he posted this in 2015 pretty intense work , far more than my poor words..... for some reason i could only post half the thread (too many words though he managed to....) so to read the read theres a massive thread after as werll go here..... he also goes into major detail- lympth is huge - people need to realise!!!
https://www.hairlosstalk.com/interact/threads/a-review-of-male-pattern-baldness-research.89751/
his post is below ....
Anyone who follows the hairloss forums will be aware of the slow progress towards effective treatments for male pattern baldness, and the regular dissapointment of the claimed breakthroughs. I think it is time to review the evidence for the historical claims, that continue to get us little in terms of effective treatments. So what entitles me to an opinion on the subject?
I am a systems engineer, with over forty years experience of building and trouble shooting complex mechanical systems. I have had to consider real world scientific principles in the function of systems, every day of my working life. These are physical laws that apply to the function of any system, be it mechanical or biological.
This is intended to review the historical body of evidence relating to male pattern baldness, and the issues with its interpretation. The emphasise being upon how claims made at the molecular level, dont hold up in terms of the systems function. I also suggest there is a systems interaction going on that very simply explains follicle miniaturisation in male pattern baldness, and what could be done about this.
The initial work of Hamilton is credited with establishing the link with androgens and male pattern baldness. Further research established that it is the androgen DHT that is the significant trigger to the male pattern baldness process. DHT being converted from T, in the dermal system largely in hair follicle DP cells by 5AR type 2.
http://www.ncbi.nlm.nih.gov/pubmed/11397903
Subsequent hair transplantation studies lead to the notion of donor dominance. The survival of follicles transplanted into the male pattern baldness area, and certain in-vitro studies lead to the following conclusion. This is that follicles have a different internal molecular make up, that leads to different direct androgen effects on follicle size. All the treatment research since in male pattern baldness, has been aimed at targeting or avoiding a direct androgen action in male pattern baldness.
There are some serious issues with this conclusion however, and so far male pattern baldness treatments based upon this have just not delivered. The problems begin when you consider this direct action, in terms of the actual in-vivo observations.
If this is correct, it means that follicles have to be feed androgens for long periods, before there is any direct response at all. The androgen induced hair growth that developes from the ears and nostrils of middle aged men, apparently takes 20 to 30 years to realise its androgen dependent. We all know that male pattern baldness can take years to develope after the initial increase in androgens at puberty, again indicating a delayed response that varies widely in individuals.
It also seems that once follicles do become directly sensitive to androgens in male pattern baldness, they become very sensitive indeed. In male pattern baldness castration removes over 90% of the available androgen stimulus, but it does not reverse male pattern baldness.
http://press.endocrine.org/doi/abs/10.1210/jcem-20-10-1309
The actual real life observations in male pattern baldness, go against everthing we know about direct hormone actions upon target cells.
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/basics/hormones.html
There is a very important point about the claim that male pattern baldness is caused by a direct hormone action. If this was true, male pattern baldness would be easy to prevent and treat. We just block the follicle androgen receptors with a topical antagonist, or anti-androgen. Topical hormone medications are effective in many conditions, and there is no technical reason that the same size antagonist molecule should have penetration issues. In fact hair follicles are recognised as being effective channels for such topicals.
http://www.inetce.com/articles/pdf/221-146-04-054-h01.pdf
The market for a topical with no systematic effects that treated male pattern baldness, and prevented it in people with a family history would be worth billions. So where is this simple fix? The experience on hair loss forums tells a different story. We know that any effect at all of topical anti-androgens only happens where there is some systematic effect.
People make all kinds of excuses for the factors refered to so far. All these so called explainations have to add complication upon complication. You can explain anything you like by adding complication, but this is not how genuine science works.
http://math.ucr.edu/home/baez/physics/General/occam.html
Also the action of androgens in male pattern baldness, has to explain all the recognised changes. The direct action notion cannot do this without adding even more complication.
There are many other factors in the male pattern baldness scalp, that demonstrate differences compared to hairy scalp. These include increased levels of DHT, increased levels of inflammatory related activity, fibrosis and a relative hypoxia. There are also significant changes in sweating capacity, and sebaceous gland hyperplasia (swelling).
