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I received many direct messages in response to a series of posts concerning a (mainly) topical maintenance regimen from about a year ago. Because I hardly visit this site anymore, but still want to help people struggling with hair loss, I made the following guide to the usage of one of the compounds in such a regimen: Bicalutamide.
Disclaimer: I do not suggest that you start using topical Bicalutamide. You should probably stick to established treatments. There are many risks associated with systemic blockade of the AR. However, since Bicalutamide is a FDA-approved compound, I do deem it safer than RU-58841 (and much more effective).
Intro & rationale
Bicalutamide is a powerful AR antagonist that is mainly used in the treatment of prostate cancer, and sometimes in transgender women. That sounds scary, and it should. Bicalutamide is a powerful compound that, when used correctly, completely blocks AR-signaling in non-mutated (i.e. every cell that is not cancerous) cells. Bicalutamide has an IC50 of about 160nM, which is about 100 times weaker than DHT. However, with correct administration this can be overcome because the local concentration of Bicalutamide will be thousands of times higher than that of DHT. The merit of Bicalutamide is that it has a 7 day half life, so it builds up in serum and tissue with repeated administration. This is why you should not apply Bicalutamide daily, but just once weekly.
Bicalutamide has been used more recently in a hair protecting topical by Dr. Will Powers, a MD specializing in MtF transitioning. This reinforces the idea that this is one of the most effective ways for hair maintenance that we have currently available.
-----------------------------------
Questions most often asked in direct message (plus a few additions of my own):
Why not use Enzalutamide or Darolutamide, two more powerful compounds?
Good question. I guess someone could. However, more is not always better. When local concentrations of Bicalutamide are thousands of times higher than T or DHT, there is not a single AR left to block. Other reasons could be that Bicalutamide has been used clinically for over 20 years and has an established safety/side effect profile. Bicalutamide is easier to get, less expensive and has less off-target effects (like GABA antagonism of Enzalutamide). Additionally, Enza and Daro are so potent that slight systemic exposure can already invoke side-effects. Bicalutamide has a wider margin of error, which makes it better suit for experimentation.
Why not use RU-58841?
Similar as above. In addition, RU-58841 has a very short half life, demanding twice/thrice a day applications (overnight blockade may be incomplete and AR activation may occur anyway). With a longer acting AR antagonist, there are no such issues. Furthermore, RU-58841 can have unpredictable and potentially dangerous side-effects. There is no data on long term safety in humans at all.
Will I regrow hair with Bicalutamide?
Very unlikely. Hair can possibly only be regrown with full-blown MtF transitioning, Minoxidil or highly experimental compounds (Finasteride and Dutasteride sometimes also yield results in terms of regrowth, but can be hit-or-miss). That said, I do not have many data points. Above is mainly based on anecdotal RU-58841 reports, which is an inferior agent. Bicalutamide will give you a good shot at maintaining the hair you have right now, in a convenient way with once weekly applications.
Will I experience side effects?
Impossible to say. This depends on individual genetics, scalp permeability, needling depth, baseline T levels, etc. etc. Once you experience side effects stop applying the topical immediately. Side effects will dissipate within a couple of days. Resume with 1/3 - 1/4th of the concentration you started with (even if that is lower than 1mg/mL).
Bicalutamide is not working for me
Firstly, it depends on what you define by 'working'. This topical is working when you can maintain your hair over a longer period of time (months - years). If you cannot maintain on this topical, I truly believe your hairloss is no longer induced by AR overactivation. There is a plethora of other factors that can cause hair loss (thyroid disorders, high prolactin, high or low estrogen, disbalances between local estrogen and progesterone, other medications etc. etc.). This topical should protect hair from androgenic hair loss. You may not regrow hair even if your hairloss is androgenic, see above. Unfortunately, androgenic hair loss is scarring, and semi-permanently lost hair can often only be recovered by extreme regima or aggressive (oral) minoxidil. Minoxidil is the most powerful agent against full-spectrum hairloss anno 2023, safe MtF HRT for androgenic hair loss only (both can come with heavy side effects, and especially HRT is absolutely unjustified for hairloss).
Will my androgen receptors upregulate in response to Bicalutamide?
