For bryan and Foote.

[michael barry]

Dave.
I had thought (again from reading "somewhere") that the maker of RU58841, had decided to not seek approval for it for whatever reason. I hope Im wrong. I'd love to see the trials published to compare with macauque frontal growth of vellus/to/terminals. To me, something that effectively blocked androgen receptors in a nice clear fluid form for a twenty-four hour period, could give men the freedom to quit propecia (Ive read enough posts to believe some men really do face a few sides from finasteride).

It would really seem to be the "answer" to halting further baldness, especially for a young fella just starting to see recession. The fact that it brought some vellus hairs back from the dead gives real hope to some of us with recession (I still have alot of vellus peach fuzz in my receeded temples like alot of men do).

I wish I knew why the maker dropped off on RU. Even if their was a "slight" amount of systemic absorption........it would proboably not be much worse than finasteride/dutasteride side effects and RU apparently is much more effective in the front (if youre a macaque anyway). Ive seen a few threads (one in particular on hairsite) where a guy says he's lost strength in the weightroom on dutas and another guy swears up and down his face has "aged" quickly since getting on it. Made me wonder....

On another topic related to lymphatic drainage.....Tom Hagerty stated on his website that draining the upper scalp lymph might be good because pushing the metabolic waste products that might accumulate in areas with decreased capillaries, etc. might lessen the immune systems "interest" in the area. He admits its speculative on his part. A good cold water rinse in the shower (Pickart and George Michael of the long hair salons both advise this) might not be so bad after all?

Stephen,
You had stated on another thread that you thought DHT might affect pumping in the lymph drainage system in the body (Im guessing by either increasing activity of the muscles that "pump" the fluid away from the skin. Is there any way a scientist could test this conclusively? It would seem that a guy on dutasteride should lose almost all his hair if that was so wouldnt it? If that turns out to be "not true", I wonder what DHT's function is other than the known prostate enlargement/hairloss functions?? Ive wondered about that guy who said he'd lost strength at they gym. Maybe we really do need this demonized hormone after all.

 

[2tone]

Dave.
I had thought (again from reading "somewhere") that the maker of RU58841, had decided to not seek approval for it for whatever reason. I hope Im wrong.

On another topic related to lymphatic drainage.....Tom Hagerty stated on his website that draining the upper scalp lymph might be good because pushing the metabolic waste products that might accumulate in areas with decreased capillaries, etc. might lessen the immune systems "interest" in the area. He admits its speculative on his part. A good cold water rinse in the shower (Pickart and George Michael of the long hair salons both advise this) might not be so bad after all?

Stephen,
You had stated on another thread that you thought DHT might affect pumping in the lymph drainage system in the body (Im guessing by either increasing activity of the muscles that "pump" the fluid away from the skin. Is there any way a scientist could test this conclusively? It would seem that a guy on dutasteride should lose almost all his hair if that was so wouldnt it? If that turns out to be "not true", I wonder what DHT's function is other than the known prostate enlargement/hairloss functions?? Ive wondered about that guy who said he'd lost strength at they gym. Maybe we really do need this demonized hormone after all.

Is androgenic alopecia a result of endocrine effects on the vasculature?
B. A. Caleb Santiago Hernandez


Discussion



It is widely accepted that dihydrotestosterone plays a significant role in the pathogenesis of Androgenic alopecia. What escapes current understanding is the mechanism by which dihydrotestosterone causes balding [5]. Much research has focused on the direct effects of DHT on the pilosebaceous unit [6]. What has not been discussed greatly is the possibility of balding being a result of the indirect effects of DHT, in particular its effects on the vasculature supplying the scalp.

The focus of this essay is to propose a novel hypothesis involving a physiological mechanism by which DHT exerts its effect on the scalp via structural and anatomical changes on the vasculature. These hypothetical changes result in a reduced blood supply to the scalp, and in time, atrophy of the hair follicle.

There are two fundamental premises to this hypothesis:

1. That androgenic alopecia is associated with decreased blood flow and subsequently decreased oxygen delivery to the scalp.
2. Dihydrotestosterone affects the vasculature in such a way as to cause diminished hemodynamic properties and thus diminished blood flow to the target tissues.

For the first premise there is already a fair amount of supporting literature and studies. In particular Goldman et al. [7] have observed that men suffering from androgenic alopecia had significantly lower partial pressure of oxygen values (Po2) in the areas of their scalp affected by balding versus unaffected areas, when measured using a transcutaneous Po2 sensor. Moreover Goldman et al. observed that when the men with balding were compared to non-bald controls, the balding men had significantly lower Po2 in the areas of balding scalp than the same areas in the non-bald controls [7].

In another study by Klemp et al. [8] subcutaneous blood flow was measured in subjects using a xenon washout method. Klemp and his colleagues observed that the subcutaneous blood flow was significantly lower in balding subjects than in subjects without balding [8].

Another group has taken a different approach to establishing an association between decreased perfusion of the scalp and hair loss. Toshitani et al. [9] developed a device to increase the blood flow and perfusion to the scalp. Subjects‘ cutaneous blood flow rates were measured using laser Doppler flowmetry before and after implementation of the device. Toshitani and his associates observed an increase in cutaneous blood flow, following use of the device. They also observed that subjects using the device obtained a 40% efficacy rate for hair regrowth following long-term use of the device [9].

There are also traditional physiologic observations of ischemia resulting in loss of hair. A good example is the manifestation of vascular insufficiency in the lower extremities as a loss or thinning of the leg hair [10]. It is also noteworthy that researchers have observed a positive correlation between smoking (a known contributor to peripheral vascular disease) and an increased risk for baldness in observational studies [11].

