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

[IdealForehead]

Can confirm that this particular non responder to anti androgens is also a non responder to 1.5g seti daily

Seti by definition will in my opinion always be weaker than something like topical darolutamide for a myriad of reasons.

This is the mechanism for Seti:

Seti blocks one downstream inflammatory mediator of hairloss induced by androgen receptor binding. Only one. If you want a downstream anti-inflammatory, anti-histamines do this and more. I would love to see topical desloratadine vs. oral seti in a study. I think that would be an interesting matchup. The anti-histamine might be the underdog in that match but I bet it would be at least close.

By contrast, darolutamide in sufficient doses has the capacity to block all your androgen receptors so no androgen can even bind and no inflammatory cascade can begin.

These two approaches are not comparable.

The benefit of seti is that it may be much safer long term and may not have negative fertility or androgen deprivation side effects like daro. Androgen deprivation sides are no fun. Also, seti can be brought to market since it's safe for others, while using daro on your scalp will always turn you into a walking potential biohazard to others. "Warning: Do not touch scalp". "Do not touch anything scalp has touched". Topical daro can never be a commercial product. People should not use this in general.

I think seti is a good idea for people who want to steer clear of anti-androgens altogether by working completely downstream, at a trade-off likely of efficacy. If it is well proven in the studies, cheap, and safe, I would definitely give it a go as a way to reduce my daro dose.

As for you Georgie, I'm sorry to hear that, but I'm not surprised. I still hope you get better with a better estrogen balance, though as I've admitted to you before, that's just my hope. Time will tell. If not, then maybe your idea to try sulfasalazine down the road might not be bad, just in case the biopsies missed something.

 

[DavidsDome]

Desloratadine sounds interesting since it is supposed to affect PGD2 and IL-4, IL-6 and more.
Which is all beneficial for our hair.
Sadly it also reduces PGE2 I just discovered...
Although I know that you, @IdealForehead , see that as a good thing.

desloratadine citrate disodium could significantly decrease the levels of lymphocytes releasing PGE2, LTB4, IL-4, IL-5, TNF-α.
http://www.ijcem.com/files/ijcem0019483.pdf

 

[Georgie]

Seti by definition will always be weaker than something like topical darolutamide for a myriad of reasons.

This is the mechanism for Seti:

View attachment 84921
Seti blocks one downstream inflammatory mediator of hairloss induced by androgen receptor binding. Only one. If you want a downstream anti-inflammatory, anti-histamines do this and more. I would love to see topical desloratadine vs. oral seti in a study. I think that would be an interesting matchup. The anti-histamine might be the underdog in that match but I bet it would be at least close.

By contrast, darolutamide in sufficient doses has the capacity to block all your androgen receptors so no androgen can even bind and no inflammatory cascade can begin.

These two approaches are not comparable.

The benefit of seti is that it may be much safer long term and may not have negative fertility or androgen deprivation side effects like daro. Androgen deprivation sides are no fun. Also, seti can be brought to market since it's safe for others, while using daro on your scalp will always turn you into a walking potential biohazard to others. "Warning: Do not touch scalp". "Do not touch anything scalp has touched". Topical daro can never be a commercial product.

I think seti is a good idea for people who want to steer clear of anti-androgens altogether by working completely downstream, at a trade-off likely of efficacy. If it is well proven in the studies, cheap, and safe, I would definitely give it a go as a way to reduce my daro dose.

But if no other anti-androgen has worked for you, there's no reason daro or seti would. They're all working on the same cascade, just at different levels.

As for you Georgie, I'm sorry to hear that, but I'm not surprised. I still hope you get better with a better estrogen balance, though as I've admitted to you before, that's just my hope. Time will tell. If not, then maybe your idea to try sulfasalazine down the road might not be bad, just in case the biopsies missed something.

Mmm. I suppose considering that seti does work as an alternative to AA’s, it’s not unreasonable to assume that it would be ineffective for myself.

Today the shedding began. It’s very, very bad. This used to happen when I’d miss a pill for a day, and a few days later shedding would rain down like a f*****g hairloss apocalypse. Same thing except well.. I don’t know when this will end. Or if.

I began sulfa yesterday at 500mg to start. I feel fine thus far and will see if I can increase to 1.5mg over a few weeks times.

