Aromatase and 3HSD incidence

[parisienne]

O#27 Aromatase and oxidative 3a-hydroxysteroid dehydrogenases are
present in human hair follicles and regulate intrafollicular DHT levels

Rolf Hoffmann. Dept of Dermatology, Philipp University, Marburg, Germany

Dihydrotestosterone (DHT) is the most important trigger of
androgen-dependent hair growth. The intrafollicular concentration of DHT
is mainly regulated by steroid 5a-reductase. However, recent data from
other tissues revealed that DHT levels can also be modulated via the
action of aromatase or oxidative 3a-hydroxysteroid dehydrogenases
(3HSD). We therefore addressed the questions whether aromatase and 3HSD
are present in human hair follicles and whether their enzymatic activity
can be modulated. By the use of immunohistochemistry, quantitative
analysis of steroids with HPLC and direct measurement of enzyme
activity, we were able to detect aromatase mainly in the epithelial
parts of the hair follicle, whereas 3HSD was mainly expressed in the
dermal papilla. In addition, were able to show thataromatase activity
in isolated intact human hair follicles is modulated by 17b-estradiol in
such way that in comparison to the controls, we noticed a concentration-
and time-dependent increase of aromatase activity in
17b-estradiol-incubated female hair follicles (e.g. 24h: 1nM = + 18%,
100nM = + 25%, 1µM = + 57%; 24h: 1nM = +18%, 48h: 1nM = +25%). Moreover,
we noticed that the dermal papilla is able to convert the weak androgen
3a-Androstenediol back to DHT via 3HSD. In summary, our ex vivo results
suggest that aromatase and 3HSD are present in the hair follicle and act
antagonistically. In theory the aromatase pathway may diminish the
amount of intrafollicular testosterone available for conversion to DHT,
whereas 3HSD adds additional DHT. Our results suggest that increasing
aromatase or inhibiting 3HSD activity are novel approaches to stop the
development or progression of DHT-mediated processes of hair growth such
as androgenetic alopecia.



Any input on this ?

I was wondering if :

1 - an increased activity of 3a-hydroxysteroid dehydrogenases could be responsible for further hair loss in patients that do not respond to finasteride/dutasteride

2 - a lack of aromatase local activity could be responsible for further hair loss in patients that do not respond to finasteride/dutasteride, supposing that lacking aromatase would make harder the transformation of the elevated levels of testosterone into oestrogen in lieu of DHT.

Maybe it's just plain broscience, I have no idea, it's 2AM, the hormones are pissing me off and I need explanations !

 

[buckthorn]

Parisseane,
Cure us. Please.

 

[parisienne]

Parisseane,
Cure us. Please.

Can't try harder.

 

[SniperWolfMR]

There is clearly 1 huge missing piece in this hair loss puzzle...

 

[buckthorn]

Off topic - but what do you mean the hormones are messing you up?

 

[parisienne]

Nooo I said pissing me off. As hormones mechanisms are so hard to understand and modify it's annoying.

Oh and you're the actual scientist here not me ! So you, find the cure haha

 

[Afro_Vacancy]

Increasing aromatase sounds like an awful idea for men, lol.

Might be good for women. Keep in mind if you get breast cancer, they likely put you on aromatase inhibitors.

 

[buckthorn]

Nooo I said pissing me off. As hormones mechanisms are so hard to understand and modify it's annoying.

Oh and you're the actual scientist here not me ! So you, find the cure haha

hahaha...I am no scientist, I haven't been in the lab for 8 years. I am already too sucked into the world of hair loss to get sucked into all the compounds and pathways. I know it's an endless loop. let the real scientists figure it out. I hear that if you derma roll your armpit and then derma roll your head, you will regrow hair though. o.k. I will stop polluting your thread. Good luck!

 

[parisienne]

Increasing aromatase sounds like an awful idea for men, lol.

Might be good for women. Keep in mind if you get breast cancer, they likely put you on aromatase inhibitors.

Yes ! That's what I thought as too much aromatase causes gyno haha. But we already have something weak enough to be used in both genders, you know that 17 B alfastradiol "pantostin" gel. Concerning my own case, if I could get some 17Ba and cook a topical with an higher concentration that'd be great I think.

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hahaha...I am no scientist, I haven't been in the lab for 8 years. I am already too sucked into the world of hair loss to get sucked into all the compounds and pathways. I know it's an endless loop. let the real scientists figure it out. I hear that if you derma roll your armpit and then derma roll your head, you will regrow hair though. o.k. I will stop polluting your thread. Good luck!

Oh wow really ? Well I guess it's still better than - you know - the other parts that were mentioned haha.

 

[Afro_Vacancy]

Does the increased off of gyno make it a more attractive product to women?

 

[parisienne]

When mentioning gyno I was answering to the first statement you expressed,

But I don't know, depends I guess !

 

[Sweuser]

Can you link the article, please?

 

[Dench57]

Interesting find, thank you. Confirms what we know about aromatase and estrogen being good for hair.

Yes ! That's what I thought as too much aromatase causes gyno haha. But we already have something weak enough to be used in both genders, you know that 17 B alfastradiol "pantostin" gel. Concerning my own case, if I could get some 17Ba and cook a topical with an higher concentration that'd be great I think.