Logically speaking, yes. However, I am not sure if this has been shown for AR antagonists specifically. Not every receptor type upregulates in response to an antagonist (but most do). It is not clear whether T downregulates AR's, so the opposite may or may not apply for (specific) AR antagonists. Anyway, the local concentration of Bicalutamide will vastly override any potential increase in receptor density. There is no need to worry about this except for maybe when withdrawing from topical Bicalutamide (if upregulation occurs). This is why it has to be used indefinitely.
Addendum: Pyrilutamide
Pyrilutamide is a new topical-only drug that is very promising for androgenic hair loss maintenance. However, it is still very expensive and (long term) side effects have not been established yet. The potency is around 10 times that of Bicalutamide, but due to a diminished half life (which can also be a positive to avoid systemic sides) the effective potency lies closer to that of Bicalutamide, or may even be lower. It's main strength lies not in the potency but in the (likely) lower probability of systemic side effects. This comes at the cost of the inconvenience of applying daily.
Additions
There are many possible additions, depending on the risk tolerance of an individual. Most effective is without a doubt oral Minoxidil, but it can be heavy on the side effects. I will not give an in-depth review here of all compounds that may be added, do your own research! Some other things that I have used (topically) in the past with varying success are (arbitrary order): Tretinoin, Cyclosporine A, Phenytoin, Estradiol microdose, CHIR99021, Purmorphamine, Valproate, variety of PGD2 antagonists, prostaglandins. I am still using topical Dutasteride @2mg/mL and oral Dutasteride @0.5mg/day. In terms of effectiveness, they would rank as: Oral Dutasteride >= topical Bicalutamide > topical Dutasteride. I apply my topical once weekly due to Bica & Duta's long half lifes.
Personal
I am still maintaining my NW2-2.5, as I expect to do for the rest of my life (at least against androgenic hair loss).
-----------------------------------
Guide
How to make the topical:
Dissolve 0.1 to 5mg/mL pure Bicalutamide powder* in 98% Ethanol. For concentrations >1mg/mL, the ethanol should be boiled in order for it to dissolve. You can boil ethanol by placing it in a closed flask in boiling water. When using Bicalutamide pills, one should ideally crush the pills into the smallest pieces possible and dissolve this into boiling ethanol. Use a coffee filter to remove fillers. I never did this, but it should not be too hard. One application should be between 1 and 5mL (temples-only to full scalp).
Added note: you probably cannot use Vodka for this, since it contains too much water. Bicalutamide will quickly fall out of solution by using water-based vehicles. I would not recommend DMSO either, as this would greatly increase systemic exposure. I have not experimented with other vehicles. Rubbing alcohol may be fine depending on scalp sensitivity. Use pure ethanol whenever possible.
The concentration should be determined based on personal experimentation. Personally, I am using 1mg/mL, which is already on the higher side. You will quickly notice when you overstepped on the concentration, because (subtle) systemic effects will become apparent. Reduce concentration immediately. This is the riskiest part from this regimen, but this calibration has to be performed only once. The range 0.1-5mg/mL is just an indication and may be tailored to personal needs. 5mg/mL is likely to be close to the maximum you will be able to dissolve in ethanol (going higher is not needed anyway). Use the topical only once weekly! This is very important, because applying more often will greatly increase the propensity for systemic side effects.
Microneedle the scalp lightly before applying the topical. This ensures the compound is absorbed. Needle depth should be 0.2-1mm depending on personalisation. You can wash the scalp minutes after applying; the ethanol dries in seconds. When not needled before application, it is unlikely that Bicalutamide can reach high enough local concentrations to effectively block the AR.
-----------------------------------
I believe this is one of the most convenient (once weekly applications, never a greasy scalp anymore), safest (in terms of the AR antagonist angle!) and effective methods for hair maintenance available to us right now. I encourage everyone to share experiences and to do your own research before attempting this! There is a wealth of scientific literature available on Bicalutamide. I have not cited these sources because there are a lot, and my priorities now lie elsewhere in life. Therefore, I will likely not return to these forums again. Keep in mind that I don't have the answers to most questions either (as does anyone else), but the literature is ever expanding. You will be most likely to find your answers there. Above all, I encourage discussion to ensure safe experimentation. Good luck to you all!
