Finasteride didn't work for you? So, did DUT?

[dm90]

Just a side note. Theres alot of fear mongering about Fin and DUT on here, yet theres a a sizable group of forum users interested in JAK inhibitors. That is pure insanity to me.

[JohnMPB]

I've heard this theory thrown around recently on various forums and Dr. Proctor, who is very well versed in hair loss agrees that it's quite a possibility...

It's likely fin and dut perform almost the same over the long term in regards to mpb. The idea is there is only type 2 5ar in the dermal papilla which Finasteride is a specific inhibitor. Dut inhibits both forms but type 1 is located in other tissues such as the sebaceous gland. So far there are mainly only 6 month studies showing dut outperforms fin in that timeframe but there are no 1+ year studies to show whether or not dut just works faster.

As we see from other studies, fin continues to increase hair counts beyond 1 year. So the question is does dut really outperform fin in regards to hair counts or just work faster over the short term?

Anti androgens can only get you so far with mpb. It's somewhat rare to see people regrow hair just on fin or dut. Even castrates don't regrow much but can halt their mpb. Hair loss is very complex and from my minimal understanding just chasing the idea that decreasing androgens as much as you can will have diminishing returns IMO, fwiw, just sayin.

[dm90]

I believe it all goes back to the original pseudoherms discovery. Type 2 deficiency results in no AGA, therefore one can infer that there is no type 1 in the DP. I agree that if a person has a good response to fin, maximum dht reduction of 90%, DUT wont outperform fin by much of any degree. However, remember that 10% of people who take fin experience a progression of AGA over 5 years. I believe its because these are the individuals that are on the left side of the DHT reduction bell curve. I see alot of posters say that if fin doesnt work dut wont really either, but to me that just cant be the case. This is because DUT pretty much eliminates all type 2 in the DP for everyone. Remember the standard deviation is so small compared to fin. In the long run i'd say DUT will produce better results everytime compared to fin. Yes hairloss is a complex disregulation of several pathways that leads to hair miniaturization, but remember its all started by the initial androgen stimulation. Understanding the pharmacology of the two drugs also supports that DUT is superior at maitenance. FIN reduces DHT to its maximum effectiveness very rapidly, with 24 hours of its first dose. However fin has a halflife of 8 hours and DHT can fluctuate even if you take it daily. DUT takes a long time to reach a steady state, but once it does youre DHT levels will pretty much remain at their lowest levels. However reaching a steady state on DUT takes 3 months of 0.5 mg daily. Now i have read studies that there are people with genotypes that respond better to fin, however this is pretty rare to my understanding. I'm not saying anyone should jump on DUT, i'm merely saying that if you understand the basic facts about AGA and the pharmacology of DUT its not a ridiculous statement to say that AGA cant progress on DUT. Regrowth is another story, I have read numerous studies on the mechanism of action for minoxidil and basically minoxidil works be forcing some of the pathways disregulation by DHT back into regulation. Really its pretty phenominal all the things minoxidil does, its just that damn sulfotransferase enzyme. If we all had it aga would be essentially cured for many sufferers.

[JohnMPB]