The second premise (that androgens cause changes in the vasculature, which result in narrowing of the vessel lumen and thus a subsequent decrease in tissue perfusion) is now addressed. Although little research has been done in this area there are some studies that demonstrate a relationship between circulating dihydrotestosterone and the vasculature.

Studies on baboons by McGill and Sheridan [12] have demonstrated the presence of DHT receptors in the endothelial cells of these animals. Another study by Fujimoto et al. [13] has demonstrated that DHT stimulated the proliferation of vascular smooth muscle cells. Using this information it is logical to propose that if the cells of the internal vascular wall proliferate, the lumen’s cross-sectional area will decrease in size. That is, there is an inverse relation between internal vessel-wall hypertrophy and vessel lumen diameter. A decreased cross-sectional area of the lumen will result in increased resistance to flow and subsequently reduced blood flow.

Androgens may also decrease blood flow through the vasculature by a different mechanism as well. Namely, that of increasing platelet aggregation and thus, increasing the likelihood of atherosclerotic plaque formation. Ajayi et al. [14] has observed that young men given replacement doses of testosterone post-orchiectomy demonstrated an increase in platelet aggregation. Increased platelet aggregation increases the likelihood of vessel-lumen narrowing via plaque formation, resulting in diminished blood flow.

By combining the information from both premises, a novel hypothesis on the pathogenesis of androgenic alopecia is created. This new hypothesis states that androgenic alopecia is a result of the conversion of testosterone to dihydrotestoterone, via 5 α-reductase. Dihydrotestosterone is then transported to the target organs (in this case the vessels supplying the scalp). Dihydrotestosterone then effects structural and anatomical changes in the vasculature. These changes consist of hypertrophy of the internal vascular walls (i.e. smooth muscle and endothelium) resulting in a reduced lumen size. There is also an increased adhesion capability of the platelets, increasing the likelihood of plaque formation on the vessel walls. Both these changes, over a longitudinal period of time, result in diminished blood flow to the pilosebaceous unit and subsequently diminished hair growth. Just as in many other organ systems, the subsequent decrease in nutrition and oxygen delivery result in atrophy [15]. In this case, atrophy and miniaturization of the hair follicle [16].

There are various possibilities for testing this hypothesis. There is the potential for human studies, where biopsies taken from bald men could be compared to men without baldness (of similar age and level of health) by histological analysis, to determine if there is a significant difference in lumen size and vessel wall thickness between both groups. This can be combined with biochemical studies measuring the amounts of key androgens, androgen receptors, and enzymes (i.e. Dihydrotestosterone, DHT receptor, and 5 α-reductase, etc.) present within both groups. Androgen, androgen receptor, and enzyme levels could then be compared to vessel lumen diameter in both the bald and the non-bald groups to determine if there is a relationship between the concentrations of these bio-chemicals and vessel constitution in bald and non-bald groups of men.

Another possibility for study is the use of animal models comparing the vasculature of androgen-sensitive (i.e. androgenically bald) animals to androgen insensitive or possibly castrated (i.e. reduced androgen level) animals. Using this study model, vessel cross-sections could be analyzed between both groups to determine if any significant difference is present between the bald (i.e. androgen affected) and non-bald animal groups.

With both study models it would be of great importance to take samples of various vessel types from within the typical area of pattern baldness. This would be advantageous in that it would allow the researcher to determine which vessel type (i.e. medium size arteries or arterioles, etc.) is most affected by androgens.
Conclusion

Some researchers have experimented with the hypothesis of vascular insufficiency as a cause of balding [7, 8, 9 and 11]. To the author’s knowledge, none have presented this hypothesis as a mechanism by which androgens effect a state of vascular insufficiency leading to baldness.

The author also recognizes that this proposed hypothesis is not mutually exclusive of any direct effects androgens may produce on the pilosebaceous unit itself. In fairness to those who have done research in this area, it is entirely possible that there are endocrine effects at both the pilosebaceous unit and the vasculature, that result in androgenic balding.
[17].

 

[S Foote.]

Just point out to us all Bryan where these or "ANY" other studies, "ACTUALLY" measure the comparitive size of sebaceous glands in bald, pre-bald, and hairy tissue??

This was my point as you are well aware! There is "NO" such evidence, just assumptions based on hamster flank and other irrelevant studies.

Even the section you highlighted as it it "means" something, states sebaceous gland "enlargement" as a "hypothesis" to explain the results, "NOT" a proven fact!!?

No, that is absurd as anyone can see from reading the abstracts. The hypotheses had nothing to do with whether or not sebaceous glands are enlarged in balding scalps, which is something that can and has been measured.

The stated correlation is not based on obscure observations, but is well documented in the literature. Show us the queries and corresponding database name(s) that you used to try to locate the relevant information.

[quote="S Foote.":511f9]Show me a study that "ACTUALLY" proves by direct measurment, that sebaceous glands in the balding human scalp "ENLARGE" compared to pre-balding?

Can't you read? Does it have to include an interactive slide-show or something?[/quote:511f9]

Buls**t

Stop dancing around, and post something that is "well documented" in the literature as you try to claim.

If it is well documented that sebaceous glands in the balding scap enlarge, show us the references?

S Foote.

 

[S Foote.]

Michael, this is a perfect example of how Bryan tries to mislead people in these issues!

The results of follicle cell samples from the male pattern baldness and hairy areas, only "differ" when exposed to androgens in-vivo, "IF" the samples were "already" different!

