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

[Georgie]

I’m considering just orally consuming it at about 50mg a day.

 

[Georgie]

You'd be better off applying 10 mg twice a day to your scalp like i did at the start in case your problem just needs stronger androgen blockade to solve. There's no benefit to castrating the rest of your body or wasting the med on the rest of your body. The only reason to go systemic is if you are unable to get sufficient scalp castration at the maximum dissolvable dose.

In my case at 10 mg twice a day my scalp became so dry and flaky from the androgenic shutdown it was completely impossible to tolerate further. Greater castration would have been unproductive as that was already too much. You will need a tiny bit of DMSO at these high doses (1-2%) which will increase systemic absorption so if you want systemic effect you will still get some.

Since the scalp is what you want to castrate it makes sense to hit it with the max dose you can topically before wasting it by intentionally diluting it through the whole body with oral administration.

Daro has absolutely no skin absorption problems from anything I've studied regarding it's structure, size, or solubility. It is easy for me to feel systemically in high doses. If you are not getting side effects or benefits, it might provide some direction to increase the dose a bit to see if that is more successful. My personal approach with this agent was always to use the highest amount topically i could physically tolerate. Long term that has come to around 6 mg per day. But for someone else that threshold might be higher.

We all likely have differing degrees of androgen sensitivity and will experience benefits and side effects at different doses. Maxing out topical application before considering oral will still always make the most sense.

Well I use 5-6ml a day which is 10-12mg already, but I guess I could just try doubling or tripling this dose. I’m thinking 5mg/ml so 25-30mg daily because I use it only once. I mean I could always just go totally ham and do like 10mg/ml but I doubt I’d be able to dissolve it.

You know, I keep wondering if retrograde alopecia’s primary issue is even androgenic/dht. All of us who have it don’t respond at all to hormonal treatment really. I could be wrong here (anyone with retrograde please chime in if this is the case). I mean sure, there is miniturisation but what I don’t understand is how it affects “non androgenic” areas. My nape has receded half way up my head again, now worse than baseline, and I’m sitting here thinking what the f***? I don’t understand.

 

[Georgie]

I was just wondering - for all the current non-responders (let’s see if I can remember a few) @whatevr @Sanchez1234 @SteveTabernack @itchymadscalp @SpaceInvader
I know I’ve forgotten many.
How would you guys feel about trying mg132 (proteasome inhibitor) in a gb? I believe the standard dose is roughly 19mg/ml in dmso, cycled on for 3 weeks, then off for 3-4. It’s expensive as all f*** but the potential it holds is immense.

 

[IdealForehead]

Well I use 5-6ml a day which is 10-12mg already, but I guess I could just try doubling or tripling this dose. I’m thinking 5mg/ml so 25-30mg daily because I use it only once. I mean I could always just go totally ham and do like 10mg/ml but I doubt I’d be able to dissolve it.

You know, I keep wondering if retrograde alopecia’s primary issue is even androgenic/dht. All of us who have it don’t respond at all to hormonal treatment really. I could be wrong here (anyone with retrograde please chime in if this is the case). I mean sure, there is miniturisation but what I don’t understand is how it affects “non androgenic” areas. My nape has receded half way up my head again, now worse than baseline, and I’m sitting here thinking what the f***? I don’t understand.

Wow you're using more than I can handle already. That's a lot. No side effects from the daro?

If high dose anti-androgen doesn't work, I might guess androgens are likely not part of the signal chain that's destroying your hair, and you need to try working through other signal chains as we've discussed.

The guy in this thread who used the mega proven enza doses topically and orally and had no response but yet responds to other anti-androgens might have had an androgen receptor mutation that conferred resistance against enza. This would be freakishly rare (like my dutasteride resistance) but it has been documented as possible for enza.

 

[Georgie]

Wow you're using more than I can handle already. No side effects from the daro? If that's the case, you could always keep going up until you either get sides or results. From what I recall of the solubility (just going from memory) 10 mg/mL would dissolve fine with 2-5% DMSO if you really want to try it.

If high dose anti-androgen doesn't work, androgens are likely not part of the signal chain that's destroying your hair, and you need to try working through other signal chains as we've discussed.

The guy in this thread who used the mega proven enza doses topically and orally and had no response but yet responds to other anti-androgens might have had an androgen receptor mutation that conferred resistance against enza. This would be freakishly rare (like my dutasteride resistance) but it has been documented as possible for enza. No known mutations exist to confer resistance against daro.

