A start in the potential importance of the wider Hormonal (androgen) metabolism apart from 5a reductase & 5a DHT

[curlwaves]

Part 1 androgen metabolism.
While I'm sure there's been conversations about this. I feel like there should be more conversations and studies.

I feel like part of the problems in Androgenetic Alopecia is also things like hormone metabolism.
Hormones are really complex and I think for that reason people and even scholars don't always dive as deep as they should.

I'll insert the graph I got from wiki. Showing mostly androgen pathway. I think the interesting part starts from testosterone downward. What this graph seems to show is what many others graphs seem to ignore. Most only show the left side and not the right. Obviously this is only one side. And estrogens and other hormone groups likely are important as well. But potentially aligning these right can give us a favourable profile to work towards all while trying to manage other factors.

Graph 1: androgen metabolism

Definitely fill in gaps in the puzzle because I'm in no ways near a complete hypothesis or solutions!!!

So my frustration/confusion surrounding this is that the left side (alpha) is alot more prominent and studied compared to the right (beta).
We see alot of studies implicating and getting good results managing 5A! REDUCTASE enzyme nd 5 A! DHT hormone.
So based on that I have a feeling this is mostly the "bad" guy involved in terms of actually causing damage.

The reason why I feel that way is What I find interesting in this study on the vascular aspect of androgens. And it showed differences between different androgens, obviously. 5a DHT is more androgenic and less affect on vasodilation than testosterone. But not just that, it's more androgenic and way less vasodilating that 5beta DHT. Which seems to be less studied and present. While many people seem to say that vasodilation and blood flow doesn't have sh*t to do with hair loss. I think any logically thinker would beg to differ. Without blood flow tissue can simply not sustain let alone thrive.
Changing that balance be beneficial in reducing androgenic impact. All the while improving vasodilation. Few people talk about these differences but they seem extremely important. Obviously I have to put a disclaimer that this is not a study on hair. But promising nonetheless

Study link: androgen vascular

Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites - PMC

The marked sexual dimorphism that exists in human cardiovascular diseases has led to the dogmatic concept that testosterone (Tes) has deleterious effects and exacerbates the development of cardiovascular disease in males. While some animal studies ...

pmc.ncbi.nlm.nih.gov

I do think we need to look into also the effects of different metabolites as well
Looking at the metabolites left to right below DHT.
We see that depending on the isomer and the enzyme you get 4 different types which are then metabolised to 4 other metabolites.

The first metabolite (alpha)and it's secondary metabolite function both as weak androgens. Androsterone is often used as a measure for doping testing I believe. But is potentially problematic in that It can be converted back to DHT using the same enzymes according to wiki. Making this alpha pathways partly like a loop. Which may partly be responsible for the loop like aspect we see in Androgenetic Alopecia.

The second metabolite (beta)
Is kind of different it actually binds to estrogen receptor (beta), is a weak estrogen. And supposedly anti proliferate for prostate cancer cells. And beneficial affects of anxiety, depression etc. it can be synthesized from DHT and dhea. Showing this could be potentially beneficial. It's metabolite has weak androgens activity tho.

It's hard to find good information on the metabolites of 5b DHT. Apart from etiocholanolone which seems to be involved in fever/ the immune system. Which may or may not be beneficial right now I'm inconclusive.

There's not enough info on managing various enzymes apart from finasteride and dusteride. And that some are implicated in hirusitism.

I suspect that changing enzyme balances apart from 5a reductase can be even more beneficial.
For example increasing 5B Reductase. Or increasing 3b hsd and 17b hsd. This would reduce 5a DHT impact and potential improve things simultaneously.
But information is sparse.

One thing that would be good is to look into the safest pathways. Due to the fact that some metabolites and hormones can be synthesized through backdoor pathways. And looking into hormone interactions.

Definitely would appreciate anyone who could add to this.
So I'll leave it here for now until I have more time.

