Back to the roots: Causes and effects of elevated DHT

[karankaran]

As a nanotechnology researcher, some of you here give me hope that not all is lost and science is still alive. Your efforts in understanding science behind male pattern baldness or your insistence on putting scientific evidence and reasoning over pseudo science is highly encouraging. But it is also true that we are in a minority. A poll today said that only 20% of americans believe in big bang and when it comes to 7th century world view vs science, the 7th century world view always wins. It is truly discouraging.

 

[Helios]

As a nanotechnology researcher, some of you here give me hope that not all is lost and science is still alive. Your efforts in understanding science behind male pattern baldness or your insistence on putting scientific evidence and reasoning over pseudo science is highly encouraging. But it is also true that we are in a minority. A poll today said that only 20% of americans believe in big bang and when it comes to 7th century world view vs science, the 7th century world view always wins. It is truly discouraging.

Religion is one of the main things that keep people dumb. Think i read somewhere that a high % of people in America also think dinosaurs and people used to coexist. :doh:

If only the amount of money that goes to religion was invested in science, we would all be happy campers with full heads of hair. Sadly large amounts of money are pumped into someone's imaginary friend.

 

[karankaran]

Religion is one of the main things that keep people dumb. Think i read somewhere that a high % of people in America also think dinosaurs and people used to coexist. :doh:

If only the amount of money that goes to religion was invested in science, we would all be happy campers with full heads of hair. Sadly large amounts of money are pumped into someone's imaginary friend.

Yes, sarah palin believes that dinos and humans lived together and when matt damon made fun of it, some people said they will never watch his movies again. Among a certain section in america, people who criticize dumb things are boycotted and people who take anti science stances which might endanger lives of children (read anti vacccine), are celebrated and hailed as heroes.

Anyways, before this thread becomes a discussion about something else, lets refocus it on the topic.

I think TNF-alpha 'MIGHT' (just a conjecture) have a role to play. The reason why i think so is because i read that some researchers while trying to target DKK1 now also focus on inhibiting TNF-alpha , which is upstream of DKK1. Curcumin is supposed to be a inhibitor , so is green tea. People say bio-availability is a problem but i read that bioperine , along with certain formulations , increase the bio-availability to meaningful levels. and if you take it 3-4 times a day to maintain levels through out the day, it just 'MIGHT' inhibit TNF-alpha.

Btw, there was some conjecture in HairLossTalk.com that inflammation might be a cause of elevated DHT? Any thoughts on that? and btw, i did start taking GREEN TEA+SOY, but i felt if it decreases T , it is not good and i left it and i had such a huge shed.

 

[Python]

Religion is one of the main things that keep people dumb. Think i read somewhere that a high % of people in America also think dinosaurs and people used to coexist. :doh:

If only the amount of money that goes to religion was invested in science, we would all be happy campers with full heads of hair. Sadly large amounts of money are pumped into someone's imaginary friend.

You have to remember why religion is there in the first place, it helps us cope with the fact of inevitable death.
Some scientists say that there is a section in the brain for religion, this might be the case.

I myself don't believe in religion but most regular people simply have a different brain, and it forces religion on them. Once we find life in another planet is the day all these religions will end, we're getting closer and there's nothing those churchies can do. No religion can accept life in another planet, science will win eventually.

 

[benjt]

Btw, there was some conjecture in HairLossTalk.com that inflammation might be a cause of elevated DHT? Any thoughts on that? and btw, i did start taking GREEN TEA+SOY, but i felt if it decreases T , it is not good and i left it and i had such a huge shed.

No, it is the other way around, cf. Post #57 in this thread.

And guys, if you want to talk about religion or ignorant people, do that somewhere else please. While I agree with most of your points, that is simply not the topic of this thread.

I would really appreciate if this thread does not get sidetracked into a discussion of "common misconceptions". The latter is interesting but not the topic of this extremely important thread. what I mentioned on estrogen was a quote from costarelis...
I also cited studies on the DHT <---> IGF channel.

Where? I could not find them in this thread.

 

[Python]

No, it is the other way around, cf. Post #57 in this thread.

And guys, if you want to talk about religion or ignorant people, do that somewhere else please. While I agree with most of your points, that is simply not the topic of this thread.


Where? I could not find them in this thread.

