3alpha-hydroxysteroid reductase and hair loss - a theory from Tressless

[fugged]

Next time someone tells you the ancient Egyptians were communicating with aliens and had all this crazy knowledge, remember they rubbed hippo fat on their heads for hair loss.

 

[fugged]

I cant say Ive kept up on the science enough to refute or get too emboldened by this, and it does seem to have some bold claims and un cited statements along with some possible contradictions, but he isn't claiming credit and its a possible cheap solution that doesn't seem overly profitable so it should be carefully and thoughtfully disproven, not sarcastically and over-dismissively imo.. since we know from experience that we tend to do this very easily this when communicating online. On the other hand, its a bit ironic that some of these things, like procyanidin B2 is already marketed for hair loss.. not saying this is happening here, but its not beyond the scope of clever a**h** humans to come up with something like this to spread false hopes, knowing full well it will eventually translate into thousands of desperate online lurkers purchasing something online... While hope may be out there, so, for sure, are the sharks.

 

[pegasus2]

No its not, half the science is wrong and he's coming to conclusions without providing any proof that his claims are true. It's fiction.

For instance he also claims when hairs are transplanted into bald areas other (not transplanted hairs) start growing besides the graft (they don't) and claims this is due to qoroum sensing... which it isn't.

An example of Qoroum sensing is when you pluck a follicle and it sends signals to surrounding ones to grow. Putting a graft in the scalp does not have the same effect and theres no evidence that it does.. yet he's decided thats a fact and hasn't cited anything.

He does it constantly throughout. Anyone reading this and giving it a modicum of legitimacy is wasting their time

Sweet! A half transplant will yield a full head of hair.

 

[kidcurry96]

I cant say Ive kept up on the science enough to refute or get too emboldened by this, and it does seem to have some bold claims and un cited statements along with some possible contradictions, but he isn't claiming credit and its a possible cheap solution that doesn't seem overly profitable so it should be carefully and thoughtfully disproven, not sarcastically and over-dismissively imo.. since we know from experience that we tend to do this very easily this when communicating online. On the other hand, its a bit ironic that some of these things, like procyanidin B2 is already marketed for hair loss.. not saying this is happening here, but its not beyond the scope of clever a**h** humans to come up with something like this to spread false hopes, knowing full well it will eventually translate into thousands of desperate online lurkers purchasing something online... While hope may be out there, so, for sure, are the sharks.

Maybe there is some some science behind the theory but I dont know enough about hairloss to refute it. I dont know if the supplements being touted could do any damage.

 

[Seuxin]

Hi guys,

For information, i used Sulphoraphane 4 month , 6 month ago ( i'm on Oral dutasteride + Minoxidil ( containing tretinoine, melatonine, adenosine and WAY ).

Not a single regrowth or hair improvement related to the add of Sulphoraphane. You can try it...it's cheap.

 

[czecha]

There is no doubt that an altered hormonal synthesis cascade is one of the main drivers of baldness.
Since we know that epitestosterone is lacking in balding follicles that potentially implicates a lack of 17a-hydroxysteroid-dehydrogenase. The upregulated androgen receptors & 5-AR in balding follicles are more likely to be a result of that, rather than the cause themselves (as the missing anti-androgen would regulate both of those factors). It is then quite plausible that the dysregulation involves more enzymes, 3a-HSD could also be one of the affected ones.

Of course the question is where the whole chain starts, which we don't really have enough information to answer. Research about the true etiology of baldness at a more insightful level than 'muh DHT & genetics' is needed and lacking, unfortunately.

I find the theory kind of interesting because I stumbled on Androstenedione like 2 days prior in some research. Here is what I researched:

high dose finasteride and dutasteride users seem to be reporting more hair growth and side effects than on low doses, despite the dht inhibition curve being flat. This includes experiments by @pegasus2 and @ChemHead as well as another trusted member on discord. So my logic was another hormone must be up or downregulated more dose dependent than dht thru 5ar inhibition.

then i stumbled on a study in which up to 100mg finasteride were given to patients. 1990 i think. They had same hormonal changes than normal dose finasteride users. Except that in high doses androstenedione was upregulated but not in low doses. They only did this for 11days tho so no hair results were reported.

one guy on HairLossTalk.com also linked a hairlosshelp thread and said „this guy cured his male pattern baldness with 50mg finasteride/day“ but the link has expired/hlh doesn’t exist anymore

i think finding out what happens on high dose finasteride would be interesting. I’m doubtful it just comes down to a few more % of dht inhibition

maybe raising androstenedione is what grows hair
It also seems to grow boobs though

"In men, too much androstenedione may lead to an imbalance in oestrogen and testosterone production, leading to changes such as breast development. Depending on the cause of the excess androstenedione, other changes, such as the testes becoming smaller, might also occur."

