Androsterone - A Potent Steroidal Aromatase Inhibitor

haidut

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It is well-known in medical circles (at least in doctors over 50) that some androgens like DHT are potent aromatase inhibitors (AI). In fact, before the advent of modern AI drugs like letrozole, anastrozole and fadrozole the 5-AR androgens were a mainstream therapy for estrogen-receptor-positive breast, uterine, and ovarian cancers. The synthetic DHT analog Drostanolone (Masteron) is still officially approved by the FDA as an AI drug for these cancers.
Drostanolone - Wikipedia, the free encyclopedia

Older studies, which led to the development of Masteron, discovered that virtually all androgenic steoroids derived through the activity of the 5-AR enzyme are highly potent AI chemicals and can lower estrogen synthesis in low micromolar concentrations. The 5-AR derived steroids androsterone, DHT, and 5-alpha androstanedione were the most potent AI chemicals, and a concentration of just 1 microMol inhibits aromatase activity and estrogen synthesis by more than 90% in breast cancer cells. Androsterone was more potent than even DHT. Even modern drugs like letrozole take up to a week to achieve such results and often with pretty bad side effects. In order to achieve a concentration of 1 microMol, a dose of no more than 2mg - 3mg androsterone or DHT is needed. This effectiveness of such a low dose for these steroids is further confirmed by a study with the steroidal AI drug exemestane, which is basically a synthetic derivative of DHT / androsterone. In that second study, using just 2.5mg exemestane daily lowers estrone sulfate levels by more than 70% and higher doses of the drug were NOT more effective. The other reason I like this study is that as you can see older studies clearly recognized the fact that estrone sulfate (E1S) is the true biomarker for estrogenic load/activity while newer studies use estradiol on purpose to show that postmenopausal women have estrogen "deficiency".
Finally, given progesterone's estrogen "receptor" antagonism and aromatase inhibition (but weaker than androsterone), and pregnenolone's aromatase inhibition - a combination of pregnenolone, progesterone and androsterone in about equal doses (2mg - 3mg) each per dose (taken 1-3 times daily) would likely create a blockbuster anti-estrogen without the feminizing effects of progesterone for males.


Pregnenolone, Progesterone And Androsterone Are Aromatase Inhibitors

http://press.endocrine.org/doi/abs/10.1210/jcem-62-2-314
Aromatase activity in the breast and other peripheral tissues and its therapeutic regulation. - PubMed - NCBI
"...Studies using [3H]androstenedione (A) demonstrated that this substrate can be aromatized to estrone (E1) in homogenates of breast carcinoma tissue and breast adipose tissue, in breast carcinoma and breast adipose stromal cells in culture, and in cultured adipose stromal cells from sites remote from the tumor. Using cultured breast carcinoma cells, it was shown that estrogen formation was stimulated by cortisol (10(-6) M) and inhibited by endogenous 5 alpha-reduced androgens: 5 alpha-androstene-dione greater than androsterone greater than dihydrotestosterone greater than epiandrosterone greater than 3 alpha- and 3 beta- androstanediol. It was also shown that 19-nortestosterone and 19-norandrostenedione (10(-6) M) inhibited E1 formation by 80%. Progesterone (10(-6) M) had no effect on aromatase activity, while the progestational agent R5020 (10(-6) M) caused a 70% inhibition. These studies emphasize that a variety of compounds can influence aromatase activity and that drugs which are used as aromatase inhibitors in patients with breast carcinoma may have multiple sites of action."
"...At concentrations as low as 10-8 M, 5a-A inhibited EI formation by greater than 50%. At a concentrations of 10-6 M, 5a-A, AND, and DHT inhibited the conversion of A to E1 by 90% or greater while inhibition with EPI, 3a-A-diol and 3p-A-diol was between 50% and 70% and with ETIO, it was 20%. The cortisol-stimulated increase in E1 formation could be inhibited by 5a-A (10-6 M)."

