If DHT IS the cause of YOUR hairloss...

[misterium]

If DHT for a fact IS the cause of hairloss for some of us.. and for conversation sake let's just say my hairloss is a result of DHT, then why would finasteride NOT block my DHT?

In other words, how come some people 'do not respond' to finasteride? Why would finasteride block one person's DHT and help their follicles, but not work to block another person's DHT?

.. If you have male pattern baldness, and you use finasteride and do not respond to it, does this mean your male pattern baldness is not caused by DHT? Does this mean that male pattern baldness for that person is caused by something other than DHT?

Please explain to me.

 

[Radio]

People have differing levels of all hormones, DHT (and by association testosterone) will be higher in some than in others.

I believe normal testosterone levels in a human male are around 400 to 750 ng/dl, so it would be considered 'normal' (and presumably common) for one person to have almost twice the level of a hormone when measured against another person.

You also might be a gay.

 

[socks]

Ummm that is one possibility Radio


To understand this issue a little better Misterium it would help to understand a little more about androgenetic alopecia as well as Finasteride. Allow me to help.


First off, the main known cause of androgenetic alopecia is the potent androgen DHT. Free roaming testosterone infuses into hair follicles cells from the bloodstream. The 5ar enzyme then converts the testosterone into DHT. The DHT binds to the androgen receptor which then signals the cell nucleus of the presents of androgens. The cell nucleus then "expresses" certain genetic code that has a negative effect on the growth of the hair follicle; The hair follicle atrophies and, eventually, dies permanently.

Now, there are *TWO enzymes that convert testosterone into DHT. The type I 5ar and the type II 5ar. The type II 5ar is thought to be the more "important" of the two enzymes as it is the type II 5ar that is present inside the hair follicle cells. DHT is an "unstable" androgen and breaks down rapidly. Therefore the damage that occurs from DHT does not come from DHT in the blood infusing into the hair follicle or DHT on the scalp excreted via sebum. Damage from DHT comes from the DHT that has been formed inside the hair follicle cell. It is important to note that specific type I 5ar inhibitors (such as Merck's MK386) was shown to have no effect on androgenetic alopecia. Furthermore, pseudohermaphrodites (men born without the ability to make the type II 5ar but can make the type I 5ar) never go bald!


So, now we established the main known cause of androgenetic alopecia, how it creates atrophy of the hair, and what specific enzyme is mainly responsible for all the DHT production inside the hair follicle cell. Lets talk about Finasteride


Finasteride is a specific type II 5ar inhibitor with no affinity for either the type I 5ar nor the ARs (androgen receptors). Finasteride, when taken in doses of 1mg) reduces the type II 5ar by about 80% and lowers overall blood serum levels of DHT levels by 65% (the difference is from the type I 5ar). DHT in the scalp in lowered slightly less at about 55% - 60%. This reduction brings the production of DHT to near castration levels (without all the nasty side-effects of not having your testicles)!. However, Finasteride does increase both testosterone and estradiol levels by about 15%. Why? Because by stopping testosterone from being converted into DHT more testosterone is left unconverted and free to roam your body. Some of this extra testosterone is then converted into estradiol (an estrogen) by the aromatase enzyme. This results in about a 15% increase in both the latter mentioned hormones from baseline.

Now, as I explained in the first section on androgenetic alopecia, androgenetic alopecia is a result of the potent androgen DHT being created and binding to the ARs inside the hair follicle cell. The more "sensitive" your ARs are to androgens the less DHT needed to cause hair to atrophy. So, since finasteride isnt stopping all the DHT from being formed inside the hair follicle cell and since other androgens such as testosterone (which is now elevated from finasteride) can also contribute to the androgenic response inside the hair follicle cells, complete cessation of androgenetic alopecia is not always achieved depending on the individual.


Now, there may be other variables as well. However, my fingers hurt so I'll leave it at that.

 

[Radio]

the presents of androgens

nobody gets left out at chritmas. :fun: resent:

 

[chewbaca]

If DHT for a fact IS the cause of hairloss for some of us.. and for conversation sake let's just say my hairloss is a result of DHT, then why would finasteride NOT block my DHT?

In other words, how come some people 'do not respond' to finasteride? Why would finasteride block one person's DHT and help their follicles, but not work to block another person's DHT?