Pantostin is 17a estradiol and is approximately 100x less estrogenic than 17b estradiol iirc. Hence why it can be used safely by men, whereas using 17b estradiol is pretty much a guarantee of feminization, even using topically.

More on 17a (Alfatradiol)

The drug inhibits the conversion of testosterone to the metabolite dihydrotestosterone (DHT) by suppressing 5α-reductase activity5. In addition, by inhibiting 17β-dehydrogenase, it impedes the conversion process of androstenedione to testosterone, resulting in a reduction in the syntheses of testosterone and DHT6. It also accelerates the conversion of testosterone to estradiol by stimulating aromatase, decreasing the level of testosterone and leading to a reduction in DHT7. In addition, the drug has been reported to stimulate the generation of hair follicular matrix cells

 

[parisienne]

Can you link the article, please?

Hej hej, here it is. http://alt.baldspot.narkive.com/oX5EhPE2/effects-of-aromatase-and-3hsd-on-dht-levels It's freaking old, can't get why there hasn't been more internet excitement towards it ?

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Interesting find, thank you. Confirms what we know about aromatase and estrogen being good for hair.



Pantostin is 17a estradiol and is approximately 100x less estrogenic than 17b estradiol iirc. Hence why it can be used safely by men, whereas using 17b estradiol is pretty much a guarantee of feminization, even using topically.

More on 17a (Alfatradiol)

Hey Denchetta thank you, much clearer now.
Do you have any source for 17b ?
Plus what do you think about 3HSD? First time I read about this little b**ch in Androgenetic Alopecia world.

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"[FONT=museo_sans_500regular] Hair stopped growing on the shaved skin of mice treated with a biologically active form of estrogen — 17-beta estradiol — even though the animals were at an age when hair growth should continue. And, when the researchers applied an estrogen blocker called ICI 182,780 just twice, tissue studies one week later showed hair follicles beginning to sprout hair." [/FONT]http://www.regrowth.com/remedies/estrogen-blocker-grows-hair/

Ok now that's confusing.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412238/ (ell-canell - pantostin - test) - 17a oestradiol promotes hair growth

Plus I've read some anecdotal results of some women losing hair when treated with 17b oestradiol to stop menopause related symptoms.

Sounds like even though 17b is the most estrogenic form, it can lead to further hair loss, which is not the case with 17a..

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http://www.endocrine-abstracts.org/ea/0007/ea0007p216.htm

These results show that the biologically active oestrogen, 17beta-oestradiol, can inhibit human hair growth in vitro, by reducing the rate of growth, which parallels the in vivo effects seen in rodents. Studies are in progress to determine whether these effects are mediated via ERalpha or ERbeta.

 

[Swoop]

Estrogen = godly for scalp hair follicles.

Good study about estrogen and the hair follicle http://press.endocrine.org/doi/full/10.1210/er.2006-0020.

Difference in expression of ERa and ERb occipital scalp vs vertex in balding men;

To identify differences in the transcription of AR in defined two sites, their mRNA levels were examined. In all samples, mean mRNAs of AR were 3.4- fold higher in VERTEXDPCs than those from occipital scalp (Fig. 1A). These site-specific different expressions of AR were consistent inWestern blot (Fig. 1B). VERTEXDPCs showed 1.9-fold higher AR expression than their counterparts, consistent with the results of cultured DPCs from hair follicles from the frontal and occipital scalp [2]. Immunohistochemical study showed that AR was localized to the nuclei of the VERTEXDPCs at the anagen stage (six of eight samples), although not all the DPCs were positive (Fig. 1C). In sebaceous gland, AR immunoreactivity was mostly confined to the nuclei of the basal cells as previously described (Fig. 1D) [4].

Reversely, ERa mRNA expression levels were 2.2- fold higher in OCCIPUTDPCs than in their counterparts. ERb mRNA was consistently highly expressed by 4.2- fold in OCCIPUTDPCs versus VERTEXDPCs (Fig. 2A). ERa protein was consistently elevated in OCCIPUTDPCs by 1.8-fold higher versus vertex and ERb was also definitely increased in DPCs from non-balding scalps, with a 1.8-fold stronger intensity

 

[parisienne]

Yess Swoop ! I was hoping you would swing by at some point. Thanks !

 

[Swoop]

Swoop, I can't send you PM because it says you're PM storage is overloaded. Can you delete some messages? I have some things to ask you. Thanks!

Thanks , done.

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I have read less about FPHL though, but I don't think that estrogen would have permanent deleterious effects for female scalp hair follicles. Women have way more aromatase activity in frontal hair follicles than men.

When women go on aromatase inhibitors they often experience hair loss (http://www.ncbi.nlm.nih.gov/pubmed/24197658). Another example here; http://annonc.oxfordjournals.org/content/24/6/1710.long.

Women who suffer from PCOS which is characterized of elevation of androgens also often experience hair loss on the scalp, meanwhile they might get more hairy on other areas (hirsutism).

Are there any reasons to believe it would be bad for women scalp hair follicles?

 

[GRme11]

Old thread, but it is still very important.

