Can someone explain why exactly reversing slick bald areas is so difficult?

[KO1]

I would say the main reason reversing slick bald areas is, as per Cotsarelis, the progenitor cell population simply does not exist in the bulge in bald areas. The dermal papilla is all but gone, either dead or senescent, so there is not much happening.

Even then, occaisionally some guys do regrow hair on slick bald areas with meds like fin and minox, there is one guy who has gotten regrowth on gefitinib.

My opinion: a few things need to be done. We need to convince the stem cells in the bulge to proliferate and form progenitor cells. I suspect the best way we have for that is wounding+Wnt-PGD2+PGE2. Hand in hand is we need to rebuild the dermal papilla. That I have no idea how to do.

[bbbeeeppp3]

@bbbeeeppp3

It is possible to reverse damage and to regrow hair in androgenetic alopecia. I have gone myself NW4 to NW2 with treatments (Now a NW1 though). I have seen reversal of androgenetic alopecia to great extent and sometimes full. It's also known in literature. It's just not common at all. Estrogen + castration is the best method known of sometimes causing (full) reversal of androgenetic alopecia.

Anyway there are all different forms of hairloss

- Androgenetic alopecia (reversible)
- Alopecia areata (reversible, auto-immune, mechanism fully understood)
- Scarring Alopecia's (irreversible, fibrosis & scarring)
- Senescence (aging) alopecia (unknown)

To answer your question though why it is so difficult. There is one answer; nobody full understands yet. However multiple researchers are pointing out extremely hard evidence lately to important factors which are implicated in androgenetic alopecia;

- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828374/
- http://www.ncbi.nlm.nih.gov/pubmed/17989730
- http://www.ncbi.nlm.nih.gov/pubmed/18702626
- http://www.ncbi.nlm.nih.gov/pubmed/25647436
- http://www.papersearch.net/view/deta...l_key=27731029

There are like 3 or 4 more studies of other researchers who point out the same problems. Anyway you don't need to read them as they might be hard to understand. I can translate it to you in a simple manner though. Your hair follicle consists of different types of cells. Your whole body does. Every cell is a little organism, literally a working horse. Every cell can decide his own cell fate. A cell can decide to profilerate, they can die (apoptosis), and they can also lock itself (senescence). Among some other actions.

Now your hair follicle consists of a extremely important type of mesenchymal type of cells. These cells initially kind of made your whole hair follicle when you were in the embryogenesis state. These cells are called the dermal papilla. They can be seen as a master regulator of the hair follicle. I don't exactly remember how much dermal papilla cells there are present in every hair follicle but I think the number was 500. They are the mastor regulator of the hair follicle basically. They also harness the androgen receptors of the hair follicle.

Now I think you already know androgens are bad. Imagine now the androgens coming through the blood attaching to the androgen receptor to the dermal papilla. These 500 cells of the dermal papilla receive that signal. However in a person with androgenetic alopecia something is causing them to get stressed out like hell. The researchers refer to this as "oxidative stress" & "dna damage" in the studies I just showed you. You remember that I mentioned that cells can decide their own cell fate right? Well so these researchers point out that these cells react to this stress. After all prolonged stress isn't good at all for cells and they adapt in an efficient manner. What do they do? Every cell individually at a certain moment has had enough of it and goes in a permanent lock of cell arrest. That's how they shield itself from the stress from preventing further damage. Problem is this lock is extremely hard to unlock. They locked itself down for a reason and the pathways responsible for this are a extremely important function of the cells in your body. Without them you wouldn't survive. This mechanism also protects you from oncogene (cancer) transformation for example.

Now the fun thing is remember; estrogen? Estrogen has impact on these pathways and can override this cell fate lock. A fun fact is also with that that estrogen is seen as a cancerous compound. There is way more proof for these researchers that this really seems to be the problem. This is also the case when you observe AGA. For instance the amount of dermal papilla cells correlate with hair size. So if you have 500 dermal papilla cells in a normal cell fate you have a fully terminal hair. However when some of these cells decide to die or adopt a state of cell arrest your hair follicle get's smaller.

Anyway that's it in a nutshell. You can basically kinda view androgenetic alopecia like premature aging of the cells. I can only give you one tip furthermore; Try to work with the current treatments we have. The outlook for the coming 10 years is pretty bad to give better options than we have currently. You can come very far with current methods too. Take the matter in your owns hands. Wishing & hoping for better treatments is a joke. Most likely it isn't going to come short-term or mid-term. Good luck!