There are suggestions that an increased inflammatory activity triggered by androgens, is significant in follicle miniaturisation in the male pattern baldness area. The latest being the hype about PGD2. So far we are all aware that what happens in mice and tissue culture, means very little when it comes to human male pattern baldness.
On the surface the process of male pattern baldness seems very complex, with many associated factors. In my experience with complex systems, you have to look for the common factor. If you can find a common factor, this usually makes sense of and gives order to the events and changes. This can sort out what is causal in a change, and what are just downstream effects.
I think we need to take another look at the early data that generated this direct androgen action, and the different response of follicles notion. The key here is hair transplantation, and why some methods succeed, while others fail. Understanding the real mechanisms of this, is the key to the future of male pattern baldness treatment.
Continued below.
- - - Updated - - -
The early hair transplantation studies used large grafts by todays standards. The original Orentreich study used grafts of four milimeters diameter. This is a good historical article on hair transplantation.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840892/
The initial studies that used these large grafts ran for up to two years, and the results generated two possibilities. The survival of terminal follicles transplanted into the male pattern baldness area, was either because of internal follicle differences or effects very close to the follicles. Further testing could have established which of the two possibilities it was, but such testing was just not done.
Instead hair transplantation moved largely into the commercial field, along with the assumption that the follicles were different than the originals in the male pattern baldness area.
What is important about the studies with the early large grafts, is what was not seen. Nowadays there are clinics that specialise in the repair of problems assosiated with the early large grafts. One problem being the loss of hair in the center of these, leaving only terminal hair growing around the circumference of the grafts.
http://www.bernsteinmedical.com/res...spects-of-repair-and-basic-repair-strategies/
This common hair loss in grafts from 3-5 mm diameter, is not seen in modern smaller grafts. The reason offered for this is hypoxia, or poor oxygen supply before proper healing and restoration of graft blood supply.
The big problem with this, is that there was no mention of this hair loss in the early studies that ran for up to two years. If as now accepted this was common in the then most used 4 mm grafts, why wasn't this apparent during the period of treatment sessions? As it was these large grafts continued to be used from the 1950's right up to the early 80's. If this was an early effect, customer complaints alone would have driven the move to smaller grafts far earlier.
Any unbiased review of the limited data about large grafts, would conclued that this hair loss is longer term and consistent with the continuation of male pattern baldness in these grafts. The question should be why does hair continue to grow long term around the edges?
More recent studies have questioned the early assumptions, and demonstrated an influence of the surrounding tissue upon transplanted hair growth.
http://newhair.com/pdf/mp-2002-donor-dominance.pdf
One recent study effectively refutes the claim that follicles survive in transplantation, because of internal factors. Quote:
"Balding Hairs Grow Long and Thick on Immunodeficient Mice"
Because immunodeficient mice do not reject foreign tissues, they will accept transplants of human hairs that can then be studied. We transplanted both miniaturized and normal hair follicles from scalp affected by common balding. Our study found that miniaturized hair follicles can quickly regenerate once removed from the human scalp; in fact they grew as well as or better than the transplanted normal, non-balding hair follicles as assessed by their diameter and length achieved at 22 weeks.
Krajcik RA, Vogelman JH, Malloy VL, Orentreich N.
Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice. Journal of the American Academy of Dermatology 48(5):752-59, 2003."
According to the direct action and androgen sensitivity claim, this result is just not possible. There were more than enough androgens in those mice to feed the alledged direct within the follicle process, and sensitivity of male pattern baldness follicles.
There was also no immunology present in the historical in-vitro studies, that claimed to prove opposite direct actions of androgens on follicle cells. No immune mediated direct action of androgens excuse then, for the results of this study.
The really inportant thing about this study is it demonstrates that human male pattern baldness follicles can recover, and that the in-vivo action is external. Again we must look for the common factor in all this apparent complication.
