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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. Jonnyyy

    Jonnyyy Senior Member My Regimen

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    What Norwood are you?
     
  2. IdealForehead

    IdealForehead Senior Member My Regimen

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    I was at worse a deep NW2 with thinning to the NW3 distribution (evident under fluorescent light with my hair pulled back).

    I'm at present a regular NW2 with no deep thinning. My right temple/corner looks verging on a NW1.5 at present, while my left is still a good NW2 but improved.

    Certainly if I continued the orals I am confident I would make it back to NW1 based on the hair growth I was already getting. But stopped cyproterone as of yesterday. It has a 40 hour half life, so it will take some time to get out of my system.

    I think the topical Daro + RU + minoxidil should continue the positive progress but we will see.
     
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  3. Sanchez1234

    Sanchez1234 Experienced Member

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    I hope so man. You had to get of the cypro sooner or later.

    What is you current regime / topical mix? Anything changed? Just orderer 1 gram from LUO and trying to copy your topical :)

    Got a 1.5mm roller as well.
     
  4. IdealForehead

    IdealForehead Senior Member My Regimen

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    I'm trying not to compulsively over update because we all know these things are measured in weeks and months not days, but as far as I can tell, it's still growing back. It's looking the best it's looked in a long time. Every 2-3 days I can see an apparent improvement that does not seem subtle to me personally. I have very fast growing hair naturally, so now that it's growing back at the corners, I'm seeing that quickly as well I think.

    I was actually just looking at it in the mirror today and also thinking Jeez my body looks like mediocre sh*t lately. After looking at my hairline recovery, I had the idea I might even try test-e injections again. I did once before but stopped as it made my hair fall out at a massive rate. If/when I hit NW1, I might try test-e again. I have a feeling I could even get away with it while on the daro. We'll see.

    One thing at a time. NW1 first. Then that.

    I'm estimating another 1-2 months for NW1 at this rate. I'm hoping I'm not being overly optimistic. I'm prone to that sometimes. But the regrowth is not slowing down or stopping yet from anything I can see. If it slows I'll pop minoxidil tabs again until it gets where I need it. Hopefully won't be needed.

    It's kind of crazy. Just two months ago to the date I was PANICKING because I thought I was definitely going to keep going bald until there was nothing left and I would kill myself over it because I couldn't bear the thought, etc. Now I'm just assuming my NW1 is already pretty much just a matter of 1-2 more months and thinking about playing with steroids next.

    One interesting thing to note is how much less oily my scalp is. I mean it's really oil free. My hair stays so non-greasy. I think this has to do with the fact the sebum glands in the scalp (as with all over the body) are androgen stimulated, and I've now essentially castrated my scalp. Nizoral is drying too, but usually I still would get greasy by the next day. Now not at all. I'm now using conditioner after Nizoral because it's so dry overall.

    Also just a minor update on propanediol and minoxidil. I still prefer propanediol personally over propylene glycol, but I am noticing it is hard to get minoxidil above somewhere between 3.5-4%. Even at 4% I am getting dust sedimenting out. 3.5% from what I recall dissolved perfectly. So if getting max minoxidil is important to you probably stick to PG. For me it doesn't matter as I plan to get off minoxidil long term anyway. Just FYI.
     
    #64 IdealForehead, Nov 11, 2017
    Last edited: Nov 11, 2017
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  5. Ollie

    Ollie Senior Member My Regimen

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  6. IdealForehead

    IdealForehead Senior Member My Regimen

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    Xi'an Lyphar on Alibaba is the cheapest. Up to now I've bought from Kane but the prices are insane for the amount I'm using. At some point I'll get them tested. I've bought from multiple places now.
     
    #66 IdealForehead, Nov 11, 2017
    Last edited: Nov 11, 2017
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  7. CinnamonRoll

    CinnamonRoll Established Member My Regimen

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    Is that Lyphar Chem's official Alibaba? Because Lyphar is an actual chemical manufacturer. It would surprise me if they were selling powders directly.
     
    #67 CinnamonRoll, Nov 13, 2017
    Last edited: Nov 13, 2017
  8. IdealForehead

    IdealForehead Senior Member My Regimen

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    All my suppliers I buy from on Alibaba make their own powders (or at least claim to).

