Beyond DHT (article)

Wagner83

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DHT often gets shuttled to areas of high estrogenic activity to control cellular proliferation caused by estrogen and estrogenic metabolites. Same thing happens in breast in prostate cancer - these patients have high DHT levels in breast and prostate but it is there to control estrogen when progesterone is low or not available at all. The 5-androstenediol is a potent estrogen, and a much potent estrogen than it is an androgen. So, a build up of 5-androstenediol will also tend to cause local accumulation of DHT to control the damage and thus DHT gets the blame.

Interesting ; I see a lot of fat people with very good looking beard do you think dht could be involved here as a defensive mechanism? To a certain extent wouldn)'t the body try to increase dht (since it's the most potent androgen) in tissues to counter the effects of too much estrogens? But afaik dht levels are inversely correlated with belly fat, maybe it's again a question of tissue levels vs blood levels.

Something like sorghum shows signs of increasing 5-ar activity and yet it increases hair loss a whole lot. To be fair I saw cyanide, nitrate and iron could be present in decent amounts in sorghum depending on how it's grown (Cyanide (prussic acid) and nitrate in sorghum crops), so despite potentially increasing 5-ar, containing b3 and magnesium in good amounts , it's pretty awful.
I would love to see the chemicals which increase 5-ar activity isolated.
 
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TubZy

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The 11-keto DHT is basically the same as DHT but with a much longer half life. The claims about DHT and hair loss are based exclusively on its androgenicity and in that respect there is no difference between 11-keto DHT and regular DHT. I did not see reports of hair loss from 11-keto DHT and also the few human studies with actual DHT using anywhere from 25mg up to 100mg daily did not report a single case of increased hair loss. So, to me the direct role of DHT as a cause in hair loss is largely disproven just as it is in prostate cancer. It may have an association with hair loss, but just like cholesterol it is probably there to repair the damage caused by something else. Even mainstream medicine has wizened up to the fact that DHT is not a direct cause and now says the issue is "genetic" and DHT is just the "trigger".
My personal guess is that one of the unsaturated -diol metablites of DHEA is the primary trigger of hair loss. Especially, the delta-5-androstenediol also known as hermaphrodiol, is what I suspect is a prime cause in MPB and prostate cancer.
5-Androstenediol - Wikipedia
https://web.wpi.edu/Pubs/ETD/Available/etd-102707-170420/unrestricted/JGroufThesis.pdf

I suspect the build up of 5-androstenediol from DHEA is a direct result of suboptimal metabolism characterized by excessive reductive environment and high estrogen. In such an environment, DHEA can serve as an emergency oxidizing agent generating 5-androstenediol as a direct metabolite. Similar things happen with pyruvate being used as an oxidizing agent when NADH levels are too high, which generates lactate in the process.
DHT often gets shuttled to areas of high estrogenic activity to control cellular proliferation caused by estrogen and estrogenic metabolites. Same thing happens in breast in prostate cancer - these patients have high DHT levels in breast and prostate but it is there to control estrogen when progesterone is low or not available at all. The 5-androstenediol is a potent estrogen, and a much potent estrogen than it is an androgen. So, a build up of 5-androstenediol will also tend to cause local accumulation of DHT to control the damage and thus DHT gets the blame.
Keep in mind that if androgenic steroids were the direct cause of MPB then androgen receptor antagonists would be the cure for MPB. I am not aware of successful trials, animal or human, with AR antagonists like flutamide showing inhibition of hair loss or regrowth of hair. This failure of androgen receptor antagonist IMO completely disprove the role of DHT in MPB. The (poor) prostate cancer patients who got flutamide did not experience even a hair-width of regrowth (pun in tended). And the association of MPB and prostate cancer is well known. So, whatever is causing the hair loss is likely not a strong (or at all) androgen receptor agonist like DHT.
Finally, niacinamide, which promotes androgen signalling and binding of DHT to the androgen receptor not only does not increase hair loss but it being studies for hair regrowth.
Just my 2c.

