Estrone Sulfate Source of Estrone and Estradiol Formation in Isolated Human Hair Roots: identification of a pathway linked to hair growth phase, and subject to site-, gender- and age-related modulations.

J Clin Endocrinol Metab. 2014 Jan 16:jc20132607. [Epub ahead of print]
Estrone Sulfate Source of Estrone and Estradiol Formation in Isolated Human Hair Roots: identification of a pathway linked to hair growth phase, and subject to site-, gender- and age-related modulations.
Wehner G, Schweikert HU.

Background: The present study investigated the metabolism of estrone sulfate into bioactive estrogens in the human hair root, including the effects of hair growth phase, anatomical site, gender and age. Methods: Healthy male (n=18) and female (n=20) subjects were investigated. Growing (anagen) and resting (telogen) hair roots were collected from selected scalp and body sites. Results: Estrone sulfate metabolism in the hair root yielded substantial levels of estrone and estradiol. Estrogen synthesis exceeded that associated with aromatization of androgens in a previous study. In subjects <50 years, estrogen synthesis in scalp hair was lower in men than in women. Comparable levels of estrogen formation were observed in: (i) male and female axillary and pubic hair; and (ii) male beard hair. These levels were higher than the estrogen levels detected in the in scalp hair of men aged <50 years. With increasing age, estrogen synthesis increased in men and decreased in women. In telogen hair from all body sites the capacity to form estrone from estrone sulfate remained unaffected, whereas the ability to form estradiol decreased by 62% and 86 % in men and women, respectively. Conclusions: Estrogen formation from estrone sulfate in sexually dimorphic hair is linked to the hair growth phase, and is subject to gender- and age-related modulations. The magnitude of the in situ estrogen synthesis from estrone sulfate and the selective arrest of estradiol synthesis at the end of the hair cycle suggest that this pathway plays a crucial role in the regulation of human hair growth.

So we shouldn't be trying to reduce estrogen too much?

Sorry for the bump, but this is a very interesting study.  

If I understand correctly, the study states that these follicles were isolated which means they weren't exposed to circulating serum hormones.  Furthermore, estrone sulfate was produced by means other than androgen aromatization in male scalp follicles and the production of estrone sulfate increased with age.

I recall reading a similar study some years back which stated that estrone sulfate concentrations were higher in balding temple/hair line follicles than in their non balding counterparts.  I think estrone sulfate is a key piece of the puzzle, more so than DHT (all male scalp hair follicles have high concentrations of DHT, not all male scalp hair follicles have high concentrations estrone).  Estrone is the strongest activator of estrogen receptor alpha.  Estrogen receptor alpha signaling up regulates androgen receptors.  I believe that estrogen receptor alpha stimulation, or lack there of, is what determines the sensitivity of hair follicles to DHT.  High estrone and estradiol levels will increase estrogen receptor alpha signaling thereby sensitizing cells to the negative effects of DHT (inflammation, suppression of IGF-1, etc. etc.)

In my experience, targeting estrone is much more effective than DHT reduction.  Transdermal zinc sulfate (inhibits aromatase) and magnesium chloride applied to the temples along with internal k2, selenium, and iodine (converts estrone to estriol) provided regrowth where DHT inhibitors failed to do so in the past.  Some other changes I've noticed when reducing estrone: facial hair that is softer and less coarse, leaner muscle mass (no bulk), flatter pecks (no puffiness), smoother skin, and an overall younger sense of well being.

My question is, what causes us to over produce estrone sulfate in the first place?  Especially in younger males. I'm sure insulin resistance plays a role, but there has to be more to it than that. What behaviors/tendencies/diets created and promoted the genetics that dictate high estrone production in males?

baller234 wrote:

In my experience, targeting estrone is much more effective than DHT reduction.  Transdermal zinc sulfate (inhibits aromatase) and magnesium chloride applied to the temples along with internal k2, selenium, and iodine (converts estrone to estriol) provided regrowth where DHT inhibitors failed to do so in the past.

So have you had temple regrowth with this?

It's a little more complicated than this. However, I would suggest looking into the Beta receptor more closely. This is key, as in Beta Estrogen receptor.