The pre-balding, "normal" follicles in macaques, that are known to bald in response to androgens, do "NOT" change into balding mode when directly exposed to androgens in-vitro!!

So future balding follicles are no different in their direct response to androgens than any other scalp follicle from outside the male pattern baldness area.

This is what disproves the current theory of a direct action of androgens on follicles, and is something Bryan always conveniently forgets to mention :wink:

ROTFLMFAO!!! You seem to hang your hat on the simple fact that nobody knows yet what causes pre-pubertal hair follicles eventually to become sensitive to androgens (in the male pattern baldness sense). But guess what, Stephen: it's a House of Cards. Do you think that one missing piece of information is going to convince any serious scientist that YOUR nutso theory is correct? Wake up and smell the coffee, my friend.

Bryan

It is precisely because of this big hole in the current theory, that can only be filled by "inventing" an un-precedented "mechanism, that the smarter scientists now question this theory.

You don't see this as a problem in the theory you support Bryan, thats fine!

S Foote.

 

[S Foote.]

[quote="michael barry":94263]If you are arguing that the dermal papilla "CHANGE THEIR REACTION TO ANDROGENS" after the skin fluids put the "SQUEEZE" on them, that would take some reaction heretrofore UNKNOWN in biology. Think about it dermal papilla recieves androgens in puberty......releases growth enhancers. But at 25, tissue fluid pressures rise and the very same dermal papilla recieves androgens through an androgen receptor and releases growth inhibitors instead, due to the genetic instructions "changing" in response to fluid pressures. Thats akin to saying my eyeballs start to "hear noises" if Im in a room with no light isnt it?

Michael, you touch on the central issue when you say quote:

"If you are arguing that the dermal papilla "CHANGE THEIR REACTION TO ANDROGENS" after the skin fluids put the "SQUEEZE" on them, that would take some reaction heretrofore UNKNOWN in biology. "

This is exactly what i am saying happens.

The "squeeze" as you put it, induces contact inhibition of growth in an early stage of follicle enlargement in anagen. So the result is miniaturised follicles.

Whilst we don't yet know all the details of the pathways involved in contact inhibition, we do know that contact inhibition effects the same molecullar pathways involved in the action of TGF Beta-1.

LOL!!! That's not good enough, Stephen! You have to find another example in biology where contact inhibition caused a CHANGE IN THE RESPONSE OF SOME BODY TISSUE TO ANDROGENS WHICH CONSISTED OF THE UPREGULATION OF TGF BETA-1. We're not going to let you get away with a form of "guilt by association"! It's "Put-Up or Shut-Up Time" for you: either find an example of that happening somewhere else, or get your butt back to the drawing-board.

Bryan[/quote:94263]

I did precisely what you ask above in a previous debate as you know Bryan, and i certainly don't have to "prove" anything to "you" do i :wink:

I am not going to go around in circles with you on these issues Bryan, it's Christmas eve and i have a social life.

You have been given all the supporting evidence for my arguments, if you don't think my arguments are valid, thats fine.I really don't care Bryan!

Luckily for all those who want to see some progress in understanding male pattern baldness, the actual experts are thinking again as i have posted.

Merry Christmas Bryan

S Foote.

 

[S Foote.]

Stephen,
You had stated on another thread that you thought DHT might affect pumping in the lymph drainage system in the body (Im guessing by either increasing activity of the muscles that "pump" the fluid away from the skin. Is there any way a scientist could test this conclusively? It would seem that a guy on dutasteride should lose almost all his hair if that was so wouldnt it? If that turns out to be "not true", I wonder what DHT's function is other than the known prostate enlargement/hairloss functions?? Ive wondered about that guy who said he'd lost strength at they gym. Maybe we really do need this demonized hormone after all.

I think DHT is important as a performance enhancing male hormone, largely because it increases lymphatic drainage. This increased tissue fluid turnover would increase nutrient supply and waste removal in tissues.

This would be important in the building and performance of muscle, in particular.

It is not technicaly difficult to measure the tissue fluid levels in tissue using various tests, if there is the will to do these tests?

Removing all androgens will not necessarily restore hair growth to pre-puberty levels, as we know. So the effects of dutasteride over time will be interesting, but also dangerous in my opinion.

I will not be posting again for a few days over Christmas.

Happy Christmas

S Foote.

 

[Bryan]

LOL!!! That's not good enough, Stephen! You have to find another example in biology where contact inhibition caused a CHANGE IN THE RESPONSE OF SOME BODY TISSUE TO ANDROGENS WHICH CONSISTED OF THE UPREGULATION OF TGF BETA-1. We're not going to let you get away with a form of "guilt by association"! It's "Put-Up or Shut-Up Time" for you: either find an example of that happening somewhere else, or get your butt back to the drawing-board.

I did precisely what you ask above in a previous debate as you know Bryan, and i certainly don't have to "prove" anything to "you" do i :wink:

You have never once given me such an example, and it saddens me that you cannot bring yourself to acknowledge the truth, even on Christmas.

Bryan

 

[michael barry]

Can anyone take the time to restate an example in biology where contact inhibition changes the response of any particular tissue's response to androgens? I'd like to see that myself. It would be interesting.


2tone, What you posted is interesting and informative. For my two cents however, I think this. Cyclosporin, a strong immunosuppressant used in organ regection drugs, internally was 80% effective treating andro-alopecia. Does nothing for DHT.....it just weakens your immune system drammatically. Balding hairs were transplanted from men to immune-deficient mice and they grew back to normal size even though they were like vellus hairs on the men before. Dr. Peter Proctor states on his website that microscopically baldness looks a lot like organ rejection (i.e. the immune system is why our bodies reject transplanted organs).