The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture. - PubMed - NCBI
"...Four cell lines, each derived from a primary tumor from a patient with breast carcinoma, were grown to confluence in alpha-Minimum Essential Medium with 15% fetal calf serum and incubated for 24 h with [3H]androstenedione. The two lines (SA and PP) with the lowest formation of estrone and estradiol (less than 0.1% conversion) were the most active in the formation of the 5 alpha-reduced androgen metabolites androsterone (AND), 5 alpha-androstanedione (5 alpha-A-dione), and dihydrotestosterone (DHT). The two lines with the highest aromatase activity (DM and MD) had the lowest formation of 5 alpha-reduced metabolites. To determine if the 5 alpha-reduced androgen metabolites formed within the breast carcinoma cells could influence aromatase activity, the MD line was further studied. After 24-h preincubation with AND, DHT, or 5 alpha-A-dione at concentrations of 10(-6), 10(-7), and 10(-8) M, [3H]androstenedione was added to the culture medium, and aliquots were removed at 0, 4, 8, and 24 h. An 8-h incubation period was found to be optimum for inhibition studies. In comparison to control levels of estrone (2.5%) and estradiol (0.35%) formation, inhibition of aromatization was evident with all three compounds at 10(-8) M, with 5 alpha-A-dione producing the greatest inhibition (50%). At 10(-7) M, inhibition ranged from 45% (AND) to 70% (5 alpha-A-dione), and at 10(-6) M, inhibition was greater than 90% for each compound. 5 alpha-A-dione produced slightly greater inhibition than AND or DHT at each concentration tested. Since each of these compounds was capable of inhibiting aromatization, the cumulative effect of these 5 alpha-reduced metabolites could be an important factor in the intracellular regulation of aromatase activity."


Steroid modulation of aromatase activity in human cultured breast carcinoma cells. - PubMed - NCBI
"...Cortisol and steroids with progestational or androgenic activity were studied to determine the effects of these steroids on the conversion of androstenedione (A) to estrone (E1) in human cultured breast carcinoma cells. Cortisol (10(-6) M) stimulated aromatase activity in two estrogen unresponsive cell lines (MD, DM) and in an estrogen responsive cell line (MCF7) with the maximum stimulation occurring during confluence. Cortisol inhibited the replication of MCF7 cells but not MD and DM. Dihydrotestosterone, androsterone and 5 alpha-androstanedione (10(-6) M) inhibited the conversion of A to E1 by greater than 90% under basal and cortisol stimulated conditions. Progesterone (10(-6) M) had no effect on aromatase activity while the progestational agent R5020 (10(-6) M) produced a 30% inhibition. The anabolic steroids 19-nortestosterone and 19-norandrostenedione which also have progestational activity inhibited the conversion of A to E1 in a dose dependent manner with 90% inhibition at 10(-6) M. Danazol (10(-6) M) a drug with both androgenic and progestational activity inhibited E1 formation by 30%. Under the same conditions, the known inhibitor of aromatase, 4-hydroxyandrostenedione (10(-6) M) decreased E1 formation by more than 90% and aminoglutethimide (10(-6) M) caused only 25% inhibition. These studies demonstrate that endogenous and exogenous steroids may have significant effects in modulating the local formation of estrogens from androgen precursors in cultured breast carcinoma cells. This effect on estrogen formation may be a factor in the biological response of breast tissue."


FSH-induced aromatase activity in porcine granulosa cells: non-competitive inhibition by non-aromatizable androgens. - PubMed - NCBI
"...To examine whether other 5-reduced C19 androgens also inhibit FSH-induced aromatase activity, granulosa cells were cultured for an initial induction period of 48h in the presence and absense of FSH with or without 0.5uM/L DHT, 5α-androsterone, 5α-androstane-3α,17β-diol, 5α-androstane-3α,17β-dione and 5β-androstane-3,17-dione. After the induction, the cells were incubated for an additional 6h. All the androgens tested were effective in significantly (p<0.05) reducing the aromatization of testosterone (Fig. 5). 5β-androstanedione was the most effective (57%) while DHT was the least (33%) when compared with cultures containing only FSH (Fig. 5, insert)."


Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor. - PubMed - NCBI
"...Exemestane is a novel orally active irreversible aromatase inhibitor and our study shows its effectiveness in suppressing both serum E1 (estrone) and E2 (estradiol) levels when given in repeated doses. A significant reduction in serum oestrone sulfate (E1S) oestrogen levels was also obtained with the lowest dose of 2.5 mg. The difference in the percentage of E2 reduction obtained with the lowest dose does not seem to be due to any lesser efficacy in inhibiting E2 synthesis, but more probably to the lower E2 baseline values of these patients. Our data also show an effective reduction of E1S levels in the 2.5 mg group, similar to that observed by Evans et al. (1992) using higher single doses."
 
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tca300

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@haidut Sorry to keep bothering you. Is this study saying more than 2.5 mg of Androsterone wasn't more effective at lowering estrogen? It kinda seems like its saying 2.5mg was the most effective for lowering estrone sulfate. Sorry again! Im super tired and cant make heads or tails of this.
 

haidut

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@haidut Sorry to keep bothering you. Is this study saying more than 2.5 mg of Androsterone wasn't more effective at lowering estrogen? It kinda seems like its saying 2.5mg was the most effective for lowering estrone sulfate. Sorry again! Im super tired and cant make heads or tails of this.

The study is about exemestane, which is very similar to androsterone. I posted it to show that you don't need mega dosing with steroid AI to get the desired effect. It said that 2.5mg exemestane is just as effective as the higher doses, not more effective. I am suggesting it is better to use low dose as it avoids the bad sides such as loss of libido and joint pain and mood disorders.
 

TheHound

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The study is about exemestane, which is very similar to androsterone. I posted it to show that you don't need mega dosing with steroid AI to get the desired effect. It said that 2.5mg exemestane is just as effective as the higher doses, not more effective. I am suggesting it is better to use low dose as it avoids the bad sides such as loss of libido and joint pain and mood disorders.

is exemestane also androgenic?
 

tca300

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The study is about exemestane, which is very similar to androsterone. I posted it to show that you don't need mega dosing with steroid AI to get the desired effect. It said that 2.5mg exemestane is just as effective as the higher doses, not more effective. I am suggesting it is better to use low dose as it avoids the bad sides such as loss of libido and joint pain and mood disorders.
Ok thank you! You mentioned that androsterone is more effective than DHT at lowering estrogen. If I may ask, was it significantly more effective? And are you saying you think androsterone is better in low doeses because it powerfully lowers estrogen or are you talking about exemestane being better in low doses? Thank you!
 

haidut

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Ok thank you! You mentioned that androsterone is more effective than DHT at lowering estrogen. If I may ask, was it significantly more effective? And are you saying you think androsterone is better in low doeses because it powerfully lowers estrogen or are you talking about exemestane being better in low doses? Thank you!

I did not mention androsterone and AI, the study I posted did and compared it to DHT. The exemestane study was posted just as an example of a very similar steroid AI being effective in "low" doses. So, androsterone, being very similar, should also be beneficial even in low doses.
Bottom line - I post studies that claim certain things and provide some guidelines so people can do their own experiments. You should not take this study to mean that androsterone is more effective AI (compared to exemestane) for everybody.
 

tca300

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I did not mention androsterone and AI, the study I posted did and compared it to DHT. The exemestane study was posted just as an example of a very similar steroid AI being effective in "low" doses. So, androsterone, being very similar, should also be beneficial even in low doses.
Bottom line - I post studies that claim certain things and provide some guidelines so people can do their own experiments. You should not take this study to mean that androsterone is more effective AI (compared to exemestane) for everybody.
Sorry, I didn't mean to say you said that, Its hard sometimes to differentiate between your words and the studies, I need to pay better attention. Thank you for all your help!
 

DaveFoster

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Letrozole is more potent than exemestane anyway, but it's pretty toxic. 99% estrogen antagonism is not a fun experience.
 

Koveras

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Letrozole is more potent than exemestane anyway, but it's pretty toxic. 99% estrogen antagonism is not a fun experience.