 

[IdealForehead]

Desloratadine sounds interesting since it is supposed to affect PGD2 and IL-4, IL-6 and more.
Which is all beneficial for our hair.
Sadly it also reduces PGE2 I just discovered...
Although I know that you, @IdealForehead , see that as a good thing.

desloratadine citrate disodium could significantly decrease the levels of lymphocytes releasing PGE2, LTB4, IL-4, IL-5, TNF-α.
http://www.ijcem.com/files/ijcem0019483.pdf

Keep in mind that study is commenting on lymphocytes which are white blood cells that likely have little effect on the hair loss process. We would need to know what they do to to cells that are more relevant for hair growth. For example, here was a study that showed increased PGE2 release by cetirizine in monocytes, another blood cell:

https://www.hairlosstalk.com/intera...ace-look-like-sh*t.109593/page-3#post-1582962

It's hard to draw conclusions from either of such tangential findings.

Personally I am not going out of my way to raise PGE1/PGE2 levels as these are pro-aging and pro-inflammatory pathways. So I do not worry one way or another about what anti-histamines do to PGE1/2.

I think antihistamines make sense as we have two studies showing they work well, they are very safe, and the male pattern baldness itch may well be histamine related. On a chemical level we know they are broadly anti-inflammatory as well. That's good enough for me.

 

[Georgie]

Keep in mind that study is commenting on lymphocytes which are white blood cells that likely have little effect on the hair loss process. We would need to know what they do to to cells that are more relevant for hair growth. For example, here was a study that showed increased PGE2 release by cetirizine in monocytes, another blood cell:

https://www.hairlosstalk.com/intera...ace-look-like-sh*t.109593/page-3#post-1582962

It's hard to draw conclusions from either of such tangential findings.

Personally I am not going out of my way to raise PGE1/PGE2 levels as these are pro-aging and pro-inflammatory pathways. So I do not worry one way or another about what anti-histamines do to PGE1/2.

I think antihistamines make sense as we have two studies showing they work well, they are very safe, and the male pattern baldness itch may well be histamine related. On a chemical level we know they are broadly anti-inflammatory as well. That's good enough for me.

Or if you can get your hands on pure pge2 that doesn’t cost you your soul and a shipping fee, then you could use it along with growth factors as it is implicated in the stimulation of stem cell production http://stemcell.childrenshospital.o...oosting-drug-goes-from-fishtank-to-bedside-2/

 

[strandman]

Daro is now $250/g from Luo

 

[Georgie]

Daro is now $250/g from Luo

bullshit. Are you serious?

 

[Georgie]

The prices are all coming down. Strandman found there were a bunch of people on Lookchem offering cheaper prices, so I told him to try playing hardball with Luo to get a better price, and he succeeded.

It will be $40/gram in a year or two. There's nothing inherently expensive about daro except that up to now only ~5 factories were making it. As it gets closer to market, more and more people are gonna make it. It's gonna be ridiculously cheap.

Oral dosing is hundreds of mg per day for prostate cancer. So the price will settle at a very low point, because to be used for prostate cancer you need many many grams of it.

This is going to be a very very very popular drug for prostate cancer. It's the best drug available for it.

Great. Now lets get them to start making PGE2 and powder growth factors. I may be inclined to actually buy more daro and mega dose it with those prices. I'm feeling the topical AA's with minimal systemic sides given that i'm already pounding my liver with a zillion other drugs.

 

[SpaceInvader]

Daro is now $250/g from Luo

That was quick. I did find it for 450/g before.

So now it costs roughly the same around what 5g of MDV would cost.

 

[Georgie]

I'm tempted to get a new quote from Luo without mentioning that I've seen his prices for other people, just to see if he tries to rip me off.

 

[PeggyPeterson]

Hi people,

A few pages back, a member asked if anybody on Daro has shown any improvement. How about now? Besides @IdealForehead anyone else shown success? What’s the benchmark for success? maintenance + growth?

I’ve recently been prescribed 25 mg spironolactone and .25mg oral minoxidil. Just curious how that How stacks up against Daro?

Efficacy study on my prescribed dosage found here.
https://onlinelibrary.wiley.com/doi/pdf/10.1111/ijd.13838

 

[kawnshawn]

Hi people,

A few pages back, a member asked if anybody on Daro has shown any improvement. How about now? Besides @IdealForehead anyone else shown success? What’s the benchmark for success? maintenance + growth?