 

[whatevr]

I find the theory kind of interesting because I stumbled on Androstenedione like 2 days prior in some research. Here is what I researched:

high dose finasteride and dutasteride users seem to be reporting more hair growth and side effects than on low doses, despite the dht inhibition curve being flat. This includes experiments by @pegasus2 and @ChemHead as well as another trusted member on discord. So my logic was another hormone must be up or downregulated more dose dependent than dht thru 5ar inhibition.

then i stumbled on a study in which up to 100mg finasteride were given to patients. 1990 i think. They had same hormonal changes than normal dose finasteride users. Except that in high doses androstenedione was upregulated but not in low doses. They only did this for 11days tho so no hair results were reported.

one guy on HairLossTalk.com also linked a hairlosshelp thread and said „this guy cured his male pattern baldness with 50mg finasteride/day“ but the link has expired/hlh doesn’t exist anymore

i think finding out what happens on high dose finasteride would be interesting. I’m doubtful it just comes down to a few more % of dht inhibition

maybe raising androstenedione is what grows hair
It also seems to grow boobs though

"In men, too much androstenedione may lead to an imbalance in oestrogen and testosterone production, leading to changes such as breast development. Depending on the cause of the excess androstenedione, other changes, such as the testes becoming smaller, might also occur."

Well, I am glad you brought this up, because there is this quite old study which sheds some light on the matter.

5 alpha-reductase inhibitors, chemical and clinical models - PubMed

An active site model of 5 alpha-reductase type 2 isoenzyme on an "active-analog approach" and based on 4-azasteroidal inhibitors has been constructed to evaluate the effects on the inhibitory potency of substituents on the steroid A ring. This model has proven able to predict the potential...

pubmed.ncbi.nlm.nih.gov

Relevant quotes:

For finasteride, which is already used for the treatment of BPH and was recently proposed for the treatment of alopecia, IC50 in prostate and scalp homogenates have been measured as 5.9 +/-0.3 nM and 310+/-33 nM, respectively. (>50 times less effective in scalp than in prostate)

With these experimental data, a concentration of 94 nM causes a calculated 85% inhibition of prostate homogenate 5aR. McConnell et al. measured the DHT reduction in prostatic tissue after 7 days administration of finasteride at 5 mg/day in BPH patients and found '85% DHT reduction versus placebo. The same concentration causes only 25% inhibition of scalp homogenate 5aR.

Dallob et al.18 measured the DHT reduction in scalp skin after 28 days administration of 5 mg/day of finasteride to balding men and found a 35% reduction from baseline.

It is possible to extrapolate from the IC50 curve of finasteride in scalp homogenates that to obtain a level of inhibition similar to that with 5 mg of finasteride in the prostate the concentration in plasma needs to be 1 mM, a value obtained after bolus administration of 50 mg of finasteride.


So basically, the pharmacodynamics of the drug are not in your favor at all. Finasteride inhibits DHT far more effectively in the serum, prostate, and most other tissues than in the scalp where you actually want it, and to achieve the same inhibition in the scalp as you get in the prostate, you'd have to take 50 mg. At which point taking Dutasteride seems like a better option.

 

[czecha]

Well, I am glad you brought this up, because there is this quite old study which sheds some light on the matter.

5 alpha-reductase inhibitors, chemical and clinical models - PubMed

An active site model of 5 alpha-reductase type 2 isoenzyme on an "active-analog approach" and based on 4-azasteroidal inhibitors has been constructed to evaluate the effects on the inhibitory potency of substituents on the steroid A ring. This model has proven able to predict the potential...

pubmed.ncbi.nlm.nih.gov

Relevant quotes:

For finasteride, which is already used for the treatment of BPH and was recently proposed for the treatment of alopecia, IC50 in prostate and scalp homogenates have been measured as 5.9 +/-0.3 nM and 310+/-33 nM, respectively. (>50 times less effective in scalp than in prostate)

With these experimental data, a concentration of 94 nM causes a calculated 85% inhibition of prostate homogenate 5aR. McConnell et al. measured the DHT reduction in prostatic tissue after 7 days administration of finasteride at 5 mg/day in BPH patients and found '85% DHT reduction versus placebo. The same concentration causes only 25% inhibition of scalp homogenate 5aR.

