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

Discussion in 'Antiandrogens - Propecia, Dutasteride, etc.' started by DavidsDome, May 4, 2017.

  1. Sanchez1234

    Sanchez1234 Experienced Member

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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.
     
  2. whatevr

    whatevr Senior Member My Regimen

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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.
     
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  3. Sanchez1234

    Sanchez1234 Experienced Member

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    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?
     
  4. Sanchez1234

    Sanchez1234 Experienced Member

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    Why try MDV first? Daro is superior in everyway and much more safe (in theory).
     
  5. Sanchez1234

    Sanchez1234 Experienced Member

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    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.
     
  6. whatevr

    whatevr Senior Member My Regimen

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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.


    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.
     
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  7. Sanchez1234

    Sanchez1234 Experienced Member

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    Can i have your TV if it al goes wrong?



    Kiddin ;). You are officialy a pioneer!
     
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  8. whatevr

    whatevr Senior Member My Regimen

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    Awesome. Never thought I'd see the day this soon.

    So once again how many mg of Darolutamide did you apply in 2 mL ?
     
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  9. Sanchez1234

    Sanchez1234 Experienced Member

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    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?
     
  10. ElTioLaBota

    ElTioLaBota Experienced Member My Regimen

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    Ill stay tunned and may be in two weeks ill take the plunge and try dato...
     
  11. IdealForehead

    IdealForehead Senior Member My Regimen

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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.
     

    Attached Files:

    #51 IdealForehead, Oct 29, 2017
    Last edited: May 11, 2018
  12. Sanchez1234

    Sanchez1234 Experienced Member

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    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.
     
    #52 Sanchez1234, Oct 30, 2017
    Last edited: Oct 30, 2017
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  13. ElTioLaBota

    ElTioLaBota Experienced Member My Regimen

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    And 0,2mg did work for your hair?
     
  14. nicksparrow

    nicksparrow Established Member My Regimen

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    How was 6mg decided on btw?
     
  15. abcdefg

    abcdefg Senior Member

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

    IdealForehead Senior Member My Regimen

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    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.
     
    #56 IdealForehead, Nov 1, 2017
    Last edited: Nov 4, 2017
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  17. IdealForehead

    IdealForehead Senior Member My Regimen

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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.
     
    #57 IdealForehead, Nov 1, 2017
    Last edited: Nov 4, 2017
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  18. TylerDurdenn

    TylerDurdenn Established Member My Regimen

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    Wow, seems too good to be true. Really wanna get my hands on this stuff soon!
     
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  19. Sanchez1234

    Sanchez1234 Experienced Member

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    Any updates? Test wise or side effect wise.
     
  20. IdealForehead

    IdealForehead Senior Member My Regimen

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    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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