Firstly, the initial study posted by @parisienne is the famous study about the aromatization that 17a-Estradiol (Alfatradiol) provides. So there is a misconception regarding 17a and 17b-Estradiol. Check it here: https://pubmed.ncbi.nlm.nih.gov/12190948/

"Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstendione to estrone takes place, which might explain the beneficial effects of estrogen treatment of Androgenetic Alopecia."

What I posted a few months back:

In my opinion, Alfatradiol seems to be underrated. Maybe the 0.025% it's not very much or maybe is enough for others, but with higher doses, someone might achieve better results. Forget it to act as a DHT blocker when someone is already on Finasteride or Dutasteride because the latter will do the job, outperforming Alfatradiol in the 5AR blockade. The interesting part of Alfatradiol is the increment in Aromatase Activity and the capability to block 17β-HSD. We know that Aromatase is so important for Hair Follicles and I believe that's the most interesting part of Alfatradiol. Furthermore, as much as it can block the 17β-HSD it's a plus as well because is blocking the conversion of T to Androstenedione, thus promoting the conversion to the Estrogens, Estrone, and Estradiol. The only problem is the ERα receptor binding affinity (or maybe is not?)

1)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412238/ (Mechanism)
In the treatment of androgenetic alopecia, the action mechanism of 17α-estradiol is to suppress 5α-reductase activity, which impedes the conversion of testosterone to the more potent metabolite DHT. In addition, it inhibits 17β-dehydrogenase activity, resulting in a slowing of the conversion process of androstenedione to testosterone. As a result, there is a reduction in the synthesis of testosterone and DHT. On the other hand, by stimulating aromatase, the conversion of testosterone to estradiol is accelerated, hence, testosterone is reduced. It thus acts to ultimately reduce DHT. In addition, it has been reported to accelerate the generation of hair follicular matrix cells.

2)https://pubmed.ncbi.nlm.nih.gov/9284093/ (Aromatase/5AR levels on Scalp)
Findings revealed that both women and men have higher levels of receptors and 5alpha-reductase type I and II in frontal hair follicles than in occipital follicles, whereas higher levels of aromatase were found in their occipital follicles. There are marked quantitative differences in levels of androgen receptors and the three enzymes, which we find to be primarily in the outer root sheath of the hair follicles in the two genders. Androgen receptor content in female frontal hair follicles was approximately 40% lower than in male frontal hair follicles. Cytochrome P-450-aromatase content in women's frontal hair follicles was six times greater than in frontal hair follicles in men. Frontal hair follicles in women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively than frontal hair follicles in men. These differences in levels of androgen receptor and steroid-converting enzymes may account for the different clinical presentations of androgenetic alopecia in women and men.

3)https://pubmed.ncbi.nlm.nih.gov/12190948/ (17a-Estradiol Induces Aromatase Activity)
For the topical treatment of androgenetic alopecia (Androgenetic Alopecia) in women, solutions containing either estradiol benzoate, estradiol valerate, 17beta- or 17alpha-estradiol are commercially available in Europe and some studies show an increased anagen and decreased telogen rate after treatment as compared with placebo. At present, it is not precisely known how estrogens mediate their beneficial effect on Androgenetic Alopecia-affected hair follicles. We have shown recently that 17alpha-estradiol is able to diminish the amount of dihydrotestosterone (DHT) formed by human hair follicles after incubation with testosterone while increasing the concentration of weaker steroids such as estrogens. Because aromatase is involved in the conversion of testosterone to estrogens and because there is some clinical evidence that aromatase activity may be involved in the pathogenesis of Androgenetic Alopecia, we addressed the question of whether aromatase is expressed in human hair follicles and whether 17alpha-estradiol is able to modify the aromatase activity. Herewith we were able to demonstrate that intact, microdissected hair follicles from female donors express considerably more aromatase activity than hair follicles from male donors. Using immunohistochemistry, we detected the aromatase mainly in the epithelial parts of the hair follicle and not in the dermal papilla. Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstenedione to estrone takes place, which might explain the beneficial effects of estrogen treatment of Androgenetic Alopecia.

4) Affinities:
Other investigators have found diverse affinities, as well: Kuiper et al. (1997) [44] reported an affinity of 17 α-E2 to ERα of 58% of the relative affinity of 17 β-E2, and 11% to ERβ, while Torand-Allerand et al. (2005) [26] reported an affinity of 17 α-E2 bindings to human recombinant ERα and ERβ of 51 and 64% compared to 17 β-E2, respectively. Kaur et al. (2015) [45] indicated an affinity of 17 α-E2 to ERα to be 40-times lower than 17 β-E2.”

5)General Information for 17a-Estradiol (Recent):

Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α​

https://www.biorxiv.org/content/10.1101/2020.06.02.130674v1.full (or here: https://pubmed.ncbi.nlm.nih.gov/33289482/)

6) Comparison with Topical Finasteride: (But the thing here is: What if you combine them? Different Mechanisms and you need to yield every possible positive effect)

Efficacy of Topical Finasteride 0.5% vs 17α-Estradiol 0.05% in the Treatment of Postmenopausal Female Pattern Hair Loss: A Retrospective, Single-Blind Study of 119 Patients

Efficacy of Topical Finasteride 0.5% vs 17α-Estradiol 0.05% in the Treatment of Postmenopausal Female Pattern Hair Loss: A Retrospective, Single-Blind Study of 119 Patients.​

Regarding now 3a-HSD:
From wiki:

"3α-Hydroxysteroid dehydrogenase (3α-HSD or aldo-keto reductase family 1 member C4) is an enzyme that in humans is encoded by the AKR1C4 gene. It is known to be necessary for the synthesis of the endogenous neurosteroids allopregnanolone, THDOC, and 3α-androstanediol. It is also known to catalyze the reversible conversion of 3α-androstanediol (5α-androstane-3α,17β-diol) to dihydrotestosterone (DHT, 5α-androstan-17β-ol-3-one) and vice versa."

