So look ok, WHAT changes as we age to trigger hair loss?

[Hoppi]

I decided to start this because it feels like an important thing, and I was looking into it after my thread I started about the prostate.

Does anyone know WHY suddenly one day guys can start losing hair? Like it's perfect for so long and then one day BANG.

And please, no vague comments like "the male pattern baldness gene gets switched on" or whatever, because even if you believe that, it must DO something when it gets switched on to cause hair loss.

So like, from what I've read, as we age:

Testosterone decreases.
DHT stays fairly static.
Estrogen increases.
5-alpha reductase type 2 activity _apparently_ decreases.

I am unsure about the number of androgen receptors on follicles.

The prostate also enlarges in size of course, which provides another question, as the same enzyme that triggers hair loss (type 2 5-alpha reductase) also is the one that converts testosterone to DHT in the prostate. That is why finasteride causes the prostate to shrink.

So... WHY. Unless the prostate is sitting down there spewing out DHT (which would surely spike the DHT of older men)... like.. can anyone make sense of this riddle?

Thanks,

Hoppi

 

[Bryan]

So... WHY. Unless the prostate is sitting down there spewing out DHT (which would surely spike the DHT of older men)... like.. can anyone make sense of this riddle?

I've explained this "riddle" over and over and over and over on hairloss sites, but some people just don't get it. Let's step through it one more time, just for your benefit:

1) DHT produced in the prostate affects _mainly_ the prostate. DHT doesn't have much of a role as an endocrine hormone.

2) An important study with stumptailed macaques provided an important clue as to why male pattern baldness gets worse as we get older: scalp hair follicles get more sensitive to androgens with age, it's not that the levels of androgens themselves necessarily increase with age. Testosterone given to hair follicles from young macaques had no effect on them at all, but the same amount of testosterone given to hair follicles from older monkeys caused the usual and expected growth-suppression. The same thing almost certainly happens in humans, too!

 

[theShade]

If the problem was purely androgen/hormonal than all of our hair everywhere on the whole body would be affected the same by them all at the same time. Of course this is not the case.

Clearly there is a mechanism within the actual hair follicle organs themselves (this mechanism AFAIK is triggered by androgens, which bind to the receptors and cause a series of chemical reactions). The 'programming' so to speak of these follicles are defined by genetics (not to say though that things such as diet don't play a part in their expression, they may well do). Hair follicles activate and deactivate at certain ages; in the same way as body hair doesn't start growing until puberty so too does hair loss not initiate until the end of puberty or later.

It is an interesting question though, as to what precisely the mechanism is that enables the receptors/follicles to be age-sensitive. It is evidently not just the result of a change in androgen-levels. While it is clear that androgens trigger the effect, I myself do not have any knowledge on the chemistry involved, as to how those androgens can have a certain (or rather no effect) on receptors when a person is 20, and then have a different effect when the person is 30. Bryan maybe you can fill us in?

 

[Hoppi]

But if that's true, then why is it that prostate size and male pattern baldness have been shown to correlate in studies? And why is it that my body hair increase accompanied my male pattern baldness perfectly?

 

[raj47]

i belive in sensitivity and may be time on that person at what age it will trigger
if you started bald at 17 you may get relive with in 29 or 30 ,if you start to bald at 30 you may relive at 40~49,if you get it at 50 it may upto you death.

any one please explain how hair transplant works on the bald area?

 

[Bryan]

It is an interesting question though, as to what precisely the mechanism is that enables the receptors/follicles to be age-sensitive. It is evidently not just the result of a change in androgen-levels. While it is clear that androgens trigger the effect, I myself do not have any knowledge on the chemistry involved, as to how those androgens can have a certain (or rather no effect) on receptors when a person is 20, and then have a different effect when the person is 30. Bryan maybe you can fill us in?

Hey, an even bigger question is what accounts for the paradoxical OPPOSITE effect of androgens on body hair and scalp hair: androgens suppress the growth of scalp hair, but actually stimulate the growth of (most) body hair. Scientists are working to understand these differences as we speak.

 

[Bryan]

But if that's true, then why is it that prostate size and male pattern baldness have been shown to correlate in studies?