*I will not discuss sourcing here, but there are multiple reliable Chinese sources available. Always have the compounds tested at a third party facility before using them!
Disclaimer: I do not suggest that you start using topical Bicalutamide. You should probably stick to established treatments. There are many risks associated with systemic blockade of the AR. However, since Bicalutamide is a FDA-approved compound, I do deem it safer than RU-58841 (and much more effective).
Intro & rationale
Bicalutamide is a powerful AR antagonist that is mainly used in the treatment of prostate cancer, and sometimes in transgender women. That sounds scary, and it should. Bicalutamide is a powerful compound that, when used correctly, completely blocks AR-signaling in non-mutated (i.e. every cell that is not cancerous) cells. Bicalutamide has an IC50 of about 160nM, which is about 100 times weaker than DHT. However, with correct administration this can be overcome because the local concentration of Bicalutamide will be thousands of times higher than that of DHT. The merit of Bicalutamide is that it has a 7 day half life, so it builds up in serum and tissue with repeated administration. This is why you should not apply Bicalutamide daily, but just once weekly.
Bicalutamide has been used more recently in a hair protecting topical by Dr. Will Powers, a MD specializing in MtF transitioning. This reinforces the idea that this is one of the most effective ways for hair maintenance that we have currently available.
-----------------------------------
Questions most often asked in direct message (plus a few additions of my own):
Why not use Enzalutamide or Darolutamide, two more powerful compounds?
Good question. I guess someone could. However, more is not always better. When local concentrations of Bicalutamide are thousands of times higher than T or DHT, there is not a single AR left to block. Other reasons could be that Bicalutamide has been used clinically for over 20 years and has an established safety/side effect profile. Bicalutamide is easier to get, less expensive and has less off-target effects (like GABA antagonism of Enzalutamide). Additionally, Enza and Daro are so potent that slight systemic exposure can already invoke side-effects. Bicalutamide has a wider margin of error, which makes it better suit for experimentation.
Why not use RU-58841?
Similar as above. In addition, RU-58841 has a very short half life, demanding twice/thrice a day applications (overnight blockade may be incomplete and AR activation may occur anyway). With a longer acting AR antagonist, there are no such issues. Furthermore, RU-58841 can have unpredictable and potentially dangerous side-effects. There is no data on long term safety in humans at all.
Will I regrow hair with Bicalutamide?
Very unlikely. Hair can possibly only be regrown with full-blown MtF transitioning, Minoxidil or highly experimental compounds (Finasteride and Dutasteride sometimes also yield results in terms of regrowth, but can be hit-or-miss). That said, I do not have many data points. Above is mainly based on anecdotal RU-58841 reports, which is an inferior agent. Bicalutamide will give you a good shot at maintaining the hair you have right now, in a convenient way with once weekly applications.
Will I experience side effects?
Impossible to say. This depends on individual genetics, scalp permeability, needling depth, baseline T levels, etc. etc. Once you experience side effects stop applying the topical immediately. Side effects will dissipate within a couple of days. Resume with 1/3 - 1/4th of the concentration you started with (even if that is lower than 1mg/mL).
Bicalutamide is not working for me
Firstly, it depends on what you define by 'working'. This topical is working when you can maintain your hair over a longer period of time (months - years). If you cannot maintain on this topical, I truly believe your hairloss is no longer induced by AR overactivation. There is a plethora of other factors that can cause hair loss (thyroid disorders, high prolactin, high or low estrogen, disbalances between local estrogen and progesterone, other medications etc. etc.). This topical should protect hair from androgenic hair loss. You may not regrow hair even if your hairloss is androgenic, see above. Unfortunately, androgenic hair loss is scarring, and semi-permanently lost hair can often only be recovered by extreme regima or aggressive (oral) minoxidil. Minoxidil is the most powerful agent against full-spectrum hairloss anno 2023, safe MtF HRT for androgenic hair loss only (both can come with heavy side effects, and especially HRT is absolutely unjustified for hairloss).
Will my androgen receptors upregulate in response to Bicalutamide?
