/dutasteride.

Also I have to comment that this vehicle composition is very nice. I can't recommend 1,3-propanediol enough as a propylene glycol replacement. Again, anyone interested can buy it here. Very cheap. Much smoother and silkier than propylene glycol. More soothing on the scalp. Dissolves minoxidil and other agents very well. I love it.

The 3.5% minoxidil dissolved so well in fact, I just added another 78 mg minoxidil to the remaining 15.5 mL of solution to bump it to 4%. Dissolved beautifully as well. I will keep going to see what the max minoxidil this solvent composition can handle is.

As for what you mentioned earlier about awareness for darolutamide, I think we're actually quite lucky here, and have little to worry about. Unlike RU58841, this will NOT remain an underground drug. Regardless of anything we do, unless there is some catastrophic failure in Phase III testing (highly unlikely), Bayer is bringing this to market in 3-5 years, with an intention to make hundreds of millions of dollars a year from it.

This is a superior drug to any on the market for prostate cancer and it will be huge. At that point, all the Chinese factories will be making it for $40/gram at MOST just like enzalutamide now. We will then all be able to easily afford to mix even 1% solutions.

I doubt there's anything we can do to meaningfully shift the price curve at this stage, even with more awareness. Great if more guys want to try it. I will keep posting my experience and purity results from testing. But either way, I think the big price change is going to come from Bayer and Phase III finishing above all else.

Additionally, with Replicel soon coming to market and possibly offering a way to confer actual permanent DHT resistance from injections of DHT resistant stem cells, it occurs to me we might actually be coming to an end of an era. This is the end of the era where unlucky men have to resort to swallowing castration level drugs to stop our hair loss.

In 5 years, it is actually starting to seem like things are actually going to change. I mean actually for real. Because we actually already have the technology now. It's not a fantasy anymore. It just needs to become more affordable, with longer safety data, and more mainstream.

f*****g crazy really. Pretty sure the next generation won't have any of these problems at all. The idea of taking cyproterone, spironolactone, or estrogen for hair loss will likely sound even crazier to them than it does to an average person now.

It's kind of bittersweet being on the edge of a revolution. Wish I never had to worry about any of this. As do we all I'm sure. The amount of mental and physical energy my hair loss has consumed for me is astounding. Still, better to be here, than 20 years ago when even RU wasn't available, and there was no way to learn everything we have learned. And it will be remarkable to possibly watch the end of male pattern baldness.

Hehe, you sound like a sales man. Your enthusiasm is contagious :)

Anyway, you've applied couple of times. Some people notice sides (like ball ache) right away.
Did you notice any (negative) effect?
 

ElTioLaBota

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Everything seems absolutely fine so far. I haven't noticed anything systemically at all. Although as I said before, I am not the best "test subject" for this since I'm already on a pretty strong nuke regimen. The only way my regimen could be stronger for me given than finasteride/dutasteride don't work on me would be to add estrogen (which I'm not prepared to do at this stage).

So my point is if I develop any of those problems I would be far more likely to blame the massive dose of cyproterone tabs I'm taking.

I honestly doubt anyone at all would notice a 6 mg twice daily darolutamide application. Except that if it works your hair might grow back. Otherwise as I said it's only 1% of the castration dose due to the short serum half life.

Just to update on minoxidil, 4% looks like the max that solvent composition can handle. Looks like propanediol is likely near identical to propylene glycol for minoxidil solubility. If I drop the oral minoxidil I'll increase the propanediol to 50%, drop the ethanol to 30% and make it 5% minoxidil. But otherwise I will keep it the same as this feels good.

I'm feeling very calm overall. My hair anxiety was at a fevered pitch in September and that's why I joined here, started taking all those tablets, and doing crazy things like ordering and testing darolutamide.

As a combination of all things (increased RU to 7.5%, added back topical minoxidil, then added oral minoxidil and spironolactone which changed last week to cypro, now adding daro), I feel like I can finally relax.

The hair has been growing back really nicely already at my corners. I think it would be almost humanly impossible to keep losing hair on this regimen. My dick still shockingly works as well.

The real test of daro will come for me when cypro eventually gives me major sexual dysfunction or gyno. Because then I will drop it and RU+daro will be my only antiandrogens. But I'm gonna try to ride out cypro as long as I can, so that may be weeks or months from now.

Until we get there, I'm just gonna try to relax, focus on getting a few confirmatory tests done, and not think too much about my hair at all.

That's the real gift of a good regimen, isn't it? The freedom not to think about it anymore. To just live your life.

I can promise I will not just "disappear" (unless I drop dead) and I will follow through on sharing results from all the tests I have promised as well as periodic updates.

But I'm gonna do my best to spend as little time on here as possible and just let the magic work. I need to think about actual life, and live actual life. Not just obsess over hair.