I think i’ll Try 10mg/ml. I don’t get any sides at all, and none from duta anymore either.

 

[Sanchez1234]

I was just wondering - for all the current non-responders (let’s see if I can remember a few) @whatevr @Sanchez1234 @SteveTabernack @itchymadscalp @SpaceInvader
I know I’ve forgotten many.
How would you guys feel about trying mg132 (proteasome inhibitor) in a gb? I believe the standard dose is roughly 19mg/ml in dmso, cycled on for 3 weeks, then off for 3-4. It’s expensive as all f*** but the potential it holds is immense.

Sounds interesting Georgie. Never heard of it though. Has it ever been tested on humans? Will research more after the weekend!

 

[Georgie]

Sounds interesting Georgie. Never heard of it though. Has it ever been tested on humans? Will research more after the weekend!

No but people have used it with success of their own accord. It’s expensive though so it’s difficult to get on your own. Best price I found was $250 for 100mg. You need about 500mg for 26ml. If we did a large order maybe we could talk them down.

 

[SteveTabernack]

No but people have used it with success of their own accord. It’s expensive though so it’s difficult to get on your own. Best price I found was $250 for 100mg. You need about 500mg for 26ml. If we did a large order maybe we could talk them down.

What sort of results are we talking? That is really crazy expensive even if we one could get it down quite a bit.

And yeah, what the f*** is this retrogade man. Has anyone EVER even managed to somewhat reverse retrogade?

Would you think the treatmeants for regular male pattern baldness and retrogade are identical @IdealForehead ?

 

[Georgie]

What sort of results are we talking? That is really crazy expensive even if we one could get it down quite a bit.

And yeah, what the f*** is this retrogade man. Has anyone EVER even managed to somewhat reverse retrogade?

Would you think the treatmeants for regular male pattern baldness and retrogade are identical @IdealForehead ?

I have searched to the ends of the internet to find what causes retrograde. Can’t seem to find any answers other than it’d aggressive, hard to treat and occurs In both genders. Maybe there’s a particular hormonal aspect to it, maybe it’s hereditary to a degree, maybe it’s something else bizarre. What I have noticed by speaking with others who have it however, is that hormonal manipulation does nothing to help it. I still can’t get my head around why this pattern exists.

So essentially partial proteasome inhibitors have a dual mode of action. One is that is totally blocks androgen receptors
https://www.ncbi.nlm.nih.gov/m/pubmed/12119296/

Secondly, it causes rapid fibroblast proliferation and stem cell activation. So it switches on the anangen phase fast, and hugely shortens Tologen. https://www.ncbi.nlm.nih.gov/m/pubmed/23963711/
Others on the private forums have used it, and it tends to work within about 14 days. It’s basically a holy grail treatment but no one is rich enough to do it long term. Like I said, I’d like to try to talk this supplier down if I can get a few orders.

 

[Georgie]

Also, @SteveTabernack @Sanchez1234 and anyone else who was interested, here’s some more info about Proteasome inhibitors.
Note that PSI is still the best for for hair growth, but mg is cheaper, and has a better safety profile. Neosil was actually working on bringing a PPI topical out like 10 years ago called Neosh101 but the company went bust. Sad, because it was incredibly promising.

http://immortalhair.forumandco.com/...inhibit-nf-kb-promote-b-catenin-grow-hair-how

 

[Georgie]

Also, @SteveTabernack @Sanchez1234 and anyone else who was interested, here’s some more info about Proteasome inhibitors.
Note that PSI is still the best for for hair growth, but mg is cheaper, and has a better safety profile. Neosil was actually working on bringing a PPI topical out like 10 years ago called Neosh101 but the company went bust. Sad, because it was incredibly promising.
I mean, it’s an AR blocker, stem cell, fibroblast, and epidermal growth factor activator, works fast as f*** and could replace everything. I don’t know why this hasn’t been picked up and run with.

http://immortalhair.forumandco.com/...inhibit-nf-kb-promote-b-catenin-grow-hair-how

 

[Kornel]

Found on another hairloss forum: "Worth noting that at a 0.5% solution, 100mg of PSI basically lasts you 2 months (21 days of application and then 5-6 weeks off before your next 21 day cycle).
So 1 gram/1000mg = 20 months (following the protocol of 21 days of application followed by 5-6 weeks off)."