But this is the perfect place to talk about religion. Since everyone here stopped believing soon after they started losing their hair, just like me.

 

[uncomfortable man]

Science must and will be the new religion. John Travolta and Tom Cruise are watching...

 

[drgs]

My theory is early exposure to testosterone at adolescence (early blooming)

Testosterone alters gene expression involved in dopamine pathways in the midbrain substantia nigra to favor androgenic responses/more AR mRNA, this promotes conversion of T to DHT or makes you more sensitive to DHT
Pretty much forever, but this is a continuous process, but the scale at puberty at which it happens is much higher.
Anabolic steroids increase AR receptors at any age, also forever

Like late bloomers are tall, early bloomers are bald

Early puberty is also common in girls, and is induced by diet, now more so than 50 years ago

This + genetic factor

 

[benjt]

drgs, that theory actually does make a lot of sense. Many processes in the development of secondary sexual characteristics are feed-forward processes, e.g., chest hair development. As Dr. Cotsarelis explained, even follicle neogenesis only works under a sustained feed-forward process with Fgf9 and Wnt.

Do you have any papers on this, or can you provide sources related to that?

 

[Ventures]

I don not know how true is the fact that when we get older our androgen receptors - AR become more sensitive, including AR in hair follicles which determine response to androgens. But if assume AR all over the body become more sensitive, then older people would not lose their vitality, they would be masculine even in old age, and in quite good shape, and gain muscles easily - and we know that is not the case when we get older.

Maybe AR selectively increase their sensitivity in some areas (like scalp, and skin), but this is certainly not the case in other tissues like muscles ? So, I don't know how correct is a statement in old age our receptors become more aggressive and sensitive.

There is another example which disproves this in some way. Castration suppresses total androgen stimulus drastically, and even DHT and total T are decreased significantly, receptors in hair follicles of castrated men don't become more sensitive. If they would castrated person would still tend to continue to bald and loose hair slowly, and we know that's not the case. There is even another fact according to study posted by Brian, regarding that the rest of the T is produced in adrenal glands, castration suppresses T level by 90-95 % and DHT level only by 70 %. (*) So we can say supression in DHT is similar what we get using finasteride. As we know for sure castratation stops /halts male pattern baldness. So these data impose new questions:


(*) http://www.hairlosstalk.com/interac...8-DHT-levels?p=1089431&viewfull=1#post1089431


1. Why AR in castrated men because of significant reduction of all andrgens don't become so sensitive during time, so the rest of DHT circulating around (which is as mentioned before 30-10 % according to study), start to kill hair follicles ?


2. If DHT after castration is reduced by 70 % or more, which is quite the same suppresion level of DHT in finasteride (70 %) and dutasteride (90 %) users, how is it possible finasteride and dutasteride are not so effective in halting male pattern baldness as castration ?


Obviously that's probably due to a more complete suppression of androgens than just what you get with finasteride. Castration causes about the same DHT suppression as finasteride, but in the same time causes a very striking reduction of testosterone, compared to what you get with finasteride (which actually tends to go UP a little). This proves that T and other androgen hormones play huge role in Male patern baldness regarding their influence in autoimmune-response, fibrosis etc.

 

[xRedStaRx]

My theory is early exposure to testosterone at adolescence (early blooming)

Testosterone alters gene expression involved in dopamine pathways in the midbrain substantia nigra to favor androgenic responses/more AR mRNA, this promotes conversion of T to DHT or makes you more sensitive to DHT
Pretty much forever, but this is a continuous process, but the scale at puberty at which it happens is much higher.
Anabolic steroids increase AR receptors at any age, also forever

Like late bloomers are tall, early bloomers are bald

Early puberty is also common in girls, and is induced by diet, now more so than 50 years ago

This + genetic factor

This has very little to do with male pattern baldness. In fact, it's entirely irrelevant.

I don not know how true is the fact that when we get older our androgen receptors - AR become more sensitive, including AR in hair follicles which determine response to androgens. If AR all over the body become more sensitive, then older people would not lose their vitality, they would be masculine even in old age, and quite good shape, and gain muscles easily - and we know that is not the case when we get older.

Maybe AR selectively increase their sensitivity in some areas (like scalp, and skin), which is certainly not the case in other tissues like muscles ?