I can't tell much, but I will stand to 3a-Diol-G.

"3α-Androstanediol glucuronide (3α-ADG) is a metabolite formed from human androgens; compounds involved in the development and maintenance of sexual characteristics. It is formed by the glucuronidation of both dihydrotestosterone and testosterone, and has been proposed as means of measuring androgenic activity.
In women the adrenal steroids, dehydroepiandrosterone sulfate, androstenedione, and dehydroepiandrosterone are the major precursors of plasma 3α-ADG, accounting for almost the totality of circulating 3α-ADG. Levels of 3α-ADG decrease significantly with age.
3α-ADG is used as a marker of target tissue cellular action. 3α-ADG correlates with level of 5α-reductase activity (testosterone and 3α-androstanediol to dihydrotestosterone) in the skin. Concentrations of 3α-ADG are associated with the level of cutaneous androgen metabolism."


I kinda experience it with my 3a-Diol-G levels, which is a major metabolite of DHT. When these levels were low, my hair felt better and in general, the androgen activity on the scalp is lower(possibly). At least they are correlating:

"Several factors may be involved in the pathogenesis of female baldness. Androgens originating from the adrenal gland (eg, DHEA), ovary (eg, DHEA and testosterone), and hair follicle cells (eg, DHT and 3a-diol G) have been implicated. Plasma levels of DHEA and its sulfate decline with age, as do those of androstenedione, while testosterone and free testosterone levels remain about the same regardless of age ion rp^g serum levels of DHT, testosterone, 3a-diol G, and SHBG correlate with the peripheral metabolic activity of the target organs on the precursor hormones.10" All scalp hairs are exposed to the same androgen concentrations, but the balding follicles are genetically susceptible to the androgen factor. The androgen factor and genetic factor are thought to operate through a central system, possibly the cyclic adenosine monophosphate protein kinase system, to affect the metamorphosis of the terminal into the vellus-type follicle. Its effects on the proliferation and metabolism of the matrix cell of the hair follicle may be central to the balding process. The peripheral (ie, extraglandular) conversion of androgens is particularly important in women since it is the major route by which testosterone is formed. The conversion of testosterone and DHEA to DHT and the androstanediols occurs in the skin through the 5a-reductase and 17/3-hydroxysteroid dehydroge¬ nase systems.1516 Studies on isolated plucked scalp hairs have demonstrated that testosterone metabolism in both the nonbalding man and woman occurs primarily through the 17/î-hydroxysteroid dehydrogenase system to androstenedione and secondarily through the 5«-reductase system to dihydrotestosterone. In balding men, the rate of 5a-reductase activity is increased, leading to increased concentrations of dihydrotestosterone.18 The major metabolites of dihydrotestosterone, when incubated with skin and skin structures from the scalp, are 3a-diol G and 3/3-diol G. The increased activity of dihydrotestosterone in the balding scalp may be reflected in slightly increased concentrations of 3a-diol G in the tissue and plasma. The sex hormone binding protein is a /3-globulin, which is synthesized in the liver. The binding of androgens to this transport protein is physiologically and pathologically important since it appears that it is the proportion of the androgen not bound to SHBG that is biologically active. Decreased production of SHBG has been reported in hirsutism, polycystic ovarian disease, exogenous androgens, and syndromes of androgen excess. The decreased SHBG provides a better index for hyperandrogenicity than do either the total or free testosterone levels. Changes in the concentration of binding protein alter the availability of androgens, which bind to the cells that affect androgen clearance. The higher clearance rate results from an increase in peripheral metabolism reflected in increased plasma levels and excretion of 5a-reduced metabolites such as 3a-diol G. The 3a-diol G levels are markedly elevated in the plasma of many patients with idiopathic hirsutism and have been used as a marker of peripheral androgen action. This study supports the concept of increased androgen production in some subjects with female pattern baldness, as reflected by the depressed SHBG level and slightly increased 3a-diol G level compared with those in both the control group of women and women with male pattern baldness. The marked increase of the 3a-diol G/SHBG ratio suggests that these women may be losing hair due to genetically sensitive hair bulbs responding to a small excess of androgen but without the maximal androgen expression of hirsutism, acne, or virilism. Our results did not confirm increased serum testosterone levels or an increased serum T/SHBG ratio in female patients with male pattern baldness, as had been suggested in previous reports. We also were not able to confirm previous findings of elevated DHEA sulfate levels in the subjects with female pattern baldness. The T/SHBG ratio was not a helpful marker for this type of hair loss. This study suggests that a low SHBG level and an increased ratio of 3a-diol G to SHBG are characteristic of the female pattern type of hair loss in young women. It is interesting to speculate that decreased SHBG concentrations result in increased availability of androgens for uptake and subsequent metabolism in the hair follicle in this group of women. Further study is needed to clarify the role of androgens and their relationship to the genetic factors that determine the effects of androgen metabolism in susceptible hair follicles in balding women."