Dallob et al.18 measured the DHT reduction in scalp skin after 28 days administration of 5 mg/day of finasteride to balding men and found a 35% reduction from baseline.

It is possible to extrapolate from the IC50 curve of finasteride in scalp homogenates that to obtain a level of inhibition similar to that with 5 mg of finasteride in the prostate the concentration in plasma needs to be 1 mM, a value obtained after bolus administration of 50 mg of finasteride.


So basically, the pharmacodynamics of the drug are not in your favor at all. Finasteride inhibits DHT far more effectively in the serum, prostate, and most other tissues than in the scalp where you actually want it, and to achieve the same inhibition in the scalp as you get in the prostate, you'd have to take 50 mg. At which point taking Dutasteride seems like a better option.

So the flat dht curve is complete cope because what happens in tissue is much more important than serum...
Whats with the androstenedione? Would there be a safe way to boost it without nuking dht?

 

[whatevr]

So the flat dht curve is complete cope because what happens in tissue is much more important than serum...
Whats with the androstenedione? Would there be a safe way to boost it without nuking dht?

Bingo.

Re- androstenedione, I had to look it up.

"endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepiandrosterone (DHEA)."

On first glance I would say that if it is helping hair it is probably because it converts into estrone and then into estradiol, but I am not sure.

 

[Catagen]

So the flat dht curve is complete cope because what happens in tissue is much more important than serum...
Whats with the androstenedione? Would there be a safe way to boost it without nuking dht?

Yes, serum is irrelevant. 2.5mg dutasteride wipes out almost 80% of scalp DHT in this study(https://pubmed.ncbi.nlm.nih.gov/17110217/) vs 0.5mg which does around 50% which is not much better then finasteride which is around 40%. The higher the dose the better then inhibition. Interesting enough taking 2.5mg dutasteride caused 222% scalp T increase.

Bingo.

Re- androstenedione, I had to look it up.

"endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepiandrosterone (DHEA)."

On first glance I would say that if it is helping hair it is probably because it converts into estrone and then into estradiol, but I am not sure.

What do you think about Ray Peatists and their methods.

 

[whatevr]

What do you think about Ray Peatists and their methods.

A lot of the stuff there (increasing thyroid, vitamin D, supplements) boosts androgens, and they like inhibiting estrogen, so it's a good way to lose even more hair very fast. No good IMO.

 

[Catagen]

A lot of the stuff there (increasing thyroid, vitamin D, supplements) boosts androgens, and they like inhibiting estrogen, so it's a good way to lose even more hair very fast. No good IMO.

Indeed, their leader is bald and fat. And Danny Roddy was never balding.
I presume they buy into the theory that hair loss is caused by excess estrogen and lack of androgens, which is shown in practice, with pictures, to not be true.
They claim they can regrow multiple norwoods, however they haven't posted a single picture.

 

[whatevr]

Indeed, their leader is bald and fat. And Danny Roddy was never balding.
I presume they buy into the theory that hair loss is caused by excess estrogen and lack of androgens, which is shown in practice, with pictures, to not be true.
They claim they can regrow multiple norwoods, however they haven't posted a single picture.

I think it's a good approach for general health, and that may be what most of the members there are interested in, which is fine, but it should be known then that this is at odds with keeping your hair. Roddy is someone who never had male pattern baldness, and he's luring in noobs promising them they'll keep their hair, which is disingenuous at best.

 

[Catagen]

I think it's a good approach for general health, and that may be what most of the members there are interested in, which is fine, but it should be known then that this is at odds with keeping your hair. Roddy is someone who never had male pattern baldness, and he's luring in noobs promising them they'll keep their hair, which is disingenuous at best.

I dont even think that they have a good approach for general health which is based off mice models. Maybe they once did, today they are all conspiracy theorists.

 

[Selb]

Yes, serum is irrelevant. 2.5mg dutasteride wipes out almost 80% of scalp DHT in this study(https://pubmed.ncbi.nlm.nih.gov/17110217/) vs 0.5mg which does around 50% which is not much better then finasteride which is around 40%. The higher the dose the better then inhibition. Interesting enough taking 2.5mg dutasteride caused 222% scalp T increase.

What do you think about Ray Peatists and their methods.