AR sensitivity does not increase with age, nor do androgen levels in most cases.

The thing is, male pattern baldness is very misunderstood. It is a cumulative process of androgenic miniaturization. Just like how facial hair can keep growing and sprouting in some individuals well into their 30s. It takes years of androgen exposure to fully miniaturize a hair follicle to the point of barely penetrating the scalp skin. Not to mention, your hair gets weaker as you age, naturally. This compounds the effect of androgenic alopecia, even though your androgen levels are less than that of puberty and early 20s.

Hope this helps.

- - - Updated - - -

There is another example which disproves this in some way. Castration suppresses total androgen stimulus drastically, and even DHT and total T are decreased significantly, receptors in hair follicles of castrated men don't become more sensitive. If they would castrated person would still tend to continue to bald and loose hair slowly, and we know that's not the case. There is even another fact according to study posted by Brian, regarding that the rest of the T is produced in adrenal glands, castration suppresses T level by 90-95 % and DHT level only by 70 %. (*) So we can say supression in DHT is similar what we get using finasteride. As we know for sure castratation stops /halts male pattern baldness. So these data impose new questions:


(*) http://www.hairlosstalk.com/interac...8-DHT-levels?p=1089431&viewfull=1#post1089431


1. Why AR in castrated men because of significant reduction of all andrgens don't become so sensitive during time, so the rest of DHT circulating around (which is as mentioned before 30-10 % according to study), start to kill hair follicles ?


2. If DHT after castration is reduced by 70 % or more, which is quite the same suppresion level of DHT in finasteride (70 %) and dutasteride (90 %) users, how is it possible finasteride and dutasteride are not so effective in halting male pattern baldness as castration ?


Obviously that's probably due to a more complete suppression of androgens than just what you get with finasteride. Castration causes about the same DHT suppression as finasteride, but in the same time causes a very striking reduction of testosterone, compared to what you get with finasteride (which actually tends to go UP a little). This proves that T and other androgen hormones play huge role in Male patern baldness regarding their influence in autoimmune-response, fibrosis etc.

I didn't catch the edit, so I'll respond to this as well.

First of all, I need a recent study showing DHT levels following castration in human models. Brian's study is probably pre-90's. I'm not denying his findings, I just want to build further on it's implications. Preferably something more recent.

But generally, what happens during castration is a sharp drop in testosterone levels, which in turn causes a feedback loop increasing the ratio of DHT/T to maintain androgenic function. I'm not sure if '70%' is the proper value however. I haven't looked at it in any case.

Finasteride and Dutasteride are very effective against male pattern baldness, they should block the balding process from androgen exposure by a great deal, especially with dutasteride, and if started early enough to prevent initial damage.

Testosterone does not play a role in male pattern baldness, at all. It's just too weak to have an androgenic effect on hair, compared to DHT.

 

[Ventures]

Testosterone does not play a role in male pattern baldness, at all. It's just too weak to have an androgenic effect on hair, compared to DHT.

I think that is not true, T definitely plays certain role in male pattern baldness. DHT has the greatest effect on Dermal papilla miniaturisation, but T alone can also trigger and continue that process. I believe, In vitro studies confirmed that.


After all, what is the difference between T and DHT ? It is basicly the same hormone, DHT only has two hydrogen atoms more added to its chemical structure which causes its greater affinity to AR. All androgen hormones can bind to AR and activate certain male pattern baldness genes. The only difference is how effective they bind, so affinity of binding is significant reason why some androgens are potent and some less in scalp hair loss.


T and DHT have almost the same chemical structure, except DHT (di-hydro-testosterone) has two H atoms more which provides its ability to bind more effectively to AR and passes genetical instructions to nucleus of the cell. Regarding that only difference between T and DHT is their affinity to AR (how successfully they bind) but not instructions they transmit. Therefore if DHT causes male pattern baldness then there is no reason to suspect T does not.

I can't find new study study which shows T and DHT levels respectively, but here is study which describes Testosterone level after surgical castration:

http://www.ncbi.nlm.nih.gov/pubmed/23769268

..... Traditionally, castration was considered to be achieved if testosterone levels were lowered to a threshold of 50 ng/dl (1.73 nmol/l), a definition determined more by measurement methods derived from the use of old assay methods than by evidence. Serum testosterone levels in three-quarter patients after surgical castration drop to less than 20 ng/dl (0.69 nmol/l)......