Information is gathered exclusively from this study:https://pubmed.ncbi.nlm.nih.gov/2943232/

So, when I checked my 3a-Diol-G levels again a few months back, they were almost in the high-end levels, and my hair quality was worse. Probably because of the higher androgen activity on the scalp? (Could it be)
(August 2019: Started Topical Finasteride:Baseline levels of DHT: 541 pg/ml
Otober 2019: DHT levels:302 pg/ml
January 2020: DHT levels:298 pg/ml-After starting Oral Finasteride as well ( I was already on it for about 3 weeks-0.5mg 3 times/week)
May 2020: DHT levels:313 pg/ml-I jumped into 1mg daily from 31st of March. I jumped to 0.5mg everyday from mid February
June 2020: DHT levels:283 pg/ml- I even tested 3a-Diol-G which is far a strongest indicator than DHT alone. 3a-Diol-G is a major DHT metabolite and it can converts back to DHT as well. It came low at 1.3 ng/ml while the range is: 3.4-22.
September 2020: DHT levels: 383 pg/ml
January 2021: DHT levels: 550 pg/ml !!! Back to baseline!-I checked as well my PSA levels and it was 0.23 ng/ml but I don't have baseline levels unfortunately.
May 2021 (Latest): I skipped DHT this time and tested only 3a-Diol-G. I got a result of: 16.1 this time!!! It makes sense, doesn't it? Higher DHT->Higher metabolite->Higher Androgenicity overall. I assume that my DHT is still high!-----Upregulated 5AR+Upregulated potent Androgen metabolites (3a-diol-G), destructive combination I guess.)


Another study (males this time):
"Serum 3a-androstanediol glucuronide (3a-Adiol-G) is considered to be an indicator of peripheral tissue androgen metabolism. Precursor circulating androgens are converted in peripheral tissue to dihydrotestosterone (DHT), which is ultimately metabolized to 3a-Adiol-G and secreted from the cell. Elevated serum 3a-Adiol-G concentrations have been reported in women in hyperandrogenic states. We studied 44 consecutive male medical students for chest hair density, acne, and serum dehydroepiandrosterone sulfate (DHEA-S), total testosterone (total T), free and albumin-bound (bioavailable) T (bio T), and 3a-Adiol-G concentrations. Although there was a considerable overlap of serum 3a-Adiol-G values among the groups defined by hair density or acne scores, we found statistically significant correlations between serum 3a-Adiol-G and chest hairiness (P = 0.0034), acne (P = 0.0005), and a combined chest hairiness and acne score (P = 0.0018). There was no significant correlation between these clinical parameters and the levels of precursor androgens. There was, however, a strong correlation between serum 3a-Adiol-G and bio T (P = 0.0005), suggesting that in men serum 3a-Adiol-G levels may be dependent upon available free and albumin-bound T. The correlations in men of serum 3a-Adiol-G with chest hair density, acne, and the hairiness and acne index supports the hypothesis that the serum levels of 3a-Adiol-G reflect the extent of androgen action in peripheral tissues."

Study:https://pubmed.ncbi.nlm.nih.gov/2972739/

As for the estrogen receptor alpha, I can't provide much information because it is somewhat complex. I will provide though one of the most detailed studies about Estrogens on hair follicles: https://academic.oup.com/edrv/article/27/6/677/2355194 (I will stand that the effects seem to be HIGHLY gender-sex specific and different when it comes to animals and humans. At least this is my understanding. Also, maybe Alfatradiol potency is not great for the ERα effects, since it is not as strong as 17b-Estradiol. Like @pariesienne said above, 17b inhibited hair growth while 17a not. and this is mentioned in the above study as well: Oh and Smart found that, in mice, topical E2 administration to clipped dorsal skin arrested hair follicles in telogen and produced a profound and prolonged inhibition of hair growth, whereas treatment with the biologically inactive stereoisomer 17α-estradiol did not alter hair growth.)

I will include as well a translated german study for Alfatradiol. Is one of the most detailed because there are males as well.

TL;DR: Aromatase is very important for hair follicles as we know. 3a-Diol-G is probably a great indicator for androgen activity in tissues, including the scalp as well. Maybe it's worth it for someone to give at least a try to Alfatradiol, as it should stop testosterone and androstenedione as well to some extent, but not to Alfatradiol alone. Combination therapy is always the point, you need to connect as many dots as you can with all the mechanisms available.

Thanks for reading and sorry for any mistakes.

 

[Liqurt]

Old thread, but it is still very important.

Firstly, the initial study posted by @parisienne is the famous study about the aromatization that 17a-Estradiol (Alfatradiol) provides. So there is a misconception regarding 17a and 17b-Estradiol. Check it here: https://pubmed.ncbi.nlm.nih.gov/12190948/

"Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstendione to estrone takes place, which might explain the beneficial effects of estrogen treatment of Androgenetic Alopecia."

