Alfatradiol, Aromatization of Hair Follicles and 3a-Diol-G.

[GRme11]

According to this old thread:

https://www.hairlosstalk.com/interact/threads/aromatase-and-3hsd-incidence.98015/

I will give some insights to Alfatradiol and 3a-Diol-G.

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.

*Link for the 2005 study: https://www.thieme-connect.de/products/ejournals/html/10.1055/s-2005-870188
*Use a pdf translator.

TL;DR: Aromatase is very important for hair follicles, as we know. Estrogen Receptors Alpha and Beta are still kind of complex for me to explain them better and more detailed. 3a-Diol-G is probably a great indicator for androgen activity in tissues, including probably 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 have to connect as many dots as you can with all the mechanisms available.

Thanks for reading and sorry for any mistakes.

 

[Liqurt]

Bump

 

[GRme11]

https://www.pnas.org/content/pnas/93/22/12525.full.pdf

Above is the full study of Oh and Smart (1996):
1) 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.

2)To determine if 17-β-estradiol could influence hair growth, the dorsal hair of 6-week-old CD-1 FEMALE mice was clipped with electric clippers and the dorsal surface treated twice weekly with topical applications of either 10 nmol 17-β-estradiol, 10 nmol 17-α-estradiol, an inactive stereoisomer, or acetone vehicle from the 6th week of age to the 16th week of age. Treatment with 17-β-estradiol had a potent inhibitory effect on dorsal hair growth. As shown in Fig. 1(see study), 100% of the acetone-treated mice as well as the mice treated with the inactive stereoisomer, 17-α-estradiol, demonstrated full hair regrowth by 13 weeks of age. In contrast, mice treated with 17-β-estradiol did not demonstrate any full hair regrowth by 16 weeks of age. Some of the 17-β-estradiol-treated mice did demonstrate a partial patchy hair regrowth that involved less than 10% of the total clipped area. At 12 weeks of age, 20% of the 17-β-estradiol-treated mice demonstrated such partial patchy hair regrowth and by 15 weeks of age 40% of the 17-β-estradiol-treated mice demonstrated such partial patchy hair regrowth. Treatment of older mice with 17-β-estradiol also blocked hair regrowth (data not shown). These results demonstrate that topical treatment with 17-β-estradiol potently blocks hair growth.

3)Jumping a bit to conclusions:
Our results provide evidence that an estrogen receptor pathway within the dermal papilla regulates the telogen-anagen transition of the hair follicle. This conclusion is based on following experimental results: (i) 17-β-estradiol blocks hair growth and arrests hair follicles in the telogen phase of the hair cycle; (ii) 17-α-estradiol, an inactive stereoisomer, does not block hair growth; (iii) estrogen receptor antagonist ICI 182,780 causes the hair follicle to exit telogen and enter anagen thereby initiating hair growth; and (iv) the estrogen receptor is expressed in skin and its expression is localized to the nuclei of cells of the dermal papilla of the telogen follicle. The fact that estrogen is produced by the hair follicle itself and the estrogen receptor is predominately expressed in the dermal papilla suggest that estrogen is an endogenous paracrine regulator of hair follicle cycle.

*Check the study, many details.

Now, let's move on way back to 1980:

[Local therapy of androgenetic alopecia with 17 alpha-estradiol. A controlled, randomized double-blind study (author's transl)] - PubMed

In a controlled, randomized double-blind study, 51 patients with androgenetic alopecia and increased hair loss (telogen rate greater than 20%) were treated by local application of hair lotions with and without 17 alpha-estradiol (0.025%) for a period of at least 6 months. Before and after...

pubmed.ncbi.nlm.nih.gov

Abstract​

In a controlled, randomized double-blind study, 51 patients with androgenetic alopecia and increased hair loss (telogen rate greater than 20%) were treated by local application of hair lotions with and without 17 alpha-estradiol (0.025%) for a period of at least 6 months. Before and after therapy trichograms were taken and evaluated under standardized conditions. In 63% of the treated patients a reduction of the amount of telogen hairs appeared, whereas in the control group the same reduction was found in only 37% of the cases. Similarly, in the treated group only 11% of the patients worsened, in contrast to 50% of the control group who showed an increased telogen rate (greater than 10%). The amount of growing anagen hairs and of seborrhea did not change significantly in both groups. Side effects were not seen. These findings indicate that hair lotions containing 17 alpha-estradiol may have a therapeutic value in reducing androgenetic hair loss, if applied topically for a long period of time, similar to 17 beta-estradiol. However, no regrowth of new hair was found.


Finally, the below study is the one that concludes that 17α-Estradiol is a pretty weak 5AR inhibitor, but it can inhibit the other weak androgens via 17β-HSD, like androstenedione, as of course was mentioned by the conclusions of the other studies as well.