Clin Exp Pharmacol Physiol. 2017 Jan 16. doi: 10.1111/1440-1681.12731. [Epub ahead of print]
The sex-dependent effects of letrozole on anxiety in middle-aged rats.
Borbélyová V1, Domonkos E1, Csongová M1, Kačmárová M2, Ostatníková D3, Celec P1,4,5, Hodosy J1,3.

Aromatase catalyzes the conversion of testosterone to estradiol and is involved in physiological effects of sex hormones on brain functions. Animal experiments have shown that the aromatase inhibitor, letrozole, can induce anxiety in young ovariectomized females that are used as a model of aging. Whether or not these effects would be similar in intact middle-aged animals is unknown. The aim of our study was to analyze the effects of letrozole on anxiety in middle-aged rats of both sexes. Fifteen months old male and female rats were treated daily with either letrozole or vehicle for 2 weeks. The elevated plus maze was used to test anxiety-like behavior. Sex differences were found not only in plasma concentrations of testosterone but also in the effects of letrozole treatment on plasma testosterone (P<0.05). The interaction between sex and treatment was also proven in locomotor activity (P<0.05) and time spent in the open arms of the elevated plus maze (P<0.05). Letrozole-treated male rats spent 95% less time in the open arms of the elevated plus maze than the control rats did (P<0.05) suggesting an anxiogenic effect of aromatase inhibition. This difference was not found between letrozole-treated and vehicle-treated females. In contrast to previous experiments on young animals, letrozole seems to induce anxiety in male but not in female middle-aged rats. This sex-specific effect might be related to sex differences of estrogen and androgen signaling in aging brains. These results should be taken into account in clinical applications of letrozole, especially in men. This article is protected by copyright. All rights reserved.
 

haidut

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Aromasin is synthetic DHT/androsterone?? Can you share where you found this?

Well, I should have said "synthetic derivative of androstenedione". Androstenedione is very similar to T, and maybe less so to DHT and androsterone. T has OH group at position 17 instead of ketone, and androsterone is the other way around. Google "exemestane androstenedione derivative" for more info.
 

Texon

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It is well-known in medical circles (at least in doctors over 50) that some androgens like DHT are potent aromatase inhibitors (AI). In fact, before the advent of modern AI drugs like letrozole, anastrozole and fadrozole the 5-AR androgens were a mainstream therapy for estrogen-receptor-positive breast, uterine, and ovarian cancers. The synthetic DHT analog Drostanolone (Masteron) is still officially approved by the FDA as an AI drug for these cancers.
Drostanolone - Wikipedia, the free encyclopedia

Older studies, which led to the development of Masteron, discovered that virtually all androgenic steoroids derived through the activity of the 5-AR enzyme are highly potent AI chemicals and can lower estrogen synthesis in low micromolar concentrations. The 5-AR derived steroids androsterone, DHT, and 5-alpha androstanedione were the most potent AI chemicals, and a concentration of just 1 microMol inhibits aromatase activity and estrogen synthesis by more than 90% in breast cancer cells. Androsterone was more potent than even DHT. Even modern drugs like letrozole take up to a week to achieve such results and often with pretty bad side effects. In order to achieve a concentration of 1 microMol, a dose of no more than 2mg - 3mg androsterone or DHT is needed. This effectiveness of such a low dose for these steroids is further confirmed by a study with the steroidal AI drug exemestane, which is basically a synthetic derivative of DHT / androsterone. In that second study, using just 2.5mg exemestane daily lowers estrone sulfate levels by more than 70% and higher doses of the drug were NOT more effective. The other reason I like this study is that as you can see older studies clearly recognized the fact that estrone sulfate (E1S) is the true biomarker for estrogenic load/activity while newer studies use estradiol on purpose to show that postmenopausal women have estrogen "deficiency".
Finally, given progesterone's estrogen "receptor" antagonism and aromatase inhibition (but weaker than androsterone), and pregnenolone's aromatase inhibition - a combination of pregnenolone, progesterone and androsterone in about equal doses (2mg - 3mg) each per dose (taken 1-3 times daily) would likely create a blockbuster anti-estrogen without the feminizing effects of progesterone for males.