Thanks brother for the detailed response. I 100% agree, but what are your thoughts on the PGD2 theory. I have tested setipiprant and OC000459 (pgd2 inhibitors) and they have stopped my shedding and itch but did get some side effects (insomnia, fatigue, runny nose etc.). Do you think raised PGD2 levels in the scalp are just another sign of damage too? Peat suggest aspirin can help with hair loss -inhibiting prostaglandins through PGD2 possibly or enhancing the mitochondria function.

Regarding the AR theory, there are actually a few AR antagonist out (research grade) that the hair loss/bodybuilding community uses such as:

Here is the company for CB 03 01 (breezula) Breezula

I have used both before and they both produced side effects similar to finasteride causing me to quit, but worked to an extent in stopping hair loss and thickening hair. I'm not sure on the exact mechanism but it looks like CB 03 01 converts to cortisol when entering the skin after it binds/blocks the AR which makes it "safer" (not my words) compared to RU 58841 which can bind to any AR in the body.

I would try 11 keto dht, but can't handle DMSO so if anyone on here wants to try topically give it a shot and see what happens to your hair.
 
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The 11-keto DHT is basically the same as DHT but with a much longer half life. The claims about DHT and hair loss are based exclusively on its androgenicity and in that respect there is no difference between 11-keto DHT and regular DHT. I did not see reports of hair loss from 11-keto DHT and also the few human studies with actual DHT using anywhere from 25mg up to 100mg daily did not report a single case of increased hair loss. So, to me the direct role of DHT as a cause in hair loss is largely disproven just as it is in prostate cancer. It may have an association with hair loss, but just like cholesterol it is probably there to repair the damage caused by something else. Even mainstream medicine has wizened up to the fact that DHT is not a direct cause and now says the issue is "genetic" and DHT is just the "trigger".
My personal guess is that one of the unsaturated -diol metablites of DHEA is the primary trigger of hair loss. Especially, the delta-5-androstenediol also known as hermaphrodiol, is what I suspect is a prime cause in MPB and prostate cancer.
5-Androstenediol - Wikipedia
https://web.wpi.edu/Pubs/ETD/Available/etd-102707-170420/unrestricted/JGroufThesis.pdf

I suspect the build up of 5-androstenediol from DHEA is a direct result of suboptimal metabolism characterized by excessive reductive environment and high estrogen. In such an environment, DHEA can serve as an emergency oxidizing agent generating 5-androstenediol as a direct metabolite. Similar things happen with pyruvate being used as an oxidizing agent when NADH levels are too high, which generates lactate in the process.
DHT often gets shuttled to areas of high estrogenic activity to control cellular proliferation caused by estrogen and estrogenic metabolites. Same thing happens in breast in prostate cancer - these patients have high DHT levels in breast and prostate but it is there to control estrogen when progesterone is low or not available at all. The 5-androstenediol is a potent estrogen, and a much potent estrogen than it is an androgen. So, a build up of 5-androstenediol will also tend to cause local accumulation of DHT to control the damage and thus DHT gets the blame.
Keep in mind that if androgenic steroids were the direct cause of MPB then androgen receptor antagonists would be the cure for MPB. I am not aware of successful trials, animal or human, with AR antagonists like flutamide showing inhibition of hair loss or regrowth of hair. This failure of androgen receptor antagonist IMO completely disprove the role of DHT in MPB. The (poor) prostate cancer patients who got flutamide did not experience even a hair-width of regrowth (pun in tended). And the association of MPB and prostate cancer is well known. So, whatever is causing the hair loss is likely not a strong (or at all) androgen receptor agonist like DHT.
Finally, niacinamide, which promotes androgen signalling and binding of DHT to the androgen receptor not only does not increase hair loss but it being studies for hair regrowth.
Just my 2c.