I believe it all goes back to the original pseudoherms discovery. Type 2 deficiency results in no AGA, therefore one can infer that there is no type 1 in the DP. I agree that if a person has a good response to fin, maximum dht reduction of 90%, DUT wont outperform fin by much of any degree. However, remember that 10% of people who take fin experience a progression of AGA over 5 years. I believe its because these are the individuals that are on the left side of the DHT reduction bell curve. I see alot of posters say that if fin doesnt work dut wont really either, but to me that just cant be the case. This is because DUT pretty much eliminates all type 2 in the DP for everyone. Remember the standard deviation is so small compared to fin. In the long run i'd say DUT will produce better results everytime compared to fin. Yes hairloss is a complex disregulation of several pathways that leads to hair miniaturization, but remember its all started by the initial androgen stimulation. Understanding the pharmacology of the two drugs also supports that DUT is superior at maitenance. FIN reduces DHT to its maximum effectiveness very rapidly, with 24 hours of its first dose. However fin has a halflife of 8 hours and DHT can fluctuate even if you take it daily. DUT takes a long time to reach a steady state, but once it does youre DHT levels will pretty much remain at their lowest levels. However reaching a steady state on DUT takes 3 months of 0.5 mg daily. Now i have read studies that there are people with genotypes that respond better to fin, however this is pretty rare to my understanding. I'm not saying anyone should jump on DUT, i'm merely saying that if you understand the basic facts about AGA and the pharmacology of DUT its not a ridiculous statement to say that AGA cant progress on DUT. Regrowth is another story, I have read numerous studies on the mechanism of action for minoxidil and basically minoxidil works be forcing some of the pathways disregulation by DHT back into regulation. Really its pretty phenominal all the things minoxidil does, its just that damn sulfotransferase enzyme. If we all had it aga would be essentially cured for many sufferers.

You make some great points. The fluctuation of DHT levels is true, but nobody knows what's going on within the DP which is really what matters. It's easy to get caught up in the DHT reduction numbers but one thing that Dr. Proctor brought up was that with greater DHT reduction, there is a higher chance of reflex hyperandrogenicity- which is potentially very bad for hair. I've seen posts online of people complaining of huge sheds or losing hairline once switching over to dut and this reflex hyperandrogenicity could explain that. His point was that most people with prostate cancer (as we know these drugs were created to address prostate issues) very strong antiandrogens like flutamide are not enough as they too cause reflex h so these patients simultaneously get castrated as well during their treatments. If we could get 1 year and beyond hair count numbers like we have for fin, this would be all we need.

Makes you wonder....was Avodart pulled because it didn't work as well as fin or even possibly worse over the long term? It's also hard for me to believe the sides for Avodart are less than propecia just due to the fact that serum DHT levels are decreased so much by Avodart and type 1 5ar is reduced by 50%.

[dm90]

Damn everytime i type my long message in response to this my laptop freezes >.>. Anyway in response to the upregulation of the AR from androgen deprivation i found this http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069023/. It examines the AR concentratiosn in the stromal and epithelia cells of men reporting persistent sexual side effects from fin. Consensus is yes upregulation does occur in both the stromal and epithelial tissues. However it is much greater in the stromal, prostatic cells. Theres a 2 fold increase in the prostatic cells and roughly only a 20% increase in the epithelial tissue. Good news for our hair, not so good for our prostates. This upregulation in the epithelial tissue, if it reigns true for the greater population (this was a small study), would not offset the DHT reduction of fin and definitely not for DUT. Interestingly enough nerve density and structure remained unchanged. Ive never been worried about PFS, but upregulated expression in stromal tissue,leading to hyperplasia, seemed a very real and believable concern to me. I will continue to take these medications because my hair is just that important to me, yeah it may be reckless but its my body, but I mean this isnt something that should be ignored

[BaldingHelpMe]

DUT takes a long time to reach a steady state, but once it does youre DHT levels will pretty much remain at their lowest levels.

It takes three months for dut to get to your body?? Says who? Where did you get this info? Also, it doesn't make sense. From the leaflet, it says the medicine will get to your bloodstream in a few hours after taking it.

[dm90]

I said it takes three months to reach a "steady state". A steady state is a term used in pharmacokinetics where the drug is ingested at the same rate it is removed, this means the concentration remains steady in your blood. This is why people talk about "loading doses" with avodart.

[tedwuji]

I said it takes three months to reach a "steady state". A steady state is a term used in pharmacokinetics where the drug is ingested at the same rate it is removed, this means the concentration remains steady in your blood. This is why people talk about "loading doses" with avodart.

It crosses blood brain barrier which is not relevant to an obession with maximizing the reduction of androgens but castration side-effect is also irrelevant under parallel logic.