 

[Jakejr]

Maybe you are on to something I’m not a expert on hormones, but males are healthy for the most part whether they have hair or no hair.. So it’s just part of nature.. DHT at some point starts to signal hair follicle/stem cells to stop growing..And this deterioration affects balding & non balding areas.. Also affects pigmentation of hair turning grey .. than white .. DHT may in fact be healthy to have.. so by severely reducing it may have unwanted side effects..
But I appreciate your creativity & effort

 

[Carbons]

Maybe you are on to something I’m not a expert on hormones, but males are healthy for the most part whether they have hair or no hair.. So it’s just part of nature.. DHT at some point starts to signal hair follicle/stem cells to stop growing..And this deterioration affects balding & non balding areas.. Also affects pigmentation of hair turning grey .. than white .. DHT may in fact be healthy to have.. so by severely reducing it may have unwanted side effects..
But I appreciate your creativity & effort

Not sure that's entirely true? Aren't there stats that show heart disease is higher in balding people? May well indicate there is system wide damage to the vascular system that also impacts hair surely?

 

[curlwaves]

Not sure that's entirely true? Aren't there stats that show heart disease is higher in balding people? May well indicate there is system wide damage to the vascular system that also impacts hair surely?

I agree. Studies do seem to support that.
And we need to keep in mind DHT is potent! We don't need nearly as much to have an affect. Furthermore testosterone does alot as well. I'm not saying it has to be eliminated a 100% but it's likely many people have too high levels.

And the point of this post, the metabolism is also very important. If it doesn't turn into the metabolites it may overdo it's function leading to more problems.

 

[coolio]

Bad health can make baldness worse, and yet the primary cause of baldness is not usually bad health. Those two things can both be true at once.

Malnourishment correlates with short height. But most short guys are not malnourished.

Same principle with bald men and high DHT. Most bald guys don't have too much DHT, they have hair follicles that respond too strongly to normal amounts of DHT.

Blocking DHT is a shitty way to try to fight the problem. It works (barely at all, with side effects) but that doesn't prove it's a decent solution in the big picture. We need something better and IMO we're wasting our time trying to find new & interesting ways to block DHT. You can chemically castrate a balding man and he still won't regrow a lot of hair. The whole approach just doesn't work very well, period.

 

[curlwaves]

Bad health can make baldness worse, and yet the primary cause of baldness is not usually bad health. Those two things can both be true at once.

Malnourishment correlates with short height. But most short guys are not malnourished.

Same principle with bald men and high DHT. Most bald guys don't have too much DHT, they have hair follicles that respond too strongly to normal amounts of DHT.

Blocking DHT is a shitty way to try to fight the problem. It works (barely at all, with side effects) but that doesn't prove it's a decent solution in the big picture. We need something better and IMO we're wasting our time trying to find new & interesting ways to block DHT. You can chemically castrate a balding man and he still won't regrow a lot of hair. The whole approach just doesn't work very well, period.

I do not agree in the slightest. You're comparing apples to oranges. And I feel like you didn't truly read my post because it doesn't just touch on the androgen pathway.

Healthier people do tend to suffer less from hair loss. And as we age our health decreases and guess what alopecia increases.

Do people actually have a study to support this "sensitivity thing". I'm not saying it's not true at all. But sensitivity is like a baby words way of trying to explain it to people that don't know anything about Androgenetic Alopecia.

Different studies show increases in expression of various negative factors. Which is not the same. High DHT is not a clear statement. You have localized DHT and serum DHT. There have been studies showing high serum DHT but not all show this correlation. What this could mean is that localized DHT can be independently harmful regardless of serum. But that high serum may still contribute to damage. Rather than DHT not being implicated at all.

Some people do have regrowth. Secondly damage does not automatically reverse just by removing a trigger. When you cut yourself many people have scars forever. Not all damage heals perfectly and many people with injuries suffer life long. The same principle goes for Androgenetic Alopecia as well. Damage may not naturally reverse even when the triggers are gone. Hence why prevention is better than healing.

That's where a big problem is trying to reverse the damage rather than just removing triggers. This doesn't mean anti androgens aren't beneficial. Not going anti would allow alopecia to persist and lead to worse outcomes.

So the benefits are there especially when some studies have shown benefits to taking them preemptively like hormone balancing herbs or foods.
So I don't agree at all. Anti androgens are important but I do agree we need to support it more to fight other factors. But the base should be there.