Pregnenolone, Progesterone And Androsterone Are Aromatase Inhibitors

Formation of 5α-Reduced Androgens in Stromal Cells from Human Breast Adipose Tissue* | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic
Aromatase activity in the breast and other peripheral tissues and its therapeutic regulation. - PubMed - NCBI
"...Studies using [3H]androstenedione (A) demonstrated that this substrate can be aromatized to estrone (E1) in homogenates of breast carcinoma tissue and breast adipose tissue, in breast carcinoma and breast adipose stromal cells in culture, and in cultured adipose stromal cells from sites remote from the tumor. Using cultured breast carcinoma cells, it was shown that estrogen formation was stimulated by cortisol (10(-6) M) and inhibited by endogenous 5 alpha-reduced androgens: 5 alpha-androstene-dione greater than androsterone greater than dihydrotestosterone greater than epiandrosterone greater than 3 alpha- and 3 beta- androstanediol. It was also shown that 19-nortestosterone and 19-norandrostenedione (10(-6) M) inhibited E1 formation by 80%. Progesterone (10(-6) M) had no effect on aromatase activity, while the progestational agent R5020 (10(-6) M) caused a 70% inhibition. These studies emphasize that a variety of compounds can influence aromatase activity and that drugs which are used as aromatase inhibitors in patients with breast carcinoma may have multiple sites of action."
"...At concentrations as low as 10-8 M, 5a-A inhibited EI formation by greater than 50%. At a concentrations of 10-6 M, 5a-A, AND, and DHT inhibited the conversion of A to E1 by 90% or greater while inhibition with EPI, 3a-A-diol and 3p-A-diol was between 50% and 70% and with ETIO, it was 20%. The cortisol-stimulated increase in E1 formation could be inhibited by 5a-A (10-6 M)."

The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture. - PubMed - NCBI
"...Four cell lines, each derived from a primary tumor from a patient with breast carcinoma, were grown to confluence in alpha-Minimum Essential Medium with 15% fetal calf serum and incubated for 24 h with [3H]androstenedione. The two lines (SA and PP) with the lowest formation of estrone and estradiol (less than 0.1% conversion) were the most active in the formation of the 5 alpha-reduced androgen metabolites androsterone (AND), 5 alpha-androstanedione (5 alpha-A-dione), and dihydrotestosterone (DHT). The two lines with the highest aromatase activity (DM and MD) had the lowest formation of 5 alpha-reduced metabolites. To determine if the 5 alpha-reduced androgen metabolites formed within the breast carcinoma cells could influence aromatase activity, the MD line was further studied. After 24-h preincubation with AND, DHT, or 5 alpha-A-dione at concentrations of 10(-6), 10(-7), and 10(-8) M, [3H]androstenedione was added to the culture medium, and aliquots were removed at 0, 4, 8, and 24 h. An 8-h incubation period was found to be optimum for inhibition studies. In comparison to control levels of estrone (2.5%) and estradiol (0.35%) formation, inhibition of aromatization was evident with all three compounds at 10(-8) M, with 5 alpha-A-dione producing the greatest inhibition (50%). At 10(-7) M, inhibition ranged from 45% (AND) to 70% (5 alpha-A-dione), and at 10(-6) M, inhibition was greater than 90% for each compound. 5 alpha-A-dione produced slightly greater inhibition than AND or DHT at each concentration tested. Since each of these compounds was capable of inhibiting aromatization, the cumulative effect of these 5 alpha-reduced metabolites could be an important factor in the intracellular regulation of aromatase activity."