[tedwuji]

They're different animals, but completely pointless distinctions. They are also are irrelevant to fin/dut effectives in treating hairloss. The 98% figure i stated was dermal papilla type 2 dht, which as far as we know is the only relevant DHT with regards to hairloss, remember its an autocrine response not paracrine. Serum DHT is just the DHT concentration in the entire body, which includes scalp DHT. Yes most are well versed in the reduction percent curve of finasteride, approx 70% serum, and dutasteride approx 90%. But You have to understand what these numbers mean. Why can serum dht be reduced by 90% while scalp dht is only reduced by 50%? Because DHT isnt evenly concentrated throughout the body. Type 2 is heavily concentrated in the prostate and dermal papilla while type 1 is present in the sebaceous glands and brain. Neither have any significant concentration in the skeletal muscle. Sebaceous glands are in the scalp and therefore there is a significant concentration of the type 1 isoform. Finasteride has no affinity for this isoform and dutasteride, while it does reduce it, doesnt have nearly as strong of an affinity for it as it does for the type 2. Secondly and the most important point is the ratio of type 1 to type 2 in the body. The majority of DHT in the body is converted from the type 2 isoenzyme. I approximately 70-80% of total dht actually. Firstly FIN reduces total serum dht by 70%. Secondly FIN has no affinity for the type 1 isoenzyme, therefore that 70% reduction is completely type 2. Well 70 is about 90% of 80. So given the perfect response finasteride reduces type 2 dht by 90%. This means there is only 10% DHT left in the dermal papilla, the only important DHT. DUT has 3x affinity for the type 2 isoenzyme over finasteride, this means significantly more type 2 is reduced leaving next to no traces of the hormone in the follicle. Lastly, yes type 1 is present in the brain tissue, and dutasteride can pass the blood brain barrier. That isnt really relevant to the point im making.

It crosses blood brain barrier which is not relevant to an obession with maximizing the reduction of androgens but castration side-effect is also irrelevant under parallel logic.

[dm90]

It crosses blood brain barrier which is not relevant to an obession with maximizing the reduction of androgens but castration side-effect is also irrelevant under parallel logic.

I don't quite understand the statement here. I wasn't arguing the safety long term safety of dutasteride, nor was I advocating its use. I was simply comparing the pharmokinetics of the drug to finasteride and offering an explanation as to why dut will work when finasteride fails. As for the blood brain barrier, several medications cross it, finasteride does however the type 2 enzyme doesnt appear to be present in brain tissue. As for the reduction statement I made that seemed to provide some confusion here is a study to confirm what I have said. http://onlinelibrary.wiley.com/doi/1...06.00053.x/pdf

"However, finasteride decreases prostatic DHT concentrations
(where the Type II enzyme predominates) by as much as 90%"

However there is a standard deviation by about 20% leaving some to only have around a 60% reduction in type 2. Dutasteride has 3x the affinity for the type II isoform and a much lower SD. The original question for this thread is asking if DUT will succeed when fin has failed, and the answer to that question is it more than likely will.

I'm not here to argue the safety profile of a drug or persuade someone to take anything. Sertraline crosses the blood brain barrier, it has to in order to work, and its rate of sexual side effects are much higher than and A5RI, some studies have shown the rates are as high as 30-40%. Also persistent sexual dysfunction is well documented for this medication, however the same paranoia doesnt seem to surround SSRI's possibly because depression, ocd, and anxiety are taken much more seriously while hairloss is considered an issue of vanity. I'm not demonizing SSRI's either, I believe they help alot of people who desperately need it. Some are completely emotionally crippled by hairloss and finasteride doesnt work for everyone. People need an objective understanding of available treatments so they can decide for themselves what course of action to take. In closing ill reiterate once more that if finasteride isnt stopping your hairloss its most likely due to the drug not reducing adequate type 2 DHT, which dutasteride will in most cases remedy this.