Why isn't there a more efficient DHT inhibitor?

[shyyguy123]

I'm referring specifically to hair loss obviously..

We've got dutasteride but it unnecessarily inhibits the type 1 5ar enzyme if you're taking it for hair loss. The research we have suggests that type 1 has little to nothing to do with hair loss. It's great at blocking almost all of the type 2 enzyme but it doesn't seem healthy to inhibit nearly all of type 1 5ar too for no reason.

finasteride selectively inihibit type 2, which is great for hair loss, and doesn't have much effect on type 1. That certainly seems like the healthier combo to me, but it only blocks 85-90% compared to dutasteride's 98-99%.

I guess my question is why can't/haven't they come out with a combo of the 2? An inhibitor that shuts down 98-99% of type 2 5ar like dutasteride but leaves type 1 alone like finasteride?

 

[jbrog1987]

Good question. Curious about this myself..

 

[Agustin Araujo]

I've had thoughts myself about that before. If I remember correctly, Dutasteride has a stronger binding to the Type II 5-AR enzyme than Finasteride. I myself have been taking 0.5 mg of Dutasteride daily since 12/28/2014 for treating my male pattern baldness and have had no problems with the medication. I don't ever worry about Type I 5-AR enzyme inhibition.

 

[Wolf Pack]

I think I wondered myself this ages ago. That a pure type 2 5 AR inhibitor would be great, something like taking out 100%. My guess is finasteride taking out close to 90% of the type 2 enzyme in the clinical trials has shown to be enough for maintenance for most male pattern baldness sufferers.

But yes, it would be nice if there was a drug that took out 100% of the type 2 5-AR enzyme. I wish we could have a surgical procedure to permanently destroy the enzyme activity at the hair follicle. That way we wouldn't even need to keep taking a pill, not that it's hard. Only issue is this wouldn't be reversible and if you got side effects you would be in trouble.

 

[Dench57]

Don't forget 5AR type III which has only been discovered recently. Inhibited by both dutasteride and finasteride.

 

[abcdefg]

Don't forget 5AR type III which has only been discovered recently. Inhibited by both dutasteride and finasteride.

Yeah that fact is a little worrying because I dont remember the biological model for finasteride mentioning that anywhere leading me to believe they had no idea that existed back then. They never did any safety studies on whether its safe to inhibit this enzyme too because they never knew.

 

[g.i joey]

well the drugs been out for about 20+ years im sure all these lawsuits would use type 3 as the culprit for their patients problems... IMO merck would have been exploited on this by now.

 

[Dench57]

Like I said, it has only been discovered recently, long after dutasteride/finasteride became available. There are some extensively detailed studies outlining the role of type III and the potential consequences of type III inhibition but I don't have the energy to read them nor the intelligence to draw any meaningful conclusions. Way above my level.

 

[Wolf Pack]

I might take a read but I just can't be bothered this late, tired from work. I think the key is there is still 30% dht circulating on finasteride for your body to use. Most will be type 1 and some of 3. 2 Is safe to inhibit for the majority. Hell people take dutasteride fine, for the majority no dht is not a problem. I don't buy all this biological model stuff, it's nice but it's not necessary. Many drugs don't have it and are safe.

I actually think these drugs are very safe unless something surprising comes out, unlikely as its so many years and post marketing research is done. It don't interact with other medications and don't effect the cardio, renal, neural and hepatic system in a big way. In that sense its distinct to other meds.

 

[Rudolphus]

We must remember that Dutasteride at a daily dosage of 0.5mg only inhibits half of the 5ar-1 enzyme, so it still leaves half of this enzyme untouched. I personally doubt that a 50% reduction in the activity of this enzyme is of any major significance. Natural DHT levels from both 5ar-1 and 5ar-2 vary widely between different individuals anyway, and the amount of DHT from 5ar-1 that you are left with after 50% has been removed by Dutasteride would still likely be well within normal limits. Now if you were to take 2.5mg of Dutasteride daily, you'd be inhibiting around 85% of 5ar-1, and that would be a much bigger cause for concern.

Not much is known about the recently discovered type 3 alpha reductase enzyme of which Dutasteride at 0.5mg achieves complete inhibition and Finasteride at the standard dose achieves near-complete inhibition. Evidence shows that it has a critical role in cell metabolism, and that its main function is to synthesize a specific type of alcohol called "dolichol". This alcohol has an essential role in protein folding within the endoplasmic reticulum of cells for the very beginning stages of glycosylation. Evidence also suggests that 5ar-3 converts testosterone to DHT. However, there have been several cases of humans born with 5ar-3 deficiencies or abnormalities, and these individuals have no apparent sexual anomalies, which seems to contradict this supposed androgenic involvement of 5ar-3.