I’ve always suspected that it’s tissue dht that’s more dose dependent compared to serum dht inhibition. Though it’s surprising that for a lot of people, 1 mg finasteride or 40% scalp dht inhibition as you said is effective to stop or slow balding

 

[joaopassos4444]

I cant say Ive kept up on the science enough to refute or get too emboldened by this, and it does seem to have some bold claims and un cited statements along with some possible contradictions, but he isn't claiming credit and its a possible cheap solution that doesn't seem overly profitable so it should be carefully and thoughtfully disproven, not sarcastically and over-dismissively imo.. since we know from experience that we tend to do this very easily this when communicating online. On the other hand, its a bit ironic that some of these things, like procyanidin B2 is already marketed for hair loss.. not saying this is happening here, but its not beyond the scope of clever a**h** humans to come up with something like this to spread false hopes, knowing full well it will eventually translate into thousands of desperate online lurkers purchasing something online... While hope may be out there, so, for sure, are the sharks.

I would like to answer some of this questions, but HLS doesn't allow me privileges. How long do I have to wait to post a reply with enough words here?

 

[joaopassos4444]

Apparently I can use few words, if someone please could copy paste my other post, I adress things that are pertinent here and I hope you guys could help validate or refute, but at least have a look at some things that have been neglected for over 70 years of hair loss research.

https://www.reddit.com/r/tressless/comments/myybke

 

[joaopassos4444]

Everything that increases 3ADH grows hair, like minoxidil, procyanidin and even brocoli sprouts. Everything that decreases 3ADH induces early hair loss like nicotine and accutane etc. This is the best I got. Nicotine source (https://www.sciencedirect.com/science/article/abs/pii/S0024320588800018) The apparent 5α-reductase activity was unaffected by nicotine and cotinine. The inhibitors produced a marked effect on activity of HSD when used in concentrations achieved in humans who smoke cigarettes. The results suggest that nicotine and cotinine are competitive inhibitors of the HSD, an important enzyme involved in the metabolism of DHT and produce an accumulation of DHT. These products of cigarette smoking could alter androgen action in tissue such as skin and prostate.

About SSRI I will actually adress a comment another user posted on the post:


"I believe you've connected the dots for me. After reading your post, I immediately searched for studies linking depression and 3alpha enzymes. Get a load of this: "Concentrations of 3alpha-reduced neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy with selective serotonin re-uptake inhibitors (SSRIs)." (Source: https://pubmed.ncbi.nlm.nih.gov/16344854/)



Furthermore, millennials are seemingly experiencing hair loss earlier than previous generations. It's no surprise that our rates of depression are also higher. I imagine that issues like chronic stress can also play a role, but this also explains the fact that "The prevalence of personality disorders in subjects with androgenetic alopecia proved to be significantly higher than the prevalence of such diagnoses in the general population. Women did not show a higher prevalence of personality disorders or more psychopathologic symptoms than men" (Source: https://pubmed.ncbi.nlm.nih.gov/8024274/) I believe it's a commonly observed fact that personality disorders are closely correlated with depressive symptoms as well.



And even more, it turns out (to no one's surprise now with this hypothesis) that there's some indication sulforaphane has a positive effect on depression in studies with mice: https://amosinstitute.com/blog/sulforaph

So for SSRI lots of other things come in the game, so it won't even make a difference because anyone on SSRI already has some underlaying issue preventing hair regrow like stress, so it won't be much help if the 3ADH was already below baseline, and I don't think I can prove this but then again not enough studies to draw conclusions.

 

[joaopassos4444]

f*****g applemets and procyanidin b2, I remember this scam cos I actually believed the hype and ordered some and then it later came out that the authors of the study misappropriated patient result photos from other studies as their own smh

Hi dude, do you have a source on that? I posted the study and at least I should also cite this, because the whole post has been hijacked by sulforaphane supplements and procyanidin b2 talk, instead of 3ADH, which was the point of the whole post.

 

[joaopassos4444]

Survival rates are dictated by handling of grafts by a physician/technician rather than anything else

Obviously, but hair follicules are organs, when placed in a new place they induce a cascate of events leading to new vascularization and actually modulate the surrounding tissues to accomodate the new organ/functions. If a miniturized HF is trasplanted, we are talking about an organ that has been marked for destruction and that all the pathways are ones that induce senescence, so in the new location the modulation will lead to more senescence. On the other hand healthy HF modulate the surroundings resulting in a healthy enviornment for hair grow, allowing correct pathways signaling to be activated in the new location. Besides maybe quorum sensing is not thecnically corretc, but is somehow similar, and also rare but this happens sometimes, the imediate follicules around a new transplanted one sometimes recover.