    Luo's staff from Chengdu make their own darolutamide and can make other chemicals like stemoxydine on request:
    Chengdu Henghui Pharmaceutical Co., Ltd.
    http://henghuipharm.lookchem.com/
    service@2hpharm.com

    Geekee Biochem I just ordered desloratadine from on Alibaba also makes their own desloratadine (or claims to):
    http://geekee.en.alibaba.com/

    Xi'an Lyphar makes their own RU58841/minoxidil. I discussed their RU synthesis method with their sales staff who talked to the techs that do it and they had rational answers. They provided me their own in house NMR data for both minoxidil and RU.

    That's common in China. These are small factories with 10-20 chemists and they just mix chemicals and sell them online. It's their business model. They can get away with it because there are so few regulations in China. And these are not controlled substances, so at least where I live, it is legal to order them online or import them in reasonable quantities. This makes it a viable business model. Your laws may vary.

    Running a similar lab in North America or Europe would cost 10x as much. Look at prices on Sigma-Aldrich or Caymen Chem for example. It's insane what they charge. But there is accountability there and guaranteed quality.

    With Chinese sources, the risk is yours. They are not regulated. If you do order from a Chinese supplier, you should probably get anything you order tested, and of course, realize and accept that anything you order or use is at your own risk. That goes double for things like darolutamide or RU which aren't even approved for human use of any kind outside of controlled research trials. For all we know, RU and daro could cause all sorts of long term problems that haven't been elucidated yet.

    I have also posted before that I consider topical antiandrogens risky and inadvisable for anyone who is living with small children or potentially pregnant women, as it may transfer over time to them and potentially affect their development. Half of minoxidil ends up on the pillow in studies. Probably half of topical RU/daro/enza would too.

    I don't stress a lot about these things myself personally. I live alone, no one touches my hair, and I'm comfortable with the potential unknown risks to my health. But these drugs aren't a joke, and neither is ordering chemicals online from random Chinese suppliers. Not only is there no guarantee you'll get what you order, there's no guarantee it will be safe, even if it is was what you asked for.
     
    #68 IdealForehead, Nov 13, 2017
    Last edited: Nov 13, 2017
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  9. CinnamonRoll

    CinnamonRoll Established Member My Regimen

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    Yeah, I'm aware of Lyphar because they were one of the only two places manufacturing MK-677 and selling to the public about a year and a half ago. I had no idea they made RU58841 powder. It's not really as cheap as I'd expected. It's pretty similar to Chemyo's pricing.

    I don't think I'm down to try Darolutamide yet. I'm about an Norwood 2.5 and have been maintaining for 3-4 years. I suspect the window to regrow back to Norwood 1.7 or so has closed. But I may try if some people have results and only modest sides.
     
  10. IdealForehead

    IdealForehead Senior Member My Regimen

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    RU58841 prices:
    Xi'an Lyphar = $210 USD for 30 grams including shipping.
    Chemyo = $330 USD for 30 grams plus shipping.
    Purity Prod = $330 USD for 30 grams plus shipping.
    Kane = $460 USD for 30 grams including shipping.
     
    #70 IdealForehead, Nov 13, 2017
    Last edited: Nov 13, 2017
  11. IdealForehead

    IdealForehead Senior Member My Regimen

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    Final Thoughts

    Okay guys, looks like this is it for me. I've been off the orals at least a week now and my hair is still rapidly growing back. I'm now at what would be likely termed by most a "NW1.5" on both sides. And I have fuzz which continues to thicken to my NW1. It doesn't appear to be slowing at all. I don't think it would be humanly possible to be recovering hair faster than I have been over the past two months.

    At this point, I have already recovered enough hair in the past two months (starting from a deep NW2 with thinning to NW3) that I have nothing further to worry about regarding hair loss. Even if I didn't get another single follicle back I would be fine based on the contour of the incisions that will happen during my forehead reduction (for a large forehead I was born with) which is pending.

    So that's it for me. My hair anxiety is dead. I have a bit of anxiety about my surgery and need to make sure the expansion goes as planned, we aim for the right target, and the scarring is minimal, but other than that, I now know I will not lose more hair. Ever. I consider my hair loss functionally cured. I expect to hit my full NW1 within the next 2-3 months at this rate. Though even this is unnecessary for me.

    It feels like an enormous weight has been lifted from my shoulders. I have struggled with failed and half failed treatments for 4 years. To finally find some things that have worked and worked well has been life changing. It's time for me to stop thinking about hair so much and focus on my pending surgery as well as all the things I have been neglecting in my personal life. eg. I have a pile of bills next to me I haven't paid for two months. Not because I don't have the money, but because all my mental energy has been going into hair. It's time to get back to my hobbies and living my life.