.. If you have male pattern baldness, and you use finasteride and do not respond to it, does this mean your male pattern baldness is not caused by DHT? Does this mean that male pattern baldness for that person is caused by something other than DHT?

Please explain to me.

There is also something known as DHT senstivity...if u are genetically programmed to be sensitive to even a small amount, the blocking 80% DHT whic propecia will not work..U need to block 100% ...this is the reaon why propecia does not work for some people....

 

[Guest]

I think there are also other reasons for male pattern baldness that we don't yet fully understand. Yes, I agree that DHT may be the main culprit but I also feel that there are other factors at play. I think diet plays a big role.

 

[Bryan]

However, Finasteride does increase both testosterone and estradiol levels by about 15%. Why? Because by stopping testosterone from being converted into DHT more testosterone is left unconverted and free to roam your body.

Socks, people have been saying that on hairloss sites for YEARS, but I don't think that's an accurate explanation. What I believe is the correct explanation for the testosterone increase that usually accompanies finasteride usage is that the brain sees the sharp decline in DHT which it then interprets as a decline in overall androgenic stimulation, so it releases more LH (luteinizing hormone) as a signal to the testes to increase the production of testosterone.

If the explanation you proposed (and everybody else always assumes that same thing) were correct, LH levels would actually go DOWN, not UP.

Bryan

 

[Bryan]

There is also something known as DHT senstivity...if u are genetically programmed to be sensitive to even a small amount, the blocking 80% DHT whic propecia will not work..U need to block 100% ...this is the reaon why propecia does not work for some people....

There is yet another possible factor, too, which people always overlook: a fundamentally different response to DHT and other androgens. Didn't you ever consider that maybe some people who just never ever experience male pattern baldness have scalp hair follicles that have more of the characteristics of BODY hair follicles?? Think about this simple question: why does DHT make beard hair (for example) grow nice and big and strong? It's because of a different RESPONSE to androgens that beard follicles have. And maybe people who are highly resistant to balding have scalp hair follicles with characteristics that are more along those same lines.

Bryan

 

[Radio]

Bryan, anything to say on the 'gay' thing?

 

[socks]

However, Finasteride does increase both testosterone and estradiol levels by about 15%. Why? Because by stopping testosterone from being converted into DHT more testosterone is left unconverted and free to roam your body.

Socks, people have been saying that on hairloss sites for YEARS, but I don't think that's an accurate explanation. What I believe is the correct explanation for the testosterone increase that usually accompanies finasteride usage is that the brain sees the sharp decline in DHT which it then interprets as a decline in overall androgenic stimulation, so it releases more LH (luteinizing hormone) as a signal to the testes to increase the production of testosterone.

Bryan,

That is an interesting insight! To me, and maybe I'm wrong, but it didnt make sense that testosterone and estradiol would both increase by 15%... You would think testosterone would spike higher... So, do you think it is possible that the spike of testosterone is higher then 15% due to both the inhibition of the 5ar and the body's only "compensating response" but that number is then dragged down as some of that extra testosterone is converted into estradiol (leveling out at a 15%/15%)?


Regardless, I would think by reducing DHT by 60% overall there should be a measurable and significant increase in free testosterone asides from the body's own "compensating response" no? Not that the later doesnt play a role but do you feel that the later is the most responsible party for the testosterone increase? If so, what impact do you feel the reduction of the 5ar has?

 

[Dinzy]

Could it also be possible that DHT binds to the follicle while it is still healthy and producing a good hair and causes it to atrophy over its next growth cycle? This could result in an apparent lack of effectiveness of finasteride over the first year or two.

 

[Britannia]

The incidence of Propecia failing to work is reported by Merck to be only 17%. I beleive the reason Propecia fails in this small percentage is due to the pharmadynamics of the drug as opposed to the pharmakinetics. For those of you who are unsure about the difference between the two, pharmadynamics refers to the absorption, metabolism and distribution of the drug throughout the body. Some people (very few - estimates vary between 7%-19%) simply cannot absorb and have benefits from ANY medication taken orally. This is because either the drug is not being absorbed or broken down or distributed correctly by the body. Because the incidence of Propecia not working is only 17% (as reported by Merck) I believe that the failure of Propecia in these patients is due to pharmadynamics and not the action of the drug itself (pharmakinetics).