What I posted a few months back:

In my opinion, Alfatradiol seems to be underrated. Maybe the 0.025% it's not very much or maybe is enough for others, but with higher doses, someone might achieve better results. Forget it to act as a DHT blocker when someone is already on Finasteride or Dutasteride because the latter will do the job, outperforming Alfatradiol in the 5AR blockade. The interesting part of Alfatradiol is the increment in Aromatase Activity and the capability to block 17β-HSD. We know that Aromatase is so important for Hair Follicles and I believe that's the most interesting part of Alfatradiol. Furthermore, as much as it can block the 17β-HSD it's a plus as well because is blocking the conversion of T to Androstenedione, thus promoting the conversion to the Estrogens, Estrone, and Estradiol. The only problem is the ERα receptor binding affinity (or maybe is not?)

1)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412238/ (Mechanism)
In the treatment of androgenetic alopecia, the action mechanism of 17α-estradiol is to suppress 5α-reductase activity, which impedes the conversion of testosterone to the more potent metabolite DHT. In addition, it inhibits 17β-dehydrogenase activity, resulting in a slowing of the conversion process of androstenedione to testosterone. As a result, there is a reduction in the synthesis of testosterone and DHT. On the other hand, by stimulating aromatase, the conversion of testosterone to estradiol is accelerated, hence, testosterone is reduced. It thus acts to ultimately reduce DHT. In addition, it has been reported to accelerate the generation of hair follicular matrix cells.

2)https://pubmed.ncbi.nlm.nih.gov/9284093/ (Aromatase/5AR levels on Scalp)
Findings revealed that both women and men have higher levels of receptors and 5alpha-reductase type I and II in frontal hair follicles than in occipital follicles, whereas higher levels of aromatase were found in their occipital follicles. There are marked quantitative differences in levels of androgen receptors and the three enzymes, which we find to be primarily in the outer root sheath of the hair follicles in the two genders. Androgen receptor content in female frontal hair follicles was approximately 40% lower than in male frontal hair follicles. Cytochrome P-450-aromatase content in women's frontal hair follicles was six times greater than in frontal hair follicles in men. Frontal hair follicles in women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively than frontal hair follicles in men. These differences in levels of androgen receptor and steroid-converting enzymes may account for the different clinical presentations of androgenetic alopecia in women and men.

3)https://pubmed.ncbi.nlm.nih.gov/12190948/ (17a-Estradiol Induces Aromatase Activity)
For the topical treatment of androgenetic alopecia (Androgenetic Alopecia) in women, solutions containing either estradiol benzoate, estradiol valerate, 17beta- or 17alpha-estradiol are commercially available in Europe and some studies show an increased anagen and decreased telogen rate after treatment as compared with placebo. At present, it is not precisely known how estrogens mediate their beneficial effect on Androgenetic Alopecia-affected hair follicles. We have shown recently that 17alpha-estradiol is able to diminish the amount of dihydrotestosterone (DHT) formed by human hair follicles after incubation with testosterone while increasing the concentration of weaker steroids such as estrogens. Because aromatase is involved in the conversion of testosterone to estrogens and because there is some clinical evidence that aromatase activity may be involved in the pathogenesis of Androgenetic Alopecia, we addressed the question of whether aromatase is expressed in human hair follicles and whether 17alpha-estradiol is able to modify the aromatase activity. Herewith we were able to demonstrate that intact, microdissected hair follicles from female donors express considerably more aromatase activity than hair follicles from male donors. Using immunohistochemistry, we detected the aromatase mainly in the epithelial parts of the hair follicle and not in the dermal papilla. Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstenedione to estrone takes place, which might explain the beneficial effects of estrogen treatment of Androgenetic Alopecia.

4) Affinities:
Other investigators have found diverse affinities, as well: Kuiper et al. (1997) [44] reported an affinity of 17 α-E2 to ERα of 58% of the relative affinity of 17 β-E2, and 11% to ERβ, while Torand-Allerand et al. (2005) [26] reported an affinity of 17 α-E2 bindings to human recombinant ERα and ERβ of 51 and 64% compared to 17 β-E2, respectively. Kaur et al. (2015) [45] indicated an affinity of 17 α-E2 to ERα to be 40-times lower than 17 β-E2.”

5)General Information for 17a-Estradiol (Recent):

Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α​

https://www.biorxiv.org/content/10.1101/2020.06.02.130674v1.full (or here: https://pubmed.ncbi.nlm.nih.gov/33289482/)

6) Comparison with Topical Finasteride: (But the thing here is: What if you combine them? Different Mechanisms and you need to yield every possible positive effect)

Efficacy of Topical Finasteride 0.5% vs 17α-Estradiol 0.05% in the Treatment of Postmenopausal Female Pattern Hair Loss: A Retrospective, Single-Blind Study of 119 Patients

Efficacy of Topical Finasteride 0.5% vs 17α-Estradiol 0.05% in the Treatment of Postmenopausal Female Pattern Hair Loss: A Retrospective, Single-Blind Study of 119 Patients.​

Regarding now 3a-HSD:
From wiki:

"3α-Hydroxysteroid dehydrogenase (3α-HSD or aldo-keto reductase family 1 member C4) is an enzyme that in humans is encoded by the AKR1C4 gene. It is known to be necessary for the synthesis of the endogenous neurosteroids allopregnanolone, THDOC, and 3α-androstanediol. It is also known to catalyze the reversible conversion of 3α-androstanediol (5α-androstane-3α,17β-diol) to dihydrotestosterone (DHT, 5α-androstan-17β-ol-3-one) and vice versa."