    So I will share my final thoughts on all of this here.

    Recipes
    I have been playing with multiple variants of ways to mix darolutamide. I have been mixing 20 mL at a time, and applying 2 mL twice a day, so this is every 5 days. I will likely go back to my usual approach of mixing 40 mL at a time (every 10 days) soon but right now this is fine for me.

    Kirkland Minoxidil Base
    This is by far the easiest approach. It means starting with Kirkland minoxidil and just adding ingredients to that.

    18 mL 5% Kirkland minoxidil
    2 mL DMSO

    Custom Base
    I do not intend to stay on minoxidil long term as it is making my face look like sh*t, so I will be returning to my custom base very soon. Propylene glycol does not particularly irritate me, though I have tried to stay away from it in principle due to it being a known irritant. Propanediol and dipropylene glycol are suggested by many skin sites to be less irritating, but they dissolve less minoxidil (max ~3.5% final solution concentration).

    This I have been mixing as follows:

    10 mL propanediol (or propylene glycol, or dipropylene glycol)
    6 mL 94%+ ethanol
    2 mL water
    2 mL DMSO

    Actives
    I have been adding the following actives to these 20 mL volumes of base:

    100 mg darolutamide (0.5%) - Source: Luo from Chengdu, tested once and correct.
    1.5 g RU58841 (7.5%) - Sources: Kane, Xi'An Lyphar, Purity Prod - testing of all pending.
    1 g niacinamide (5%) - source: Herbstoreusa.com
    0.7 g minoxidil (3.5%) - Source: Xi'an Lyphar, tested once and correct (only needs to be added to 'custom base', as Kirkland already has minoxidil in it)
    (200 mg desloratadine (1%) - Source: Geekee Biochem, I will be adding this in the next few weeks, currently in the mail)

    Darolutamide Concentration
    As I posted in another thread, darolutamide 0.1% will likely beat 5% RU58841, so anything above that is likely sufficient. I have been using 0.5% as I am interested in maximum affordable results. Already this is costing me a fortune, but I can manage it, so that is why I chose that percent.

    A 1-2% darolutamide solution would likely be stronger than any topical anti-androgen in existence and probably impractical to be bothered with making.

    I think 0.1-0.5% or at max 1% are probably the useful darolutamide concentration ranges, and I may play within that range in the future. I may drop RU58841 altogether down the road, as although daro has a longer serum half life it does not cross the blood brain barrier and thus I think it may be cleaner as a drug, though I am not actually sure. Perhaps the shorter half life of RU makes RU cleaner. Can't really say at this point. So I will probably just play with the doses of each to see what I feel over time.

    Why Topical Anti-Androgens are Theoretically Superior to Oral
    If I was starting with hair loss and I was an average guy, I would still just start with finasteride & minoxidil, as this has a 94% of significant regrowth and a >90% chance of no significant side effects.

    But there are several reasons topical anti-androgens are theoretically superior to oral.

    Side effects
    The first and primary reason is that we don't need androgen blockade through our entire body - just our scalp. In principle, using a focal topical anti-androgen will reduce the risk of systemic side effects for obvious reasons.

    Powerful oral anti-androgens like spironolactone and cyproterone are horrible to take. I can't say what it feels like to take finasteride and dutasteride, since they don't do anything to my body at all (like taking sugar pills for me). But I can say I feel immensely better off spironolactone/cypro than on them. Even after just a week. Orals work, but they can be unpleasant.

    Potency
    The second and more important reason is that standard oral treatments like finasteride are limited in their effectiveness by definition of how they work.

    Finasteride 1 mg daily only reduces scalp DHT by at most 64%. (ref) Other studies have suggested less, and that dutasteride has a roughly equivalent scalp effect. Neither finasteride nor dutasteride affect testosterone levels. Testosterone binds to the androgen receptor with 1/3 to 1/5 the affinity of DHT.

    So with finasteride or dutasteride, you have ~64% reduction in DHT binding and zero reduction in testosterone binding. Is it any wonder some guys can't reverse the miniaturization of their follicles when this is the maximal effect of these medications? There are still plenty of androgens (both DHT & test) to continue to inhibit your recovery!