if you use DHT, you are skipping over the testosterone step, if you have high DHT all ready, theoretically, you will have low testosterone all ready due to stress. i wonder what the implications would be to do this & continue it more in a hair loss situation. if test is low, then prolactin would be high, although DHT does have prolactin lowering effects theoretically, i wonder if it is enough to kickstart the system, similar to progesterone. test has many functions, i wonder what some of the effects would be to systemically raise DHT, but have low testosterone and high prolactin.:

Dihydrotestosterone (DHT) was administered percutaneously in a dose of 125 mg twice daily for 10 days to 12 normal men. Basal plasma levels of testosterone (T), 17 beta-estradiol (E2), and LH were measured every 2 days in these men and every 5 days in subjects from a control group receiving placebo. The daytime course of plasma hormone levels between two DHT applications was studied in six men. LRH tests were performed in nine men before and on day 10 of DHT administration. Plasma levels of free T and free E2, and T - E-binding globulin capacity and affinity were measured in six men before and on days 5 and 10 of DHT administration. Before DHT administration, there was no difference in basal plasma levels of T, DHT, E2, and LH between the control and the DHT-treated group. In the latter group, plasma DHT levels increased sharply from 0.52 +/- (+/- SE) to 3.70 +/- 0.92 ng/ml on day 2 (P less than 0.001) during DHT treatment. Plasma T, E2, and LH levels decreased significantly from 7.33 +/- 0.74 to 1.33 +/- 0.54 ng/ml (P less than 0.001), from 46 +/- 5 to 20 +/- 3 pg/ml (P less than 0.01), and from 7.8 +/- 1 to 4.2 mIU/ml (P less than 0.05), respectively. Except for a small decrease in plasma DHT (P less than 0.05) 12 h after the previous DHT application, hormone levels were stable during the time between the two DHT treatments. The responses of LH and FSH to LRH were not different before and on day 10 of DHT administration. Plasma levels of free T and free E2 as well as those of total T and E2 decreased; however, the percentages of unbound T and E2 were not different before and during DHT administration. T - E-binding globulin capacity and affinity were not modified by DHT administration. Changes in plasma DHT levels were negatively correlated with those in The results of this study demonstrate that 10-days DHT administration has an inhibitory effect on the hypothalamo-pituitary-testicular axis in normal men.

Effects of 10 days administration of percutaneous dihydrotestosterone on the pituitary-testicular axis in normal men. - PubMed - NCBI

Twenty-seven men completed all study procedures. Serum DHT levels increased nearly sevenfold, while testosterone levels decreased in men treated with daily transdermal DHT gel but were unchanged in the placebo-treated group (P < 0.01 between groups). In contrast, intraprostatic DHT and testosterone concentrations on d 28 were not different between groups (DHT: placebo = 2.8 ± 0.2 vs. DHT gel = 3.1 ± 0.5 ng/g; T: placebo = 0.6 ± 0.2 vs. DHT gel = 0.4 ± 0.1, mean ± se). Similarly, prostate volume, prostate-specific antigen, epithelial cell proliferation, and androgen-regulated gene expression were not different between groups.

Dihydrotestosterone Administration Does Not Increase Intraprostatic Androgen Concentrations or Alter Prostate Androgen Action in Healthy Men: A Randomized-Controlled Trial

Thanks brother for the detailed response. I 100% agree, but what are your thoughts on the PGD2 theory. I have tested setipiprant and OC000459 (pgd2 inhibitors) and they have stopped my shedding and itch but did get some side effects (insomnia, fatigue, runny nose etc.). Do you think raised PGD2 levels in the scalp are just another sign of damage too? Peat suggest aspirin can help with hair loss -inhibiting prostaglandins through PGD2 possibly or enhancing the mitochondria function.

Regarding the AR theory, there are actually a few AR antagonist out (research grade) that the hair loss/bodybuilding community uses such as:

Here is the company for CB 03 01 (breezula) Breezula

I have used both before and they both produced side effects similar to finasteride causing me to quit, but worked to an extent in stopping hair loss and thickening hair. I'm not sure on the exact mechanism but it looks like CB 03 01 converts to cortisol when entering the skin after it binds/blocks the AR which makes it "safer" (not my words) compared to RU 58841 which can bind to any AR in the body.

