Assessment of the usefulness of dihydrotestosterone in the diagnostics of patients with androgenetic alopecia.

Postepy Dermatol Alergol. 2014 Aug;31(4):207-15. doi: 10.5114/pdia.2014.40925. Epub 2014 Sep 8.
Assessment of the usefulness of dihydrotestosterone in the diagnostics of patients with androgenetic alopecia.
Urysiak-Czubatka I, Kmieć ML, Broniarczyk-Dyła G.

INTRODUCTION:
Androgenetic alopecia (AGA) is the most common form of hair loss. Clinically observed hair loss is due to the continuous miniaturization of affected hair follicles. Genetic factors and androgenic factors especially dihydrotestosterone (DHT), which is a testosterone tissue metabolite, play major roles in the pathogenesis of AGA. However, expert opinions about the usefulness of DHT in the diagnosis of this type of alopecia are divided.
AIM:
To evaluate the usefulness of DHT level in patients with androgenetic alopecia compared with the control group.
MATERIAL AND METHODS:
The study comprised 49 subjects: 19 women and 9 men with androgenetic alopecia. The control group consisted of 17 healthy women and 4 men without hair loss.
RESULTS:
Increased serum concentrations of DHT were observed in patients with androgenetic alopecia (17 women, 5 men), but also in the control group. The differences in mean values of DHT were not significant according to the types of alopecia and the control group. Increased serum concentrations of DHT were not correlated with the advance of alopecia.
CONCLUSIONS:
Dihydrotestosterone is the most influential androgen and seems to play a very important role in the pathogenesis of androgenetic alopecia. Based on the results of our study and others, the most important factors would appear to be the genetically-determined sensitivity of the follicles to DHT and their different reactions to androgen concentration.

CS, since hair follicles are genetically sensitive to dht then how does heavy metal toxicity play a role in AGA or follicle sensitivity to dht?

If this study showed the issue is more with follicles being genetically sensitive then wouldn't it be harder/next to impossible to treat with natural methods?

Heavy metal toxicity affects gene expressions. It also lowers the bodies abilities to control inflammation, absorb nutrients and so on.

theseeker86 wrote:If this study showed the issue is more with follicles being genetically sensitive then wouldn't it be harder/next to impossible to treat with natural methods?

That could also only mean that the only thing that you inherit is how much and where 5a-reductase is distributed in your scalp. Since multiple studies showed that all follicles can miniaturize if there are enough levels of androgens everywhere in the scalp. And how much testosterone binds to 5a-reductase is heavily correlated with hypoxia. So I don't believe in any of this genetic crap, or in other words, it's controllable if you know how. There are also studies that showed that, the less ml/l oxygen in the blood in the scalp the more dht. So more hypoxia, bigger dht/estradiol ratio. And estradiol in form of alfatradiol is used as a topical for androgenetic alopecia rofl. Someone talked about this and posted the studies few weeks/a month ago.

Androgens increase toxicity sensitivity. Good examples of this are conditions such as autism (observing the rate of boys vs girls) or Parkinson's disease...notice that women only get it after menopause (not before).

Also estrogen receptor beta is generally lower in MPB, thus providing a greater impact of androgen toxic sensitivity.

Heavy metals are a potent driver of oxidative stress, not just impairing the thyroid, but also increasing inflammation.

When antioxidant enzymes are not limited by toxins, 5-AR can be attenuated.

So what is exactly happening with 5-AR when you are NOT balding and you're a male? Does it simply aid in estrogen metabolism rather than androgen in the scalp or does it have another specific role?

CausticSymmetry wrote:Androgens increase toxicity sensitivity. Good examples of this are conditions such as autism (observing the rate of boys vs girls) or Parkinson's disease...notice that women only get it after menopause (not before).

Also estrogen receptor beta is generally lower in MPB, thus providing a greater impact of androgen toxic sensitivity.

Heavy metals are a potent driver of oxidative stress, not just impairing the thyroid, but also increasing inflammation.