Bryan Shelton's pictures attest that he had a little regrowth over a two year period using Prox-N from Dr. Proctor. Prox-N is basically various SuperOxide Dismutases and peptides which fight the superoxides the body releases in an immune system attack agaisnt a particular area. The immune system attack against the hair follicles SEEMS TO DAMAGE THE BLOOD VESSELS feeding the follicles.

If I had to guess a baldness etiology it would look something like this. A guy has too many androgen receptors in his male pattern baldness area. He also makes a good level of DHT in his follicles, skin, and bod. The papilla, after recieving enough androgens in predisposed male pattern baldness areas, releases growth inhibitors that slow down cell division in the other parts of the follicle, and various bad things happen ensuingly. The immune system (perhaps ctyokines from follicle cells communicate with immuno-cells somehow, who knows?) begins to attack the follicle. The micro-capillaries that feed the follicle suffer from immuno attack and get smaller. Less hemoglobin (oxygen in blood) and growth factors from the blood reach the follicle. Keratinocytes cant produce as well resulting in a smaller follicle. Growth inhibitors released by the papilla also cause follicle to shrink. Less blood and white blood cells lead the skin around the follicle to be undernourished all the while enduring some of the immune system attack due to close proximity to the follicle. Collagen synthesis slow, collagen fibers thicken and HARDEN around the follicle, making it progressively harder for follicle to re-enlarge in next anagen phase. Telogen, catagen phases lengthen. The hair is a "signaler" for skin regeneration-Pickart. Less rejuvunation of the skin becaue of this. Immuno-attack and shrinking follicle and fibrosis and small blood vessels and low amounts of oxygen (and white blood cells to fight bacteria, fungi) to the scalp result. Baldness via miniaturization begins in earnest.

I agree with you and Tom Hagerty that reduced blood flow to microcapillaries to the scalps upper layers obviously happen in baldness. I think the immuno-attack is what does it.

I also believe due to personal observation that many men have thinnish hair with small circumference in even their hippocratic wreaths (like the drummer in Coldplay) and that even the wreath hairs have some androgen receptors and suffer a little immuno attack, but not enough to kill'em.

I currently use the big three plus a copper peptide as a regimine just because of this......I think the peptide is mucho important for these reasons.

 

[michael barry]

Stephen,
I seen this and thought of you when I saw it. Is it just me, or do these women look like they have thicker hair http://www.bevhills.com/hairlow.html

They had a hairline "lowering" procedure where some tissue expander inserted under their hair "somehow" and in the after pics....their hair looks thicker to me, not because of the hairline being necessarily lower.....but the thickness of the hair itself looks improved.

Even I have had to wonder from time to time when I hear of someone who has had a head injury having their hair grow thicker on one side of the head than the other. I seen a soldier on TV who had his head injured (badly too....poor sole, their is a big dent in his upper temple back to the top) have the hair on the injured side look a little thicker than the other side did to me. Have you ivestigated this "little" pheonoma to see If Ive just stumbled onto a couple of "freak" examples, or is it a trend. Merry Christmas by the way to all on the board....Bryan, Dave, 2tone, Stephen, hairlosstalk, onlookers

 

[Bryan]

Balding hairs were transplanted from men to immune-deficient mice and they grew back to normal size even though they were like vellus hairs on the men before.

Michael, not to be nit-picky, but let's be precise about the details: the back of a mouse is not an ideal milieu in which to grow human hairs. None of the transplanted human hairs grew to full size on the mice, not even the terminal ones...they were all "stunted" to some degree; however, the imortant fact here is that the miniaturized human hairs regrew EQUALLY AS WELL as the terminal ones, although neither ones were full size.

I agree with you and Tom Hagerty that reduced blood flow to microcapillaries to the scalps upper layers obviously happen in baldness. I think the immuno-attack is what does it.

I wouldn't assume that it works in either particular direction. In other words, does the reduced blood flow result in balding, or does balding result in reduced blood flow? We know that VEGF is released by hair follicle cells, so there may simply be less blood flow around the hair follicle as it miniaturizes just because there is less VEGF being released by the follicle itself. It's a chicken-or-the-egg type of question! :wink:

I also believe due to personal observation that many men have thinnish hair with small circumference in even their hippocratic wreaths (like the drummer in Coldplay) and that even the wreath hairs have some androgen receptors and suffer a little immuno attack, but not enough to kill'em.

Michael, that almost certainly has FAR less to do with the presence or absence of androgen receptors (ALL human hair follicles have androgen receptors, according to Whiting) than it does a different RESPONSE to androgens. The hippocratic wreath is sort of a "transition zone" where hair follicles start to go from being SUPPRESSED by androgens (like at the very top of the scalp), to being relatively UNAFFECTED by androgens, to being STIMULATED by androgens (like in beard hair, for example). I've been on a bit of a campaign the last few months to try to get people to stop focusing quite so much on relatively minor issues like quantities of androgen receptors, levels of androgens, etc. There's more to it all than just that.

Bryan

 

[2tone]

I agree with you and Tom Hagerty that reduced blood flow to microcapillaries to the scalps upper layers obviously happen in baldness. I think the immuno-attack is what does it.

I wouldn't assume that it works in either particular direction. In other words, does the reduced blood flow result in balding, or does balding result in reduced blood flow? We know that VEGF is released by hair follicle cells, so there may simply be less blood flow around the hair follicle as it miniaturizes just because there is less VEGF being released by the follicle itself. It's a chicken-or-the-egg type of question! :wink:

Yes it is

Now the procedure for turning back the clock of hair cycle growth is to damage the psilosebaceous zone follicle tissue and all .
This seems natural for the follicle unit to regress under such treatment ..