    By contrast, a high dose topical anti-androgen formulation (like RU58841 5-10% and or darolutamide 0.1-0.5% 2 mL twice daily) can conceptually block and inhibit all your androgen receptors, against both test and DHT.

    The potential effectiveness is much greater! At a minimum, it suggests that guys getting inadequate results on finasteride or dutasteride would likely benefit from a topical anti-androgen, although as I will discuss next, this is not possible to generally recommend for various reasons.


    Also, this comparison is premised on the idea that topical antiandrogens aren't getting too rapidly "washed away" from the dermal papilla by blood flow, which we don't know for sure. If a topical anti-androgen gets washed away too quickly or rapidly, then it will of course be ineffective. So although topical anti-androgens can in theory be more effective and less side effect prone, that is only if they remain bound for long periods or there is a scalp "reservoir" of chemical to maintain the blockade.

    Why You Still Shouldn't Actually Use Topical Antiandrogens

    The biggest problem with topical anti-androgens is we have none that are truly approved for topical use. RU58841 is an experimental compound with almost no studies in humans and no long term safety studies. Darolutamide has not even been approved yet for prostate cancer, there are zero studies for its topical use in humans, and there is no long term safety data. Even once darolutamide does become approved for prostate cancer, it will be a powerful prescription drug and you will not likely see doctors prescribing it topically for hair use.

    For all we know long term RU or daro use could lead to unknown problems like heart failure or cancers from their metabolic breakdown products. I don't think that's likely, but the point is no one really knows.

    Even worse, in order to obtain these anti-androgens for topical use, you must currently obtain them from factories in China. This is a bad idea for many reasons. The primary of which is you don't know what you are getting. I have been getting my compounds tested by NMR and mass spec, but even then, there are risks. Let's say you have a 99% purity compound, but because this is unregulated, what if the 1% impurity is something dangerous? It takes a lot of testing to figure this out. And do you test every batch for the rest of your life? What if you get a bad batch?

    The other big problem with topical anti-androgens is that they could potentially pose risks to others around you. Minoxidil studies showed that half of what a man applies to his scalp will end up on his pillow at night. Most likely the same would apply for a topical like daro or RU. Topical anti-androgens can have implications and risks for those who are living with you in general.

    What happens if you're sharing your bed with a pregnant spouse? How much is going to transfer to her? How much will transfer if she runs her hand through your hair? How much will transfer over time from you leaning your head on the couch each day? How much are you going to spread around the house when your daro/RU soaked hair sheds naturally through the day all over the house? And perhaps she's the one who cleans it up? How much gets spread around your bathroom each day from your application process and handling things with your contaminated hands?

    What happens to the fetus if they are exposed to low levels of anti-androgens through pregnancy? What if you have small children in the house and they are similarly exposed to low levels of powerful anti-androgens as they grow and eventually progress through puberty?

    You could really end up f*****g things up. I live alone. I wash my hands a lot. I don't touch my hair during the day. So this doesn't apply to me. But it could apply to a lot of guys.

    So I want to be very clear: I have experimented with these topical anti-androgens because from my perspective I had no choice. finasteride and dutasteride didn't work for me, and cypro/spironolactone were intolerable. But I do not in any way recommend anyone else does this.

    If you haven't read the site's disclaimer, now would be a good time.

    I am posting this to share my experience and for academic interest, not to recommend anyone follow my footsteps. To the contrary, I recommend no one does this. Perhaps if a researcher reads this, it may be helpful to them, as I think a clinical trial of topical darolutamide would be very helpful to the hairloss community.


    Thanks

    As a last note, I just want to say I appreciate all the support and positive attitude from this site. The moderators do a wonderful job of keeping discussions productive. Thank you to everyone who contributed to this and every other discussion we've had. I've learned an enormous amount, and I hope my posts have been informative too.

    If it weren't for sites like this, I would still be balding and feeling depressed, suicidal, and hopeless over it. And instead, I'm growing back hair and I have great hope for the future.

    I still have a few unrelated things I want to post about on this site before disappearing completely. But as my problem is essentially solved from my perspective, this is the beginning of the end for my contributions to the site and participation here.

    I wish you guys all the best and good luck with things as well. I hope we can all beat this disease. There is no better feeling than when you are winning.
     
    #71 IdealForehead, Nov 15, 2017
    Last edited: Nov 15, 2017
  12. jonnywalker93

    jonnywalker93 Established Member My Regimen

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    @IdealForehead

    I think every one who follows this thread appreciates your in-depth reporting, so a huge thanks for this :)

    I completely understand that you want to leave this forum behind and move on, but I think I can speak for everyone when I say that future updates from your side would be fantastic....like a tiny update about how things are going every 3 months or so.