They correlate, but only superficially, in the sense that both are generally caused by an increase in androgenic stimulation after puberty; and even THAT correlation is weakened somewhat by differences in the increase in sensitivity to androgens that I mentioned earlier. I personally started balding only in my early 40's, whereas others can start balding as early as their teenage years.

Hoppi, I want you to understand the meanings of the words "endocrine", "paracrine", and "autocrine". You won't believe me if _I_ explain them to you, so please Google them; I'm sure Wiki has some good explanations for you! DHT (like from the prostate) doesn't have much of a role as an endocrine hormone, it's mainly an autocrine or paracrine androgen.

Here is the first result from a quick search I did myself:

http://www.vivo.colostate.edu/hbooks/pa ... mones.html

•Endocrine action: the hormone is distributed in blood and binds to distant target cells.
•Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood.
•Autocrine action: the hormone acts on the same cell that produced it.

 

[Hoppi]

I understand And also I'm glad that we agree on the correlation between prostate size and male pattern baldness, whatever the underlying reason might be!

So erm, yes like.. the big question in my head is what is it that makes DHT now more potent, as men age? Like, you hear these stories of men yeah, suddenly getting male pattern baldness problems at whatever age, it often does seem to happen quite quickly.

Now, if as you have said and studies seem to indicate, that DHT does not increase with age, then I would imagine the only other explanation is that the body's response to it's androgens increases. This is then going to be.. either an increase in 5ar2 expression (explaining of course the prostate size increase and the hair follicle death/growth) or an increase in the number of androgen receptors?

And wow this is fascinating! It's finally explaining to me why this odd condition kicks in seemingly out of the blue!

 

[Bryan]

So erm, yes like.. the big question in my head is what is it that makes DHT now more potent, as men age?

I don't think DHT is becoming more "potent", I think the cellular response to DHT and other androgens is increasing.

Now, if as you have said and studies seem to indicate, that DHT does not increase with age, then I would imagine the only other explanation is that the body's response to it's androgens increases. This is then going to be.. either an increase in 5ar2 expression (explaining of course the prostate size increase and the hair follicle death/growth) or an increase in the number of androgen receptors?

An increase in 5ar2 expression would cause an increase in DHT. An increase in the number of androgen receptors might have something to do with an increase in the intensity of the androgenic stimulus in the body, of course; personally, I don't think people give enough consideration to a possible increase in the cellular response to a given amount of androgenic stimulation.

 

[bigentries]

I believed the hair follicle started to damage as more androgens were available (a reason why some people with no hair loss have a huge shed after using anabolic steroids). I didn't know about the macaque study.

Bryan, do you know if any other primates experience infantile hair loss as many human babies do?
I understood that hair loss in babies was linked to the unusually high testosterone levels babies have, so it was the same mechanism as hair loss in post-puberty humans, but for some reason, babies are able to grow their hair back.

 

[Hoppi]

So erm, yes like.. the big question in my head is what is it that makes DHT now more potent, as men age?

I don't think DHT is becoming more "potent", I think the cellular response to DHT and other androgens is increasing.

Now, if as you have said and studies seem to indicate, that DHT does not increase with age, then I would imagine the only other explanation is that the body's response to it's androgens increases. This is then going to be.. either an increase in 5ar2 expression (explaining of course the prostate size increase and the hair follicle death/growth) or an increase in the number of androgen receptors?

An increase in 5ar2 expression would cause an increase in DHT. An increase in the number of androgen receptors might have something to do with an increase in the intensity of the androgenic stimulus in the body, of course; personally, I don't think people give enough consideration to a possible increase in the cellular response to a given amount of androgenic stimulation.

Ah very well spotted about an increase in 5ar2 expression causing an increase in serum DHT, I didn't think of that!

Hm, so is it perhaps the number of androgen receptors?

I ask because, if it's possible to outline the exact change in the body that leads to male pattern balding, then we will be very well placed I think to offset or reverse it.

Additionally, one would imagine that simply reversing/reducing/offsetting this precise change would cause no side effects, as the person was healthy with that androgen response before, why wouldn't they be now?

What do you think?

I wonder what it is!

 

[theShade]

I ask because, if it's possible to outline the exact change in the body that leads to male pattern balding, then we will be very well placed I think to offset or reverse it.