The pictorials of the follicle unit i have seen show an upward migrating hair base structure until it reaches the stable zone for vellus hair growth . At this point the blood delivery syatem has had to follow the base of the follicle as it rises ..


The base of the follicle structure rises to about the level of the gland outlet .

The added path for delivery and perhaps more importently elimination of cellular products would have to be compromised to some degree imo

However the cellular switch is triggered it would have to do in reverse what the inflammatory effect of the vellus hair switch operated .. Somehow the follicle unit must be made able to descend/fall as it were and take the blood supply capiliaries with it .

I can understand completely the correspondence with lymphatic issues because the circulation cycle path runs through the veins into the smallest capilliaries into the cellular processes and then is scavenged as it were through the passicve circulation of the Lymph glands themselves ..

Clearly the simplist bottlenecks for circlulation issues are the Capiliaries , cellular transport/flow and Lymphatic drain ..

Redusing DHT is not such a big issue imo . I think time will show quite clearly that it is the inefficient elimination of the combination of DHEA and other Adrenal gland products that at certain 'irreversable moments" ellicit the immune system response .. BUT remember the the immune system inflammation we are discussing requires cortisols and other adrenal mechanisms to be active in response .. that steroids are very solyubl;e in the Sebum means that the reserve of temporary peaks in adrenal out[puts can be stored in the gland and released over an extended period .. Its working out how to mechanically flick the switch back to the same follicle strucute that is allways going top be the issue . Eliminating DHEA/DHT does not in itself rearrange the tissue structures ..



My Question is .. If the follicle is to revert , is it the Width or the Depth that is first ??

 

[michael barry]

Bryan,
That is terriffic information. I appreciate it. Ive never considered that the smaller follicle releasing less VEGF might be what makes the capillaries grow smaller (they are servicing a tinier philo unit).

2tone, your interests in "eliminating cellular products" sounds like you might like Tom Hagerty's scalp excerscise. Its done by wrinkling the forehead, relaxing it, the pulling back the ears......twice a day for about 10 minutes. Tom believes that it pushes down metabolic waste away from the follicles thus quickening lymph draingage, while simultaneously producing excercise-induced angiogenesis above, bringing more oxygen, blood (and the various growth factors therein) back towards the hairs.

Ive read that the smaller intermediary and vellus follicles dont reside as deeply in the scalp as the terminal ones do also.

You stated that you were looking to "mechanically flick the switch back to the same follicle structure that is always going to be the top issue".....man, I tell ya, the more Ive learned about baldness......the more Im inclined to agree wtih you that some sort of gene therapy (if thats the kind of flick switching youre referring to) is proboably the only real long term solution myself. Its so much more complicated that just producing too much male hormones isnt it? However, the finasteride results do at least seem to indicate cutting hormones to predisposed follicles is a good thing doesnt it?

 

[Bryan]

...man, I tell ya, the more Ive learned about baldness......the more Im inclined to agree wtih you that some sort of gene therapy (if thats the kind of flick switching youre referring to) is proboably the only real long term solution myself. Its so much more complicated that just producing too much male hormones isnt it?

How androgens cause balding is complicated, but nevertheless, removing androgens is sufficient to stop it. We've known that androgens are necessary and are a prerequisite for balding for the last 65 years.

Bryan

 

[2tone]

Bryan,

2tone,

You stated that you were looking to "mechanically flick the switch back to the same follicle structure that is always going to be the top issue".....man, I tell ya, the more Ive learned about baldness......the more Im inclined to agree wtih you that some sort of gene therapy (if thats the kind of flick switching youre referring to) is proboably the only real long term solution myself. Its so much more complicated that just producing too much male hormones isnt it? However, the finasteride results do at least seem to indicate cutting hormones to predisposed follicles is a good thing doesnt it?

Yes in a therapeutic manner cutting Dhea/DHT to the follicles seems like a GREAT idea .. my feeling is that it is during crucial relatively "short" significant episodes (puberty etc) that 'switches' the cycle of hair growth . I think the DHT blockers are doing a relatively good job, but i dont think that blocking DHT recreates the tissue structures for Terminal hair growth in itself .. It is my expectation that blocking DHT production wikll prove useful especially over a relatively short period whereby hair growth and tissue structures are readjusted to growing "terminal" type hairs .

Foote's hypothesis at least gives the enquiring mind opportunity to see the subsystems in action so to speak ,, and by seeing the greater cast of characters we are able to write greater scripts ..

I think cutting DHT to follicles is a very important componant of the whole process .. its my opinion that DHT blocking will continue to be used .. but one thing is being shown by all the casual results out there -- hair growth does not seem to "switch" back in purely a low DHT environment .. a plasible hypothesis presents itttself that Hormones may trigger some entropic event leading to vellus growth but that the route back up the hill might find DHT blocking to be its last step not its first one when the path has to be travelled in reverse..

It seems that biological processes are very complex , the reality is that often the path from DNA to tissue metabolism is only 3-4 steps and the list of co-factors etc might only comprise 5-10 significant items ,, but the physical structure of the epidermis/psilosebaceous unit might need some alternate physical 'priming]' as it were to enable the scar tissue and cotisols and all the other healing remnants from the earlier battle to be cleared away and replaced ..