 

[Bryan]

That is an interesting insight! To me, and maybe I'm wrong, but it didnt make sense that testosterone and estradiol would both increase by 15%...

Why not? Since estrogen is produced directly from testosterone, and assuming that the supply of testosterone is the limiting factor in estrogen production (I think that's a quite reasonable assumption), then one would expect testosterone and estrogen to parallel each other rather closely. If testosterone were to double for some weird reason, then estrogen would also likely double. If it were to triple, then so would estrogen (in theory, of course)...

BTW, I believe the accepted figure for the testosterone increase during finasteride usage is more like 10%, not 15%.

You would think testosterone would spike higher...

Why?

So, do you think it is possible that the spike of testosterone is higher then 15% due to both the inhibition of the 5ar and the body's only "compensating response" but that number is then dragged down as some of that extra testosterone is converted into estradiol (leveling out at a 15%/15%)?

No, I personally think it's just a direct function of the "compensating response". Here's a statement right out of the PDR (Physician's Desk Reference) in the section on Proscar, meaning that the following is the accepted position of the FDA:

"...Increases of about 10% were observed in luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in patients receiving Proscar, but levels remained within the normal range."

In other words, I believe that the simplest explanation here (as prescribed by Ockam's Razor) is the correct one: testosterone rises the same amount as LH, which seems to clearly indicate that the brain is trying to re-establish the missing androgenic stimulation caused by the relative lack of DHT.

Regardless, I would think by reducing DHT by 60% overall there should be a measurable and significant increase in free testosterone asides from the body's own "compensating response" no? Not that the later doesnt play a role but do you feel that the later is the most responsible party for the testosterone increase?

Absolutely! Socks, think about this for just a moment: the production of androgens (testosterone, specifically) is under TIGHT control in the body! The brain has T production on a very short leash. The brain is the quarterback! It calls the shots! If you were to inject testosterone into your bloodstream, resulting in higher levels than what the brain expects to see, I guarantee you that your LH level will go DOWN in response, in an effort to "normalize" that T level. The fact that LH and FSH levels go UP rather than DOWN when you take finasteride seems to me to be a strong indication that the brain is making a deliberate effort to RAISE testosterone levels. It's not just an inconsequential and coincidental side-effect of having less T metabolized into DHT. In my humble opinion, of course! :agree:

Bryan

 

[Radio]

as prescribed by Ockam's Razor

Bryan, do you know of any online sites where I could get one of these razors without a prescription ?



PS. 'Ockham' or 'Occam' is good but not 'Ockam'.

 

[sam-]

Ummm that is one possibility Radio


To understand this issue a little better Misterium it would help to understand a little more about androgenetic alopecia as well as Finasteride. Allow me to help.


First off, the main known cause of androgenetic alopecia is the potent androgen DHT. Free roaming testosterone infuses into hair follicles cells from the bloodstream. The 5ar enzyme then converts the testosterone into DHT. The DHT binds to the androgen receptor which then signals the cell nucleus of the presents of androgens. The cell nucleus then "expresses" certain genetic code that has a negative effect on the growth of the hair follicle; The hair follicle atrophies and, eventually, dies permanently.

Now, there are *TWO enzymes that convert testosterone into DHT. The type I 5ar and the type II 5ar. The type II 5ar is thought to be the more "important" of the two enzymes as it is the type II 5ar that is present inside the hair follicle cells. DHT is an "unstable" androgen and breaks down rapidly. Therefore the damage that occurs from DHT does not come from DHT in the blood infusing into the hair follicle or DHT on the scalp excreted via sebum. Damage from DHT comes from the DHT that has been formed inside the hair follicle cell. It is important to note that specific type I 5ar inhibitors (such as Merck's MK386) was shown to have no effect on androgenetic alopecia. Furthermore, pseudohermaphrodites (men born without the ability to make the type II 5ar but can make the type I 5ar) never go bald!