    Otherwise this might end up as the cure that no one uses, because no one dares to try it if it is horribly expensive and no long-term experiences are reported.
     
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  13. sunchyme1

    sunchyme1 Senior Member My Regimen

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    DONT LEAVE US YOU f****r!
     
  14. IdealForehead

    IdealForehead Senior Member My Regimen

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    That's fair enough guys. I realized after posting this I am getting ahead of myself as well. A lot of the rapid growth I have had was likely from the oral minoxidil which I am not continuing (very fast stimulant but unpleasant). And it will take more time to be absolutely sure I am in a secure place and still gaining well.

    So I will definitely post back to update at any of the following milestones or events:
    • I hit NW1 (no guarantee, many people get vellus that doesn't terminalize)
    • I start to lose ground (ie. 'back on cypro I go', aka 'time to buy a noose')
    • 1-3 months passes to update on my general status
    • I get my final forehead reduction surgery done
    • I notice intolerable or obvious side effects and have to change formulation
    • I get a batch of something tested and it comes back with a problem
    I think that should cover it.

    But besides that I'm not going to spend all day on here compulsively posting and researching anymore. I'm just going to sit back, relax, get back to life, and wait to see what happens.
     
    #74 IdealForehead, Nov 15, 2017
    Last edited: Nov 15, 2017
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  15. kj6723

    kj6723 Senior Member My Regimen

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    Sorry you're leaving us but glad you've found peace. Your knowledge is clearly an asset to the community
     
  16. Ollie

    Ollie Senior Member My Regimen

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    @IdealForehead do you think by using such strong topical anti-androgens your receptors will get up regulated to be hypersensitive to DHT in the future ?

    Looking forward to those test results from the different suppliers though. Whenever I'm applying kane's stuff I'm also wondering if its just nothing or worse just powdered DHT as some sick joke.
     
  17. IdealForehead

    IdealForehead Senior Member My Regimen

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    I plan to be on these forever. So hypersensitivity in the future does not matter to me as long as a sufficient androgen receptor blockade is maintained. I think your body can only upregulate receptors to a certain degree. If your body could infinitely upregulate androgen receptors to overcome antagonism, it would be impossible to use oral meds like darolutamide to effectively shut down prostate cancer (chemical castration) as the prostate cancer would also just keep upregulating androgen receptors until some test/DHT got through.

    If a person uses a sufficiently high dose of topical androgen receptor antagonist, in theory it should overwhelm any compensatory regulations and blockade should be maintained. ie. Even if the hair follicles create another 30% more androgen receptors, if they're being flooded with a sufficient amount of darolutamide it won't make a damn bit of difference.

    The only practical questions with topical androgen receptor antagonists that need to answered (besides the safety ones listed above) for hair are:
    • How much antagonist is needed to flood all the androgen receptors of the dermal papillae throughout the scalp?
    • How long will the antagonist remain bound to the target androgen receptors before it is 'washed' or diffuses away out of the scalp?
    Question one tells you how much dosage is needed per application. Question two tells you how often re-application will be needed. Unfortunately, we don't have much real data to apply for either question, except the barest info from the primarily animal-based RU58841 trials that were done. So it's mostly speculative.
     
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  18. Ollie

    Ollie Senior Member My Regimen

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    Awesome reply dude. Thanks for that
     
  19. Sanchez1234

    Sanchez1234 Experienced Member

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    Great post as always! I should receice my DARO today according to FedEx.

    I do have one some stats for users who think about using it. Please correct me if im wrong. The % does not really matter when its about sides. Its about the total amount of mg you use over your scalp.

    Per 1ML you apply 5mg Daro (0.5%). If you only apply like 1ml at first a day on frontal part it lasts you 200 days and costs €2.5 dollar a day.

    1ml (0.5%mg) is 5 times stronger dan 5%RU.

    @IdealForehead uses 2ml a day, which is 10mg a day and costst €5 a day (without the other ingredients)
     
  20. Recon_s

    Recon_s Established Member My Regimen

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    Without pictures/evidence of this actually working I find it hard to buy the whole darolutamide hype...theoretically it sounds great and I hope it actually works but something seems fishy to me? anyone else feel the same?
     
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