Michael , i think a ultrasound device of some sort that could soften certain structures of the epidermal tissue would be interesting , i dont think the issue is simply a circulation one . I believe the issue is a combination of events , I think circulation issues are pretty much autonomous ,, the bloodwill find its way ,, the plasma leaks back to the lymph glands .. these things are givens ,, but some other thin might need to intervene to give the thin flesh its fuller life back again . Its my opinion that hair atop of the head serves a physical property of transferring heat outwards and protecting from heat inwards , but that these natural menchanisms are being blocked , it is clearing the blockage that is a primary interest of mine , the blockage may or may not have anything to do with any of the other controlling factors (DHT/Sebum/lymph/o2/capilliaries..etc.. etc)

The pattern of hair growth indicates to me that the primary site of marginal hair loss will be at the edge of the "wreath" , and the edge of the circular structure leads a person to consider the centre when they stop to consider it properly .. so i would say the sites of most interest are about the margins of the wreath and at the centre/vertex of the scalp ..


As to wether Width or Length would be the controlling dimension for follicle hair growth , i am of the opinion that width should be the controlling factor , in that a wider follicle opening will enable a willing follicle to grow bigger , but that a longer follicle would still be a thin follicle ..

 

[michael barry]

Bryan,
You stated that "removing androgens is sufficient to stop it (balding)". The reason I was wondering about that were some statements on Dr. Proctor's site. He states that "even, CASTRATION, the commonly used treatment for prostate cancer, generally doesn't do a lot for balding and hair loss". He (Proctor) goes on to state that "the weakest antiandrogen on paper (propecia), it seems to be as effective as the others (stronger antiandrogens like cyoctal) in baldness treatment. My experience is that oral finasteride works about as well as topical spironolactone, about a 50% response rate, at one year"
The bit about castration not being all that effective set me to wondering. Ive read that in many instances, anti-androgens are not effective in older men treating AA. Proctor further states on his site "castrated males have other sources of androgens and can still experience pattern loss."

Proctor had a paragraph under the title "Emerging Model for Pattern Balding" that really "reset" my thinking back when I read it. It stated that "balding begines when male sex hormones do 'something' to the scalp hair follicle which causes it to be read as a 'foreign body'. Your immune system mounts an attack on the hair follicle. The MAIN DAMAGE in pattern hair loss is proboably immunologically-mediated. Damage to lining of blood vessels, which PRODUCES hair growth factors, makes the balding process worse". That being said, we all know that if I guy is castrated before puberty, he wont bald at all, and have hair like a woman usually does.

Bryan, you may not agree with that. Dave may not either. You pointed out that the follicle itself makes VEGF and a shrinking follicle makes less of it, so the microcapillaries may not enlarge enough to service the smaller follicle for that reason. Or perhaps cytokines somehow tell the microcapillaries that a shrinking follicle is above the capillaries and the need isnt there for them to properly enlarge. I'll never forget reading a baldness article by the Doctor Ivy Greenwell that stated (Have NO CLUE who studied this) that skid row drunks have the lowest incidence of baldness and university professors the highest. She stated in the article that she believed that it was the constant dialation of peripheral blood vessels that alchoholism brings (and the obvious fact that drunks only produce about half their normal levels of T in the first place). She is not a baldness expert however, but is a well respected Doctor. You pointed out that was a chicken-or-the-egg type argument. I think your right until some conclusive experimentation can be done. Problem is, and I think you'll agree with this, is how could science experiment in vitro on something like that? Back to the "mucho complexity in AA" epithet, no?

2tone,
You mentioned flicking the swithers and cutting DHT "during crucial relatively short signifigant episodes" that "switches" the cycle of hair growth could be helpful. Ive read that others think much the same thing, and suggested that sometime during puberty "something" happens to the follicles that make them "sensitive" to androgens (proboably based on the fact that pre-pubescent eunuchs wont bald even with androgen injections, but post pubescent eunuchs WILL bald if given androgen injections, even if they had great hair before). Kevin McElwee states that on Keratin.com (but Stephen said he could find no documentation backing that claim up, and Keratin.com doesnt provide any {Im staying outta that}). Perhaps a topical anti-androgen could be administered to boys 11-13 that wouldnt be systemically absorbed and see what happens to their hair in ensuing years? Maybe twins that expect to bald early in life......treat on and not the other? See if it at least delayed baldness?

You also mentioned that a "ultrasound device" could soften certain structures......would be interesting (to perhaps remodel tissue Im guessing from the immuno/hormonal/inflammatory events that have taken place in them previously so the follicle has an environment to re-enlarge in?). Here is a pubmed study on ELECTROMAGNETIC therapy with essential oils and baldness.....[url]http://www.ncbi.nlm.nih.go ... t=Abstract[/url] . Apparently, at the 26 week mark....the results were a decrease in hairloss in 83% of volunteers and a 20% increase in hairs over baseline in 53% of patients. An electophysiologic effect on the quiescent hair follicle was supposedly the "rationale of this phenomenon". 6 months does not a trial make, and the essential oils have been used in hairloss for a long time, so Im not claiming anything works etc. There is a company that markets an electomagnetic hair helment with essential oils called the Bx3 someting or other in Europe. This pubmed study was from the University of Medicine in Montpellier France (the Bx3 thingy is from Europe). Im as skeptical as the next guy........so who knows.