I’ve recently been prescribed 25 mg spironolactone and .25mg oral minoxidil. Just curious how that How stacks up against Daro?

Efficacy study on my prescribed dosage found here.
https://onlinelibrary.wiley.com/doi/pdf/10.1111/ijd.13838

No one still at this point has seen results other than idealforehead. This is the first time daro has ever been tried for hairloss that we know of, so to say how spironolactone and oral minoxidil compare would be pretty pointless.

Over the next two years hopefully the price can drop down drastically to a point where people can trial it in bigger doses so we can get a better idea how much potential it really has.

 

[PeggyPeterson]

No one still at this point has seen results other than idealforehead. This is the first time daro has ever been tried for hairloss that we know of, so to say how spironolactone and oral minoxidil compare would be pretty pointless.

Over the next two years hopefully the price can drop down drastically to a point where people can trial it in bigger doses so we can get a better idea how much potential it really has.

I’m glad Ideal has found a functional cure for himself. However I’m now really curious why the 2-3 others didn’t see results. I hope you all find something that works well for you!

 

[PeggyPeterson]

Thanks Ideal, that makes sense. Would you say female hair loss has less to do with androgens than male hair loss? It’s quite a tricky one because I’ve read studies showing that finasteride 1 mg doesn’t show any statistically significant hair growth/maintenance, but once its increased 2.5mg-5mg, there seems to be some mild improvement.

There was also an interesting case study published by my dr showing remarkable Re growth with 250 mg flutamide for a 35 year old women who didn’t respond to spironolactone and Minoxidil. If spironolactone, flitamide, and finasteride are all antiandrogens, it seems like the cause of hair loss is at different points. In that case study I mentioned, it feels like the problem was the androgen receptor rather than DHT level.

Anyway, I just hoping this spironolactone+minoxidil dosage I receive does the trick. I’ll need to do this around my pregnancy planning and feeding, hopefully the post partum hair loss doesn’t exacerbate it.

I’ve read the studies you reference Regarding the anti-collagen effect of minoxidil and I relayed it to my dr, who’s meant to be the best in the country..didn’t seem to know about it. So frustrating how a supposed hair loss experts isnt really at the frontier of Androgenetic Alopecia treatment.

@Georgie have you been diagnosed with Androgenetic Alopecia? Any chance it is CTE?

 

[inmyhead]

No one still at this point has seen results other than idealforehead. This is the first time daro has ever been tried for hairloss that we know of, so to say how spironolactone and oral minoxidil compare would be pretty pointless.

Over the next two years hopefully the price can drop down drastically to a point where people can trial it in bigger doses so we can get a better idea how much potential it really has.

I'm sad too that nobody else got daro results, IdealFH seems like a smart guy, but why he hasn't provided any pictures? Thats the thing which concerns me.

 

[IdealForehead]

Thanks Ideal, that makes sense. Would you say female hair loss has less to do with androgens than male hair loss? It’s quite a tricky one because I’ve read studies showing that finasteride 1 mg doesn’t show any statistically significant hair growth/maintenance, but once its increased 2.5mg-5mg, there seems to be some mild improvement.

There was also an interesting case study published by my dr showing remarkable Re growth with 250 mg flutamide for a 35 year old women who didn’t respond to spironolactone and Minoxidil. If spironolactone, flitamide, and finasteride are all antiandrogens, it seems like the cause of hair loss is at different points. In that case study I mentioned, it feels like the problem was the androgen receptor rather than DHT level.

Anyway, I just hoping this spironolactone+minoxidil dosage I receive does the trick. I’ve read the studies you reference Regarding the anti-collagen effect of minoxidil and I relayed it to my dr, who’s meant to be the best in the country..didn’t seem to know about it. So frustrating how a supposed hair loss experts isnt really at the frontier of Androgenetic Alopecia treatment.

@Georgie have you been diagnosed with Androgenetic Alopecia? Any chance it is CTE?

I think female hair loss is definitely more complex than male hair loss, because female hair loss is hair loss that is occurring despite the fact that women have <10% the androgen levels as men (ref). This would suggest that women who suffer hair loss have hair follicles that are remarkably sensitive to androgens, or they are suffering hair loss from mixed or nonandrogenic issues, which are harder to pin down.