I would try 11 keto dht, but can't handle DMSO so if anyone on here wants to try topically give it a shot and see what happens to your hair.

it increases scalp inflammation not directly on hair, but when systematically applied
 
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I noticed no such thing. How much were you using?

i think if you are in "hair losing" mode all ready, it is going to be negative for you, if you have normal levels of prolactin and testosterone and thyroid and progesterone and all that, i think it will wok well for you
 

LeeLemonoil

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I begin to think that "circumventing" Testosterone to achieve higher DHT, not only in scalp but in general, is probably beneficial.
As we see, there are pathways that not include synthesis of Test, like the Progesterone-backdoor and via 5a-Androstanedione.
That might be the reason that Test does not lower that much in aging. It's probably better regarded as a dual-substrate for Dht and estrogens, leaning more towards the Est side.

@haidut
thanks for the explainations, it gained me another perspective to the mechanisms of hairloss. High 4-delta in place of more "beneficial" Androgens I've also long suspected to be involved in many pathological conditions for some time now.

On another note, as I've outlined in the threa "ß-Ionone as a DHT-analouge", brave souls with bald heads could try out ß-Ionone topically and see what the effects are.
It binds to the same olfactory receptor as DHT in both prostate cells and in melatocytes and some other skin cells and, more importantly, indues the same actions as DHT.
If an olfactory receptor would also be expressed in tissues in the scalp, it might prove beneficial. But I'm not aware scalp-tissue has been researched for those class of receptors yet. If there are some, then hairloss might involve quite some different mechanisms mediated by androgens/DHT than just AR-related stuff. Think about it, ß-Ionone, dirt cheap, might have numerous health-applications and can't be patented - so research into it might stall before it even begins.

It's a fat-soluble terpene, so it penetrates well by itself already. If diluted into MCT-oil or other carrier oils, it should reach target tissues very very well
 

LeeLemonoil

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The 5α-androstanedione pathway to dihydrotestosterone in castration-resistant prostate cancer. - PubMed - NCBI

Although the path from adrenal precursor steroids to DHT was generally thought to require 5α-reduction of testosterone, recent data suggest that it instead involves conversion from Δ-androstenedione by steroid-5α-reductase isoenzyme-1 to 5α-androstanedione, followed by subsequent conversion to DHT. The 5α-androstanedione pathway to DHT therefore bypasses testosterone entirely.
 
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1kT

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The 5α-androstanedione pathway to dihydrotestosterone in castration-resistant prostate cancer. - PubMed - NCBI

Although the path from adrenal precursor steroids to DHT was generally thought to require 5α-reduction of testosterone, recent data suggest that it instead involves conversion from Δ-androstenedione by steroid-5α-reductase isoenzyme-1 to 5α-androstanedione, followed by subsequent conversion to DHT. The 5α-androstanedione pathway to DHT therefore bypasses testosterone entirely.
Over 24 hours, DHT formation from 4-dione increased gradually and was significantly higher compared to that generated from testosterone (study).
 
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I begin to think that "circumventing" Testosterone to achieve higher DHT, not only in scalp but in general, is probably beneficial.
As we see, there are pathways that not include synthesis of Test, like the Progesterone-backdoor and via 5a-Androstanedione.
That might be the reason that Test does not lower that much in aging. It's probably better regarded as a dual-substrate for Dht and estrogens, leaning more towards the Est side.

@haidut
thanks for the explainations, it gained me another perspective to the mechanisms of hairloss. High 4-delta in place of more "beneficial" Androgens I've also long suspected to be involved in many pathological conditions for some time now.

On another note, as I've outlined in the threa "ß-Ionone as a DHT-analouge", brave souls with bald heads could try out ß-Ionone topically and see what the effects are.
It binds to the same olfactory receptor as DHT in both prostate cells and in melatocytes and some other skin cells and, more importantly, indues the same actions as DHT.
If an olfactory receptor would also be expressed in tissues in the scalp, it might prove beneficial. But I'm not aware scalp-tissue has been researched for those class of receptors yet. If there are some, then hairloss might involve quite some different mechanisms mediated by androgens/DHT than just AR-related stuff. Think about it, ß-Ionone, dirt cheap, might have numerous health-applications and can't be patented - so research into it might stall before it even begins.