Steroid modulation of aromatase activity in human cultured breast carcinoma cells. - PubMed - NCBI
"...Cortisol and steroids with progestational or androgenic activity were studied to determine the effects of these steroids on the conversion of androstenedione (A) to estrone (E1) in human cultured breast carcinoma cells. Cortisol (10(-6) M) stimulated aromatase activity in two estrogen unresponsive cell lines (MD, DM) and in an estrogen responsive cell line (MCF7) with the maximum stimulation occurring during confluence. Cortisol inhibited the replication of MCF7 cells but not MD and DM. Dihydrotestosterone, androsterone and 5 alpha-androstanedione (10(-6) M) inhibited the conversion of A to E1 by greater than 90% under basal and cortisol stimulated conditions. Progesterone (10(-6) M) had no effect on aromatase activity while the progestational agent R5020 (10(-6) M) produced a 30% inhibition. The anabolic steroids 19-nortestosterone and 19-norandrostenedione which also have progestational activity inhibited the conversion of A to E1 in a dose dependent manner with 90% inhibition at 10(-6) M. Danazol (10(-6) M) a drug with both androgenic and progestational activity inhibited E1 formation by 30%. Under the same conditions, the known inhibitor of aromatase, 4-hydroxyandrostenedione (10(-6) M) decreased E1 formation by more than 90% and aminoglutethimide (10(-6) M) caused only 25% inhibition. These studies demonstrate that endogenous and exogenous steroids may have significant effects in modulating the local formation of estrogens from androgen precursors in cultured breast carcinoma cells. This effect on estrogen formation may be a factor in the biological response of breast tissue."


FSH-induced aromatase activity in porcine granulosa cells: non-competitive inhibition by non-aromatizable androgens. - PubMed - NCBI
"...To examine whether other 5-reduced C19 androgens also inhibit FSH-induced aromatase activity, granulosa cells were cultured for an initial induction period of 48h in the presence and absense of FSH with or without 0.5uM/L DHT, 5α-androsterone, 5α-androstane-3α,17β-diol, 5α-androstane-3α,17β-dione and 5β-androstane-3,17-dione. After the induction, the cells were incubated for an additional 6h. All the androgens tested were effective in significantly (p<0.05) reducing the aromatization of testosterone (Fig. 5). 5β-androstanedione was the most effective (57%) while DHT was the least (33%) when compared with cultures containing only FSH (Fig. 5, insert)."


Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor. - PubMed - NCBI
"...Exemestane is a novel orally active irreversible aromatase inhibitor and our study shows its effectiveness in suppressing both serum E1 (estrone) and E2 (estradiol) levels when given in repeated doses. A significant reduction in serum oestrone sulfate (E1S) oestrogen levels was also obtained with the lowest dose of 2.5 mg. The difference in the percentage of E2 reduction obtained with the lowest dose does not seem to be due to any lesser efficacy in inhibiting E2 synthesis, but more probably to the lower E2 baseline values of these patients. Our data also show an effective reduction of E1S levels in the 2.5 mg group, similar to that observed by Evans et al. (1992) using higher single doses."
 

Texon

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Joined
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Messages
432
It is well-known in medical circles (at least in doctors over 50) that some androgens like DHT are potent aromatase inhibitors (AI). In fact, before the advent of modern AI drugs like letrozole, anastrozole and fadrozole the 5-AR androgens were a mainstream therapy for estrogen-receptor-positive breast, uterine, and ovarian cancers. The synthetic DHT analog Drostanolone (Masteron) is still officially approved by the FDA as an AI drug for these cancers.
Drostanolone - Wikipedia, the free encyclopedia

