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

[PeggyPeterson]

I cannot and will not ever go bald. Ever

If only scientists had your tenacity in finding a cure.

I also told my dr about Daro.. he didn’t know what that was until he googled it.

I guess the positive thing is that since it is for a more important cause, prostate cancer, dermatologists can ride on the coat tails of urologists.

Ideal, I’m guessing you will be regularly doing blood tests and what not to see if there’s any abnormal readings. An update on any significant issues like that would be great. I don’t intend on using Daro yet, but it’s certainly something I’m looking into if other treaatment options fail.

Speaking of my current treatment option,

Anyone who’s been on spironolactone for the long term know whether it’s effect wears out? What’s the long term safety profile? And how does it fair compared to other antiandrogens ? Ive heard of RU vs -mide vs finasteride on this forum, but never spironolactone.

 

[IdealForehead]

If only scientists had your tenacity in finding a cure.

I also told my dr about Daro.. he didn’t know what that was until he googled it.

I guess the positive thing is that since it is for a more important cause, prostate cancer, dermatologists can ride on the coat tails of urologists.

Ideal, I’m guessing you will be regularly doing blood tests and what not to see if there’s any abnormal readings. An update on any significant issues like that would be great. I don’t intend on using Daro yet, but it’s certainly something I’m looking into if other treaatment options fail.

Speaking of my current treatment option,

Anyone who’s been on spironolactone for the long term know whether it’s effect wears out? What’s the long term safety profile? And how does it fair compared to other antiandrogens ? Ive heard of RU vs -mide vs finasteride on this forum, but never spironolactone.

This is all just from my own basic understanding, but from what I've read in the daro studies, daro doesn't have a significant likelihood of inducing hormonal changes, because it doesn't cross the blood-brain barrier. So hormonal changes aren't a concern of mine. They are primarily mediated by the brain, and negligible daro is getting to my brain.

The bigger concern for me would be things like sperm count or penis atrophy from androgen deprivation long term. My brain might be protected from the daro, but my dick and testicles are not. I don't think I'll ever have kids, so this isn't a huge concern for me either. Just on principle, I would have liked to have gotten a before and after sperm count, but I was in no mood to care about my sperm at the time I got on daro, so that is too late now.

I was on spironolactone for a few weeks. Again, this is just anecdotal, but I found it very hard to take. At the doses needed for strong effect (100-200 mg per day) it is a very strong diuretic, at least for me. I was peeing constantly through the day. I was also having to drink 4+ litres of water a day which was nauseating and exhausting. I felt sick and tired the whole time. Probably I was starting to develop an electrolyte problem but I never got it checked.

I think anti-androgenic strength can probably be best judged by how effective a drug is in the treatment of prostate cancer, since that is the closest analog we have for hair loss. This is just my general impression, since there are not that many head to head trials, but I would guess the ladder would go:

1) Finasteride - 1-5 mg - weakest, reduces scalp DHT by maximum of ~65% but does nothing else.
2) Dutasteride - 0.5 mg - reduces scalp DHT more than finasteride, but still not completely and does nothing for testosterone.
3) Spironolactone - 100-200 mg - at high doses, a pretty potently feminizing drug. Very popular in transexual regimens. Highest risk of gyno. Killed my erections by around 70%. However, this drug is actually useless for prostate cancer as it is not strong enough for that purpose and actually has some androgen stimulating properties.
4) Cyproterone - 50-100 mg - The consensus in the tranny community is cyproterone is stronger than spironolactone, and this was my impression as well. Killed my erections by >95% (functionally dead) but was still more tolerable than spironolactone. Used for chemical castration of sexual deviants. Biggest nonsexual risks are depression and blood clots. Can be used in prostate cancer but just as an adjunct in modern treatment protocols.
5) Flutamide - True androgen receptor antagonist. Now we are getting into the real castration drugs. Can be used as a main castrating drug in prostate cancer. Not useful topically though as it must be converted into hydroxyflutamide by the liver to be active. For this reason, as stated if you're looking for an older generation androgen receptor antagonist to use topically, pick a different drug.
6) Darolumatide - Strongest and newest androgen receptor antagonist. By far the most aggressive castration drug for prostate cancer. There is nothing stronger. Has the unique benefit of negligibly crossing the blood brain barrier, unlike all the other agents listed above which very easily enter the brain.

Note that all of #3-6 block both test and DHT at the androgen receptor, to increasing degree as you go down the list. It's been my strong opinion that using an effective androgen receptor antagonist will always be more effective than agents like finasteride/dutasteride. If the androgen receptor is effectively blocked at the scalp, no androgenic damage (from either test or DHT) can happen. By contrast, just partially reducing levels of DHT (ie. with finasteride & dutasteride) still allows some degree of DHT and testosterone mediated inflammation to continue.