I can't tell much, but I will stand to 3a-Diol-G.

"3α-Androstanediol glucuronide (3α-ADG) is a metabolite formed from human androgens; compounds involved in the development and maintenance of sexual characteristics. It is formed by the glucuronidation of both dihydrotestosterone and testosterone, and has been proposed as means of measuring androgenic activity.
In women the adrenal steroids, dehydroepiandrosterone sulfate, androstenedione, and dehydroepiandrosterone are the major precursors of plasma 3α-ADG, accounting for almost the totality of circulating 3α-ADG. Levels of 3α-ADG decrease significantly with age.
3α-ADG is used as a marker of target tissue cellular action. 3α-ADG correlates with level of 5α-reductase activity (testosterone and 3α-androstanediol to dihydrotestosterone) in the skin. Concentrations of 3α-ADG are associated with the level of cutaneous androgen metabolism."


I kinda experience it with my 3a-Diol-G levels, which is a major metabolite of DHT. When these levels were low, my hair felt better and in general, the androgen activity on the scalp is lower(possibly). At least they are correlating:

"Several factors may be involved in the pathogenesis of female baldness. Androgens originating from the adrenal gland (eg, DHEA), ovary (eg, DHEA and testosterone), and hair follicle cells (eg, DHT and 3a-diol G) have been implicated. Plasma levels of DHEA and its sulfate decline with age, as do those of androstenedione, while testosterone and free testosterone levels remain about the same regardless of age ion rp^g serum levels of DHT, testosterone, 3a-diol G, and SHBG correlate with the peripheral metabolic activity of the target organs on the precursor hormones.10" All scalp hairs are exposed to the same androgen concentrations, but the balding follicles are genetically susceptible to the androgen factor. The androgen factor and genetic factor are thought to operate through a central system, possibly the cyclic adenosine monophosphate protein kinase system, to affect the metamorphosis of the terminal into the vellus-type follicle. Its effects on the proliferation and metabolism of the matrix cell of the hair follicle may be central to the balding process. The peripheral (ie, extraglandular) conversion of androgens is particularly important in women since it is the major route by which testosterone is formed. The conversion of testosterone and DHEA to DHT and the androstanediols occurs in the skin through the 5a-reductase and 17/3-hydroxysteroid dehydroge¬ nase systems.1516 Studies on isolated plucked scalp hairs have demonstrated that testosterone metabolism in both the nonbalding man and woman occurs primarily through the 17/î-hydroxysteroid dehydrogenase system to androstenedione and secondarily through the 5«-reductase system to dihydrotestosterone. In balding men, the rate of 5a-reductase activity is increased, leading to increased concentrations of dihydrotestosterone.18 The major metabolites of dihydrotestosterone, when incubated with skin and skin structures from the scalp, are 3a-diol G and 3/3-diol G. The increased activity of dihydrotestosterone in the balding scalp may be reflected in slightly increased concentrations of 3a-diol G in the tissue and plasma. The sex hormone binding protein is a /3-globulin, which is synthesized in the liver. The binding of androgens to this transport protein is physiologically and pathologically important since it appears that it is the proportion of the androgen not bound to SHBG that is biologically active. Decreased production of SHBG has been reported in hirsutism, polycystic ovarian disease, exogenous androgens, and syndromes of androgen excess. The decreased SHBG provides a better index for hyperandrogenicity than do either the total or free testosterone levels. Changes in the concentration of binding protein alter the availability of androgens, which bind to the cells that affect androgen clearance. The higher clearance rate results from an increase in peripheral metabolism reflected in increased plasma levels and excretion of 5a-reduced metabolites such as 3a-diol G. The 3a-diol G levels are markedly elevated in the plasma of many patients with idiopathic hirsutism and have been used as a marker of peripheral androgen action. This study supports the concept of increased androgen production in some subjects with female pattern baldness, as reflected by the depressed SHBG level and slightly increased 3a-diol G level compared with those in both the control group of women and women with male pattern baldness. The marked increase of the 3a-diol G/SHBG ratio suggests that these women may be losing hair due to genetically sensitive hair bulbs responding to a small excess of androgen but without the maximal androgen expression of hirsutism, acne, or virilism. Our results did not confirm increased serum testosterone levels or an increased serum T/SHBG ratio in female patients with male pattern baldness, as had been suggested in previous reports. We also were not able to confirm previous findings of elevated DHEA sulfate levels in the subjects with female pattern baldness. The T/SHBG ratio was not a helpful marker for this type of hair loss. This study suggests that a low SHBG level and an increased ratio of 3a-diol G to SHBG are characteristic of the female pattern type of hair loss in young women. It is interesting to speculate that decreased SHBG concentrations result in increased availability of androgens for uptake and subsequent metabolism in the hair follicle in this group of women. Further study is needed to clarify the role of androgens and their relationship to the genetic factors that determine the effects of androgen metabolism in susceptible hair follicles in balding women."