However, these individuals who are born with mutations in the gene that codes for 5ar-3 (and who therefore have defective or non-functioning 5ar-3) display a wide range of serious health problems (see Kahrizi syndrome, as well as Congenital Disorder of Glycosylation, Type Iq). Most notably, severe mental retardation, psychomotor retardation, serious eye problems, skin abnormalities, bone and joint abnormalities, and coarse facial features.

A hypothetical inhibitor that removes all of the DHT from 5ar-2 and none of the DHT from either 5ar-1 or 5ar-3 would be a superior treatment to both Dutasteride and Finasteride. However, pharmaceutical companies know that it would be a stupid decision to invest time and money into such an idea, especially considering how disappointing Propecia sales have been. The public interest is not in finding a better 5ar inhibitor than those that are currently available, but rather in finding a completely different alternative that is safer, better, and side-effect-free. For instance, a powerful topical anti-androgen like CB-03-01. This is where the real money is to be made.

 

[Wolf Pack]

For instance, a powerful topical anti-androgen like CB-03-01. This is where the real money is to be made.

That might get the forum excited but in the real world compliance to medication is very crucial. And sticking something on your head daily forever I can't imagine replacing finasteride as less people will use it. Sales wouldn't be great either. Especially if it does the same thing as finasteride in terms of for hair.

Rogaine sales were never that good although the foam helped increase it. Even then, people prefer the propecia pill that I speak to in real life.

Ultimately no treatment for male pattern baldness so far has done good in sales.

 

[abcdefg]

True no treatment has done well but what is that propecia and rogaine? Even rogaine probably has done pretty decently over the many years it was out. It has been reformulated a few times too. CB could do very well I think but it all depends like if it got approved OTC it would sell a ton better avoiding the cost of seeing a doctor.
Inhibiting an enzyme like type 3 is a tough thing to predict how important it really is or how much you really need. Thinking logically about things that happen in the body doesnt always lead to the right answers. Small unnoticeable changes can accumulate over time to show up as big issues making it near impossible to ever determine for sure what it was. Doesnt matter though because its propecia or bust still so not any other choice. Might be fine anyways

 

[Wolf Pack]

Personally I am not concerned about finasteride for reasons mentioned previously. Type 3 does not bother me, those congenital disorders to do with it are irrelevant. It's like saying without type 2 as a fetus/child you will end up with a small penis, scrotum. True, but it's not relevant for those who are passed puberty. People do a lot of random digging on here but the fact is in clinical trials they do literally every test (even irrelevant ones) and finasteride doesn't seem to affect anything much. Every drug will always have benefit v risk. More digging, equal more random stuff found.

Plus really we talk about type 1-3 DHT but it's all actually circulating DHT. 30% left on finasteride is still good even though it probably isn't needed either.

My main worry with dutasteride is changes in semen parameters not random chemicals. finasteride has shown to not alter it or do so very slightly which is reversible. But with dutasteride there are reports that semen parameters may be altered more and not reversible. Again, if you don't have any issues with your fertility it shouldn't pose a problem.

 

[Armando Jose]

That might get the forum excited but in the real world compliance to medication is very crucial. And sticking something on your head daily forever I can't imagine replacing finasteride as less people will use it. Sales wouldn't be great either. Especially if it does the same thing as finasteride in terms of for hair.

Rogaine sales were never that good although the foam helped increase it. Even then, people prefer the propecia pill that I speak to in real life.

Ultimately no treatment for male pattern baldness so far has done good in sales.

I am with you, but it could be possible that the "lotion" can be used only one or two days a week because hormonal changes are very resilient

 

[Rudolphus]

It is believed that CB will only need to be applied once (or was it twice?) a week in order to effectively treat male pattern baldness. The researchers anticipate that it will turn out to be considerably more effective than Finasteride, and it also has no side-effects at all because it is broken down into a completely harmless substance once it goes systemic. Assuming that CB lives up to our expectations, I think that it will be a massive breakthrough for us that will reach huge sales.

 

[Wolf Pack]

Thanks guys. I am not too clued up on future treatments. Hmm once/twice a week topical v a pill. The side effect profile of finasteride doesn't bother me. If it was much more effective I would consider it replacing finasteride. Of course we have to consider hair maintenance and regrowth. Bit of a hassle still ensuring you can cover each area of your head to ensure it antagonises the androgen receptors appropriately. Drying time e.t.c.

 

[D_Sho3]

Advice

So i'm looking to start some sort of program and see where it goes. I'm at the stage of just decided what approach I want to go. So i've done some initial research and I'm open to discussion and listening to what other users believe is the best way to go but I'm currently leading toward Rogain foam for growth, Revivogen for DHT inhibitors and Nizoral. What I am planning on doing is Shower using Nizoral, and apply both Revivogen and Rogaine but i'm not sure if I need both so I'm looking for some guidance in this area. I'm also very open to other discussions as to products.
Any assistance would be amazing!!
Thanks!!!