We may assume DHT is suppressed by at least 70-80%, of course in some patients maybe even more depending on concentracion of 5ard in their organism.

Actually, If I do basic math, then I can conclude that DHT level doesn't depend much on total T level, remember that only small fraction of total T; 5-15% of T is converted to DHT. So, it's only necessary that this tiny percentage is available, which probably can be since T is also produced in adrenal gland. Maybe we must compare before/after DHT tissue level (in scalp, skin etc.) , not just DHT serum level. Unfortunately there are no studies which analyze this.

 

[drgs]

T does not make you bald directly.
T makes you AR sensitive through masculinization, mostly in puberty, but slowly as we age as well, and then or in parallel DHT does the work over time

If not -- how men become more AR sensitive than women to begin with?
Its part of our sexual dimorphism

 

[Armando Jose]

The key is to note that hormones really important are those that are created and consumed in the vicinity of the pilosebaceous unit, biochemical route from cholesterol. Another key is that there androgens in scalp hair many years before puberty, both girls and children.

And so on.....

 

[xRedStaRx]

I think that is not true, T definitely plays certain role in male pattern baldness. DHT has the greatest effect on Dermal papilla miniaturisation, but T alone can also trigger and continue that process. I believe, In vitro studies confirmed that.


After all, what is the difference between T and DHT ? It is basicly the same hormone, DHT only has two hydrogen atoms more added to its chemical structure which causes its greater affinity to AR. All androgen hormones can bind to AR and activate certain male pattern baldness genes. The only difference is how effective they bind, so affinity of binding is significant reason why some androgens are potent and some less in scalp hair loss.


T and DHT have almost the same chemical structure, except DHT (di-hydro-testosterone) has two H atoms more which provides its ability to bind more effectively to AR and passes genetical instructions to nucleus of the cell. Regarding that only difference between T and DHT is their affinity to AR (how successfully they bind) but not instructions they transmit. Therefore if DHT causes male pattern baldness then there is no reason to suspect T does not.

I can't find new study study which shows T and DHT levels respectively, but here is study which describes Testosterone level after surgical castration:

http://www.ncbi.nlm.nih.gov/pubmed/23769268

..... Traditionally, castration was considered to be achieved if testosterone levels were lowered to a threshold of 50 ng/dl (1.73 nmol/l), a definition determined more by measurement methods derived from the use of old assay methods than by evidence. Serum testosterone levels in three-quarter patients after surgical castration drop to less than 20 ng/dl (0.69 nmol/l)......

We may assume DHT is suppressed by at least 70-80%, of course in some patients maybe even more depending on concentracion of 5ard in their organism.

Actually, If I do basic math, then I can conclude that DHT level doesn't depend much on total T level, remember that only small fraction of total T; 5-15% of T is converted to DHT. So, it's only necessary that this tiny percentage is available, which probably can be since T is also produced in adrenal gland. Maybe we must compare before/after DHT tissue level (in scalp, skin etc.) , not just DHT serum level. Unfortunately there are no studies which analyze this.

Testosterone does not play a role in male pattern baldness. In fact, testosterone is very anabolic and contributes to healthy hair follicles. In vitro studies have several limitations compared with the human body.

That's the thing. DHT is responsible for male pattern baldness, and not testosterone because DHT is an autocrine hormone with almost ten times the androgenic power of T according to some experts. It has almost 3 times the affinity, and almost 2.5 times the androgenic effect on specific tissue. That alone gives enough reasons why DHT is the prime factor towards androgenic hair loss. You won't be losing hair anytime soon with supraphysiological doses of testosterone derivative hormones and dutasteride for example.

The reason I don't believe the 70% value is because DHT is reduced from testosterone, if you don't have T, then you can't have DHT. Unless it's also the byproduct metabolite of other steroids.

5-10% of 900ng/dl will be much more than 5-10% of 50ng/dl of testosterone.

T does not make you bald directly.
T makes you AR sensitive through masculinization, mostly in puberty, but slowly as we age as well, and then or in parallel DHT does the work over time

If not -- how men become more AR sensitive than women to begin with?
Its part of our sexual dimorphism

Yes, androgens increase AR sensitivities and densities, up to a point anyway.