Georgie's case for example is challenging because her biopsies suggested it was androgenic alopecia, yet she has had diffuse body hair loss as well, which is the opposite of what would be expected in androgenic alopecia. Women who have androgenic alopecia tend to grow more body hair (hirsutism), not lose it. So it is no surprise to me she has not responded to anti-androgens despite many tries with many meds on high doses.

Women are complex also because we know estrogen signalling can exert significant effects on the hair cycle. My opinion is that ER-beta signalling is more beneficial for hair growth than ER-alpha (ref), and much of the hair loss women suffer after menopause is due to the natural shift toward estrone, which is a more ER-alpha stimulating estrogen. It is my opinion that this has also up to now been the missing element in Georgie's hair loss, as she suffered from hair loss primarily after going through menopause and going on ethinyl estradiol, which is also a predominantly ER-alpha estrogen. We will see in 6 months or so if this theory is correct, as she has now switched off the synthetic hormones to a more natural balance.

Another reason women can be complex is women in general are more prone to auto-immune conditions and thus auto-immune hair loss. You would think this would be easy to diagnose by biopsy. But I have read cases where even after repeated biopsy it is unclear (ref), and derms may consider just trying an auto-immune drug to see if it works.

My impression is chronic telogen efluvium also occurs more often in women than men. I am not sure if this is true, but there are lots of female examples in the women's hair loss section, and very few men.

Probably some of the men who have failed all anti-androgenic therapy similarly share some of these "other" issues above. ~99% of men respond to anti-androgens (based on the dutasteride studies). But as you note, a much lower percent of women respond to anti-androgens. I think the above are the primary reasons for this.

For those women who do respond to anti-androgens, then yes, just like anything else, there is a ladder of potency and efficacy. Finasteride is weaker than dutasteride. spironolactone is weaker than cypro. Flutamide is weaker than darolutamide. But if you are completely nonresponsive to anti-androgens in general, it won't matter how strong of an agent you use. You will need to figure out what the missing piece is in your hair loss. ie. What makes your hair loss "different" and attack that instead.

 

[IdealForehead]

I'm sad too that nobody else got daro results, IdealFH seems like a smart guy, but why he hasn't provided any pictures? Thats the thing which concerns me.

I have never posted pictures of myself on any forum I have visited and don't intend to now. I don't even use Facebook.

I have not been posting to convince anyone of anything, but rather to facilitate my own learning and treatment through discussion. In 2-3 months I will likely be gone from this site for good. I am just waiting for my hairline to finish healing from my forehead reduction.

 

[PeggyPeterson]

Perhaps I’m being naive, but I trust what ideal has to say. It’s not only his anecdotes however, his approach is backed by science, and if flutamide, an effective albeit risky first gen non-steroidal antiandrogen can give some regrowth, why wouldn’t darolutamide, a more potent drug that’s the second gen of this class, do the same ?

 

[PeggyPeterson]

@IdealForehead will you consider providing updates every now and then?

 

[IdealForehead]

@IdealForehead will you consider providing updates every now and then?

Absolutely if I run into intolerable side effects or some other complication, you can bet your *** I'll be running back here to brainstorm a new solution with every ounce of obsession I can muster. I cannot and will not ever go bald. Ever. Daro is my primary current means to that end. I'm happy with it. But if that has to change in the future, for any reason, so be it. I will certainly be back then.

I suppose I could try to post every 3-6 months to say "nothing's changed", but I don't know how useful that is either. One person's experiences cannot be generalized to others. People should be careful of generalizing from a few anecdotes. I'm also not trying to encourage people to use this, though I think it would be great if someone organized a proper clinical trial on its use for hair.

I'm also not sure how many useful things I'll be able to say about hair in general in 6-12 months. If I ever "come back" in the future, I doubt I will have even a tiny fraction of the knowledge on hair I have now.

Lastly, I feel like I've mostly said everything useful I can. Everything else is just speculation and individual chance. I'm not saying "I know everything". I'm just saying I've exhausted and satisfied my own curiosity, and there isn't very much mystery left to keep me engaged in it.

But, on the other hand, I have had hair anxiety since I was 10 years old, owing to my aggressively bald dad and terrible hairline since birth. Maybe I will never escape that anxiety and thus always be tethered to this place. Maybe my dreams of moving on and "forgetting" will be impossible. I guess we'll see in a few months. I do certainly hope to escape.