Ok, dustateride was not the miracle we expected, whats next?

[Bryan]

People are always talking about becoming "immune" to finasteride, or developing a "tolerance" to it, or whatever. But I've read lots of studies on that drug, and I've never seen one whit of evidence for such an effect. I've never even seen any hints or suggestions from doctors or researchers that such a thing might occur.

Bryan

 

[HARM1]

People are always talking about becoming "immune" to finasteride, or developing a "tolerance" to it, or whatever. But I've read lots of studies on that drug, and I've never seen one whit of evidence for such an effect. I've never even seen any hints or suggestions from doctors or researchers that such a thing might occur.

Bryan

Why do those with only type 1 never go bald, or do they and a much slower rate? this is something that needs to be cheaked. CAN BE:
1) DHT created by 1 is different then type 2 DHT
2)type 1 TAKES MORE TIME TO MAKE dht
3) type 1 is found in a much smaller quantity( misspelled) in the scalp or body.

I DO NOT understand why put a type 1 inhibitor if it is nit really needed. inhibition of only type 2 coukd cut down side effects alot. Any OFFICIAL ANSWER TO THIS? maybe they don't know how to inhibit only 1 kind.
and btw WHICH DRUG INHIBITS TYPE 2 BEST?

 

[Apoc]

People are always talking about becoming "immune" to finasteride, or developing a "tolerance" to it, or whatever. But I've read lots of studies on that drug, and I've never seen one whit of evidence for such an effect. I've never even seen any hints or suggestions from doctors or researchers that such a thing might occur.

Bryan

They also didn't explain why Propecia works for some and not others. Now that would be a matter worth looking into.

 

[Bryan]

Why do those with only type 1 never go bald, or do they and a much slower rate? this is something that needs to be cheaked. CAN BE:
1) DHT created by 1 is different then type 2 DHT
2)type 1 TAKES MORE TIME TO MAKE dht
3) type 1 is found in a much smaller quantity( misspelled) in the scalp or body.

You left out a fourth possibility, which is the correct answer:

4) The hair follicle dermal papilla (the "control center" of the follicle) contains predominantly the type 2 enzyme, not type 1.

I DO NOT understand why put a type 1 inhibitor if it is nit really needed. inhibition of only type 2 coukd cut down side effects alot. Any OFFICIAL ANSWER TO THIS? maybe they don't know how to inhibit only 1 kind.

There are specific inhibitors for both types. Finasteride inhibits almost exclusively the type 2 enzyme (it does have a very slight effect against type 1). Merck's experimental drug MK386 inhibits the type 1 enzyme exclusively. It's even more specific for type 1 than finasteride is specific for type 2.

Dutasteride's somewhat greater effectiveness for balding compared to finasteride is probably due mostly to its more complete inhibition of the type 2 enzyme, in my opinion.

and btw WHICH DRUG INHIBITS TYPE 2 BEST?

Dutasteride. At the recommended dose, dutasteride inhibits around 98% to 99% of the type 2 enzyme. Proscar inhibits it by about 90%. Propecia, somewhat less than that.

Bryan

 

[Aplunk1]

Where can I find information about MK386?

Do you what it was used for and if there were any serious side effects?

 

[CCS]

that new drug would be interesting for experiments. i think it will not cure hair loss. unfortunately, it will be hard to know if it helped slow hairloss if the type ii in the follicle prevented it from stopping it.

my question is, is 75% or 99% done by the typeII in the follicle, and if it is 75%, will inhibitting the other 25% from typeI be of much benifit?

 

[CCS]

I'm well aware that finasteride will always inhibit type2. that is only obvious. what i'm wondering though is will the cells every smarten up over the years and start producing more type2 in response to the lower levels? and if so, will they levels stay high for years after someone quits? or does propecia "stop working" for some people after 3-6 years (i'm talking sudden fall outs) because those low levels finally caught up to them and at a certain point the scales just tipped? Or did these men just grow more receptors over the years?

So i'm wondering if 5ar2 production rates and receptor numbers change over the years and if propecia can alter any of these numbers. I did read that some androgen cause the androgen receptor to just mutate so that it responds to a different chemical.

 

[CCS]

hypothetically, with topical dutasteride...

lets suppose my topical dutasteride gets absorbed and knocks at all the type 1 and 2 5ar in my scalp and follicles and goes to the body and diluted enough not hurt other type1 sources. what would happen to my scalp? i heard my sebacious glands might shrink. could this cause any damage or other problems?

 

[Felk]

Where can I find information about MK386?

Do you what it was used for and if there were any serious side effects?

Yes indeed, I'd love to know that as well. Intriguing

 

[HARM1]

Why do those with only type 1 never go bald, or do they and a much slower rate? this is something that needs to be cheaked. CAN BE:
1) DHT created by 1 is different then type 2 DHT
2)type 1 TAKES MORE TIME TO MAKE dht
3) type 1 is found in a much smaller quantity( misspelled) in the scalp or body.

You left out a fourth possibility, which is the correct answer:

4) The hair follicle dermal papilla (the "control center" of the follicle) contains predominantly the type 2 enzyme, not type 1.