Dr. Pickart claims copper-peptides can remodel the skin over time, and having less of them as we age is an important loss in alopecia's overtaking of one's scalp. That info is on this page here http://www.folligen.com/ if you care to look. He also claims the copper ions in peptides get about a 50% inhibition of alpha 5 type 1 in the skin. He believes his folligen "reduce(ing) the generation of DHT in your scalp". The reason some of us put stock in Pickart (and you may know this if youve trawled some hairloss discussion sites for a while) is that he invented tricomin (copper peptide product) which went through a phase one and two FDA trial before the maker (Procyte) yanked it out of the final trial. The results were good in the first two trials however (Pickart had one study on his site stating that tricomin grew a little more hair than minoxidil....,etc.). Both he and Proctor believe in SOD's (cp's evidently help the body make more of this stuff to counteract the immuno-attack). Pickart has a long page going through MANY hairloss treatments and how they are supposed to work with commentaries here http://www.reverseskinaging.com/hairregrowth.html . The aminexil product supposedly helps fight fibrosis might intrigue you with how L'Oreal (the maker) thinks it can help. I agree with your, 2tone, observation that the damage around the follicle is what must make it so hard to re-enlager shrunken hairs. Hell, enough guys have been on Dutasteride by now, that if simply cutting androgens were the answer to regaining hair.....they'da done it I'd think.

By the way 2tone, do you have a regimine for your own hair? I use the big3 (minoxidil, propecia, nizoral 2x a week) plus a peptide. Nutritionally I do a few things in regards to a low-fat diet, isoflaovones, arginine, plenty of vitamin b, flaxseed oil, etc.....I also scalp excercise. Was wondering if you had therapy suggestions/ideas. Bryan has posted pictures of his success using Proctors shampoo and Prox-N (which Ive been thinking of trying for quite some time).....Im always looking to see what folks are having/not having success with......

 

[michael barry]

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

2tone, thats the pubmed article, Im hoping this link actually sends this time.....if it doesnt and you wanna see that short 2 paragraph article, youre gonna have ta' type a long web addy (I'd never type all that right on the first try : )

 

[Bryan]

Bryan,
You stated that "removing androgens is sufficient to stop it (balding)". The reason I was wondering about that were some statements on Dr. Proctor's site. He states that "even, CASTRATION, the commonly used treatment for prostate cancer, generally doesn't do a lot for balding and hair loss". He (Proctor) goes on to state that "the weakest antiandrogen on paper (propecia), it seems to be as effective as the others (stronger antiandrogens like cyoctal) in baldness treatment. My experience is that oral finasteride works about as well as topical spironolactone, about a 50% response rate, at one year"
The bit about castration not being all that effective set me to wondering. Ive read that in many instances, anti-androgens are not effective in older men treating AA.

You have to understand what Dr. Proctor MEANS in that passage. He's also referring to the regrowth of missing hair, not just the simple cessation of further balding.

Proctor further states on his site "castrated males have other sources of androgens and can still experience pattern loss."

_I_ was the one who first brought to Dr. Proctor's attention on alt.baldspot several years ago Hamilton's 1960 study which found that castration doesn't cause very much regrowth, but it _does_ stop further balding. Dr. Proctor accepts that, although he may be being ultra-cautious and conservative in what he said on his Web site! :wink: In any event, the point I'm trying to make here is that the evidence shows that if you lower androgens ENOUGH (possibly even more than what you get from castration may be required in some unusual cases), balding will be stopped. See what I'm saying? I'm not necessarily saying that it's EASY to lower androgens enough to stop balding, just that removing them or lowering them enough (if you can do it) is sufficient to stop further balding.

Proctor had a paragraph under the title "Emerging Model for Pattern Balding" that really "reset" my thinking back when I read it. It stated that "balding begines when male sex hormones do 'something' to the scalp hair follicle which causes it to be read as a 'foreign body'. Your immune system mounts an attack on the hair follicle. The MAIN DAMAGE in pattern hair loss is proboably immunologically-mediated. Damage to lining of blood vessels, which PRODUCES hair growth factors, makes the balding process worse". That being said, we all know that if I guy is castrated before puberty, he wont bald at all, and have hair like a woman usually does.

Bryan, you may not agree with that. Dave may not either.

Sure, I agree with that in very general terms, even if I'm uncertain as to the exact extent of the immune system's role in hairloss.

Bryan

 

[Bryan]

Just point out to us all Bryan where these or "ANY" other studies, "ACTUALLY" measure the comparitive size of sebaceous glands in bald, pre-bald, and hairy tissue??

This was my point as you are well aware! There is "NO" such evidence, just assumptions based on hamster flank and other irrelevant studies.

Even the section you highlighted as it it "means" something, states sebaceous gland "enlargement" as a "hypothesis" to explain the results, "NOT" a proven fact!!

Show me a study that "ACTUALLY" proves by direct measurment, that sebaceous glands in the balding human scalp "ENLARGE" compared to pre-balding?

Never mind any changes in sebum production or anything else, my point as people can read in my post was one of sebaceous gland enlargement in the male pattern baldness scalp.

Show me some evidence of "this" Bryan?

Stephen, it's been well-documented that sebum output is closely and directly related to the size of sebaceous glands, so sebum output IS an indirect measure of their size. And some relevant evidence for male pattern baldness versus non-balding sebaceous gland size appears right here in the famous Nizoral study: "Ketoconazole Shampoo: Effect of Long-Term Use in Androgenic Alopecia", Piérard-Franchimont et al, Dermatology 1998; 196: 474-477.

From the Materials and Methods section on the first page: "A total of 39 men aged between 21 and 33 years who presented with grade III vertex Androgenetic Alopecia according to the Hamilton-Norwood classification were included in the study....Controls included 22 age-matched men who had no family history of Androgenetic Alopecia and who were unaware of changes in hair quality, density or shedding." And from the Results section on the second page: "The mean sebum casual level was significantly (p<0.05) higher in Androgenetic Alopecia subjects (115 +/- 47 ug/cm^2) than in controls (69 +/- 44 ug/cm^2)."