 

[Georgie]

Found on another hairloss forum: "Worth noting that at a 0.5% solution, 100mg of PSI basically lasts you 2 months (21 days of application and then 5-6 weeks off before your next 21 day cycle).
So 1 gram/1000mg = 20 months (following the protocol of 21 days of application followed by 5-6 weeks off)."

Psi does work better but it’s more expensive. It’s also far less stable in solution that mg.I’ll have a dog around anyway

 

[Georgie]

This is the cheapest psi I could find

 

[jonnywalker93]

This is the cheapest psi I could find

It's really hard to find any user experience with regards to this stuff, but aside from being incredibly expensive a few have mentioned stability issues. Are the guys from the private forum taking it?

 

[IdealForehead]

What sort of results are we talking? That is really crazy expensive even if we one could get it down quite a bit.

And yeah, what the f*** is this retrogade man. Has anyone EVER even managed to somewhat reverse retrogade?

Would you think the treatmeants for regular male pattern baldness and retrogade are identical @IdealForehead ?

My opinion on retrograde is simply that I would guess it represents a far more aggressive type of Norwood pattern hair loss which will eventually lead to even a poor NW7 zone in the end. ie. Almost no hair is spared because almost everything is androgen sensitive.

Given that retrograde usually accompanies faster and more aggressive thinning from the front, but still in a generally Norwood pattern, I think this is reasonable to conclude.

In principle, the treatments would be the same, but may need higher intensity to work.

In theory (but not in practice), I think the simplest way to assess whether you respond to anti-androgens in general after you fail the standard first line treatments would be to do a trial of a high dose affordable anti-androgen. For example, trialing one of the following three:

- Spironolactone 200 mg per day
- Cyproterone 100 mg per day
- Flutamide 62.5-250 mg per day

That should be considered in an ascending ladder of strength, ie. Flutamide (at the high doses) is stronger than Cypro, which is stronger than spironolactone.

If a person theoretically tried one of these high strength oral agents and noticed no change in their shed patterns (ie. no Telogen Effluvium, no decrease after 3 months), there is a good chance they simply will not respond to anti-androgens. If a person tried TWO agents from this list and had no response, almost certainly they wouldn't respond to anti-androgens.

Risks of spironolactone include electrolyte imbalances. Cypro unique risks may include depression and blood clots. Flutamide's unique risks may include liver toxicity - requires liver monitoring periodically. All could chemically castrate you or create undesirable effects, so this is just speaking theoretically - most people probably wouldn't want to go through this and these risks over hair.

Flutamide at high dose (250 mg /day) has worked in at least one documented case where spironolactone 200 mg didn't. I have attached the case report for reference if anyone wants to read it (@Georgie I'm sure - note a considerable % improvement even after 15 years of loss in that case). A larger study on flutamide at varying dose in FPHL is reviewed here for flutamide if you sign up. Their time-based results showed ~1 year to statistical significance, and ~2 years to max effect:

The article I attached suggested the following in that case of resistant FPHL which is likely the same issue of abnormal androgen hypersensitivity in variants like retrograde:

This report documents the therapeutic response of FPHL
to flutamide in a patient who has failed to respond to
spironolactone. The most likely explanation is that FPHL is
due to increased end organ sensitivity to circulating andro-
gens and flutamide is a more potent androgen receptor
antagonist than spironolactone. While we still advocate
spironolactone as a first-line therapy for FPHL, flutamide
can be considered as a second-line treatment in non-
responders. Patients should be warned about the potential
of liver toxicity and serial liver function monitoring is
required.​

That patient's prior treatment history interestingly sounded a lot like Georgie's just much with only simpler drugs tried previously:

Treatment with oral spironolactone at a dose of 200 mg per day was well tolerated; however she failed to show any significant improvement over the next 5 years despite evidence of a cutaneous antiandrogen effect with almost complete loss of secondary sexual hair. Minoxidil 5%, 1 mL topically daily was added to the treatment regimen however after 6 months of continuous usage there was no significant clinical improvement.​

For Georgie, this could be a very useful point to learn from. I have thought of your body hair loss as due to an estrogenic issue. But according to this case report, it may actually be your body hair loss is due to your anti-androgens being strong enough to shut down body hair growth while not being strong enough to shut down the hair loss process at the scalp. This would be a big conceptual difference. (!)

In principle, theoretically, daro will still likely represent the cleanest castration drug once it reaches the market.

Most men I know will not want to take castration level drugs orally for 3-6 months to find out if they can respond, and unless they are transexual almost certainly they should not.