Testosterone metabolism in human skin cells in vitro and its interaction with estradiol and dutasteride - PubMed

Since the limited knowledge of cutaneous drug metabolism can impair the development of specifically acting topical dermatics and transdermal application systems, the cell-type-specific androgen metabolism in human skin and its inhibition by drugs were investigated. Cultured human foreskin and...

pubmed.ncbi.nlm.nih.gov

Cultured human foreskin and scalp skin keratinocytes and fibroblasts as well as occipital scalp dermal papilla cells (DPC) were incubated with testosterone 10(-6) and 10(-8)M alone and in the presence of 17alpha-estradiol, 17beta-estradiol or dutasteride for 24 h. Androgens extracted from culture supernatants were subjected to thin-layer chromatography and quantified by beta-counting. In keratinocytes and DPC, dihydrotestosterone (DHT) was only formed to a low extent while androstenedione was the main metabolite. In fibroblasts, DHT formation was pronounced following 10(-8)M testosterone. Dutasteride 10(-8)M completely suppressed 5alpha-dihydro metabolite formation. 17alpha-Estradiol and 17beta-estradiol at nontoxic concentrations decreased 17-ketometabolites.

AND TO ADD FURTHER (THIS ADDS INTERESTING INFO FOR DUTASTERIDE AS WELL):

17α-Estradiol 10–4 M decreased DHT formation in fibroblasts and DPC. This concentration, however, appeared to be toxic in the MTT test, and light microscopy proved a disturbed cell morphology. In keratinocytes, DHT formation was not significantly influenced. 17α-Estradiol 10–4 and 10–5 M clearly inhibited 17-keto-metabolite formation in every cell type, and therefore 17α-estradiol is an inhibitor of 17β-HSD. Almost identical effects were obtained using 17β-estradiol (10–6 to 10–4 M) for enzyme inhibition (data not shown). In contrast, dutasteride 10–9 M specifically reduced and at a concentration of 10–8 M completely suppressed 5·-dihydro metabolite formation. With fibroblasts and DPC, sometimes dutasteride 10–9 M already induced complete inhibition.

While dutasteride inhibited DHT synthesis very potently, a reduction in the progress of androgenetic alopecia by 17α-estradiol is less likely attributed to 5a-reductase inhibition. According to our results DHT formation in fibroblasts and DPC was only influenced at a cytotoxic concentration of 10–4 M. Nontoxic concentrations of 17α-estradiol did not inhibit DHT formation in any cell type tested. Androstenedione formation, however, was reduced by incubation with 17α-estradiol 10–5 M, a concentration which was not toxic but obviously too high to be clinically relevant. The same results were obtained with 17β-estradiol (data not shown). In contrast to our results, in freshly isolated dermal papillae 17α-estradiol 10–7 M reduced DHT formation by about 20%. In rat liver slices, not only 5a-reductase inhibition but also – even more conflicting with our results – an increase in androstenedione formation was observed. Oddly enough, this effect was only seen in female but not in male rats. The clinical relevance of these observations for androgenetic alopecia is open to speculation. Additionally, a recent study in male mice has revealed an inhibitory effect of 17α and 17β-estradiol on hair growth [30] which is in contrast to the effects in man [21]. These findings clearly demonstrate that investigations of hormone-related diseases in humans clearly ask for investigations in human-derived cell populations. The low DHT formation in DPC suggests that androgen receptor antagonists may be more effective than 5a-reductase inhibitors in androgenetic alopecia. To avoid systemic side effects, antiandrogen targeting to cutaneous appendices is highly needed.

[30]:https://www.jidsponline.org/article/S1087-0024(15)30284-7/pdf
17-beta-Estradiol (10 nmol per 200 microl acetone) applied topically twice weekly to the clipped dorsal surface of C57BL/6 or C3H female mouse skin prevented hair growth, as previously described in the CD-1 mouse strain. Twice weekly topical application of the estrogen receptor antagonist, ICI 182 780 (10nmol per 200microl acetone), induced the telogen-anagen transition and produced early pigmentation appearance in skin and hair growth in C57BL/6 and C3H female mice. Whereas twice weekly topical application of 10nmol 17-beta-estradiol blocked hair growth, the intraperitoneal administration of this dose twice weekly did not block hair growth, suggesting a direct cutaneous effect of 17-beta-estradiol. We also evaluated the effect of 17-alpha-estradiol, 17-beta-estradiol, and ICI 182 780 on hair growth in male mice. As observed in female mice, 17-beta-estradiol was a potent inhibitor of hair growth and ICI 182 780 stimulated hair growth; however, unlike the results previously observed in female mice, 17-alpha-estradiol was a potent inhibitor of hair growth in male mice. These results demonstrate that (i) the route of administration of 17-beta-estradiol is critical for its ability to block hair growth; (ii) C57BL/6 and C3H mice, two commonly employed mouse strains for hair growth studies, responded to 17-beta-estradiol and ICI 182 780 in a manner similar to that described in CD-1 mice; and (iii) the hair follicles of male and female mice respond similarly to 17-beta-estradiol and ICI 182 780, but display striking sex differences in the response to 17-alpha-estradiol on hair growth.