It's a fat-soluble terpene, so it penetrates well by itself already. If diluted into MCT-oil or other carrier oils, it should reach target tissues very very well

what is beneficial about it exactly? i can see how DHT is important, but it seems to lower testosterone by skipping over it? you see low testosterone as people get older...
 

LeeLemonoil

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Yes, Test gets lower in older people, but that's part of the "normal" degenration we all face, it's not to be avoided and it does not mean that lower Test causes aging/illness.

Test is important, no doubt, given alone the qauntity. But other steroids are more important in various tissues, and it's "often" DHT or the metablites/precursor we talk about in this thread.

But to be clear, it's all based on my personal "gut feeling" right now, resulting from everything I kno about endo
 

Dante

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The 5-androstenediol is a potent estrogen, and a much potent estrogen than it is an androgen. So, a build up of 5-androstenediol will also tend to cause local accumulation of DHT to control the damage and thus DHT gets the blame.
Keep in mind that if androgenic steroids were the direct cause of MPB then androgen receptor antagonists would be the cure for MPB. I am not aware of successful trials, animal or human, with AR antagonists like flutamide showing inhibition of hair loss or regrowth of hair. This failure of androgen receptor antagonist IMO completely disprove the role of DHT in MPB. The (poor) prostate cancer patients who got flutamide did not experience even a hair-width of regrowth (pun in tended). And the association of MPB and prostate cancer is well known. So, whatever is causing the hair loss is likely not a strong (or at all) androgen receptor agonist like DHT.
Finally, niacinamide, which promotes androgen signalling and binding of DHT to the androgen receptor not only does not increase hair loss but it being studies for hair regrowth.
Just my 2c.
Sensei, I am going to ask a very stupid question. What exactly is an estrogen ? Is it something that acts via "estrogen receptors" (a few desirable compound imo also acts via "estrogen receptor" ) or is it a substance that enhances cellular proliferation, enhances profileration, slows metabolism ( i see pufa, ionizing radiation being grouped together with "estrogen"). Are there more to add to it ?
On a side note, any ideas about 5-beta-reductase?
 
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Raytoo

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The 11-keto DHT is basically the same as DHT but with a much longer half life. The claims about DHT and hair loss are based exclusively on its androgenicity and in that respect there is no difference between 11-keto DHT and regular DHT. I did not see reports of hair loss from 11-keto DHT and also the few human studies with actual DHT using anywhere from 25mg up to 100mg daily did not report a single case of increased hair loss. So, to me the direct role of DHT as a cause in hair loss is largely disproven just as it is in prostate cancer. It may have an association with hair loss, but just like cholesterol it is probably there to repair the damage caused by something else. Even mainstream medicine has wizened up to the fact that DHT is not a direct cause and now says the issue is "genetic" and DHT is just the "trigger".
My personal guess is that one of the unsaturated -diol metablites of DHEA is the primary trigger of hair loss. Especially, the delta-5-androstenediol also known as hermaphrodiol, is what I suspect is a prime cause in MPB and prostate cancer.
5-Androstenediol - Wikipedia
https://web.wpi.edu/Pubs/ETD/Available/etd-102707-170420/unrestricted/JGroufThesis.pdf