Older studies, which led to the development of Masteron, discovered that virtually all androgenic steoroids derived through the activity of the 5-AR enzyme are highly potent AI chemicals and can lower estrogen synthesis in low micromolar concentrations. The 5-AR derived steroids androsterone, DHT, and 5-alpha androstanedione were the most potent AI chemicals, and a concentration of just 1 microMol inhibits aromatase activity and estrogen synthesis by more than 90% in breast cancer cells. Androsterone was more potent than even DHT. Even modern drugs like letrozole take up to a week to achieve such results and often with pretty bad side effects. In order to achieve a concentration of 1 microMol, a dose of no more than 2mg - 3mg androsterone or DHT is needed. This effectiveness of such a low dose for these steroids is further confirmed by a study with the steroidal AI drug exemestane, which is basically a synthetic derivative of DHT / androsterone. In that second study, using just 2.5mg exemestane daily lowers estrone sulfate levels by more than 70% and higher doses of the drug were NOT more effective. The other reason I like this study is that as you can see older studies clearly recognized the fact that estrone sulfate (E1S) is the true biomarker for estrogenic load/activity while newer studies use estradiol on purpose to show that postmenopausal women have estrogen "deficiency".
Finally, given progesterone's estrogen "receptor" antagonism and aromatase inhibition (but weaker than androsterone), and pregnenolone's aromatase inhibition - a combination of pregnenolone, progesterone and androsterone in about equal doses (2mg - 3mg) each per dose (taken 1-3 times daily) would likely create a blockbuster anti-estrogen without the feminizing effects of progesterone for males.


Pregnenolone, Progesterone And Androsterone Are Aromatase Inhibitors

Formation of 5α-Reduced Androgens in Stromal Cells from Human Breast Adipose Tissue* | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic
Aromatase activity in the breast and other peripheral tissues and its therapeutic regulation. - PubMed - NCBI
"...Studies using [3H]androstenedione (A) demonstrated that this substrate can be aromatized to estrone (E1) in homogenates of breast carcinoma tissue and breast adipose tissue, in breast carcinoma and breast adipose stromal cells in culture, and in cultured adipose stromal cells from sites remote from the tumor. Using cultured breast carcinoma cells, it was shown that estrogen formation was stimulated by cortisol (10(-6) M) and inhibited by endogenous 5 alpha-reduced androgens: 5 alpha-androstene-dione greater than androsterone greater than dihydrotestosterone greater than epiandrosterone greater than 3 alpha- and 3 beta- androstanediol. It was also shown that 19-nortestosterone and 19-norandrostenedione (10(-6) M) inhibited E1 formation by 80%. Progesterone (10(-6) M) had no effect on aromatase activity, while the progestational agent R5020 (10(-6) M) caused a 70% inhibition. These studies emphasize that a variety of compounds can influence aromatase activity and that drugs which are used as aromatase inhibitors in patients with breast carcinoma may have multiple sites of action."
"...At concentrations as low as 10-8 M, 5a-A inhibited EI formation by greater than 50%. At a concentrations of 10-6 M, 5a-A, AND, and DHT inhibited the conversion of A to E1 by 90% or greater while inhibition with EPI, 3a-A-diol and 3p-A-diol was between 50% and 70% and with ETIO, it was 20%. The cortisol-stimulated increase in E1 formation could be inhibited by 5a-A (10-6 M)."

The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breast carcinoma cells in culture. - PubMed - NCBI
"...Four cell lines, each derived from a primary tumor from a patient with breast carcinoma, were grown to confluence in alpha-Minimum Essential Medium with 15% fetal calf serum and incubated for 24 h with [3H]androstenedione. The two lines (SA and PP) with the lowest formation of estrone and estradiol (less than 0.1% conversion) were the most active in the formation of the 5 alpha-reduced androgen metabolites androsterone (AND), 5 alpha-androstanedione (5 alpha-A-dione), and dihydrotestosterone (DHT). The two lines with the highest aromatase activity (DM and MD) had the lowest formation of 5 alpha-reduced metabolites. To determine if the 5 alpha-reduced androgen metabolites formed within the breast carcinoma cells could influence aromatase activity, the MD line was further studied. After 24-h preincubation with AND, DHT, or 5 alpha-A-dione at concentrations of 10(-6), 10(-7), and 10(-8) M, [3H]androstenedione was added to the culture medium, and aliquots were removed at 0, 4, 8, and 24 h. An 8-h incubation period was found to be optimum for inhibition studies. In comparison to control levels of estrone (2.5%) and estradiol (0.35%) formation, inhibition of aromatization was evident with all three compounds at 10(-8) M, with 5 alpha-A-dione producing the greatest inhibition (50%). At 10(-7) M, inhibition ranged from 45% (AND) to 70% (5 alpha-A-dione), and at 10(-6) M, inhibition was greater than 90% for each compound. 5 alpha-A-dione produced slightly greater inhibition than AND or DHT at each concentration tested. Since each of these compounds was capable of inhibiting aromatization, the cumulative effect of these 5 alpha-reduced metabolites could be an important factor in the intracellular regulation of aromatase activity."