I DO NOT understand why put a type 1 inhibitor if it is nit really needed. inhibition of only type 2 coukd cut down side effects alot. Any OFFICIAL ANSWER TO THIS? maybe they don't know how to inhibit only 1 kind.

There are specific inhibitors for both types. Finasteride inhibits almost exclusively the type 2 enzyme (it does have a very slight effect against type 1). Merck's experimental drug MK386 inhibits the type 1 enzyme exclusively. It's even more specific for type 1 than finasteride is specific for type 2.

Dutasteride's somewhat greater effectiveness for balding compared to finasteride is probably due mostly to its more complete inhibition of the type 2 enzyme, in my opinion.

and btw WHICH DRUG INHIBITS TYPE 2 BEST?

Dutasteride. At the recommended dose, dutasteride inhibits around 98% to 99% of the type 2 enzyme. Proscar inhibits it by about 90%. Propecia, somewhat less than that.

Bryan

So why not use just a type 1 inhibitor? don't you think it coukd be good for sex drive?

is it a fact that those with just type 1 will never grow bald because DHT does not get to their folicule?

FOLICULES MAKE THEIR OWN dht? SO why do they need a receptor? the receptor is located on the folicule's not in it, no ? so the folicules makes DHT, then sends it out, and brings it back in? Or is the receptor an iin- cell receptor that recepts the DHT from inside?

From where do you obtain your knowledge, are you a student of some sort?

 

[powersam]

i thought i read about that MK386 a while back and they found it had no real effect on hair loss. which goes a huge way to backing up bryans assertion that type 2 is by far and away the most significant to hair loss.

not that the pseudohermaphrodites hadnt done that already.

why is it that i can never remember where the E goes in pseudo. maybe theres a rule, like U before E except after P.

 

[Bryan]

Where can I find information about MK386?

Do you what it was used for and if there were any serious side effects?

I know of four studies on MK386. I have all of them, except for the third one below, which was only published as an abstract. There may be some others that I don't know about. Here's a brief description of them. If you want a full citation for each one, I can dig them up for you.

1) The original study by Merck which came out several years ago, shortly after MK386 was first discovered. They just provided the basic technical information about its structure. If there was any human testing at all (it's been a few years since I last read it), it was just some very preliminary stuff like giving a few doses to volunteers, then testing their blood levels of DHT afterwards. It obviously was not tested for any medical condition.

2) A year or two after that first paper, they published a second one which tested MK386 alone and in combination with finasteride in human volunteers. Not surprisingly, they found that taking the two drugs together resulted in roughly dutasteride-like levels of DHT reduction in the blood. Again, there were just standard laboratory tests. The drugs weren't tested for any medical conditions.

3) MK386 was eventually tested for male pattern baldness in the stumptailed macaque model. No noticeable difference in hair weights was achieved with the drug after a pretty good length of time.

4) The most recent study was just a year or two ago, and it was tested on acne in humans (at least, I'm pretty sure it was MK386...they referred to it by another name, but it was almost certainly MK386). It had no apparent effect on acne.

Bryan

 

[Bryan]

my question is, is 75% or 99% done by the typeII in the follicle, and if it is 75%, will inhibitting the other 25% from typeI be of much benifit?

Thre was an excellent study by Happle and Hoffman a while back. They tested both finasteride and MK386 on the dermal papillae of freshly-dissected human hair follicles, and found that MK386 had no consistent effect at all in inhibiting 5a-reductase activity, but even just 10 nM of finasteride inhibited it completely. I think the conclusion is obvious.

Bryan

 

[Bryan]

I'm well aware that finasteride will always inhibit type2. that is only obvious. what i'm wondering though is will the cells every smarten up over the years and start producing more type2 in response to the lower levels? and if so, will they levels stay high for years after someone quits? or does propecia "stop working" for some people after 3-6 years (i'm talking sudden fall outs) because those low levels finally caught up to them and at a certain point the scales just tipped? Or did these men just grow more receptors over the years?

Five-year studies of Proscar for BPH have shown no reduction of effectiveness. I don't know of any evidence that people develop any kind of "tolerance" to finasteride.

So i'm wondering if 5ar2 production rates and receptor numbers change over the years and if propecia can alter any of these numbers.

Well, Sawaya claims to have found that infamous "intense upregulation" of androgen receptors in Propecia users, but that's obviously something that happens quite quickly after starting the drug. It's just a natural cellular response.

Bryan

 

[Bryan]

Re: hypothetically, with topical dutasteride...

lets suppose my topical dutasteride gets absorbed and knocks at all the type 1 and 2 5ar in my scalp and follicles and goes to the body and diluted enough not hurt other type1 sources. what would happen to my scalp? i heard my sebacious glands might shrink.

It seems reasonable to expect them to shrink, but I've been waiting in vain ever since dutasteride came out for them to test its effect on sebaceous glands. Keep in mind that study I mentioned before about how MK386 had no effect on the course of acne (although they didn't actually test its effect on sebaceous glands or sebum production, just the overall effect on acne).

could this cause any damage or other problems?