 

[shyyguy123]

Personally I am not concerned about finasteride for reasons mentioned previously. Type 3 does not bother me, those congenital disorders to do with it are irrelevant. It's like saying without type 2 as a fetus/child you will end up with a small penis, scrotum. True, but it's not relevant for those who are passed puberty. People do a lot of random digging on here but the fact is in clinical trials they do literally every test (even irrelevant ones) and finasteride doesn't seem to affect anything much. Every drug will always have benefit v risk. More digging, equal more random stuff found.

Seems a little like blind faith to me. Sure, we may not have anything to worry about but all those clinical trials were 6 months to a year. Who knows what kind of health risks inhibiting DHT for 15-20 years can cause. We just don't know. I'd certainly rather be as safe as possible and not touch type I and III and 5ar if we don't have to.

Unfortunately it's probably just not worth the money to optimize finasteride and re-market it when it's already "good enough" in most cases. So I doubt we'll ever see an efficient hair loss DHT inhibitor that only targets type II.

 

[g.i joey]

So i'm looking to start some sort of program and see where it goes. I'm at the stage of just decided what approach I want to go. So i've done some initial research and I'm open to discussion and listening to what other users believe is the best way to go but I'm currently leading toward Rogain foam for growth, Revivogen for DHT inhibitors and Nizoral. What I am planning on doing is Shower using Nizoral, and apply both Revivogen and Rogaine but i'm not sure if I need both so I'm looking for some guidance in this area. I'm also very open to other discussions as to products.
Any assistance would be amazing!!
Thanks!!!

if it aint finasteride, you cant win.

- - - Updated - - -

Seems a little like blind faith to me. Sure, we may not have anything to worry about but all those clinical trials were 6 months to a year. Who knows what kind of health risks inhibiting DHT for 15-20 years can cause. We just don't know. I'd certainly rather be as safe as possible and not touch type I and III and 5ar if we don't have to.

Unfortunately it's probably just not worth the money to optimize finasteride and re-market it when it's already "good enough" in most cases. So I doubt we'll ever see an efficient hair loss DHT inhibitor that only targets type II.

actually, we do know, check out the study of people who took finasteride for 18 years and had no health problems or random mishaps happen compared to placebo, same amount of deaths occurred in each respective group. Finasteride has been around for 23 years, has been handling lawsuits for pfs, id say about 10-13. It doesnt get worst than what we know now.

 

[Rudolphus]

So i'm looking to start some sort of program and see where it goes. I'm at the stage of just decided what approach I want to go. So i've done some initial research and I'm open to discussion and listening to what other users believe is the best way to go but I'm currently leading toward Rogain foam for growth, Revivogen for DHT inhibitors and Nizoral. What I am planning on doing is Shower using Nizoral, and apply both Revivogen and Rogaine but i'm not sure if I need both so I'm looking for some guidance in this area. I'm also very open to other discussions as to products.
Any assistance would be amazing!!
Thanks!!!

Revivogen and Nizoral are both close to useless (if not completely useless). Minoxidil is able to work as a growth stimulant, but it doesn't interfere with the underlying balding process and will not hold on to your hair for more than a few years (five years seems to be the maximum). I know this probably isn't what you want to hear, but if you want to save your hair long-term, you will need to use Finasteride (or Dutasteride) despite the risks. Nothing else that's currently available works anything like as well.

Seems a little like blind faith to me. Sure, we may not have anything to worry about but all those clinical trials were 6 months to a year. Who knows what kind of health risks inhibiting DHT for 15-20 years can cause. We just don't know. I'd certainly rather be as safe as possible and not touch type I and III and 5ar if we don't have to.

I agree. It is much better not to touch type I and III if possible, especially considering that type I has been found to be present in the brain tissue and that type III has been shown to have a critical function in cell metabolism.

Unfortunately it's probably just not worth the money to optimize finasteride and re-market it when it's already "good enough" in most cases. So I doubt we'll ever see an efficient hair loss DHT inhibitor that only targets type II.

Well, if the molecular structure of finasteride was somehow changed to make it only target type II, it would then not be Finasteride anymore but a new drug. I agree that it is highly unlikely that a type II specific inhibitor will ever be developed at this stage. The public interest is now in discovering other forms of treatments that don't remove any of our internal DHT.

if it aint finasteride, you cant win.

Indeed.

actually, we do know, check out the study of people who took finasteride for 18 years and had no health problems or random mishaps happen compared to placebo, same amount of deaths occurred in each respective group. Finasteride has been around for 23 years, has been handling lawsuits for pfs, id say about 10-13. It doesnt get worst than what we know now.

I wasn't aware that there was an 18-year study on Finasteride side-effects. Who carried out this research, and how many participants were there? I'd like to read it if you are able to provide me with a link to it.