 

[PeggyPeterson]

You could always freeze sperm? Hopefully it’s not late now, you never know when your plans change in the future. We may also need Ideal-junior on this forum to help crack this hair loss problem haha.

So based on what you said earlier about females, would you recommend Daro if the efficacy of spironolactone/flutamide is mild but clearly noticeable? Most of the studies I’ve read on these show some improvement, but not impressive.

I’ve been hoping that spironolactone+minoxidil+seti + Botox+ estriol might be a good combo for me in the future. I’m keen to take seti after the safety/efficacy results come out.

Do you have any opinions on all those other emerging stuff i.e microwounding, wnt activator, r-equal?

 

[inmyhead]

Why should I provide pictures? Do I owe you something? Do I not have a right to my privacy?

I have given this site hundreds to thousands of hours of my time and research. I have admittedly done so for selfish reasons - to fix my own hair loss, which I have now done. But I have also done it to help people with ideas and experiments and learning about various approaches to hair loss.

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.

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 and maybe to run one or two more estrogen experiments if I can handle it (equol, estradiol).

But why are you so deffensive whenever someone asks for picture? Nobody can recognize you from hairline anyway...

 

[IdealForehead]

But why are you so deffensive whenever someone asks for picture? Nobody can recognize you from hairline anyway...

I used to hang for almost 6 years on 4chan when i was going through some unpleasant health issues and i was depressed/bored/isolated all the time. Then i hung out on one of the "PSL sites" for a while.

I don't know if youre familiar with either community, but they taught me very well how easily someone can be "doxed" or identified based on basic information in our modern age. And what trolls will do with that info if available.

Based on factors like: location, age, work field, race, descriptions like of height and facial appearance, & even a partial facial picture it is absolutely possible to "dox" someone.

In my experience, the internet is full of bitter obsessed trolls who enjoy nothing more that to find someone they disagree with or don't like and try to ruin his/her life.

There are even entire communities of people who attempt to troll and destroy the people from other troll centered communities like the ones i mentioned above (eg. kiwifarms). Ie. There are layers of trolls feeding on trolls.

The internet is an insane and dangerous place. The best protections i have considered are:

- Say nothing offensive ever - I cant do this. Like anyone, I can at times have controversial opinions on lots of subjects like politics or life in general and i like being able to speak my mind online.

Or:

- Keep elements of your life private online and don't post pictures of yourself on sites.

Obviously i have chosen #2. Am i just plain paranoid? Probably. I'm an anxious person by nature admittedly. I tend to think and worry a lot and always have. But i sleep better at night this way knowing if i post a rant on here for example about my frustrations with modern dating culture and say something "offensive", it can just be me venting and it won't follow me into my every day life.

 

[Georgie]

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?

Hey! I assume you’re female. How refreshing
May I ask how old you are, and if you’ve any other diagnosis besides Androgenetic Alopecia (PCOS, thyroid etc)?

I have been diagnosed with Androgenetic Alopecia via scalp
Biopsy, yes. My hairloss is related to very low estrogen levels and relatively high androgens levels, like you see in menopause. I’ve also got a family history of hairloss on my dads side and grandparents also, so that made me susceptible to Androgenetic Alopecia when I began losing hair.

I have read all the studies you’ve mentioned which is why I went for avodart over finasteride, and also tried topical Ru58841 (supposedly the strength equivalent of flutamide) and darolutamide. Obviously I’ve also been taking estrogen. For me sadly none have worked. It’s very odd indeed, but the more I speak to other women who have Androgenetic Alopecia, the more I realise how frustratingly ineffective pretty much all treatments are for us. When you’ve got true, diffuse Androgenetic Alopecia, it’s damn near impossible to find anything that works aside from minoxidil. I have seen on PCOS forums that mostly Flutamide is helpful, but you’ve got to remember too that these women have clear-cut hormonal issues. Where things are more vague and insidious, it becomes like trying to find the invisible needle in the haystack. It’s all guess and check. I will say that spironolactone does work for some women, but only a minority amount from what I see, and minoxidil usually works pretty well initially for women. I have heard of maybe three women having success on fina or dutasteride. As I said, most of the success I read about is from women taking flutamide, often with a low androgen index birth control pill. I’ve personally tried pretty much every hormonal treatment there is without luck. I wouldn’t recommend going hell for leather on the minoxidil either because it can cause some serious issues. I get facial bloating, rashes, increased hair shedding, synchronised loss and growth, droopy eyelids, wrinkles and the list goes on, but now I’m stuck on it.
Of course it comes down to how serious your own hairloss is, what the underlying factors are and what your genetics predetermine, but female hairloss seems to be incredibly difficult to treat. The other women who I have spoken to on this forum have all had no success also. It’s devaststing. I truly hope you are one of the lucky ones.

 

[Patrick_Bateman]

But why are you so deffensive whenever someone asks for picture? Nobody can recognize you from hairline anyway...