I don't see how it could. Sebaceous glands seem to be useless structures, anyway.

Bryan

 

[Bryan]

So why not use just a type 1 inhibitor?

For hairloss?? Because it wouldn't work, as I've been explaining.

is it a fact that those with just type 1 will never grow bald because DHT does not get to their folicule?

Yes.

FOLICULES MAKE THEIR OWN dht?

Sure.

SO why do they need a receptor?

That's how cells REACT to androgens: through androgen receptors.

First androgens bind to androgen receptors, then the androgen/androgen receptor complex enters the nucleus of the cell, where it influences androgen-sensitive gene expression.

the receptor is located on the folicule's not in it, no ?

Androgen receptors are proteins INSIDE the cell. They're in the cell's cytoplasm.

so the folicules makes DHT, then sends it out, and brings it back in? Or is the receptor an iin- cell receptor that recepts the DHT from inside?

Well, it's POSSIBLE for a molecule of DHT to leave the cell and then come back in, but that obviously happens only a small percentage of the time. The majority of the time, DHT molecules are synthesized within the cell by 5a-reductase, and then bind to androgen receptors right there within the same cell afterwards.

From where do you obtain your knowledge, are you a student of some sort?

Nope. I just read a lot about it. I have literally HUNDREDS of medical journal studies having to do with hairloss (directly or indirectly) sitting here around me. Studies on minoxidil, finasteride, dutasteride, general physiology, hair follicle physiology, steroid endocrinology, everything you can think of conceivably having to do with hairloss.

No, I don't have a life!

Bryan

 

[HARM1]

Bryan I ment why not inhibit only type 2? That would help with the other uses DHT has, withour dameging the hair. is it beacuse of growth in type 1 when usind DHT inhibitors? such growth that those with genetic lack of type 2 DO NOT get, and thats why type 1 never gets them bald?

And you sould lear biology, what do ou do in life? ou soung like a great DUDE, THX for the help.

Another thing, I am 18 teample reccecion, What do you say i need to do ? I think finasteride+AZELIC AND MINOXI - APART NOT DR.LEE's, and another dht inhibitor like revivogen, what do you think ?

If propecia brinbgs growth in 5AR enzymes or in DHT receptors in thy body, If I were to drop propecia, I could be in bigger risk for cancer caused by DHT since biiger amount would be recepted by my body, and also i would bald even faster. Is this true, and what do you think ?

THX ALOT

 

[Bryan]

Bryan I ment why not inhibit only type 2?

I agree with you. Inhibiting only type 2 is more medically conservative. Inhibiting type 1 is more of a Journey Into the Unknown.

That would help with the other uses DHT has, withour dameging the hair. is it beacuse of growth in type 1 when usind DHT inhibitors? such growth that those with genetic lack of type 2 DO NOT get, and thats why type 1 never gets them bald?

I'm not sure I understand the question. Type 1 doesn't make them go bald because type 2 is the predominant form in hair follicle dermal papillae.

Another thing, I am 18 teample reccecion, What do you say i need to do ? I think finasteride+AZELIC AND MINOXI - APART NOT DR.LEE's, and another dht inhibitor like revivogen, what do you think ?

As you may know, I'm not a big fan of azelaic acid! :wink: But just use a good combination of the various treatments that you read about on these forums, and you'll be doing the best you can.

If propecia brinbgs growth in 5AR enzymes or in DHT receptors in thy body, If I were to drop propecia, I could be in bigger risk for cancer caused by DHT since biiger amount would be recepted by my body, and also i would bald even faster. Is this true, and what do you think ?

Don't worry about cancer at YOUR young age. However, if you decide to quit taking Propecia after a while, I recommend that you slowly taper-off the drug.

Bryan

 

[HARM1]

Bryan I ment why not inhibit only type 2?

So is THERE no official answer? Can we ask a professional, or merc ?
What I ment to ask is this: Could the reason hair loss is still battled against with type 1 inhibition even tough people with just type 1 never grow bald, be the folowing: Using DHT inhibitors such as propecia increases DHT levels by more DHT receptors in the body, and more prodacrion of 5ARD--> This brings up 5AR1 to a higher level than it is found in those people with a genetic lack of type 2, and in the high numbers it gets to CAN result in harming the hair. DO you think this could be the reason? OR no matter how much 5ARD1 will climb up to it won't get to the folicules?

Why do you dislike AZELIC? I use it on my zits and i see great resaults. I use 20 precent for my zits, What is the danger using 20 precent on my scalp? I tried it and nothing bad had happend. Zits are also caused be type 2 5ar like, that was proven when they just tried a type 1 inhibitor for acne.


What does it have to do with age, and anyway think of it as a general question for all users. Is it a fact that inhibiton of DHT raises DHT receptors in the body and also the amount of 5AR? And is it knows if those paremeters come back to nornal when propecia is stopped? IF NOT it could end in cancer and rapid hair loss WHEN PROPECIA IS DROOPED.ANybody ever adress this important issue?

Sory for buging THX alot: I am 18 and my duck can still grow, will propecia hult growth?

LAST THING: What do you use friend?

 

[HARM1]

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