Additionally, one would imagine that simply reversing/reducing/offsetting this precise change would cause no side effects, as the person was healthy with that androgen response before, why wouldn't they be now?

What do you think?

I wonder what it is!

Genetic programming of hair follicles seems to be the main reason.

There is also the possibility that other hormones or rather metabolised forms of Testoserone (other than DHT, there are a lot of others) have a role to play. Levels of such hormones may rise or fall to a greater extent than DHT over the years. It is possible for example that DHT alone would not cause balding, and that a certain level of another hormone (that would probably compete with DHT to bind to androgen receptors) is also a requirement. I remember reading in Dr. Rassman's blog, that he suspected that there were more hormones involved in hairloss other than just DHT.

The only problem with this theory, is that AFAIK (may be wrong), it doesn't matter what hormone binds to a particular receptor (different hormones just have higher or lower chances to bind than others), as it is the receptor that does all the work and the result would be the same regardless of which particular hormone binded to it. Are there other receptors on hair follicles other than just angrogen receptors I wonder? I seem to remember reading something about this.

This is all speculation however.

It is an interesting question though, as to what precisely the mechanism is that enables the receptors/follicles to be age-sensitive. It is evidently not just the result of a change in androgen-levels. While it is clear that androgens trigger the effect, I myself do not have any knowledge on the chemistry involved, as to how those androgens can have a certain (or rather no effect) on receptors when a person is 20, and then have a different effect when the person is 30. Bryan maybe you can fill us in?

Hey, an even bigger question is what accounts for the paradoxical OPPOSITE effect of androgens on body hair and scalp hair: androgens suppress the growth of scalp hair, but actually stimulate the growth of (most) body hair. Scientists are working to understand these differences as we speak.

Although the precise chemistry is of course a mystery, I believe this question has an easier answer somewhat. A different chemical makeup of the follicle, would lead to a different biochemical reaction when the androgen binds to it, and thus ultimately a different visible effect. Much the same as for example, a strand of DNA that is responsible for some physical characteristic may have a slightly different makeup compared to the same strand of DNA in another person. Thus these 2 different DNA strands would translate into 2 different pieces of RNA, and these RNAs would then create different proteins and biochemicals and in different quantities, that would ultimately result in one person having different physical characteristics to another person.

On the other hand - what the mechanism is that enables the exact same follicle with a (presumably) constant chemical makeup to react differently depending on the age of a person, I don't know. The only thing I can think of is either some unknown chemical shift within the follicle, or the result of varying levels of multiple hormones as speculated on above.

 

[baller234]

I believed the hair follicle started to damage as more androgens were available (a reason why some people with no hair loss have a huge shed after using anabolic steroids). I didn't know about the macaque study.

Bryan, do you know if any other primates experience infantile hair loss as many human babies do?
I understood that hair loss in babies was linked to the unusually high testosterone levels babies have, so it was the same mechanism as hair loss in post-puberty humans, but for some reason, babies are able to grow their hair back.

Babies are able to grow their hair back because their hormone profile changes.

 

[Hoppi]

Wow This is becoming fantastically deep and intelligent, I think these are the kinds of conversations it's good to have to be honest, as it really strips the problem down to its roots.

I think if we can rule out an increase in androgen receptors on the follicles (as I think this is unlikely, but possible) then we will have fewer possibilities for the reason why hair follicles die. The problem I suppose will then have to be a change in the reaction of the follicle to androgenic stimulation.

Genetic programming of hair follicles seems to be the main reason.

But, isn't one question here what that genetic programming actually triggers? I mean, gene therapy is surely required to kill the problem at it's real root, but perhaps until then we could determine if what is triggered by our genes can be tackled specifically? I just wonder what it is.

 

[Mens Rea]

Wow This is becoming fantastically deep and intelligent, I think these are the kinds of conversations it's good to have to be honest, as it really strips the problem down to its roots.

I think if we can rule out an increase in androgen receptors on the follicles (as I think this is unlikely, but possible) then we will have fewer possibilities for the reason why hair follicles die. The problem I suppose will then have to be a change in the reaction of the follicle to androgenic stimulation.

Genetic programming of hair follicles seems to be the main reason.