Information is gathered exclusively from this study:https://pubmed.ncbi.nlm.nih.gov/2943232/

So, when I checked my 3a-Diol-G levels again a few months back, they were almost in the high-end levels, and my hair quality was worse. Probably because of the higher androgen activity on the scalp? (Could it be)
(August 2019: Started Topical Finasteride:Baseline levels of DHT: 541 pg/ml
Otober 2019: DHT levels:302 pg/ml
January 2020: DHT levels:298 pg/ml-After starting Oral Finasteride as well ( I was already on it for about 3 weeks-0.5mg 3 times/week)
May 2020: DHT levels:313 pg/ml-I jumped into 1mg daily from 31st of March. I jumped to 0.5mg everyday from mid February
June 2020: DHT levels:283 pg/ml- I even tested 3a-Diol-G which is far a strongest indicator than DHT alone. 3a-Diol-G is a major DHT metabolite and it can converts back to DHT as well. It came low at 1.3 ng/ml while the range is: 3.4-22.
September 2020: DHT levels: 383 pg/ml
January 2021: DHT levels: 550 pg/ml !!! Back to baseline!-I checked as well my PSA levels and it was 0.23 ng/ml but I don't have baseline levels unfortunately.
May 2021 (Latest): I skipped DHT this time and tested only 3a-Diol-G. I got a result of: 16.1 this time!!! It makes sense, doesn't it? Higher DHT->Higher metabolite->Higher Androgenicity overall. I assume that my DHT is still high!-----Upregulated 5AR+Upregulated potent Androgen metabolites (3a-diol-G), destructive combination I guess.)


Another study (males this time):
"Serum 3a-androstanediol glucuronide (3a-Adiol-G) is considered to be an indicator of peripheral tissue androgen metabolism. Precursor circulating androgens are converted in peripheral tissue to dihydrotestosterone (DHT), which is ultimately metabolized to 3a-Adiol-G and secreted from the cell. Elevated serum 3a-Adiol-G concentrations have been reported in women in hyperandrogenic states. We studied 44 consecutive male medical students for chest hair density, acne, and serum dehydroepiandrosterone sulfate (DHEA-S), total testosterone (total T), free and albumin-bound (bioavailable) T (bio T), and 3a-Adiol-G concentrations. Although there was a considerable overlap of serum 3a-Adiol-G values among the groups defined by hair density or acne scores, we found statistically significant correlations between serum 3a-Adiol-G and chest hairiness (P = 0.0034), acne (P = 0.0005), and a combined chest hairiness and acne score (P = 0.0018). There was no significant correlation between these clinical parameters and the levels of precursor androgens. There was, however, a strong correlation between serum 3a-Adiol-G and bio T (P = 0.0005), suggesting that in men serum 3a-Adiol-G levels may be dependent upon available free and albumin-bound T. The correlations in men of serum 3a-Adiol-G with chest hair density, acne, and the hairiness and acne index supports the hypothesis that the serum levels of 3a-Adiol-G reflect the extent of androgen action in peripheral tissues."

Study:https://pubmed.ncbi.nlm.nih.gov/2972739/

As for the estrogen receptor alpha, I can't provide much information because it is somewhat complex. I will provide though one of the most detailed studies about Estrogens on hair follicles: https://academic.oup.com/edrv/article/27/6/677/2355194 (I will stand that the effects seem to be HIGHLY gender-sex specific and different when it comes to animals and humans. At least this is my understanding. Also, maybe Alfatradiol potency is not great for the ERα effects, since it is not as strong as 17b-Estradiol. Like @pariesienne said above, 17b inhibited hair growth while 17a not. and this is mentioned in the above study as well: Oh and Smart found that, in mice, topical E2 administration to clipped dorsal skin arrested hair follicles in telogen and produced a profound and prolonged inhibition of hair growth, whereas treatment with the biologically inactive stereoisomer 17α-estradiol did not alter hair growth.)

I will include as well a translated german study for Alfatradiol. Is one of the most detailed because there are males as well.

TL;DR: Aromatase is very important for hair follicles as we know. 3a-Diol-G is probably a great indicator for androgen activity in tissues, including the scalp as well. Maybe it's worth it for someone to give at least a try to Alfatradiol, as it should stop testosterone and androstenedione as well to some extent, but not to Alfatradiol alone. Combination therapy is always the point, you need to connect as many dots as you can with all the mechanisms available.

Thanks for reading and sorry for any mistakes.

Bump

aloe Vera increases aromatase activity so would that be good to put on your scalp?


There was a post a while back of some guy using ketoconazle and aloe vera(I think he left it on his scalp over night) and got good regrow this but the pics are deleted

https://www.gourmetstylewellness.com/interact/threads/ketoconazole-shampoo-2-aloe-vera-with-pictures.33419/

 

[GRme11]

Bump

aloe Vera increases aromatase activity so would that be good to put on your scalp?


There was a post a while back of some guy using ketoconazle and aloe vera(I think he left it on his scalp over night) and got good regrow this but the pics are deleted

https://www.gourmetstylewellness.com/interact/threads/ketoconazole-shampoo-2-aloe-vera-with-pictures.33419/

Yes, if it does so, it will be good for the scalp. I believe that aromatization on the scalp, it's a very important factor that needs to be addressed in combination with the other treatments as well.