I suspect the build up of 5-androstenediol from DHEA is a direct result of suboptimal metabolism characterized by excessive reductive environment and high estrogen. In such an environment, DHEA can serve as an emergency oxidizing agent generating 5-androstenediol as a direct metabolite. Similar things happen with pyruvate being used as an oxidizing agent when NADH levels are too high, which generates lactate in the process.
DHT often gets shuttled to areas of high estrogenic activity to control cellular proliferation caused by estrogen and estrogenic metabolites. Same thing happens in breast in prostate cancer - these patients have high DHT levels in breast and prostate but it is there to control estrogen when progesterone is low or not available at all. The 5-androstenediol is a potent estrogen, and a much potent estrogen than it is an androgen. So, a build up of 5-androstenediol will also tend to cause local accumulation of DHT to control the damage and thus DHT gets the blame.
Keep in mind that if androgenic steroids were the direct cause of MPB then androgen receptor antagonists would be the cure for MPB. I am not aware of successful trials, animal or human, with AR antagonists like flutamide showing inhibition of hair loss or regrowth of hair. This failure of androgen receptor antagonist IMO completely disprove the role of DHT in MPB. The (poor) prostate cancer patients who got flutamide did not experience even a hair-width of regrowth (pun in tended). And the association of MPB and prostate cancer is well known. So, whatever is causing the hair loss is likely not a strong (or at all) androgen receptor agonist like DHT.
Finally, niacinamide, which promotes androgen signalling and binding of DHT to the androgen receptor not only does not increase hair loss but it being studies for hair regrowth.
Just my 2c.

So if I have MPB and there is cancer in my family (father, brother) do I need to take anything else now that I use Pansterone.
 

Dante

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I begin to think that "circumventing" Testosterone to achieve higher DHT, not only in scalp but in general, is probably beneficial.
As we see, there are pathways that not include synthesis of Test, like the Progesterone-backdoor and via 5a-Androstanedione.
That might be the reason that Test does not lower that much in aging. It's probably better regarded as a dual-substrate for Dht and estrogens, leaning more towards the Est side.

@haidut
thanks for the explainations, it gained me another perspective to the mechanisms of hairloss. High 4-delta in place of more "beneficial" Androgens I've also long suspected to be involved in many pathological conditions for some time now.

On another note, as I've outlined in the threa "ß-Ionone as a DHT-analouge", brave souls with bald heads could try out ß-Ionone topically and see what the effects are.
It binds to the same olfactory receptor as DHT in both prostate cells and in melatocytes and some other skin cells and, more importantly, indues the same actions as DHT.
If an olfactory receptor would also be expressed in tissues in the scalp, it might prove beneficial. But I'm not aware scalp-tissue has been researched for those class of receptors yet. If there are some, then hairloss might involve quite some different mechanisms mediated by androgens/DHT than just AR-related stuff. Think about it, ß-Ionone, dirt cheap, might have numerous health-applications and can't be patented - so research into it might stall before it even begins.

It's a fat-soluble terpene, so it penetrates well by itself already. If diluted into MCT-oil or other carrier oils, it should reach target tissues very very well
Regional scalp differences of the androgenic metabolic pattern in subjects affected by male pattern baldness. - PubMed - NCBI
this paper suggests that androstenedione formed from testosterone was higher in hairy skin than in alopecic areas ; androstanedione formed from DHT was also higher in non alopecic areas . However, they have not specified which androstenedione is it.
Wikipedia entry on Δ4-dione however
4-Androstenedione - Wikipedia does state MPB as it side-effect but it also produced opposite actions on males and females -"The side effects for men include breast development, behavioral changes,heart disease, and more. Side effects for women is that their voices will deepen and they may grow facial hair "
Btw, did ß-Ionone give you neurosteroidal benefits like DHT ?
 

TubZy

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Actually, I think @haidut is right on the AR theory as well. The two AR blockers (CB and RU) seem to block ALL androgens (T, DHT etc.) from binding to the receptor site in the scalp which would also include 5-androstenediol. A selective topical 5-androstenediol receptor blocker (if that is even possible) should regrow hair (and cure prostate cancer?) if that is indeed the case.

None of the ppl who use/used RU/CB (including me) realize what exactly it's blocking they just assume it's DHT, but I couldn't find any evidence say it only blocks DHT.

Very interesting.
 