But if a person did, and they still didn't respond to that, then they would know anti-androgens in general may be a dead end. From everything I've seen though, most people should respond to some degree to a high enough dose of a strong enough anti-androgen. If you don't respond to one agent, then another may still work.

@Georgie, I think the case report attached could be instructive for what's happening in your case and perhaps all cases of more aggressive patterned balding like retrograde. ie. Just an issue of androgen hypersensitivity and perhaps anti-androgen insensitivity that needs to be overcome with higher doses of stronger agents. But I don't know for sure.

 

[Georgie]

It's really hard to find any user experience with regards to this stuff, but aside from being incredibly expensive a few have mentioned stability issues. Are the guys from the private forum taking it?

They did and with success, but no long-term users.

 

[Georgie]

My opinion on retrograde is simply that it represents a far more aggressive type of Norwood pattern hair loss which will eventually lead to even a shitty NW7 zone in the end. ie. Almost no hair is spared because almost everything is androgen sensitive.

Given that retrograde usually accompanies faster and more aggressive thinning from the front, but still in a generally Norwood pattern, I think this is reasonable to conclude.

In principle, the treatments would be the same, but may need higher intensity to work.

I think the simplest way to assess whether you respond to anti-androgens in general after you fail the standard first line treatments is to do a trial of a high dose affordable anti-androgen. For example, trialing one of the following three:

- Spironolactone 200 mg per day
- Cyproterone 100 mg per day
- Flutamide 62.5-250 mg per day

That should be considered in an ascending ladder of strength, ie. Flutamide (at the high doses) is stronger than Cypro, which is stronger than spironolactone.

If you trial one of these high strength oral agents and notice no change in your shed patterns (ie. no Telogen Effluvium, no decrease after 3 months), there is a good chance you simply will not respond to anti-androgens. If you try TWO agents from this list and get no response, almost certainly you won't respond to anti-androgens. None of these are costly measures.

Risks of spironolactone are electrolyte imbalances. I think I was developing some on it since I felt so unwell but never got my blood checked. Cypro unique risks are depression and blood clots. Flutamide's unique risks are of liver toxicity - requires liver monitoring periodically.

Flutamide at high dose (250 mg /day) has worked in at least one documented case where spironolactone 200 mg didn't. I have attached the case report for reference if anyone wants to read it (@Georgie I'm sure - note a considerable % improvement even after 15 years of loss in that case). A larger study on flutamide at varying dose in FPHL is reviewed here for flutamide if you sign up. Their time-based results showed ~1 year to statistical significance, and ~2 years to max effect:

View attachment 86996

The article I attached suggested the following in that case of resistant FPHL which is likely the same issue of abnormal androgen hypersensitivity in variants like retrograde:

This report documents the therapeutic response of FPHL
to flutamide in a patient who has failed to respond to
spironolactone. The most likely explanation is that FPHL is
due to increased end organ sensitivity to circulating andro-
gens and flutamide is a more potent androgen receptor
antagonist than spironolactone. While we still advocate
spironolactone as a first-line therapy for FPHL, flutamide
can be considered as a second-line treatment in non-
responders. Patients should be warned about the potential
of liver toxicity and serial liver function monitoring is
required.​

That patient's prior treatment history interestingly sounded a lot like Georgie's just much with only simpler drugs tried previously:

Treatment with oral spironolactone at a dose of 200 mg per day was well tolerated; however she failed to show any significant improvement over the next 5 years despite evidence of a cutaneous antiandrogen effect with almost complete loss of secondary sexual hair. Minoxidil 5%, 1 mL topically daily was added to the treatment regimen however after 6 months of continuous usage there was no significant clinical improvement.​

For Georgie, this could be a very useful point to learn from. I have thought of your body hair loss as due to an estrogenic issue. But according to this case report, it may actually be your body hair loss is due to your anti-androgens being strong enough to shut down body hair growth while not being strong enough to shut down the hair loss process at the scalp. This would be a big conceptual difference. (!)

In principle, for anyone, daro will still likely represent the cleanest castration drug. But it is too expensive to use orally in any effective castration dose and still too experimental for this purpose.

Most men I know will not want to take castration level drugs orally for 3-6 months to find out if they can respond. But given that we have no proven "dose range" for something like topical daro, topical daro would represent greater gamble. If you want an absolute answer in the fastest way possible, and have a variant like aggressive FPHL or any type of retrograde hair loss, I think you have less leeway to f*** around, and would probably benefit from trialing something like an aggressive oral agent if you can handle the risks and side effects.