So, now we established the main known cause of androgenetic alopecia, how it creates atrophy of the hair, and what specific enzyme is mainly responsible for all the DHT production inside the hair follicle cell. Lets talk about Finasteride


Finasteride is a specific type II 5ar inhibitor with no affinity for either the type I 5ar nor the ARs (androgen receptors). Finasteride, when taken in doses of 1mg) reduces the type II 5ar by about 80% and lowers overall blood serum levels of DHT levels by 65% (the difference is from the type I 5ar). DHT in the scalp in lowered slightly less at about 55% - 60%. This reduction brings the production of DHT to near castration levels (without all the nasty side-effects of not having your testicles)!. However, Finasteride does increase both testosterone and estradiol levels by about 15%. Why? Because by stopping testosterone from being converted into DHT more testosterone is left unconverted and free to roam your body. Some of this extra testosterone is then converted into estradiol (an estrogen) by the aromatase enzyme. This results in about a 15% increase in both the latter mentioned hormones from baseline.

Now, as I explained in the first section on androgenetic alopecia, androgenetic alopecia is a result of the potent androgen DHT being created and binding to the ARs inside the hair follicle cell. The more "sensitive" your ARs are to androgens the less DHT needed to cause hair to atrophy. So, since finasteride isnt stopping all the DHT from being formed inside the hair follicle cell and since other androgens such as testosterone (which is now elevated from finasteride) can also contribute to the androgenic response inside the hair follicle cells, complete cessation of androgenetic alopecia is not always achieved depending on the individual.


Now, there may be other variables as well. However, my fingers hurt so I'll leave it at that.

WOW, what an explanation, you have explained what I’ve been looking for, thank you very much for this knowledgeable excellent explanation. :thumbs_up: :thumbs_up: :thumbs_up:

 

[socks]

That is an interesting insight! To me, and maybe I'm wrong, but it didnt make sense that testosterone and estradiol would both increase by 15%...

Why not? Since estrogen is produced directly from testosterone, and assuming that the supply of testosterone is the limiting factor in estrogen production (I think that's a quite reasonable assumption), then one would expect testosterone and estrogen to parallel each other rather closely. If testosterone were to double for some weird reason, then estrogen would also likely double. If it were to triple, then so would estrogen (in theory, of course)...

Well the reason I thought it didnt make sense for estradiol and testosterone to increase by the exact same amount is that as testosterone is converted into estrogen via the aromatase enzyme you would think testosterone would decrease.

So if you had "x" testosterone and "x" was converted into estrogen then estrogen should go up and testosterone go down. However, as you later mention about the brain keeping tight "watch" on testosterone levels could it be that as testosterone dips from the aromatase enzyme the brain just ups the levels of testosterone back up? Or do I have things confused

So, do you think it is possible that the spike of testosterone is higher then 15% due to both the inhibition of the 5ar and the body's only "compensating response" but that number is then dragged down as some of that extra testosterone is converted into estradiol (leveling out at a 15%/15%)?

Absolutely! Socks, think about this for just a moment: the production of androgens (testosterone, specifically) is under TIGHT control in the body! The brain has T production on a very short leash. The brain is the quarterback! It calls the shots! If you were to inject testosterone into your bloodstream, resulting in higher levels than what the brain expects to see, I guarantee you that your LH level will go DOWN in response, in an effort to "normalize" that T level. The fact that LH and FSH levels go UP rather than DOWN when you take finasteride seems to me to be a strong indication that the brain is making a deliberate effort to RAISE testosterone levels. It's not just an inconsequential and coincidental side-effect of having less T metabolized into DHT. In my humble opinion, of course! :agree:

Ok, to see if I got this right:

Your brain closely monitors testosterone levels. Finasteride does not lower testosterone levels so testosterone levels should still be within "normal" range. However, DHT levels *do* drop and in response the brain increases LH/FSH thus raising testosterone levels 10% above baseline.

Ok, if that is correct I have two questions:

1. Are you saying the inhibition of testosterone to DHT has no significant effect on testosterone levels?

2. If your brain is increasing testosterone production by 10% in response to lower androgen levels, why does your brain stop at 10% when you would still be running a significant androgen deficit! If DHT levels go down 60% overall how is 10% an "adequate" response from the brain?

 

[triton2]

That is an interesting insight! To me, and maybe I'm wrong, but it didnt make sense that testosterone and estradiol would both increase by 15%...