[21] Refers of course to the 1980 study:
In a controlled, randomized double-blind study, 51 patients with androgenetic alopecia and increased hair loss (telogen rate greater than 20%) were treated by local application of hair lotions with and without 17 alpha-estradiol (0.025%) for a period of at least 6 months. Before and after therapy trichograms were taken and evaluated under standardized conditions. In 63% of the treated patients a reduction of the amount of telogen hairs appeared, whereas in the control group the same reduction was found in only 37% of the cases. Similarly, in the treated group only 11% of the patients worsened, in contrast to 50% of the control group who showed an increased telogen rate (greater than 10%). The amount of growing anagen hairs and of seborrhea did not change significantly in both groups. Side effects were not seen. These findings indicate that hair lotions containing 17 alpha-estradiol may have a therapeutic value in reducing androgenetic hair loss, if applied topically for a long period of time, similar to 17 beta-estradiol. However, no regrowth of new hair was found.

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So, results are conflict a lot regarding female/male mice and, of course, female/male humans. This shows how gender/sex-specific the actions are and how complex. Although, we have seen improvements from 17α-Estradiol in humans, like the 2005 study and the others. Of course, with greater dosages, benefits will be greater. The 0.025% dose probably will give a very small boost if it works. We don't need to forget as well the COSMO study, which showed great efficacy of 17α reducing hair loss (pretty similar to topical Cyproterone Acetate 1%), but of course, at the same huge dose of 1%->http://files.investis.com/csm/presentations/RDday2010.pdf (pages 81-82). I made my conclusions above. I would tend to describe the treatment as a hit or miss, like many others we have seen all these years. Efficacy should be dose-dependent. I am adding this as a piece of needed extra information.

That's all I have to say regarding 17α-Estradiol. I hope this information sheds some light and helps others in the future when it's needed.

 

[GRme11]

More information about 3a-Diol/3a-HSD/ERα (Great study!):

Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia

Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic ...

www.ncbi.nlm.nih.gov

Dutasteride is a dual inhibitor of type I and II 5ARs and has proven to be an effective and tolerable treatment modality for MPHL. It improves hair growth in a dose-dependent manner by reduction of serum and scalp DHT [16]. The response to dutasteride varies in each individual, but genetic factors related to individual differences are unclear. In this study, we found several candidate regions associated with response to dutasteride in MPHL treatment through genotypic association tests.

In our study, the most significant exonic variant was rs72623193 located in DHRS9, that was ranked the highest in the gene-based tests. DHRS9 (dehydrogenase/reductase SDR family member 9) has been identified as a 3α-hydroxysteroid dehydrogenase (3α-HSD) [29]. It is a microsomal enzyme whereas other 3α-HSDs in the aldoketoreductase gene superfamily (AKR1C1–AKR1C4) are cytosolic enzymes. This enzyme is expressed in the human epidermis, hair follicles, and sebaceous glands [30, 31]. Since DHRS9 is involved in the synthesis of DHT from 3α-androstanediol [29], upregulation would facilitate the backdoor pathway to DHT in the scalp tissue even when 5AR is inhibited by dutasteride (S6(A) Fig). A previous study showed that there was negative correlation between the change in hair count and the percent change of scalp DHT after treatment with the 5AR inhibitor [16].

Additionally, DHRS9 possesses retinol dehydrogenase (RolDH) activity [32, 33], which converts retinol to retinal in retinoid acid (RA) synthesis (S6(B) Fig). Because DHRS9 can oxidize retinol that is bound to the cellular retinol-binding protein while many other RolDHs cannot [34, 35], it is regarded as a physiological enzyme [35]. Its expression changes during hair cycling in mice and increases in hair follicles of C57BL/6J mice that frequently develop dorsal skin alopecia. DHRS9 also increased in the hair follicles of patients with central centrifugal cicatricial alopecia [30]. Previous studies demonstrated that RA synthesis and the RA signalling system are related to hair growth and cycling [35, 36]. Furthermore, RA was reported to regulate bone morphogenetic protein and Wnt signalling pathways, which are involved in hair growth [37].