LeeLemonoil

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Regional scalp differences of the androgenic metabolic pattern in subjects affected by male pattern baldness. - PubMed - NCBI
this paper suggests that androstenedione formed from testosterone was higher in hairy skin than in alopecic areas ; androstanedione formed from DHT was also higher in non alopecic areas . However, they have not specified which androstenedione is it.
Wikipedia entry on Δ4-dione however
4-Androstenedione - Wikipedia does state MPB as it side-effect but it also produced opposite actions on males and females -"The side effects for men include breast development, behavioral changes,heart disease, and more. Side effects for women is that their voices will deepen and they may grow facial hair "
Btw, did ß-Ionone give you neurosteroidal benefits like DHT ?

@Dante
It feels grounding at 1% in a perfume. It's hard to tell if it is similar to what DHT would feel like - the neurosteroidal effects of DHT seem to result from GABAa modulation, nuclear receptor and GCP-Receptor - also possibly direct metabolism in some brain areas - unlikely that ß-Ionone will act analogously in every aspect.
It's effectve though for skin-lightening at a 10% dilutin in a carrier oil. I've performed some trials with a cell-culture
 

haidut

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Sensei, I am going to ask a very stupid question. What exactly is an estrogen ? Is it something that acts via "estrogen receptors" (a few desirable compound imo also acts via "estrogen receptor" ) or is it a substance that enhances cellular proliferation, enhances profileration, slows metabolism ( i see pufa, ionizing radiation being grouped together with "estrogen"). Are there more to add to it ?
On a side note, any ideas about 5-beta-reductase?

I think you hit the nail on the head. The traditional definition of an estrogen is just what you said first - something that binds to and activates the estrogen receptors. But that is not enough to explain the wide variety of estrogenic effects observable from exposure from things like ionizing radiation, PUFA, NO, protein deficiency, etc. So, the latter type would be called "functional" estrogens as they have the same effects on the cell as estrogen without affecting receptors much. I think both kinds are equally important and functional anti-estrogens would be any substances or activity that increases cellular differentiation, improves glucose metabolism, lowers lipolysis, inhibits the enzyme FAS, inhibits the desaturase enzyme, etc. In one of his articles Ray writes how he used to annoy his students by showing them how pretty much anything can have a "hormonal" effect depending on the context and health of organism. So, blocking estrogen "receptors" would not always be enough but it is a good start. Destroying the estrogen receptor inside the cell (as progesterone and caffeine do) while also keeping PUFA levels low, takes care of both the genomic/receptor and functional aspect of estrogenism.
 

Dante

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So, blocking estrogen "receptors" would not always be enough but it is a good start. Destroying the estrogen receptor inside the cell (as progesterone and caffeine do) while also keeping PUFA levels low, takes care of both the genomic/receptor and functional aspect of estrogenism.
Are you sure that destroying/blocking estrogen receptors is a good idea ?. A 5-AR steroid also acts via ER-beta (one could say it displaces E2 from ER-beta) but produces pro-differentiation , anti-proliferation and anti-stress,anxiolytic benefits (Wikipedia calls it an estrogen but i wouldn't , it doesn't share any property that i know with E2). Didn't you once say that receptors interactions form a many-to-many relationship?
 
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What-a-Riot

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this has me thinking: can we identify any literal or effective estrogen receptor inverse agonists?
 

haidut

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Are you sure that destroying/blocking estrogen receptors is a good idea ?. A 5-AR steroid also acts via ER-beta (one could say it displaces E2 from ER-beta) but produces pro-differentiation , anti-proliferation and anti-stress,anxiolytic benefits (Wikipedia calls it an estrogen but i wouldn't , it doesn't share any property that i know with E2). Didn't you once say that receptors interactions form a many-to-many relationship?

You have a point, I have not seen any studies on long term effects of estrogen receptor destruction. The ERb agonism is usually from metabolites like androstanediol and (maybe) androsterone, DHT itself does not have ER activity unless taken in very high doses. But I agree that something like the androstanediols could function as anti-estrogens as they bind to the same receptor but with effects opposite to those of estradiol.
 

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