Why not? Since estrogen is produced directly from testosterone, and assuming that the supply of testosterone is the limiting factor in estrogen production (I think that's a quite reasonable assumption), then one would expect testosterone and estrogen to parallel each other rather closely. If testosterone were to double for some weird reason, then estrogen would also likely double. If it were to triple, then so would estrogen (in theory, of course)...

I think that, when using 5AR blockers, the ratio of E/T elevation is probably higher than 1, because another reason (more important than T elevation from my point of view) that accounts for the raise in estrogen levels is the fact that DHT antagonizes aromatase enzyme, so if you block DHT, there is more free aromatase and ergo, for a given level of T, E levels will tend to be higher.

 

[triton2]

2. If your brain is increasing testosterone production by 10% in response to lower androgen levels, why does your brain stop at 10% when you would still be running a significant androgen deficit! If DHT levels go down 60% overall how is 10% an "adequate" response from the brain?

Let's put it this way:

1) Blocking DHT 'frees' aromatase enzyme, which implies an elevation in E/T ratio.

2) DHT antagonizes the ER, so, for a given level of E, their physiologic effect is going to be bigger.

3) ER agonism downregulates the HPTA through the ER present at the hypothalamus. The more estrogens, the more supression there will be (ever wondered why aromatase blockers tend to produce sharp raises in E levels? )

 

[Bryan]

Well the reason I thought it didnt make sense for estradiol and testosterone to increase by the exact same amount is that as testosterone is converted into estrogen via the aromatase enzyme you would think testosterone would decrease.

Well, you have a point there, of course. It would be interesting to know what approximate percentage of testosterone gets converted to estrogen in a typical, healthy young male. That information is probably available somewhere...

So if you had "x" testosterone and "x" was converted into estrogen then estrogen should go up and testosterone go down. However, as you later mention about the brain keeping tight "watch" on testosterone levels could it be that as testosterone dips from the aromatase enzyme the brain just ups the levels of testosterone back up? Or do I have things confused

Well, don't forget that estrogen is also a player in the feedback loop that controls androgen production, along with testosterone and DHT. In fact, it may even be the MAIN player! So any combination of testosterone and estrogen will help inhibit the release of gonadotropins by the brain.

Ok, to see if I got this right:

Your brain closely monitors testosterone levels. Finasteride does not lower testosterone levels so testosterone levels should still be within "normal" range. However, DHT levels *do* drop and in response the brain increases LH/FSH thus raising testosterone levels 10% above baseline.

Ok, if that is correct I have two questions:

1. Are you saying the inhibition of testosterone to DHT has no significant effect on testosterone levels?

Sure it does...it raises them by about 10% on average (that may or may not be "significant", depending on your point of view), but not by the mechanism that everyone seems to assume! :wink:

2. If your brain is increasing testosterone production by 10% in response to lower androgen levels, why does your brain stop at 10% when you would still be running a significant androgen deficit! If DHT levels go down 60% overall how is 10% an "adequate" response from the brain?

Those are all different hormones (testosterone, DHT, and estrogen) with different characteristics and different LEVELS within the body. And they don't necessarily have equal potencies at inhibiting the release of gonadotropins by the brain. For example, keep in mind that serum levels of DHT typically are on the order of only about 1/10 that of testosterone itself! Is it any wonder that even if you reduce that already small amount of DHT by another 60%, it won't really have THAT much of an effect at raising gonadotropins from the brain? See what I'm saying?

Bryan

 

[triton2]

Well, you have a point there, of course. It would be interesting to know what approximate percentage of testosterone gets converted to estrogen in a typical, healthy young male.

An amount too tiny (<1%) to have any significant impact in T levels. The only impact it has is through HPTA upregulation.

That information is probably available somewhere...

Yes!

http://www.endotext.com/male/male2/male2.htm



By the way, when you block estrogen (by means of arimidex for instance), there seems to be a pretty strong T elevation (look at the figure). I wonder to what extent those people who are blocking aromatase in an attempt to prevent/treat gynecomastia are rendering their 5AR blocker useless through the ~50% ("Both doses were associated with comparable suppression of E2 (50%), with parallel increases in testosterone and free testosterone") increase in T levels.

http://jcem.endojournals.org/cgi/content/full/85/7/2370