I've had frontal regrowth, however I've used a number of ways of capture all areas of inflammation. Iodine is definitely an important component, along with the other elements, metal detoxification and anything that is applicable to individual sensitivities.

Zinc is also important. Of course, how much one needs is the important detail. Too much of anything can be detrimental, zinc is a perfect example of this.

ElmoSuper8 wrote:

baller234 wrote:

In my experience, targeting estrone is much more effective than DHT reduction.  Transdermal zinc sulfate (inhibits aromatase) and magnesium chloride applied to the temples along with internal k2, selenium, and iodine (converts estrone to estriol) provided regrowth where DHT inhibitors failed to do so in the past.

So have you had temple regrowth with this?

Yea with transdermal minerals.  Zinc sulfate inhibits aromatase, is an anti-histamine, lowers cortisol increase T, IGF-1, and DHEA.  Magnesium chloride increase T, IGF-1, and DHEA as well as lower cortisol.  Selenium and iodine will detox estrone and estradiol into estriol which is an estrogen receptor beta agonist, increase thyroxine (converts dht to 3b-adiol, another estrogen receptor beta agonist).  

Vitamin K2 MK4

This stuff has helped me a lot. It pulls calcium out of soft tissue.  Calcium deposits increase inflammation and to achieve hair regrowth you need to have a higher tissue concentration of magnesium to calcium. I think calcium metabolism plays a large role in AGA. DHT and estrone both play big roles in calcium metabolism (DHT in the presence of estrogen receptor alpha stimulation probably promote the calcification of scalp tissue)so there is undoubtedly a connection however I do not fully understand it. 

Also, intermittent fasting.  Increases thyroxine and improves insulin sensitivity.

Also, DIM/I3C is worth looking at however they are really only a bandaid.

CausticSymmetry wrote:It's a little more complicated than this. However, I would suggest looking into the Beta receptor more closely.  This is key, as in Beta Estrogen receptor.

I've had frontal regrowth, however I've used a number of ways of capture all areas of inflammation. Iodine is definitely an important component, along with the other elements, metal detoxification and anything that is applicable to individual sensitivities.

Zinc is also important. Of course, how much one needs is the important detail. Too much of anything can be detrimental, zinc is a perfect example of this.

Yes absolutely. Estrogen receptor beta will stimulate scalp hair growth and is protective. However, I still believe in the absence of estrogen receptor alpha stimulation, AGA would never start.

CS what causes the increase in estrone synthesis as males age? Not just aromatization, but actual synthesis.

baller234 wrote:

ElmoSuper8 wrote:

baller234 wrote:

In my experience, targeting estrone is much more effective than DHT reduction.  Transdermal zinc sulfate (inhibits aromatase) and magnesium chloride applied to the temples along with internal k2, selenium, and iodine (converts estrone to estriol) provided regrowth where DHT inhibitors failed to do so in the past.

So have you had temple regrowth with this?

Yea with transdermal minerals.  Zinc sulfate inhibits aromatase, is an anti-histamine, lowers cortisol increase T, IGF-1, and DHEA.  Magnesium chloride increase T, IGF-1, and DHEA as well as lower cortisol.  Selenium and iodine will detox estrone and estradiol into estriol which is an estrogen receptor beta agonist, increase thyroxine (converts dht to 3b-adiol, another estrogen receptor beta agonist).  

Vitamin K2 MK4

This stuff has helped me a lot.  It pulls calcium out of soft tissue.  Calcium deposits increase inflammation and to achieve hair regrowth you need to have a higher tissue concentration of magnesium to calcium.  I think calcium metabolism plays a large role in AGA.  DHT and estrone both play big roles in calcium metabolism (DHT in the presence of estrogen receptor alpha stimulation probably promote the calcification of scalp tissue)so there is undoubtedly a connection however I do not fully understand it. 

Also, intermittent fasting.  Increases thyroxine and improves insulin sensitivity.

Also, DIM/I3C is worth looking at however they are really only a bandaid.

Well, sounds like you know your stuff, but for someone who isn't scientifically minded can you just throw it out to me in a way I'll understand? Lay out your regimen for me and I'll follow suit compadre  

So have you managed to stop hair loss and now you're working on regrowth?