There's you some simple evidence that sebaceous glands in Androgenetic Alopecia scalps are larger (on average) than sebaceous glands in non-balding scalps. Of course, I'm sure that you'll try to find some kind of "spin" to put on that, as usual! :wink:

Bryan

 

[S Foote.]

Just point out to us all Bryan where these or "ANY" other studies, "ACTUALLY" measure the comparitive size of sebaceous glands in bald, pre-bald, and hairy tissue??

This was my point as you are well aware! There is "NO" such evidence, just assumptions based on hamster flank and other irrelevant studies.

Even the section you highlighted as it it "means" something, states sebaceous gland "enlargement" as a "hypothesis" to explain the results, "NOT" a proven fact!!

Show me a study that "ACTUALLY" proves by direct measurment, that sebaceous glands in the balding human scalp "ENLARGE" compared to pre-balding?

Never mind any changes in sebum production or anything else, my point as people can read in my post was one of sebaceous gland enlargement in the male pattern baldness scalp.

Show me some evidence of "this" Bryan?

Stephen, it's been well-documented that sebum output is closely and directly related to the size of sebaceous glands, so sebum output IS an indirect measure of their size. And some relevant evidence for male pattern baldness versus non-balding sebaceous gland size appears right here in the famous Nizoral study: "Ketoconazole Shampoo: Effect of Long-Term Use in Androgenic Alopecia", Piérard-Franchimont et al, Dermatology 1998; 196: 474-477.

From the Materials and Methods section on the first page: "A total of 39 men aged between 21 and 33 years who presented with grade III vertex Androgenetic Alopecia according to the Hamilton-Norwood classification were included in the study....Controls included 22 age-matched men who had no family history of Androgenetic Alopecia and who were unaware of changes in hair quality, density or shedding." And from the Results section on the second page: "The mean sebum casual level was significantly (p<0.05) higher in Androgenetic Alopecia subjects (115 +/- 47 ug/cm^2) than in controls (69 +/- 44 ug/cm^2)."

There's you some simple evidence that sebaceous glands in Androgenetic Alopecia scalps are larger (on average) than sebaceous glands in non-balding scalps. Of course, I'm sure that you'll try to find some kind of "spin" to put on that, as usual! :wink:

Bryan

But this is just another of the assumptions that seems to be par for the course in hair loss and related research Bryan!

The "specific" question i asked was for evidence of increasing sebaceous gland "size" in male pattern baldness, as you claimed happened!

In the study you quote above, did the controls have the tested areas shaved for a long enough period during this testing? This would have rulled out any effect of sebum pick up by the hair reducing the scalp sebum levels measured.

In the male pattern baldness subjects, the sebum is just lying there waiting to be picked up by the sebutape, so of course there is going to be a higher reading of sebum in this case.

This has nothing at all to do with any accurate measurement of the gland size itself does it!

The trouble is Bryan, you always just cherry pick the data to suit your arguments, and fail to judge the validity in a proper scientific way.

Your interpretation of the in-vitro studies is a good example!

Despite the fact that androgens don't directly "change" follicle growth in-vitro, you still claim that androgens will directly change normal follicles into male pattern baldness follicles given time. You make this claim because male pattern baldness samples "are" directly growth restricted by androgens in-vitro.

So you have said in this thread that this is compelling evidence for a direct effect of androgens on follicle growth in-vivo.

But your assumption just cannot be right when all the evidence is considered Bryan :roll:

The mouse transplantation study you refer to here and elsewere, shows that male pattern baldness follicles can re-enlarge in the right conditions. The immuno-deficient mice are "not" androgen deficient, so there can be no "direct" effect of androgens keeping male pattern baldness follicles small can there!

If you are going to argue that the immunology that is missing in these mice is important, and androgens must therefore be "directly" effecting follicles via immune effects, then where was the "immunology" in the test tube Bryan?

You claimed that the in-vitro effect of androgens on male pattern baldness samples, was an accurate reflection of the in-vivo situation. Quite obviously it is not!

So the conclusion must be that however androgens are restricting growth in male pattern baldness follicles "directly" in the in-vitro tests, this has nothing to do with the "actual" mechanism in-vivo! The in-vitro results are not then a valid scientific model in male pattern baldness as you try to claim :wink:

S Foote.

 

[S Foote.]

LOL!!! That's not good enough, Stephen! You have to find another example in biology where contact inhibition caused a CHANGE IN THE RESPONSE OF SOME BODY TISSUE TO ANDROGENS WHICH CONSISTED OF THE UPREGULATION OF TGF BETA-1. We're not going to let you get away with a form of "guilt by association"! It's "Put-Up or Shut-Up Time" for you: either find an example of that happening somewhere else, or get your butt back to the drawing-board.

I did precisely what you ask above in a previous debate as you know Bryan, and i certainly don't have to "prove" anything to "you" do i :wink:

You have never once given me such an example, and it saddens me that you cannot bring yourself to acknowledge the truth, even on Christmas.

Bryan

What i "have" clearly shown you before as you well know, is that a cells growth response to androgens can be reversed due to the influence of another factor that alters growth gene expression within the cells.

I have recently lost all my links when my computer crashed, but this was the prostate cell type that reversed it's growth response to androgens when the cells became cancerous.

The cancerous transformation obviously alters growth gene expression. Contact inhibition also alters growth gene expression, so the prostate cell example shows that a similar "flip" in androgen response of cells could be possible because of prior changes induced by contact inhibition.

Your previous attempt to "spin" this issue just showed your ignorence of the science Bryan :wink:

S Foote.