Don't underestimate weaponized autism.

 

[Afro_Vacancy]

Sad to read that @IdealForehead is leaving.

 

[Arrade]

Sad to read that @IdealForehead is leaving.

What!!

 

[Arrade]

Sad to read that @IdealForehead is leaving.

What are you talking about

 

[Georgie]

So I finally found another woman with exactly the same hair loss problems as me, HPA axis/estrogen issues and all, who has tried almost all the same stuff and me with zero luck. She’s thinking of trying JAK inhibitors.
Anyway, good to know I’m not he only female with this kind of hair fuckery.

 

[PeggyPeterson]

@Georgie thanks for the kind words.
I’m 26, no PCOS or thyroid issues, and androgen level is a bit high. I haven’t had a biopsy, just a check up..

It is indeed a really frustrating condition to have. I haven’t even started on the meds yet, but looking at the studies is getting me a bit nervous.

From what I read, spironolactone has a 40% chance of maintenance, 40% of improvement, and the rest show know success.. I’m hoping I’m in that 80%. Anecdotally however, I hear the treatments are useless, don’t know what to believe anymore

Speaking of genetics, I read the following

“Using common genetic variants with a minor allele frequency of at least 1%, GCTA-GREML analysis found that 47.3% (SE 1.3%) of the variance in baldness can be explained by common autosomal genetic variants, while 4.6% (SE 0.3%) can be explained by common X chromosome variants.“

I originally thought the X chromosome was the only determinant, but this is a relief, you see My Pa also has Androgenetic Alopecia. I just hope it doesn’t get passed on to my kids. My partner doesn’t have any signs of Androgenetic Alopecia on his side.

 

[Georgie]

@Georgie thanks for the kind words.
I’m 26, no PCOS or thyroid issues, and androgen level is a bit high. I haven’t had a biopsy, just a check up..

It is indeed a really frustrating condition to have. I haven’t even started on the meds yet, but looking at the studies is getting me a bit nervous.

From what I read, spironolactone has a 40% chance of maintenance, 40% of improvement, and the rest show know success.. I’m hoping I’m in that 80%. Anecdotally however, I hear the treatments are useless, don’t know what to believe anymore

Speaking of genetics, I read the following

“Using common genetic variants with a minor allele frequency of at least 1%, GCTA-GREML analysis found that 47.3% (SE 1.3%) of the variance in baldness can be explained by common autosomal genetic variants, while 4.6% (SE 0.3%) can be explained by common X chromosome variants.“

I originally thought the X chromosome was the only determinant, but this is a relief, you see My Pa also has Androgenetic Alopecia. I just hope it doesn’t get passed on to my kids. My partner doesn’t have any signs of Androgenetic Alopecia on his side.

What is your hairloss pattern? Diffuse? Just on top? Temple or hairline recession? Do you shed a lot of hair?

It’s all guess and check as I said. So I think if indeed it is Androgenetic Alopecia, your best starting point is spironolactone. If that’s a fail, you can look into maybe cyproterone acetate (although studies should it is on par with spironolactone efficacy-wise), flutamide, fina or duta (these last two are probably out though since you seem to be interested in having children).
You may like to try topicals also if you don’t like the idea of consuming things systemically. For example you can buy topical spironolactone, finasteride and RU. You may like to use minoxidil but I honestly hate the stuff and wouldn’t recommend it as the very first treatment.

If all of these fail, you can look into the more obscure things like your pgd2 inhibitors, pge2 upregulators and/or pge2 itself, growth factors, prp etc. Sadly the less options you have though, the more expensive things get. Keep me updated with how things turn out. Happy to throw my 2 cents in where needed.

 

[Arrade]

I want to try this but I also want to make kids.... damn

 

[Georgie]

I want to try this but I also want to make kids.... damn

It supposedly had very little systemic absorption

 

[IdealForehead]

I want to try this but I also want to make kids.... damn

For reference, finasteride and dutasteride both have proven negative potential effects on sperm count yet people still overwhelmingly take them for hair loss. See here for what finasteride and dutasteride do to sperm in just 6 months:

In both treatment groups, total sperm count, compared with baseline, was significantly decreased at 26 wk (D, -28.6%; F, -34.3%)

https://www.ncbi.nlm.nih.gov/pubmed/17299062
​

Here's an article that talks about 24 men at a fertility clinic who took finasteride for hair loss for 4-5 years and had low sperm count from it. After discontinuation, their sperm counts quadrupled on average, and nine men went up 11.6 times:

After stopping finasteride, sperm count increased significantly from 32.34 to 127.62 M/mL (P=0.002). Sperm count increased across the range of values prior to discontinuation of finasteride, including an 11.6-fold increase among nine men.

https://www.medpagetoday.com/endocrinology/infertility/41424​

finasteride and dutasteride can then be expected to reduce sperm count by 28-34% after 6 months for average men, and up to 75-91% by 4-5 years in susceptible men.