We also found that response to dutasteride may be associated with variants of genes involved in steroid hormone metabolism, such as SRD5A1, ESR1, and CYP19A1 (S6(A) Fig). The product of SRD5A1 is type I 5AR, which is a target of dutasteride. Dutasteride inhibits both type I and II 5ARs, while finasteride selectively inhibits type II 5AR. Therefore, a variation in SRD5A1 might affect the subject’s response to dutasteride during treatment for MPHL. However, SRD5A2 encoding type II 5AR was not associated with response to dutasteride.

In addition to androgens, it has long been known that oestrogen also effects hair follicle growth by binding locally expressed oestrogen receptors (ERs) [43]. ESR1 encodes ERα, which is 1 of 2 distinct isoforms of ERs. CYP19A1 converts androstenedione to estrone (E1) and testosterone to 17β-estradiol (E2). It has been reported that ERα is maximally expressed during telogen, and E2 inhibits hair growth [44, 45]. Moreover, E2 modifies androgen metabolism in pilosebaceous units [43].

 

[GRme11]

Study 44 refers to: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC38025/

The hair follicle is a cyclic, self renewing epidermal structure which is thought to be controlled by signals from the dermal papilla, a specialized cluster of mesenchymal cells within the dermis. Topical treatments with 17-beta-estradiol to the clipped dorsal skin of mice arrested hair follicles in telogen and produced a profound and prolonged inhibition of hair growth while treatment with the biologically inactive stereoisomer, 17-alpha-estradiol, did not inhibit hair growth. Topical treatments with ICI 182,780, a pure estrogen receptor antagonist, caused the hair follicles to exit telogen and enter anagen, thereby initiating hair growth. Immunohistochemical staining for the estrogen receptor in skin revealed intense and specific staining of the nuclei of the cells of the dermal papilla. The expression of the estrogen receptor in the dermal papilla was hair cycle-dependent with the highest levels of expression associated with the telogen follicle. 17-beta-Estradiol-treated epidermis demonstrated a similar number of 5-bromo-2'-deoxyuridine (BrdUrd) S-phase cells as the control epidermis above telogen follicles; however, the number of BrdUrd S-phase basal cells in the control epidermis varied according to the phase of the cycle of the underlying hair follicles and ranged from 2.6% above telogen follicles to 7.0% above early anagen follicles. These findings indicate an estrogen receptor pathway within the dermal papilla regulates the telogen-anagen follicle transition and suggest that diffusible factors associated with the anagen follicle influence cell proliferation in the epidermis. (I discussed similar about these a bit above)

Study 45 : https://www.jidonline.org/article/S0022-202X(15)30624-2/fulltext

! These studies are reffering to mice/murines models.

Study 45 includes the below table:

Species	Reported effect	Reference
Mouse	Spontaneous hair growth is inhibited in pregnant and lactating mice	Fraser and Nay (1953)
Rat	Hair growth waves in female rats lag behind males	Emmens (1942);Johnson (1958)
Guinea pig	Local inhibition of hair growth in guinea pigs receiving topical applications of estradiol	Whitaker (1956);Jackson and Ebling (1972)
Dog	Estrogen inhibits hair growth in dogs	Gardner and De Vita (1940)
Human	Estrogen prolongs the anagen phase of human scalp hair	Schumacher-Stock (1981)

 

[Thor9]

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.”

I had written off alfatradiol (and was considering estriol) based on the video from MPMD, but this study would invalidate his argument (at least to an extent - estriol still has over twice the RBA to ERβ compared to ERα).

It may not be a bad idea to add alfatradiol to the stack. It also helps to know that alfatradiol was beneficial to male mice and rats.

Great posts.

 

[GRme11]

I had written off alfatradiol (and was considering estriol) based on the video from MPMD, but this study would invalidate his argument (at least to an extent - estriol still has over twice the RBA to ERβ compared to ERα).

It may not be a bad idea to add alfatradiol to the stack. It also helps to know that alfatradiol was beneficial to male mice and rats.

Great posts.

Thank you. It was also beneficial to male humans as per the 2005 study and the really old one in 1980, which I have mentioned above. I attached the 2005 study. I think it is the most comprehensive regarding 17α-Estradiol (Study link: https://www.thieme-connect.de/products/ejournals/html/10.1055/s-2005-870188). Also, far experienced members informed me that ERα is hardly found on the scalp/hair follicles. ERβ is the predominant one. It is mentioned in this study as well: https://pubmed.ncbi.nlm.nih.gov/12702147/. This information is being mentioned by one of the books for Androgenetic Alopecia as well.

 

[GRme11]

Link for the 2005 study: https://www.thieme-connect.de/products/ejournals/html/10.1055/s-2005-870188
*Use a pdf translator.