Going back to the original alternative explaination, of an effect very close to the follicles in transplantation. There is one external action that links together the transplantation data, and all the recognised conditions in human male pattern baldness. This involves the structure of hair follicles, and the recognised changes during the hair cycle. This external influence is based upon the original function of hair as an insulator in mammalian evolution.
pt1
https://www.hairlosstalk.com/interact/threads/a-review-of-male-pattern-baldness-research.89751/
his post is below ....
Anyone who follows the hairloss forums will be aware of the slow progress towards effective treatments for male pattern baldness, and the regular dissapointment of the claimed breakthroughs. I think it is time to review the evidence for the historical claims, that continue to get us little in terms of effective treatments. So what entitles me to an opinion on the subject?
I am a systems engineer, with over forty years experience of building and trouble shooting complex mechanical systems. I have had to consider real world scientific principles in the function of systems, every day of my working life. These are physical laws that apply to the function of any system, be it mechanical or biological.
This is intended to review the historical body of evidence relating to male pattern baldness, and the issues with its interpretation. The emphasise being upon how claims made at the molecular level, dont hold up in terms of the systems function. I also suggest there is a systems interaction going on that very simply explains follicle miniaturisation in male pattern baldness, and what could be done about this.
The initial work of Hamilton is credited with establishing the link with androgens and male pattern baldness. Further research established that it is the androgen DHT that is the significant trigger to the male pattern baldness process. DHT being converted from T, in the dermal system largely in hair follicle DP cells by 5AR type 2.
http://www.ncbi.nlm.nih.gov/pubmed/11397903
Subsequent hair transplantation studies lead to the notion of donor dominance. The survival of follicles transplanted into the male pattern baldness area, and certain in-vitro studies lead to the following conclusion. This is that follicles have a different internal molecular make up, that leads to different direct androgen effects on follicle size. All the treatment research since in male pattern baldness, has been aimed at targeting or avoiding a direct androgen action in male pattern baldness.
There are some serious issues with this conclusion however, and so far male pattern baldness treatments based upon this have just not delivered. The problems begin when you consider this direct action, in terms of the actual in-vivo observations.
If this is correct, it means that follicles have to be feed androgens for long periods, before there is any direct response at all. The androgen induced hair growth that developes from the ears and nostrils of middle aged men, apparently takes 20 to 30 years to realise its androgen dependent. We all know that male pattern baldness can take years to develope after the initial increase in androgens at puberty, again indicating a delayed response that varies widely in individuals.
It also seems that once follicles do become directly sensitive to androgens in male pattern baldness, they become very sensitive indeed. In male pattern baldness castration removes over 90% of the available androgen stimulus, but it does not reverse male pattern baldness.
http://press.endocrine.org/doi/abs/10.1210/jcem-20-10-1309
The actual real life observations in male pattern baldness, go against everthing we know about direct hormone actions upon target cells.
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/basics/hormones.html
There is a very important point about the claim that male pattern baldness is caused by a direct hormone action. If this was true, male pattern baldness would be easy to prevent and treat. We just block the follicle androgen receptors with a topical antagonist, or anti-androgen. Topical hormone medications are effective in many conditions, and there is no technical reason that the same size antagonist molecule should have penetration issues. In fact hair follicles are recognised as being effective channels for such topicals.
http://www.inetce.com/articles/pdf/221-146-04-054-h01.pdf
The market for a topical with no systematic effects that treated male pattern baldness, and prevented it in people with a family history would be worth billions. So where is this simple fix? The experience on hair loss forums tells a different story. We know that any effect at all of topical anti-androgens only happens where there is some systematic effect.
People make all kinds of excuses for the factors refered to so far. All these so called explainations have to add complication upon complication. You can explain anything you like by adding complication, but this is not how genuine science works.
http://math.ucr.edu/home/baez/physics/General/occam.html
Also the action of androgens in male pattern baldness, has to explain all the recognised changes. The direct action notion cannot do this without adding even more complication.
There are many other factors in the male pattern baldness scalp, that demonstrate differences compared to hairy scalp. These include increased levels of DHT, increased levels of inflammatory related activity, fibrosis and a relative hypoxia. There are also significant changes in sweating capacity, and sebaceous gland hyperplasia (swelling).