 

[Ventures]

Testosterone does not play a role in male pattern baldness. In fact, testosterone is very anabolic and contributes to healthy hair follicles. In vitro studies have several limitations compared with the human body.

That's the thing. DHT is responsible for male pattern baldness, and not testosterone because DHT is an autocrine hormone with almost ten times the androgenic power of T according to some experts. It has almost 3 times the affinity, and almost 2.5 times the androgenic effect on specific tissue. That alone gives enough reasons why DHT is the prime factor towards androgenic hair loss. You won't be losing hair anytime soon with supraphysiological doses of testosterone derivative hormones and dutasteride for example.

The reason I don't believe the 70% value is because DHT is reduced from testosterone, if you don't have T, then you can't have DHT. Unless it's also the byproduct metabolite of other steroids.

Like I said before, all androgens can activate balding genes. Reputable forum member, Bryan also agreed with that statement. There is no DHT or T receptor, only AR - Androgen receptor, right ?
DHT is the most prominent of course, because of its greater affinity and its local production near and inside hair follicles. If you have study which disproves this; especially studies which support fact that there are different receptors for T and DHT, please provide the link.

5-10% of 900ng/dl will be much more than 5-10% of 50ng/dl of testosterone.

But I do not know for sure is conversion and synthesis of 5ard linear; does body produce the same quantity of 5-ard, before and after castration. Let's say before castration in some individuals there were 100 units of T, and 5 units of 5ard (I or II it doesn't matter). if we assume every 5ard unit succeed to "catch" T, as result 5 DHT units have been formed, and we have 95 T units. After castration there are 10 units of T, and does body produce same number of 5ard units ? If it does, do all 5ard units would succeed to convert T, or we must change that number.

Is production of 5ard invariant; does it [FONT=arial, sans-serif]remain unchanged if androgen levels drop down ? Probably quantity production of 5ard is the same, or maybe even higher if we consider that local DHT production has role of local amplification of androgen effects. On the other hand does the T->DHT conversion process have same parameters, or we must take into account that some 5ard units don't manage to catch T because of striking reduction of T levels in bloodstream.
[/FONT]I don't understand how all mechanisms work to answer this question and if we want to give mathematical model we must consider stochastic nature of endocrinology and other facts.

Yes, androgens increase AR sensitivities and densities, up to a point anyway.

Actually there were speculations that increase in AR sensitivity is result of deprivation of androgen stimulus; as in case on finasteride or dutasteride. Some long term propecia users reported they started to rapidly lose their hair when they quitted (cold turkey) - explanation was AR were upregulated while on the drug. Bryan hasn't confirmed, or denied that speculation; he added that, after discontinuation of the drug AR should return to normal sensitivity if they were upregulated. So, if androgen levels go up (after quitting finasteride), AR should downregulate.

 

[xRedStaRx]

Like I said before, all androgens can activate balding genes. Reputable forum member, Bryan also agreed with that statement. There is no DHT or T receptor, only AR - Androgen receptor, right ?
DHT is the most prominent of course, because of its greater affinity and its local production near and inside hair follicles. If you have study which disproves this; especially studies which support fact that there are different receptors for T and DHT, please provide the link.

You are still confused about how male pattern baldness works.

The balding gene does not get 'activated'. The hair follicle miniaturizes under the cumulative effect of androgen exposure, something only DHT can do with high enough firepower to drive a hair follicle dead over a number of years. This is the simplest way I can explain it.

Brian never said testosterone causes male pattern baldness. I believe he was always in support of the pseudohermaphrodite model.

But I do not know for sure is conversion and synthesis of 5ard linear; does body produce the same quantity of 5-ard, before and after castration. Let's say before castration in some individuals there were 100 units of T, and 5 units of 5ard (I or II it doesn't matter). if we assume every 5ard unit succeed to "catch" T, as result 5 DHT units have been formed, and we have 95 T units. After castration there are 10 units of T, and does body produce same number of 5ard units ? If it does, do all 5ard units would succeed to convert T, or we must change that number.