 

[Thor9]

Thank you. It was also beneficial to male humans as per the 2005 study and the really old one in 1980, which I have mentioned above. I attached the 2005 study. I think it is the most comprehensive regarding 17α-Estradiol (Study link: https://www.thieme-connect.de/products/ejournals/html/10.1055/s-2005-870188). Also, far experienced members informed me that ERα is hardly found on the scalp/hair follicles. ERβ is the predominant one. It is mentioned in this study as well: https://pubmed.ncbi.nlm.nih.gov/12702147/. This information is being mentioned by one of the books for Androgenetic Alopecia as well.

Yes I saw the study's on male hair but I was specifically referring to the fact that it was shown to slow aging and improve metabolic parameters in mice/rats.

Its interesting that ERβ is the dominant one in the scalp...then it seems alfatradiol is a better choice than estriol.

Thanks for sharing that info.

 

[GRme11]

Yeah I wouldn't put too much stock in MPMD on the more theoretical hair loss topics

You can't just lookup binding affinities on wikipedia and pair it with the limited in vitro research on ERa vs ERb activation to arrive at the conclusion that estriol should work better than alfatradiol

Alfatradiol has recent research behind it and is literally an approved hair loss treatment, whereas estriol just has some ancient patent claims

I considered adding E3 myself until I went looking and found nothing of substance

Well, when I used homemade topical E3 for about three months (0.1%-Yes, I know low dosage), I didn't notice any improvements. I know the dose is pretty low but, still, when Alfatradiol at 0.025% is doing something, you expect something from Estriol as well. The only thing I noticed was my E3 blood levels which skyrocketed x10 times. I posted my results here, as well.

September 2020
Estriol(E3): 0.1 ng/ml (N.V: <0,16)-Baseline

***Started topical E3 mid-end October

Early January 2021
E3:1.1 ng/mL (Normal Values: 0.0-2.0)

(Let's keep in mind that hormones are fluctuating through the day and all the other factors. Maybe they used a different system to measure it the second time, but still, this is something.)

 

[zaman]

Would Alfatradiol be a bad choice for someone who is sensitive to anti-androgens and can get ED easily? Asking for a friend

 

[GRme11]

Would Alfatradiol be a bad choice for someone who is sensitive to anti-androgens and can get ED easily? Asking for a friend

At this dosage, 0.025% will probably be safe enough, but you will only know if you try.

 

[GRme11]

Dihydrotestosterone Is a Peripheral Paracrine Hormone (​

3a-Diol-G)​

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onlinelibrary.wiley.com

Androgen action in sexual tissues, especially skin and the prostate, is expressed by dihydrotestosterone (DHT) acting at the nuclear level. Dihydrotestosterone in the circulation and target tissues is almost solely derived from the peripheral conversion of secreted testosterone (T) in men and androstenedione in women. The general pathway is testosterone----DHT in equilibrium with androstanediol (3 alpha diol). However, a number of studies suggest that blood DHT or 3 alpha diol are not reliable indicators of peripheral DHT formation. This is particularly suggested by discrepancies in the specific activity of DHT in blood and urine following infusion of labeled DHT, suggesting that total body DHT formation is not reflected by blood levels. Thus, DHT should be thought of as a paracrine hormone formed and acting primarily in target tissues. 3 alpha androstanediol glucuronide (3 alpha diol G) is a major metabolite of DHT. An important site of its formation is the skin. Levels in blood and urine are increased in hirsutism and acne, and blood levels closely parallel pubertal development. 3 alpha diol G levels are especially increased in adrenal disorders of androgenicity such as andrenogenital syndrome; it is also a good marker of response to therapy. Levels are reduced in various forms of male pseudohermaphroditism. 3 alpha androstanediol glucuronide appears to be the best marker available of DHT formation in target tissues such as skin.


*In our initial clinical studies, we measured plasma 3a diol G levels in patients with idiopathic hirsutism. These cases had moderate to severe hirsutism, and almost all had increased plasma 3a diol G (Horton et al, 1982). It appeared to be a better marker than total or free testosterone.

*Our conclusion is that 3a diol G levels reflect the peripheral formation of DHT, and that most peripheral DHT is metabolized locally before entering the circulation. We also measured 3ot diol G in patients with pseudohermaphroditism due to either androgen resistance or 5ar reductase deficiency. Despite normal levels of testosterone in plasma, 3a diol G levels were low (Horton, 1983; Ertel et al, 1989).