I think I can finally start doing that again. So all is good so far. I'll post back in the next week once I find out for sure from the lab what I've been putting on my head the past few days. :)
Ill stay tunned and may be in two weeks ill take the plunge and try dato...
 

IdealForehead

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I looked into the safety study for darolutamide. They didn't report on sexual side effects. I'm guessing this is because most of these guys had advanced prostate cancer and between surgeries and other meds it was a given that their sexual function would be shot even from the start.

But gynecomastia was reported. And it was only 2.6%.

This is VERY VERY LOW for such a powerful antiandrogen. I posted a compilation and comparison of rates of gynecomastia for different antiandrogens including finasteride and dutasteride here. You can see 2.6% is very low compared to any of the strong oral antiandrogens. eg. Spironolactone goes up to 52% rate at a anti-androgenic dose that's likely much weaker than any tested dose of darolutamide.

If this tiny gyno rate for darolutamide is validated on phase III, it would mean HIGH DOSE ORAL darolutamide has an equal risk of gynecomastia as dutasteride (which is generally considered safe), despite darolutamide being dramatically more powerful.

I think this low risk may be due to: (1) the fact that darolutamide is so specific in its androgen receptor antagonism, with no partial agonist behaviors, and (2) due to the fact also that it does not significantly cross the blood brain barrier. By not acting significantly on the brain, it has less effect on overall hormone levels, unlike other antiandrogens which can affect hormone levels a great deal. By not triggering brain-dependent hormonal changes, darolutamide may be avoiding or truly minimizing the gyno risks.

To be cautious, this was a small study (72 patients), only 8 months long, and we need the big Phase III results to get the exact number over a longer period. It was also a variable dose study where all participants who were taking between 100-900 mg twice daily were all lumped together. But still those are all strong as hell doses compared to what we're talking about for hair. For reference, I am currently using only 6 mg topically twice a day.

It will be interesting to see if they try to assess sexual side effects in further studies, should their test population allow it. I would not be surprised if there is an equally low rate of sexual side effect rates.

I have often wondered how much of sexual side effects are created in the brain vs. the dick. I've been leaning towards believing these problems happen more due to hormonal changes altering activity in the brain. I think these sexual side effects occur the same way SSRIs affect sexual function - by unintentionally manipulating brain chemistry and activation/deactivation of brain circuits involved in arousal/sex.

Given that darolutamide doesn't cross the blood brain barrier, if that is true, a man may find his sexual function relatively unaffected, or at least less affected than with other drugs. Time will tell for sure.
 

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Sanchez1234

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I'm sorry. I can't stop myself. :)

I looked into the safety study for darolutamide and I was shocked by the results. I had to post.

They didn't report on sexual side effects. I'm guessing this is because most of these guys had advanced prostate cancer and between surgeries and other meds it was a given that their sexual function would be shot even from the start.

But gynecomastia, a subject of interest of mine, was reported. And it was only 2.6%.

This is VERY VERY LOW for such a powerful antiandrogen. I posted a compilation and comparison of rates of gynecomastia for different antiandrogens including finasteride and dutasteride here. You can see 2.6% is absolutely nothing compared to any of the strong oral antiandrogens. eg. Spironolactone goes up to 52% rate at a anti-androgenic dose that's likely much weaker than any tested dose of darolutamide.

If this tiny gyno rate for darolutamide is validated on phase III, it would mean HIGH DOSE ORAL darolutamide has an equal risk of gynecomastia as dutasteride (which is generally considered safe), despite darolutamide being dramatically more powerful.

I think this low risk may be due to: (1) the fact that darolutamide is so specific in its androgen receptor antagonism, with no partial agonist behaviors, and (2) due to the fact also that it does not significantly cross the blood brain barrier. By not acting significantly on the brain, it has very minimal effect on overall hormone levels, unlike other antiandrogens which can affect hormone levels a great deal. By not triggering brain-dependent hormonal changes, darolutamide may be avoiding or truly minimizing the gyno risks.

To be cautious, this was a small study (72 patients), only 8 months long, and we need the big Phase III results to get the exact number over a longer period. It was also a variable dose study where all participants who were taking between 100-900 mg twice daily were all lumped together. But still those are all strong as hell doses compared to what we're talking about for hair. For reference, I am currently using only 6 mg topically twice a day.

This could be a fantastically clean drug. It could certainly be a great anti-androgen for guys prone to gynecomastia. At our tiny topical doses, it would almost be impossible to develop gyno, if this is the true rate for high dose oral administration and our low topical doses prove adequate.

It will be interesting to see if they try to assess sexual side effects in further studies, should their test population allow it. I would not be surprised if there is an equally low rate of sexual side effect rates.