If that works, then you know you can respond to SOMETHING and just have to find what you can handle. If you still don't respond to that, then you know anti-androgens in general may be a dead end for you. From everything I've seen though, everyone should respond to a high enough dose of a strong enough anti-androgen. If you don't respond to one agent (eg. the case of enza resistance posted by a user a page or two ago), then another should work (eg. I believe he said he still responded to spironolactone).

@Georgie, this would suggest perhaps if you want to be more aggressive with your hair loss, since I know you do not worry about castration side effects, you could simultaneously increase your topical daro and add the flutamide orally you've always wanted to. I think at this point it would be quite reasonable to try, as long as you can get a liver test periodically on it.

I think the case report attached could be instructive for what's happening in your case and perhaps all cases of more aggressive patterned balding like retrograde. ie. Just an issue of androgen hypersensitivity and perhaps anti-androgen insensitivity that needs to be overcome with higher doses of stronger agents.

Oh yes I’ve great great case and anecdotal reports about flutamide (particularly from women with pcos) which is why I mentioned quite some time ago that I wanted to try it. That said, it really dose need to be taken at no less than 250mg daily to show any improvement, which sadly falls within the dangerous range for liver hepatoxicity. That said, the majority of women who I’ve seen use it also take a bcp, metformin, spironolactone and a range of other meds simultaneously without any liver issues. Of course you need to have monthly bloods. I’m unsure if I should drop duta in place of this.

That case report is insane! Amazing regrowth.

 

[IdealForehead]

Oh yes I’ve great great case and anecdotal reports about flutamide (particularly from women with pcos) which is why I mentioned quite some time ago that I wanted to try it. That said, it really dose need to be taken at no less than 250mg daily to show any improvement, which sadly falls within the dangerous range for liver hepatoxicity. That said, the majority of women who I’ve seen use it also take a bcp, metformin, spironolactone and a range of other meds simultaneously without any liver issues. Of course you need to have monthly bloods. I’m unsure if I should drop duta in place of this.

If it was a choice, and you can get the bloodwork easily enough, I would definitely drop dutasteride in favor of it.

Flutamide at 500-750 mg per day is a full blown prostate cancer dosing (ref). Dutasteride as far as I know has no role in prostate cancer since it just reduces DHT and does nothing for test. If your hair is so androgen sensitive it can continue falling out in spite of everything you've tried, I think only prostate cancer tier castration (both test & DHT) is going to be potentially useful going forward.

Despite your history, you're still a relatively young & healthy person. I doubt your liver would have any problems with flutamide with monitoring. In the emedicine study I quoted the yearly Ludwig pattern graphic from, they talk about side effects they encountered. Only a very small percent of women had liver enzyme changes and they said it was mild in all cases and no major concern.

If that still doesn't work, then you know there was nothing more from an anti-androgen perspective you could have done. But that case report should be reassuring to you, since the only strong oral antiandrogen you've been on is spironolactone, and that study shows how fallible it is. Your cypro dose was tiny (2 mg/day) and finasteride/dutasteride don't really count for the reason mentioned above.

 

[Georgie]

If it was a choice, and you can get the bloodwork easily enough, I would definitely drop dutasteride in favor of it.

Flutamide at 500-750 mg per day is a full blown prostate cancer dosing (ref). Dutasteride as far as I know has no role in prostate cancer since it just reduces DHT and does nothing for test. If your hair is so androgen sensitive it can continue falling out in spite of everything you've tried, I think only prostate cancer tier castration (both test & DHT) is going to be potentially useful going forward.

Despite your history, you're still a relatively young & healthy person. I doubt your liver would have any problems with flutamide. In the emedicine study I quoted the yearly Ludwig pattern graphic from, they talk about side effects they encountered. Only a very small percent of women had liver enzyme changes and they said it was mild in all cases and no major concern.

You could continue daro topically at the max you can afford and take 250 mg flutamide orally. That should provide incredibly powerful scalp castration.

If that still doesn't work, then you know there was nothing more from an anti-androgen perspective you could have done. But that case report should be reassuring to you, since the only strong oral antiandrogen you've been on is spironolactone, and that study shows how fallible it is. Your cypro dose was tiny (2 mg/day) and finasteride/dutasteride don't really count for the reason mentioned above.

So you can still definitely go harder than you have so far from an anti-androgen perspective. I think this would be the max.

I tend to agree. I shall have to see where I can buy some.