Thanks for the reply Swoop.

I have one followup question though, I assume that a thinning hair that's not yet slick bald is due to the follicle having a large number of senescence cells, but still enough left to grow a thin hair? If this is true, then how come hair follicles with some non-senescence DP hairs can restore themselves after the DHT related stress is removed with Dut or Fin for example, but hair follicles with a DP that is commonly full of senescence cells can't restore themselves even when the original source of stress has been removed? I'm guessing it's because the non-senescence cells can divide and replace the senescence ones after the source of stress has been removed, but when all cells are senescence this process can't occur?

Also, how did you go from a NW4 to a NW1? Dut/Fin + Min and a HT?

[Swooping]

Thanks for the reply Swoop.

I have one followup question though, I assume that a thinning hair that's not yet slick bald is due to the follicle having a large number of senescence cells, but still enough left to grow a thin hair? If this is true, then how come hair follicles with some non-senescence DP hairs can restore themselves after the DHT related stress is removed with Dut or Fin for example, but hair follicles with a DP that is commonly full of senescence cells can't restore themselves even when the original source of stress has been removed? I'm guessing it's because the non-senescence cells can divide and replace the senescence ones after the source of stress has been removed, but when all cells are senescence this process can't occur?

You are correct that senescent cells lack proliferation and they don't divide. They also show a altered gene expression. They also enlarge and show a flattened morphology. They are dysfunctional and useless basically. You know sometimes people only start showing temple recession when they are older? That’s strange because testosterone levels decline when you get older and subsequently your DHT. Kinda paradoxical isn't it? Why didn't the cells succumb when they were under higher DHT levels?

The dermal papilla cells, all of them will individually decide their cell fate under this stress and that really depends on the dosage and duration of exposure to the stress in AGA. This will differ in every individual. Also It’s not like all dermal papilla cells will say in a synchronizing state we are going to senescent now. If that would happen you would lose your hair immediately and not even have a miniaturized hair shaft. Every cell is a individual organism.

Again the dermal papilla are the most important part of the hair follicle. It is them who also instruct the bulge and progenitors cells what to do. Lower counts of dermal papilla correlates to human hair size and dermal papilla type correlates to hair type (curly, straight, zigzag etc). In mice depleting only 10 dermal papilla cells out of 25 can cause a lack of anagen onset and even less can make a difference in hair follicle size. Check these studies for example to get more on this subject.

http://www.nature.com/jid/journal/v1.../5600534a.html
http://www.ncbi.nlm.nih.gov/pubmed/23487317

When someone takes finasteride and they are lucky they might turn their miniaturized hair follicle into a terminal hair follicle again. Again from a cell perspective it’s easy to explain this. You remove the threshold of stress from the cells and DNA repair genes (or other pathways) can repair the cells if they didn’t create a lock yet, if they feel that it's the best option. Sometimes it also happens that people take finasteride and see those small vellus – half terminal hair follicles. Yet they don’t want to grow any longer to the previous state. In that specific situation some cells already decided to not repair themselves and stay into a senescent state while some didn’t adopt this cell fate “lock” yet and are healthy. Every individual will differ in this. Hope that helps a bit.

The hair follicle bulb: The dermal papilla (green cells at the center of the hair bulb) serves as both a physical and chemical niche that regulates the activity of adjacent epithelial progenitor cells (unlabelled except for a red nuclear stain) that produce the hair shaft and its surrounding inner root sheath.

Also, how did you go from a NW4 to a NW1? Dut/Fin + Min and a HT?

Yeah I went from NW4 to NW2, then I cut back in my regimen. When I cut back I became a NW3, and went for a HT. Currently only on RU. I was on minoxidil + retin-a + hydrocortisone + RU in my initial regimen.

http://s2.postimg.org/ygwwrdhbd/Hakan_preview_big.jpg
2 weeks; http://s30.postimg.org/cqzpwjasx/14days_post_op.jpg

That's my HT, 2835 grafts. Just waiting for it to grow all in now! May the hair follicle gods be with you .

[cocacola]

Do u have pictures of ur progress from ur regimen, pre-ht.