I have often wondered how much of sexual side effects are created in the brain vs. the dick. I've been leaning towards believing these problems happen more due to hormonal changes altering activity in the brain. I think these sexual side effects occur the same way SSRIs affect sexual function - by unintentionally manipulating brain chemistry and activation/deactivation of brain circuits involved in arousal/sex.

Given that darolutamide doesn't cross the blood brain barrier, if that is true, we may find our sexual function relatively unaffected, even on very high doses. Darolutamide may prove to be the first potent antiandrogen with minimal sexual side effects of any kind, even if taken orally.

This is very, very promising stuff. The more I read about this compound, the better it gets.

I hope you are right. I got gyno on 0.25mg finasteride, but 200mg RU did nothing on the gyno part.

For those who are interested. I contacted LUO en he has DARO currently in stock.
$500 for 1 gram including shipment to Europe.

I will be joining your expiriment @IdealForehead after you receive the university test results.
 
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ElTioLaBota

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I hope you are right. I got gyno on 0.25mg finasteride, but 200mg did nothing on the gyno part.

For those who are interested. I contacted LUO en he has DARO currently in stock.
$500 for 1 gram including shipment to Europe.

I will be joining your expiriment @IdealForehead after you receive the university test results.
And 0,2mg did work for your hair?
 

IdealForehead

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The gyno could just be within placebo. I mean even on placebo some men will get gyno simply from aging.

Yeah, for sure. Men who have had prostate cancer are also at very high risk for gyno due to castrations, being older, etc.

The inclusion criteria for the side effect study were:

Male patients aged >18 yr with histologically confirmed adenocarcinoma of the prostate and progressive metastatic disease were eligible, provided that their serum testosterone concentration was <0.50 ng/ml; they had received prior first-generation AR antagonist treatment (and withdrawal) and up to two previous chemotherapy regimens; had Eastern Cooperative Oncology Group performance status of 0/1; and had not received previous therapy with enzalutamide or an investigational AR antagonist
So these guys had ZERO testosterone (from castration - chemical or physical), had been treated with meds like flutamide already, had chemotherapy, were on massive doses of darolutamide, and still ONLY 2.6% of them got gyno.
 
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IdealForehead

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Just looked to confirm if I'm crazy or not, and this is the stat on enzalutamide and gynecomastia:

67 men were enrolled into the study. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12)

https://www.ncbi.nlm.nih.gov/pubmed/24739897

This was only a 6 month study for enzalutamide, and they had a 36% gynecomastia rate.

Let me remind you again, the gyno rate on darolutamide for 8 months was only 2.6%.

Enzalutamide had 14x greater gynecomastia than darolutamide on a shorter time scale.

If we are being skeptical, it's possible this pertains partly to the fact that enzalutamide was studied at full dose for all patients on this study (160 mg/day), while darolutamide was a variable dose study (from 100-900 mg twice daily). So not everyone on darolutamide had a massive full dose.

But I think this is much more directly related to the blood-brain barrier. I think gynecomastia and probably most of the sexual issues come down whether or not the drug crosses the blood-brain barrier.
 
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IdealForehead

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Any updates? Test wise or side effect wise.

Everything has tested perfect. I just ordered another 5 grams from Luo.

Very happy overall so far. I've stopped my oral minoxidil due to severe puffy eyes that were becoming permanent (24/7) - really rough stuff! Though fantastic growth promotion, not sustainable unless you want to look like an old man.

I've also cut my cyproterone to just 50 mg a day, and in a few days I will stop it. Trouble with cyproterone is it has a 30% chance of depression, and I think I've been in that 30%. My mood has been poor despite the fact that my hair is growing back and I should be excited about that.

Once those orals stop, that's when the true test of the darolutamide will begin.

In the past few weeks regardless of cause, the amount of hair I've regrown is insane. I have fuzz up to my NW1. It looks like my corners and temples have a 5 o'clock shadow. I must attribute this more to the orals than the topical since I was on the orals longer. Daro's only been ~11-12 days. But that could be contributing too.

I notice primarily with the topical daro that my scalp feels completely silent. Dead quiet. I get the very rarest breakthrough itch here or there but it's overall very well controlled. That should be a good sign. I will be adding some desloratadine for topical antihistamine once it arrives and that should finish off the last tiny bit of itch.

RU58841 controlled my itch maybe 70-80% and daro >90-95%.

But as I said, the real test will be when I am off the orals and just on topical treatment. Fingers crossed. Gonna take some pictures and I'm hoping like crazy it will just continue regrowing the way it has been.

As far as I know, very few people (if anyone) has had major regrowth on topicals alone. Perhaps it's wishful thinking, but I'm hoping this will work. Should be able to tell in a few months.
 
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