I have been thinking about the dose of darolutamide a bit more in the context of my skin dryness which as we reviewed was unexpected but definitely a potential side effect of systemic androgen deprivation. I am experiencing it on areas like my face where I am not directly applying any daro. Possibly my legs, arms, and eyes are a bit dryer as well but I can't say for sure. If so, it suggests significant systemic effect from my current dose. Time will tell.
My sexual function is still likely recovering from cypro-induced castration, and should recover in the next ~2 weeks if what I've read in studies is correct.
@Sanchez1234 I'm hoping perhaps you can observe and comment on if you notice anything on this drug sexually, as you have a cleaner starting point than me and you probably have more "normal" sexual function than me at baseline. Just please be careful of the nocebo effect and try not to overthink it. I'm sure you know all that though. I'm looking forward to hearing what you have to say or feel. It will be nice to get some added perspective from a fellow human guinea pig.
Other side effects from systemic androgen blockade due to darolutamide would be difficult to pick up in the short term as they are all very "silent". eg. You cannot clearly "feel" your bones becoming more brittle from androgen deprivation. I think in my case the skin dryness may be actually very helpful as it may help me titrate the dose to minimize systemic blockade over time as best I reasonably can.
Mulling this over has led me to review
the data again from the safety and dose-response study that was published on darolutamide. The most important figure is this:
View attachment 70725
In this study they were measuring PSA levels (a chemical made by the prostate) to judge prostate cancer activity. A major drop in the PSA would suggest the darolutamide dose was working and the cancer was effectively "castrated". Doses listed here are the total daily dose (eg. "200 mg" = 100 mg twice daily).
Without getting into too much detail because broad interpretation of this data is difficult, it is worth noting that many men had very dramatic initial suppression of PSA even on 200 mg daily (100 mg twice daily). The reason they decided on 1200 mg daily (600 mg twice daily) is for prostate cancer, they need to be sure ALL men will respond adequately to the dose they choose, and they need the effect to last long term.
From what I have learned about prostate cancer, the highly aggressive kinds that make it into these studies tend to be FREAKISHLY sensitive to androgens. Like WAY more than our otherwise healthy non-cancerous hair follicles ever could be. These prostate cancers will also mutate their DNA to fight androgen deprivation, becoming more androgen sensitive over time. That's why in figure B for 200 mg, you can see many responded very well initially, but then the PSA levels started going back up again. So they needed higher doses to fight back against the progressive mutations, which doesn't apply in hair loss or even tranny dosing.
So if 100 mg twice daily orally is enough to at least initially castrate many cases of aggressive prostate cancers, it is probably enough also to cause very severe and almost complete androgen deprivation in a normal healthy man.
For perspective on dosing, cyproterone is dosed at 50-100 mg daily for trannies, and 300 mg daily for prostate cancer (where I believe it is usually combined with other meds since cypro alone won't stop prostate cancer). So the tranny dose is 1/6 to 1/3 of the "partial response" prostate cancer dose for this med. In the most aggressive case scenario, perhaps it can then be concluded that as low as 16-33 mg twice daily orally of darolutamide could be an effective tranny dose for many men.
I am applying 10 mg twice daily to my scalp which is not too far off that range.
As I've said many times this is mostly guesswork and any conclusions I am drawing are weak since we have so little information to work from. It's a bit frustrating. Like trying to put together a puzzle with half the pieces missing. We really need some human studies either topically for hair or orally for MTF sex change to get some better perspective on appropriate dosing ranges.
But I think it's fair to say that the amount that should be needed topically for hair while minimizing systemic side effects should be very, very, very low. I still think I'm overdosing myself with the amount I'm using, but I will continue the dose longer to see for sure. If my skin and eyes continue to dry out or my sexual function does not normalize, I will cut down to 5 mg twice a day and then see what happens.
I'm gonna try to do what I said I was going to do before and just give it some time. Stop obsessing (if I can). Stop compulsively reading journal articles and searching Pubmed for random sh*t I have to start re-inflating my expander so I need to focus on that as well as work and some other things and just let this do what it's going to do for a while. I'll update if/when I drop the dose.