When antioxidant enzymes are not limited by toxins, 5-AR can be attenuated.

Also, DHT upregulates TNF, IL-6 and DKK-1. There are studies showing these 3 being inversely correlated with WNT/b-catenin and BMP , and mechanical loading downregulating/upregulating them respectively, but nevermind that, I wonder if you know what happens with 5-AR specifically when it's not reducing T to DHT , and what effect does it have on lipid metabolism if it does, when being unbound with T or being in estrogen metabolism if it is?

Have studies been conducted looking at potential chemical, biological differences between sensitive follicles and non-sensitive follicles?

I'm assuming that all people are exposed to the same level of toxicity, some are more sensitive than others.

Also, could toxicity play a role in Metabolic syndrome and Insulin Resistance?

Kazbar here's a few interesting studies which I'm qonna quote.

http://www.google.com/patents/US5480889

"Estradiol synthesis, however, should be stoichiometrically decreased in a hypoxic environment. Three moles of oxygen are required to convert one mole of testosterone to one mole of estradiol. In a hypoxic region, the ratio of DHT to estradiol (DHT/estradiol) should be increased. Sawaya has shown that men with MPB have nearly a two fold increase in 5-?-reductase activity of hair follicles in balding frontal scalp, than in hair bearing occipital scalp. However, hair follicles in the frontal region had nearly three times less aromatase activity than hair follicles in the occipital region in men with MPB. Sawaya, M. E. Ann. N.Y. Acad. Sci. 1991:642:376-383. Finding that the DHT/estradiol ratio is elevated in bald scalp as compared to hair bearing scalp in MPB subjects, is consistent with what would be expected in a hypoxic tissue environment. [00065]


If one were to develop a gradual local tissue hypoxia of the frontal scalp, the DHT/estradiol ratio might increase locally to a critical level at which point receptor hormone interactions might result in down regulation or inhibition of hair follicle cell function. In turn, this might result in the ultimate conversion of terminal hair to villus hair, and the development of MPB. This inhibition may take the form of altering the number of hair follicle cells in anagen phase as compared to telogen phase.
"


http://www.ncbi.nlm.nih.gov/pubmed/22266320


"...Hypoxia alone did not induce a detectable ARE-mediated response in the absence of DHT. DHT-induced AR transcriptional activity was dramatically increased by hypoxia..."

http://www.ncbi.nlm.nih.gov/pubmed/16931898

"These data suggest that DPC from nonbalding scalp regions do have the capacity to undergo apoptosis, but need a high androgen stimulus. The present study provides an interesting new pathogenetic approach in androgenetic alopecia."

Thanks.

Kazbar wrote:Thanks.

Couple those studies with something like this:
http://www.worldhairloss.org/index.php/hairloss/page2-featuredcontributors/the_mechanics_of_male_pattern_baldness

and you'll get where I'm going to.

Hi all

Very interesting post - I'm very confused by the whole hypoxia thing. Why are there topicals (Loreal do one) that state that hypoxia helps with hair growth? FRom the posts above, it seems it would only make things worse!

averagejoe001 wrote:Hi all

Very interesting post - I'm very confused by the whole hypoxia thing. Why are there topicals (Loreal do one) that state that hypoxia helps with hair growth? FRom the posts above, it seems it would only make things worse!

It can't be a good thing and I think there were already explainings on this elaborating that they are causing temporary periods of hypoxia rather than chronic hypoxia (which is a complete counter-effect since brief periods of hypoxia are doing an inverse effect of what chronic hypoxia is doing).

Keanoseg wrote:

averagejoe001 wrote:Hi all

Very interesting post - I'm very confused by the whole hypoxia thing. Why are there topicals (Loreal do one) that state that hypoxia helps with hair growth? FRom the posts above, it seems it would only make things worse!

It can't be a good thing and I think there were already explainings on this elaborating that they are causing temporary periods of hypoxia rather than chronic hypoxia (which is a complete counter-effect since brief periods of hypoxia are doing an inverse effect of what chronic hypoxia is doing).

