According to studies made by the companies that are selling the drug. Finasteride and pyri and cb are completely safe. But the fact is there is no way in hell they are not lying because many people had side effects.
So yeah maybe I’m just too sensitive to anti androgens in all forms. If fluridil gives me side effects then it’s pretty much over for me yes.
this is a long post but I understand the issue and having something of a similar problem(cant tolerate finasteride not even low dose topical but haven't tried research chemicals) I think maybe we need to focus on the delivery more than on the drug at this point. I think the most limiting factor is the people gets sides and seeing how most new drugs (which can be extremely effective) focus on the androgen pathway, degraders, iRNAs, antagonists etc. we must find a way to tolerate them without sides. since hair loss is confined purely to androgenic action in the dermal papilla cells, a tiny compartment at the bottom of the follicle, targeting the drug right there could lead to high efficacy with low toxicity.
consider that maybe you use a vehicle that is complete sh*t for follicular delivery and local action like ethanol/pg is. it is not penetration pathway discriminatory, uses all 3 of them( penetration pathways:
https://ars.els-cdn.com/content/image/1-s2.0-S1359029412000234-fx1.jpg ) , penetrates everywhere on the skin and deep too. I can tell you that for CB-03-01 they did not use that vehicle, companies generally do skin permeation studies to pick the best vehicle which rarely is ethanol pg. you can read in the CB paper what vehicle they ended up using and they considered local action as a factor. they used Franz diffusion cells to gauge how much penetrates the skin and goes systemic.
a vehicle can significantly impact skin permeation and retention.
I dont think you should give up and we should strive for a solution. however I think this can only work by using a good vehicle. it can increase the drug content in the follicular cast and make it harder for the drug to get absorbed through the rest of the skin. if you use ethanol a good portion of the drug goes systemic directly thought the skin and since fluridal has a higher affinity for the androgen receptor than flutamide(yes it does. and the idea that it cant go systemic because it degrades in blood is BS because it does not degrade immediately but only after 6-7 hours which is enough time to bind an androgen receptor)
so I dont know how this is going to work. btw I am in the same position, I am looking into the vehicle route and have read enough papers to believe that the delivery mechanism can be vastly improved.
and furthermore, seeing as the importance of androgens on erectile dysfunction and libido is described in the literature, it works in ranges. and hormones fluctuated quite a lot on a daily basis. you cannot prevent a drug from going systemic completely. e.g the dermal papilla is highly vascularized and some drug will enter the circulation. however it would be quite insane if an arbitrary small amount can cause these full sides. like, that would make the body completely incapable of coping with external influences. e.g bad nutrition affects your androgen household more than a tiny dose of CB or pyrilutamide. its just a matter of restricting e.g the anti androgen at the penis as much as possible.
of course e.g in the case of finasteride, a 70% reduction in DHt has a vast impact on the system. however, I would be quite surprised if the body couldn't handle e.g a 10-20% decrease. and that should be the goal. its not a question of "does it go systemic or not", these drugs are not cyanide. and since most of them are lipophilic and quite small in molecular size, they WILL go systemic to some extent. the question is "how much goes systemic and what is the half life/modulatory half life of the drug in the system" and you want to limit that. for example finasteride half life is 7 hours but 5AR only gets resynthesized by half every 3 days. so if you dose again just because there is no finasteride left, you'll suppress DHT further. the idea is to only dose when the serum dht has stabilized again, however if we can achieve accumulation of the drug in the follicle then this is enough for efficacy.
so again, seeing as the most new drugs target the androgen part of hair loss, if we cant get the delivery right, we will miss out on ALL of those new treatments if we cant tolerate them. these treatments combined are the cure for hair loss for those who can tolerate it. and iRNA, AR degrader, 5AR inhibitor AND an AR antagonist? there will be nothing left in terms of androgenic action. the real issue is for us that we cant tolerate most of the drugs even in isolation.
the problem of AA is only a local one. going from oral to topical finasteride is a step and relieved side effects for many, however, when the topical still inhibits 35% of DHT then nothing is won for those who are very sensitive. e.g topical 0.025% topical finasteride in minoxidil dissolved inhibited 41% of my serum DHT after 3 weeks. too much for me.
we need 10-20% max for finasteride and the same reduction for the other drugs. furthermore it could allow slow release on site which would make dosing 2-3 times per week possible, even with an anti androgen like CB with a fast disassociation rate.
here for example I provide a paper on insight into topical delivery of finasteride using modern technology to limit systemic absorption and increase the drug amount where it belongs to. just a small overview
https://www.mdpi.com/1999-4923/14/2/286 for finasteride. this is new research, there are like 8 papers just from last years. for us, who are super sensitive to this stuff, using a vehicle with high follicular targeting would allow trimming down the dose and frequency which should lead to serum levels being almost undetectable.
https://link.springer.com/article/10.1208/s12249-018-1087-z as an example for anti androgens, flutamide having a similar structure to fluridil. as you can see in the stained image, most of the drug either did not penetrate the stratum corneum(external layer of the skin) or resides in the follicular cast. this could limit systemic absorption compared to ethanol(which is a strong penetration enhancer everywhere) manyfold. one could get away with less frequent dosing and smaller doses. nobody is sensitive to any amount of anti androgen, I firmly believe you are just getting too much into your system with this vehicle. if you look at figure 7 in the above paper, we want something that looks like this. most of the drug in the follicle shaft and not much drug in other compartments of the skin. some will go systemic bc the follicular casts are vascularized but only 10% of the scalp are covered in follicle so the overall area of absorption is smaller.
www.ncbi.nlm.nih.gov
the research is getting started, most of the interesting papers are from 2018-2022.
i have talked to someone in the industry and some of these are not hard to make given the right equipment. my suggestion would be to find a lab that instead of brewing up CB or pyrilutamie with who knows what's insides, find a reputable lab that can make these carriers. since its just a reformulation of an existing drug(e.g in case of fluridil or finasteride) there is no regulatory hurdle and its not an unapproved possibly unsafe steroid.
some startups are already doing trials on this (2 I can think off, one in Korea and one in Israel) however that won't be here before 2025.
btw in theory, anti androgens(receptor antagonists) should be less harmful for example for erectile dysfunction as finasteride. androgens can work through the nuclear receptor or through other means e.g there is not just one receptor, there is multiple androgen receptor "splice variants" and some of them sit in the membrane. for erections the primary effect of androgens is mediated through the membrane receptors, however an antagonist like pyrilutamide cannot block these because its a molecular different structure.
https://en.wikipedia.org/wiki/Membrane_androgen_receptor
so it is entirely possible that one anti androgen has side effects while another has not, not just based on the affinity and amount you use but also the molecule itself, what the underlying androgenic actions are etc.
im just thinking, if CB and pyrilutamide are potent enough to limit your libido even though you apply it locally and libido is mostly in the brain, then it could be powerful and potent if it is targeted right into the hair follicle shaft and thus systemic impact is minimized. I think the research section should focus more on the improved delivery of existing drugs(that DO work well) instead of doing research on bs like twist inhibitors etc. things which never will work and carry potentially high risks. basically more of the drug where it belongs to and less where it doesnt. its not that easy but I think it could work