*FIG. 4. A model for peripheral metabolism of DHT. Only a fraction of formed DHT enters the circulation. Some is metabolized to 3a diol, whereas a larger fraction is converted to androstanediol glucuronide (3a diol G), which appears in the circulation. Our studies in skin indicate that conversion is DHT -> 3a-diol -> 3a diol G.

 

[GRme11]

1) https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC424493/ (full)

Circulating dihydrotestosterone may not reflect peripheral formation:​

We compared the blood (PBDHT) and urine (PUDHT) production rate of dihydrotestosterone (DHT) in normal men and women to determine whether peripheral formation was totally reflected in blood. PBDHT was similar when measured at both sites in men (674 +/- 79 vs. 788 +/- 207 SE micrograms/d); however, PUDHT was greater than PBDHT in women (174 +/- 55 vs. 55 +/- 8 micrograms/d, P less than 0.02). Excretion rates of DHT and 3 alpha-androstanediol (3 alpha diol) were similar in both sexes despite major differences in blood levels. However, between sexes large differences were present in 3 alpha diol glucuronide (3 alpha diolG) in both plasma and urine. These observations indicate that peripheral (renal) formation of DHT and probably 3 alpha diol were not accurately determined by measurement of these steroids in blood. The large difference between blood and urine production rates in women suggests an important role of non-testosterone precursors of 5 alpha-reduced steroids. Measurements of 3 alpha diolG may provide more insight into these peripheral events.

"A practical outgrowth of this study is that it provides more direct proof that peripherally formed androgens are locally metabolized. Blood levels of these hormones may be an inadequate measure of total or peripheral formation and, as discussed, this appears to be the case for many disorders of androgen (and estrogen) formation and action. Markers of peripheral steroid production such as certain steroid conjugates may be ofconsiderable value in the evaluation of disorders of peripheral formation. "

2) https://pubmed.ncbi.nlm.nih.gov/3732528/

Measurements of 3 alpha,17 beta-androstanediol glucuronide in serum and urine and the correlation with skin 5 alpha-reductase activity:​

Serum and urinary measurements of 3 alpha,17 beta-androstanediol glucuronide (3 alpha-diol G) reflect peripheral androgen action and have been useful clinically. This study was designed to compare these levels in hirsute women, normal premenopausal and postmenopausal women, and in men and to correlate each measurement with skin 5 alpha-reductase activity (5 alpha-RA), an excellent correlate of androgenicity. Although serum 3 alpha-diol G values were similar in premenopausal and postmenopausal women, values were higher in hirsute women and in men. This pattern was similar for urinary 3 alpha-diol G but with greater overlap in values between hirsute and nonhirsute women and men. Serum 3 alpha-diol G showed a highly significant correlation with levels of genital 5 alpha-RA (r = 0.839, P less than 0.001), whereas urinary 3 alpha-diol G did not correlate. Serum and urinary 3 alpha-diol G also did not correlate with one another (r = 0.03). These data suggest that while both serum and urinary 3 alpha-diol G may be useful clinically, serum 3 alpha-diol G appears to correlate better with androgenicity and 5 alpha-RA. It is suggested further that the sources of serum and urinary 3 alpha-diol G may be somewhat different.


3)https://pubmed.ncbi.nlm.nih.gov/7672144/

Metabolism of dihydrotestosterone to 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide is greater in the peripheral compartment than in the splanchnic compartment:​

Objective: To compare the peripheral versus the splanchnic contribution to the formation of 3 alpha-diol G.

Design: Prospective study in various groups of women and men.

Setting: Reproductive Endocrine service of our University Medical Center.

Patients: Six normal ovulatory women, five hirsute women with polycystic ovary syndrome, and six normal men.

Interventions: All subjects received IV dihydrotestosterone (DHT) infusions as well as percutaneous administration of DHT. Serum was obtained at multiple time points before and after each administration of DHT.

Main outcome measures: Comparison of serum levels of DHT, 3 alpha-androstanediol (3 alpha-diol), 3 alpha-diol G, and androsterone glucuronide in the three groups.

Results: Steady-state levels of DHT were similar in the three groups and were also similar after the two different routes of administration. However, ratios of 3 alpha-diol G to DHT were significantly greater after percutaneous gel than after IV administration in all three groups. This also was the case for the ratio of unconjugated serum 3 alpha-diol to DHT. Levels of androsterone glucuronide were similar with the different routes of administration.

Conclusion: Using normal routes of administration and, in attempting to assess in vivo metabolism of DHT, our data confirm that the skin is the major site of unconjugated 3 alpha-diol and 3 alpha-diol G formation. Serum 3 alpha-diol G, therefore, appears largely to reflect skin DHT metabolism.