There's a good chance such a tiny dose of topical daro may have less of a negative effect than finasteride or dutasteride. But I don't know of course. Someone would have to study this formally with before/after sperm counts in a research trial.

 

[Arrade]

Get a sperm count before and after. I'm almost certainly overhyping the fertility risks. 6 mg per day is a quite tiny dose. Finasteride and dutasteride both have proven negative potential effects on sperm count yet people still overwhelmingly take them for hair loss. See here for what finasteride and dutasteride do to sperm in just 6 months:

In both treatment groups, total sperm count, compared with baseline, was significantly decreased at 26 wk (D, -28.6%; F, -34.3%)

https://www.ncbi.nlm.nih.gov/pubmed/17299062
​

Here's an article that talks about 24 men at a fertility clinic who took finasteride for hair loss for 4-5 years and had low sperm count from it. After discontinuation, their sperm counts quadrupled on average, and nine men went up 11.6 times:

After stopping finasteride, sperm count increased significantly from 32.34 to 127.62 M/mL (P=0.002). Sperm count increased across the range of values prior to discontinuation of finasteride, including an 11.6-fold increase among nine men.

https://www.medpagetoday.com/endocrinology/infertility/41424​

finasteride and dutasteride can then be expected to reduce sperm count by 28-34% after 6 months for average men, and up to 75-91% by 4-5 years in susceptible men.

There's a good chance such a tiny dose of topical daro may have less of a negative effect than finasteride or dutasteride.

Would daro have any effect on test or estrogen in the body?
I’m still scared of anti androgens but people seem to be fine on RU

 

[Afro_Vacancy]

Get a sperm count before and after. I'm almost certainly overhyping the fertility risks. 6 mg per day is a quite tiny dose. Finasteride and dutasteride both have proven negative potential effects on sperm count yet people still overwhelmingly take them for hair loss. See here for what finasteride and dutasteride do to sperm in just 6 months:

In both treatment groups, total sperm count, compared with baseline, was significantly decreased at 26 wk (D, -28.6%; F, -34.3%)

https://www.ncbi.nlm.nih.gov/pubmed/17299062
​

Here's an article that talks about 24 men at a fertility clinic who took finasteride for hair loss for 4-5 years and had low sperm count from it. After discontinuation, their sperm counts quadrupled on average, and nine men went up 11.6 times:

After stopping finasteride, sperm count increased significantly from 32.34 to 127.62 M/mL (P=0.002). Sperm count increased across the range of values prior to discontinuation of finasteride, including an 11.6-fold increase among nine men.

https://www.medpagetoday.com/endocrinology/infertility/41424​

finasteride and dutasteride can then be expected to reduce sperm count by 28-34% after 6 months for average men, and up to 75-91% by 4-5 years in susceptible men.

There's a good chance such a tiny dose of topical daro may have less of a negative effect than finasteride or dutasteride.

Are you planning to reduce your dosage once your regrowth is over and you can focus on maintenance?

 

[IdealForehead]

Are you planning to reduce your dosage once your regrowth is over and you can focus on maintenance?

Maybe in 3-6 months I'll take that chance. Right now I don't want to mess with anything at all since it's going well. I think 4 mg a day will be a good maintenance dose long term (down from 6 mg per day now). For reference, again, the prostate cancer dose is 300-600 mg orally twice a day. So this is already a tiny dose I'm on in that context.

Maybe I will get a sperm test done even without a baseline from before just to see in the next few months. If I am actually in the normal fertility range even on maintenance daro that would be impressive given what finasteride and dutasteride are known to do by comparison. And as long as I'm not lower than what's expected for those drugs than I can say it's probably not doing any worse.

 

[Afro_Vacancy]

Maybe in 3-6 months I'll take that chance. Right now I don't want to f*** with anything at all since it's going well. I think 4 mg a day will be a good maintenance dose long term (down from 6 mg per day now). For reference, again, the prostate cancer dose is 300-600 mg orally twice a day. So this is already a tiny dose I'm on in that context.

Maybe I will get a sperm test done even without a baseline from before just to see in the next few months. If I am actually in the normal fertility range even on maintenance daro that would be impressive given what finasteride and dutasteride are known to do by comparison. And as long as I'm not lower than what's expected for those drugs than I can say it's probably not doing any worse.

Did they actually do proper dosage studies, or is it like with finasteride, where they prescribe 1 mg/day for hairloss when 0.10 mg/day would be completely sufficient?

I'm asking because I know that your long-term goal is not just to look good for yourself (lol), but to look good for women. As such you might want to try building muscle and growing body hair at some point, which would suggest perhaps blocking DHT but not T, or using selective androgen receptor modulators such as Ostarine.