Thanks, I kinda understand now - it's more like a temporary shock treatment rather than a longer term approach? I do question the credibility altogether though, surely there must be better ways to get the job done

So SHBG doesn't mater either? There are countless reports of using DHT and T raising drugs causing hair loss, but could that be just because of up-regulating the 5ar activity.

Biffy wrote:So SHBG doesn't mater either? There are countless reports of using DHT and T raising drugs causing hair loss, but could that be just because of up-regulating the 5ar activity.

Well it certainly seems to play a role. Also DHT itself correlates with expressions like DKK-1, TNF(apoptosis) and IL-6 (inflammatory ctyokines).

This is why I'm wondering what happens with the reductase enzyme when there's no DHT activity, and what effects does it have outside of just reducing T into DHT, so in this other scenario what is it's purpose? I'd appreciate if someone could elaborate.

http://www.ncbi.nlm.nih.gov/pubmed/9620288

"...These findings suggest that the genes encoding the two 5alpha-reductase isoenzymes are not associated with male pattern baldness."

This is why I'm wondering also.

averagejoe take a look at this.

http://www.ncbi.nlm.nih.gov/pubmed/19601702

"All stretched samples had upregulated epidermal proliferation and angiogenesis. Real-time reverse transcriptase-polymerase chain reaction of epidermal growth factor, transforming growth factor beta1, and nerve growth factor demonstrated greater expression in cyclically stretched skin when compared to static stretch. Hypoxia-induced factor 1alpha was significantly upregulated in cyclically stretched skin, but poststretch analysis demonstrated well-oxygenated tissue, collectively suggesting the presence of transient hypoxia. Waveform-specific mechanical loads may accelerate tissue growth by mechanotransduction and as a result of repeated cycles of temporary hypoxia. Further analysis of mechanotransduction signaling pathways may provide additional insight to improve skin tissue engineering methods and optimize our device."

Keanoseg wrote:averagejoe take a look at this.

http://www.ncbi.nlm.nih.gov/pubmed/19601702

"All stretched samples had upregulated epidermal proliferation and angiogenesis. Real-time reverse transcriptase-polymerase chain reaction of epidermal growth factor, transforming growth factor beta1, and nerve growth factor demonstrated greater expression in cyclically stretched skin when compared to static stretch. Hypoxia-induced factor 1alpha was significantly upregulated in cyclically stretched skin, but poststretch analysis demonstrated well-oxygenated tissue, collectively suggesting the presence of transient hypoxia. Waveform-specific mechanical loads may accelerate tissue growth by mechanotransduction and as a result of repeated cycles of temporary hypoxia. Further analysis of mechanotransduction signaling pathways may provide additional insight to improve skin tissue engineering methods and optimize our device."

Thanks - very interesting! Potentially an interesting option as a short term thing. I presume if one used that Loreal topical for a really long time, that would not be a good thing!

I've been seeing people saying that gut flora can affect sensitivity to androgens, just wondering if anyone has seen any studies?

Keanoseg wrote:averagejoe take a look at this.

http://www.ncbi.nlm.nih.gov/pubmed/19601702

"All stretched samples had upregulated epidermal proliferation and angiogenesis. Real-time reverse transcriptase-polymerase chain reaction of epidermal growth factor, transforming growth factor beta1, and nerve growth factor demonstrated greater expression in cyclically stretched skin when compared to static stretch. Hypoxia-induced factor 1alpha was significantly upregulated in cyclically stretched skin, but poststretch analysis demonstrated well-oxygenated tissue, collectively suggesting the presence of transient hypoxia. Waveform-specific mechanical loads may accelerate tissue growth by mechanotransduction and as a result of repeated cycles of temporary hypoxia. Further analysis of mechanotransduction signaling pathways may provide additional insight to improve skin tissue engineering methods and optimize our device."

This is why I hold the pinch doing DT so i stretch my skin for longer