4)https://pubmed.ncbi.nlm.nih.gov/3654916/

Production of 3 alpha-androstanediol glucuronide in human genital skin:​

3 alpha-Androstanediol glucuronide (3 alpha diol-G) is produced extrasplanchnically and is a good clinical marker of androgen action in peripheral tissues. However, the direct formation of androgen glucuronides in peripheral sites such as skin has not been determined in man. Genital skin from 21 premenopausal women and 8 men and foreskin from 6 neonates were incubated with either [14C]testosterone [14C]dihydrotestosterone (DHT) to determine the production of DHT glucuronide and 3 alpha diol-G in skin. After hydrolysis of incubation medium with glucuronidase, followed by extraction and sequential chromatography, constant 3H to 14C ratios of 3 alpha diol confirmed the production of DHT glucuronide and 3 alpha diol-g. The conversion of DHT to 3 alpha diol-G was higher than the conversion from testosterone (P less than 0.05), and conversion was higher in men than in women. These data provide evidence for the direct formation of C19 steroid glucuronides by human skin.


3A-DIOL-G GENERAL INFORMATION: http://immunotech.cz/Media/Default/Page/A-G_analyte_info.pdf

The measurement of 3α-androstanediol glucuronide is a means of assessing skin androgen activity. The skin’s sensitivity to androgens depends on the presence of 5α-reductase enzyme, which converts testosterone to DHT. Accordingly, the measurement of 3α-androstanediol glucuronide is an indirect way of testing DHT and 5α-reductase activity. 3α-androstanediol glucuronide is measured in conjunction with measurement of testosterone, androstenedione, DHEA-S, and 17 hydroxyprogesterone levels. 3α-androstanediol glucuronide is a better marker than 3α-androstanediol because once formed, no conversion to DHT takes place.
A direct correlation between serum 3α-androstanediol glucuronide levels and 5α-reductase activity was found in both normal and hirsute women6 . Serum levels of 3α-androstanediol glucuronide correlate well with the presence and severity of hirsutism2 . In hirsute patients’ serum, 3α-androstanediol glucuronide levels also correlate with a clinical diagnosis of hirsutism based on a Ferriman-Gallwey score13. The test is useful in differential diagnosis of hirsutism, in connection with other markers, especially when levels of circulating androgens (testosterone, free testosterone, and DHT) are within normal limits.
Several studies have shown that in hirsute women, either with polycystic ovary syndrome (PCOS) or idiopathic hirsutism (IH), the activity of 5α-reductase in the genital skin was increased. Measurement of 3α-androstanediol glucuronide is a method by which to indirectly determine the activity of this enzyme.
---------------------------------------------------------------------------------------------------------------------------------------------------------------
AROMATASE:
1) https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8621879/ (Full)

Alleviation of Androgenetic Alopecia with Aqueous Paeonia lactiflora and Poria cocos Extract Intake through Suppressing the Steroid Hormone and Inflammatory Pathway (PL->White Peony Root):​

--------------------------------------------------------------------------------------------------------------------------------------------------------------
"Aromatase (CYP19A1) converts androgens into estrogen in scalp hair follicles. The increase in estrogen in the experiment promotes hair growth. CYP19A1 mRNA expression was much lower in the Androgenetic Alopecia-Con than in the Androgenetic Alopecia-PL (taking White Peony), Androgenetic Alopecia-PC, and Androgenetic Alopecia-MIX groups (Figure 5B). CYP19A1 mRNA expression was markedly and similarly lower in Androgenetic Alopecia-Positive and Androgenetic Alopecia-Con groups (Figure 5B).

Hair growth is also associated with Wnt signaling: Dickkopf Wnt signaling pathway inhibitor 1 (DKK1) and catenin beta-1 (β-catenin) are the central regulators of hair growth. TGF-β signaling interacts with Wnt signaling. The mRNA expression of DKK1, an inhibitor of the Wnt signaling pathway, was much higher in the Androgenetic Alopecia-Con group than in the other groups (Figure 5C). Androgenetic Alopecia-PL, Androgenetic Alopecia-PC, and Androgenetic Alopecia-MIX also reduced DKK1 expression but not to the same extent observed in the Androgenetic Alopecia-Positive group (Figure 5C). The mRNA expression of β-catenin, an indicator of Wnt signaling activation, was much lower in the Androgenetic Alopecia-Con than in the Normal-Con, Androgenetic Alopecia-Positive, and Androgenetic Alopecia-PL groups. PC and PL/PL also reduced its expression but not to the same extent as Androgenetic Alopecia-PL (Figure 5C). In addition, TGF-β2 mRNA expression was much higher in the Androgenetic Alopecia-Positive and Androgenetic Alopecia-Con group than in the other groups (Figure 5C). TGF-β2 mRNA expression was markedly lower in Androgenetic Alopecia-PL, Androgenetic Alopecia-MIX, and Normal-Con groups than Androgenetic Alopecia-Con (Figure 5C). These observations suggested that finasteride acted on Wnt signaling to promote hair growth, but PL ingestion promoted aromatase and Wnt signaling pathways."