CausticSymmetry wrote:
Zinc is also important. Of course, how much one needs is the important detail. Too much of anything can be detrimental, zinc is a perfect example of this.

What are some of the signs to look for if too much zinc is consumed?  What detrimental effects can it have?

I'm currently taking 30mg from optizinc

@baller234 - You apply that magnesium to your scalp?

ElmoSuper8 wrote:


Well, sounds like you know your stuff, but for someone who isn't scientifically minded can you just throw it out to me in a way I'll understand? Lay out your regimen for me and I'll follow suit compadre  

I don't really have a strict regimen per say.  Just tendencies.  

Keep your magnesium levels high.  I have been using transdermal magnesium chloride every day for the past two years and highly recommend it.  Ancient minerals is the brand I use but any brand is fine so long as it is pure and not contaminated with heavy metals.

Skip meals.  Intermittent fasting is beneficial for thyroid function (increases T4 conversion to T3) and, as CS has stated, proper thyroid function is paramount to maintaining and growing healthy scalp hair.

Selenium and iodine.  Selenium is essential for increasing T3 (thyroxine, thyroid hormone that increases the enzymes that metabolize carcinogenic, estrogen alpha stimulating hormones into noncarcinogenic estrogen receptor beta stimulating ones).  Iodine is a bit more tricky.  I have benefitted from smaller doses, especially when applied transdermally  on the neck.

Zinc.  I use a cheap zinc oxide cream from walmart and it is a surprisingly effective way to supplement with zinc.  I also use small amounts of Mahler's Recovery oil (zinc sulphate, magnesium chloride, and MSM).  It is important to note that zinc and magnesium have an inverse relationship.  So taking too much zinc will lower magnesium and, imo, you want to have zinc magnesium ratio that favors magnesium.  Keep your magnesium levels high.

Vitamin K2 MK4.  Decalcifies soft tissue.  Great for heart, removes plaque from arteries.  There is a direct correlation with heart attack risk and AGA and I think vitamin k2 MK4 addresses this issue.  I use the Thorne research brand.  It's pricey but by far the most effective form I've used.  Decalcify is great too, however you have to take a lot to get a high dose of MK4 and I am particularly sensitive to boron.

Vitamin C.  Plain old ascorbic acid.  Does just about everything including detox heavy metals which is incredibly important for lessening estrogen receptor alpha stimulation.

Keep Stress down.  Find a way to avoid it or deal with effectively.  Cortisol is detrimental to thyroid function and it impairs T.  Stress will deplete magnesium and zinc so it is important to keep replenishing these minerals, especially magnesium.

Diet.  I try to eat healthy (cut back on grains and eat more organic meats and veggies, good saturated fats like grassfed butter) but by no means do I adhere to a strict diet.  I indulge on junk food all to often.  



There is so much to say that I can't really address the entirety of my understanding of the pathogenesis of AGA.  For one thing, it is incredibly complex and not at all isolated.  Everything is interrelated (think buttefly effect).  Also, everyone's biochemistry is different.  I can only comment on my experiences over the past several years and what has worked for me.

So in short, keep your magnesium and zinc levels high while getting rid of undesirable heavy metals (replace them with magnesium and zinc) optimize your thyroid function, and lastly, don't obsess about it. This has helped a lot. Take proactive steps and then just let it be. Whatever happens, happens. I don't visit forums like these nearly as much as I used to and I think that is a good thing.

ElmoSuper8 wrote:So have you managed to stop hair loss and now you're working on regrowth?

To be clear, my hair loss was never "severe".  At it's worst, I had a what would be called a NW2.  I took propecia at 19 along with lots of other androgen suppressing supplements and it stopped.  I no longer take propecia (been off for over 3 years) or any other androgen suppressing supplements and my hair line is better now than it was then.  

Fortunately, I do not suffer any of the after effects from finasteride (I had sides while on,which would indicate that it is NOT still working to prevent hair loss) often reported by many people however I do not recommend DHT suppression as I think it is a short sighted and incomplete way of addressing the issue.  There are far more effective ways to treat.

theseeker86 wrote:

@baller234 - You apply that magnesium to your scalp?

Yeah directly on to the scalp.