There are suggestions that an increased inflammatory activity triggered by androgens, is significant in follicle miniaturisation in the male pattern baldness area. The latest being the hype about PGD2. So far we are all aware that what happens in mice and tissue culture, means very little when it comes to human male pattern baldness.
On the surface the process of male pattern baldness seems very complex, with many associated factors. In my experience with complex systems, you have to look for the common factor. If you can find a common factor, this usually makes sense of and gives order to the events and changes. This can sort out what is causal in a change, and what are just downstream effects.
I think we need to take another look at the early data that generated this direct androgen action, and the different response of follicles notion. The key here is hair transplantation, and why some methods succeed, while others fail. Understanding the real mechanisms of this, is the key to the future of male pattern baldness treatment.
Continued below.
- - - Updated - - -
The early hair transplantation studies used large grafts by todays standards. The original Orentreich study used grafts of four milimeters diameter. This is a good historical article on hair transplantation.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840892/
The initial studies that used these large grafts ran for up to two years, and the results generated two possibilities. The survival of terminal follicles transplanted into the male pattern baldness area, was either because of internal follicle differences or effects very close to the follicles. Further testing could have established which of the two possibilities it was, but such testing was just not done.
Instead hair transplantation moved largely into the commercial field, along with the assumption that the follicles were different than the originals in the male pattern baldness area.
What is important about the studies with the early large grafts, is what was not seen. Nowadays there are clinics that specialise in the repair of problems assosiated with the early large grafts. One problem being the loss of hair in the center of these, leaving only terminal hair growing around the circumference of the grafts.
http://www.bernsteinmedical.com/res...spects-of-repair-and-basic-repair-strategies/
This common hair loss in grafts from 3-5 mm diameter, is not seen in modern smaller grafts. The reason offered for this is hypoxia, or poor oxygen supply before proper healing and restoration of graft blood supply.
The big problem with this, is that there was no mention of this hair loss in the early studies that ran for up to two years. If as now accepted this was common in the then most used 4 mm grafts, why wasn't this apparent during the period of treatment sessions? As it was these large grafts continued to be used from the 1950's right up to the early 80's. If this was an early effect, customer complaints alone would have driven the move to smaller grafts far earlier.
Any unbiased review of the limited data about large grafts, would conclued that this hair loss is longer term and consistent with the continuation of male pattern baldness in these grafts. The question should be why does hair continue to grow long term around the edges?
More recent studies have questioned the early assumptions, and demonstrated an influence of the surrounding tissue upon transplanted hair growth.
http://newhair.com/pdf/mp-2002-donor-dominance.pdf
One recent study effectively refutes the claim that follicles survive in transplantation, because of internal factors. Quote:
"Balding Hairs Grow Long and Thick on Immunodeficient Mice"
Because immunodeficient mice do not reject foreign tissues, they will accept transplants of human hairs that can then be studied. We transplanted both miniaturized and normal hair follicles from scalp affected by common balding. Our study found that miniaturized hair follicles can quickly regenerate once removed from the human scalp; in fact they grew as well as or better than the transplanted normal, non-balding hair follicles as assessed by their diameter and length achieved at 22 weeks.
Krajcik RA, Vogelman JH, Malloy VL, Orentreich N.
Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice. Journal of the American Academy of Dermatology 48(5):752-59, 2003."
According to the direct action and androgen sensitivity claim, this result is just not possible. There were more than enough androgens in those mice to feed the alledged direct within the follicle process, and sensitivity of male pattern baldness follicles.
There was also no immunology present in the historical in-vitro studies, that claimed to prove opposite direct actions of androgens on follicle cells. No immune mediated direct action of androgens excuse then, for the results of this study.
The really inportant thing about this study is it demonstrates that human male pattern baldness follicles can recover, and that the in-vivo action is external. Again we must look for the common factor in all this apparent complication.
Going back to the original alternative explaination, of an effect very close to the follicles in transplantation. There is one external action that links together the transplantation data, and all the recognised conditions in human male pattern baldness. This involves the structure of hair follicles, and the recognised changes during the hair cycle. This external influence is based upon the original function of hair as an insulator in mammalian evolution.
pt1