The present study consistently showed that PL and PC increased CYP17A1 mRNA expression related to converting testosterone into estrogen and both elevated serum 17β-estradiol concentration. Thus, PL and PC can be a candidate of therapeutic agents for Androgenetic Alopecia, although the pathway to treat Androgenetic Alopecia may be different from finasteride.

In this study, after topical application of testosterone propionate solution, the dorsal hair growth by C57BL/6 mice was inhibited by disturbing the synchronized growth cycle at the initial stage [40]. Changes in the hair growth cycle resulted in skin color changes from fleshy pink to gray and black, as previously described [30,41]. In the present study, after C57BL/6 mice had ingested PL, hair growth in dorsal skin was quickly started, and the numbers and sizes of hair follicles increased, suggesting that hair quickly entered the growth phase. Hair growth in the Androgenetic Alopecia-PC group was slower initially but faster during the later stage. Hair growth in the Androgenetic Alopecia-MIX and Androgenetic Alopecia-Positive groups were similar. These results show that PL and PL/PC reduced the symptoms of Androgenetic Alopecia in our murine model.

Interestingly, in the present study, PL significantly reduced serum testosterone and elevated 17β-estradiol levels, reduced the mRNA expressions of pro-inflammatory cytokines (TNF-α and IL-6), and lowered NR3C2 levels in the Androgenetic Alopecia-PL group than in the Androgenetic Alopecia-PC group (p < 0.05). Thus, PL more effectively inhibited pro-inflammatory cytokines [44]. We also found that Androgenetic Alopecia-Con reduced the PPARG expression and the other treatment groups raised the expression of PPARG. The potentiation of Akt and GSK-3β phosphorylation improved Wnt signaling to protect against hair loss induced by testosterone.

In conclusion, PL (White Peony) ingestion effectively promoted hair regeneration with increased hair follicle numbers and sizes in our C57BL/6 mouse model of Androgenetic Alopecia by reducing serum testosterone and pro-inflammatory cytokines levels and steroid nuclear receptor expression and promoting the expressions of aromatase and Wnt-related transcription factors. System pharmacology analysis showed that the active ingredients of PC and PL also modulated steroid hormone receptor activity, nuclear receptor activity, and ligand-activated transcription factor activity, and these results were consistent with our animal experimental results. In clinical symptoms of hair loss, PL exhibited better protection against hair loss than PC. We concluded that PC and mixtures of PC and PL are potential treatments for Androgenetic Alopecia in an Androgenetic Alopecia murine model. This needs to be confirmed in a human study in the future.

 

[Mr. Slap Head]

weaker estrogens does not seem to be a good idea for hair. if you are a poor aromatizer try topical bica or a little dab of e2

 

[Adri23]

weaker estrogens does not seem to be a good idea for hair. if you are a poor aromatizer try topical bica or a little dab of e2

How would bica increase aromatase if the enzyme does not work as intended? Bica increase E by aromatizing T but if your body doesn't aromatize how would it increase E?

 

[GRme11]

How would bica increase aromatase if the enzyme does not work as intended? Bica increase E by aromatizing T but if your body doesn't aromatize how would it increase E?

I thought that immediately. My best bet is that Bicalutamide, by blocking the AR, would favor an estrogenic environment, like any other anti-androgen. So, that's why the combination with the 17α-Estradiol makes even more sense. Anyway, directly from the Wiki:

Although bicalutamide does not bind to the ERs, it can increase estrogen levels secondarily to blockade of the AR when used as a monotherapy in males, and for this reason, the medication can indirectly activate the ERs to a degree and hence have some indirect estrogenic effects in men.

The next option, would be indeed E2.

 

[Adri23]

Although bicalutamide does not bind to the ERs, it can increase estrogen levels secondarily to blockade of the AR when used as a monotherapy in males, and for this reason, the medication can indirectly activate the ERs to a degree and hence have some indirect estrogenic effects in men.

But that would make sense if your aromatase enzyme works properly right?

 

[GRme11]

But that would make sense if your aromatase enzyme works properly right?

Even if it wouldn't, the estrogenic environment still and the AR blockade would favor Estrogens in general. So, I guess something should happen.

 

[Adri23]

Even if it wouldn't, the estrogenic environment still and the AR blockade would favor Estrogens in general. So, I guess something should happen.

Great cause I'm gonna try topical bica twice a week for the first one or two months to speed up results.