Is production of 5ard invariant; does it remain unchanged if androgen levels drop down ? Probably quantity production of 5ard is the same, or maybe even higher if we consider that local DHT production has role of local amplification of androgen effects. On the other hand does the T->DHT conversion process have same parameters, or we must take into account that some 5ard units don't manage to catch T because of striking reduction of T levels in bloodstream.
I don't understand how all mechanisms work to answer this question and if we want to give mathematical model we must consider stochastic nature of endocrinology and other facts.

5-AR levels and activity does not really change in general. The changes are mostly signals from specific organs needing 5-AR metabolite molecules to function properly. The amount that gets converted to DHT by 5-AR depends on the amount of aromatase enzyme, SGBH, free testosterone quantities, and regulation of the androgen/estrogen ratio by the HPTA. It's generally around 5-10% in a normal healthy male. But it can be higher (or lower) otherwise, which is one of the reasons for the early prevalence of male pattern baldness in recent decades.

Actually there were speculations that increase in AR sensitivity is result of deprivation of androgen stimulus; as in case on finasteride or dutasteride. Some long term propecia users reported they started to rapidly lose their hair when they quitted (cold turkey) - explanation was AR were upregulated while on the drug. Bryan hasn't confirmed, or denied that speculation; he added that, after discontinuation of the drug AR should return to normal sensitivity if they were upregulated. So, if androgen levels go up (after quitting finasteride), AR should downregulate.

The only scientific study showing AR upregulation was in the case of exogenous sexual steroid administration. Because testosterone increases the number of ARs and their sensitivity, like it increases protein synthesis around the whole body. So even though there is a 10% increase in T from finasteride, it is unlikely to cause a huge anabolic effect either way.

Hope this helps.

 

[benjt]

The balding gene does not get 'activated'. The hair follicle miniaturizes under the cumulative effect of androgen exposure, something only DHT can do with high enough firepower to drive a hair follicle dead over a number of years. This is the simplest way I can explain it.

Would you be so kind to elaborate? You seem to have much more of a clue about the process than I do. I'm trying my best to figure out male pattern baldness/Androgenetic Alopecia from the research papers I have access to, but I lack any higher education in biology or medicine, so a "layman explanation" that goes beyond "DHT miniaturizes follicles", i.e. the single steps in the process, would be much appreciated.

 

[xRedStaRx]

Would you be so kind to elaborate? You seem to have much more of a clue about the process than I do. I'm trying my best to figure out male pattern baldness/Androgenetic Alopecia from the research papers I have access to, but I lack any higher education in biology or medicine, so a "layman explanation" that goes beyond "DHT miniaturizes follicles", i.e. the single steps in the process, would be much appreciated.

I'm actually a non-science major, so I'm not anymore qualified than you are most probably

We do not really know how exactly it happens, or why it happens. But we have some clues based on various studies. Like for example, pseduohermaphrodites never go bald. Bald scalps have higher DHT/T ratio than non-balding scalps on the same person. Finasteride improves male pattern baldness. DHT derived steroids wreck havoc on hair. And so forth.

So DHT is most likely the prime factor towards male pattern baldness. 5-AR II enzymes make up most of the tissue DHT concentration on the dermal papilla. I'll expand on this further today, I need to go atm.

 

[Armando Jose]

I'm actually a non-science major, so I'm not anymore qualified than you are most probably

We do not really know how exactly it happens, or why it happens. But we have some clues based on various studies. Like for example, pseduohermaphrodites never go bald. Bald scalps have higher DHT/T ratio than non-balding scalps on the same person. Finasteride improves male pattern baldness. DHT derived steroids wreck havoc on hair. And so forth.

So DHT is most likely the prime factor towards male pattern baldness. 5-AR II enzymes make up most of the tissue DHT concentration on the dermal papilla. I'll expand on this further today, I need to go atm.

Hi,
where is the study about pseduohermaphrodites that never go bald?. Only there is a reference from Hamilton. I did read the work and it is not very good, ancient, scarcy methods of measuring hormones, a few people, and possibly other explanation. I could say the same with women..... BTW there is eunuchs suffering baldness, in Japan.
Regarding "Bald scalps have higher DHT/T ratio than non-balding scalps on the same person" I would like very much read a study in healthy persons,..., with different DHT in different zones of scalp. It is posible that the problem arise when you suffer from common baldness, and it is a consequence, not a cause ...
The androgenetic theory have many holes.....