But, isn't one question here what that genetic programming actually triggers? I mean, gene therapy is surely required to kill the problem at it's real root, but perhaps until then we could determine if what is triggered by our genes can be tackled specifically? I just wonder what it is.

Maybe im being simplistic here as i haven't researched it like you guys

but my basic understanding is that, when male pattern baldness is triggered your receptors become sensitive to DHT. When you get past puberty your DHT levels will be high as a fully grown man. People will experience differering degrees of male pattern baldness development depending on how sensitive these follicles are and how much DHT they have attacking them. No?

Obviously there are other factors to explain how some people start balding at different ages etc but isn't that hte general premise?

 

[Hoppi]

Wow This is becoming fantastically deep and intelligent, I think these are the kinds of conversations it's good to have to be honest, as it really strips the problem down to its roots.

I think if we can rule out an increase in androgen receptors on the follicles (as I think this is unlikely, but possible) then we will have fewer possibilities for the reason why hair follicles die. The problem I suppose will then have to be a change in the reaction of the follicle to androgenic stimulation.

Genetic programming of hair follicles seems to be the main reason.

But, isn't one question here what that genetic programming actually triggers? I mean, gene therapy is surely required to kill the problem at it's real root, but perhaps until then we could determine if what is triggered by our genes can be tackled specifically? I just wonder what it is.

Maybe im being simplistic here as i haven't researched it like you guys

but my basic understanding is that, when male pattern baldness is triggered your receptors become sensitive to DHT. When you get past puberty your DHT levels will be high as a fully grown man. People will experience differering degrees of male pattern baldness development depending on how sensitive these follicles are and how much DHT they have attacking them. No?

Obviously there are other factors to explain how some people start balding at different ages etc but isn't that hte general premise?

Yeah, I think that's right However, what I'm trying to work out is what actually changes in the follicle to cause this.. I mean ok there might be a genetic trigger but.. it has to trigger something else doesn't it?

 

[Bryan]

Bryan, do you know if any other primates experience infantile hair loss as many human babies do?

I have no idea about that. Sorry.

I understood that hair loss in babies was linked to the unusually high testosterone levels babies have, so it was the same mechanism as hair loss in post-puberty humans, but for some reason, babies are able to grow their hair back.

Where did you hear about that?? If true, that would _appear_ to contradict the macaque study! I'd like to learn more about it!

 

[dr_jekyll]

I get the DHT part, I get the androgen sensitivity part and I get the age part. The science here makes sense, but... the part I dont get is why male pattern baldness occurs in such a predictable pattern? If all of the hair follicles are sensitive to dht for whatever reason, then how come hairloss starts with the frontal recession then the thinning crown and then total hairloss (or any combination of the above). Why doesnt all of the hair thin immediately into the nw7 pattern? Personally my own hair began receeding at the front, this took place over about 2 years then the crown began to thin over about another 2 years. Id love to know what causes this well known pattern... and whats the point? why would our hair evolve to fall out in such a pattern?

 

[Bryan]

I get the DHT part, I get the androgen sensitivity part and I get the age part. The science here makes sense, but... the part I dont get is why male pattern baldness occurs in such a predictable pattern?

That's the same as asking, why do hair follicles in different parts of the body react to androgens in OPPOSITE fashion? Why are scalp hair follicles suppressed by androgens, while most body hair follicles are actually stimulated by androgens? Nobody knows the answer to that question, although scientists are working on it as we speak.

If all of the hair follicles are sensitive to dht for whatever reason, then how come hairloss starts with the frontal recession then the thinning crown and then total hairloss (or any combination of the above).

Because hair follicles on the scalp are sensitive to androgens to different degrees. They aren't just ON or OFF in that regard, there's a smooth continuum of sensitivity to androgens! Furthermore, there's apparently also a continuum in scalp hair follicles in the absence or presence of various enzymes (like 5a-reductase, steroid sulfatase, and probably many others), androgen receptors, and other chemical factors which can affect the degree of the androgenic stimulus. All of that explains the "pattern" in which we see balding progress. For example, studies have shown that the frontal scalp has higher levels of 5a-reductase and androgen receptors, and very likely has a higher, more negative cellular response to androgens, in addition!

 

[dr_jekyll]

Ok, that also makes sense but what about the purpose? Why have we evolved to lose hair in this manner? Any current theories on this?