Logically speaking, yes. However, I am not sure if this has been shown for AR antagonists specifically. Not every receptor type upregulates in response to an antagonist (but most do). It is not clear whether T downregulates AR's, so the opposite may or may not apply for (specific) AR antagonists. Anyway, the local concentration of Bicalutamide will vastly override any potential increase in receptor density. There is no need to worry about this except for maybe when withdrawing from topical Bicalutamide (if upregulation occurs). This is why it has to be used indefinitely.
Addendum: Pyrilutamide
Pyrilutamide is a new topical-only drug that is very promising for androgenic hair loss maintenance. However, it is still very expensive and (long term) side effects have not been established yet. The potency is around 10 times that of Bicalutamide, but due to a diminished half life (which can also be a positive to avoid systemic sides) the effective potency lies closer to that of Bicalutamide, or may even be lower. It's main strength lies not in the potency but in the (likely) lower probability of systemic side effects. This comes at the cost of the inconvenience of applying daily.
Additions
There are many possible additions, depending on the risk tolerance of an individual. Most effective is without a doubt oral Minoxidil, but it can be heavy on the side effects. I will not give an in-depth review here of all compounds that may be added, do your own research! Some other things that I have used (topically) in the past with varying success are (arbitrary order): Tretinoin, Cyclosporine A, Phenytoin, Estradiol microdose, CHIR99021, Purmorphamine, Valproate, variety of PGD2 antagonists, prostaglandins. I am still using topical Dutasteride @2mg/mL and oral Dutasteride @0.5mg/day. In terms of effectiveness, they would rank as: Oral Dutasteride >= topical Bicalutamide > topical Dutasteride. I apply my topical once weekly due to Bica & Duta's long half lifes.
Personal
I am still maintaining my NW2-2.5, as I expect to do for the rest of my life (at least against androgenic hair loss).
-----------------------------------
Guide
How to make the topical:
Dissolve 0.1 to 5mg/mL pure Bicalutamide powder* in 98% Ethanol. For concentrations >1mg/mL, the ethanol should be boiled in order for it to dissolve. You can boil ethanol by placing it in a closed flask in boiling water. When using Bicalutamide pills, one should ideally crush the pills into the smallest pieces possible and dissolve this into boiling ethanol. Use a coffee filter to remove fillers. I never did this, but it should not be too hard. One application should be between 1 and 5mL (temples-only to full scalp).
Added note: you probably cannot use Vodka for this, since it contains too much water. Bicalutamide will quickly fall out of solution by using water-based vehicles. I would not recommend DMSO either, as this would greatly increase systemic exposure. I have not experimented with other vehicles. Rubbing alcohol may be fine depending on scalp sensitivity. Use pure ethanol whenever possible.
The concentration should be determined based on personal experimentation. Personally, I am using 1mg/mL, which is already on the higher side. You will quickly notice when you overstepped on the concentration, because (subtle) systemic effects will become apparent. Reduce concentration immediately. This is the riskiest part from this regimen, but this calibration has to be performed only once. The range 0.1-5mg/mL is just an indication and may be tailored to personal needs. 5mg/mL is likely to be close to the maximum you will be able to dissolve in ethanol (going higher is not needed anyway). Use the topical only once weekly! This is very important, because applying more often will greatly increase the propensity for systemic side effects.
Microneedle the scalp lightly before applying the topical. This ensures the compound is absorbed. Needle depth should be 0.2-1mm depending on personalisation. You can wash the scalp minutes after applying; the ethanol dries in seconds. When not needled before application, it is unlikely that Bicalutamide can reach high enough local concentrations to effectively block the AR.
-----------------------------------
I believe this is one of the most convenient (once weekly applications, never a greasy scalp anymore), safest (in terms of the AR antagonist angle!) and effective methods for hair maintenance available to us right now. I encourage everyone to share experiences and to do your own research before attempting this! There is a wealth of scientific literature available on Bicalutamide. I have not cited these sources because there are a lot, and my priorities now lie elsewhere in life. Therefore, I will likely not return to these forums again. Keep in mind that I don't have the answers to most questions either (as does anyone else), but the literature is ever expanding. You will be most likely to find your answers there. Above all, I encourage discussion to ensure safe experimentation. Good luck to you all!
*I will not discuss sourcing here, but there are multiple reliable Chinese sources available. Always have the compounds tested at a third party facility before using them!
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