Steroid modulation of aromatase activity in human cultured breast carcinoma cells. - PubMed - NCBI
"...Cortisol and steroids with progestational or androgenic activity were studied to determine the effects of these steroids on the conversion of androstenedione (A) to estrone (E1) in human cultured breast carcinoma cells. Cortisol (10(-6) M) stimulated aromatase activity in two estrogen unresponsive cell lines (MD, DM) and in an estrogen responsive cell line (MCF7) with the maximum stimulation occurring during confluence. Cortisol inhibited the replication of MCF7 cells but not MD and DM. Dihydrotestosterone, androsterone and 5 alpha-androstanedione (10(-6) M) inhibited the conversion of A to E1 by greater than 90% under basal and cortisol stimulated conditions. Progesterone (10(-6) M) had no effect on aromatase activity while the progestational agent R5020 (10(-6) M) produced a 30% inhibition. The anabolic steroids 19-nortestosterone and 19-norandrostenedione which also have progestational activity inhibited the conversion of A to E1 in a dose dependent manner with 90% inhibition at 10(-6) M. Danazol (10(-6) M) a drug with both androgenic and progestational activity inhibited E1 formation by 30%. Under the same conditions, the known inhibitor of aromatase, 4-hydroxyandrostenedione (10(-6) M) decreased E1 formation by more than 90% and aminoglutethimide (10(-6) M) caused only 25% inhibition. These studies demonstrate that endogenous and exogenous steroids may have significant effects in modulating the local formation of estrogens from androgen precursors in cultured breast carcinoma cells. This effect on estrogen formation may be a factor in the biological response of breast tissue."


FSH-induced aromatase activity in porcine granulosa cells: non-competitive inhibition by non-aromatizable androgens. - PubMed - NCBI
"...To examine whether other 5-reduced C19 androgens also inhibit FSH-induced aromatase activity, granulosa cells were cultured for an initial induction period of 48h in the presence and absense of FSH with or without 0.5uM/L DHT, 5α-androsterone, 5α-androstane-3α,17β-diol, 5α-androstane-3α,17β-dione and 5β-androstane-3,17-dione. After the induction, the cells were incubated for an additional 6h. All the androgens tested were effective in significantly (p<0.05) reducing the aromatization of testosterone (Fig. 5). 5β-androstanedione was the most effective (57%) while DHT was the least (33%) when compared with cultures containing only FSH (Fig. 5, insert)."


Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor. - PubMed - NCBI
"...Exemestane is a novel orally active irreversible aromatase inhibitor and our study shows its effectiveness in suppressing both serum E1 (estrone) and E2 (estradiol) levels when given in repeated doses. A significant reduction in serum oestrone sulfate (E1S) oestrogen levels was also obtained with the lowest dose of 2.5 mg. The difference in the percentage of E2 reduction obtained with the lowest dose does not seem to be due to any lesser efficacy in inhibiting E2 synthesis, but more probably to the lower E2 baseline values of these patients. Our data also show an effective reduction of E1S levels in the 2.5 mg group, similar to that observed by Evans et al. (1992) using higher single doses."

Haidut, thanks for this post..I have a special interest in the following part..."The other reason I like this study is that as you can see older studies clearly recognized the fact that estrone sulfate (E1S) is the true biomarker for estrogenic load/activity while newer studies use estradiol on purpose to show that postmenopausal women have estrogen "deficiency".

Finally, given progesterone's estrogen "receptor" antagonism and aromatase inhibition (but weaker than androsterone), and pregnenolone's aromatase inhibition - a combination of pregnenolone, progesterone and androsterone in about equal doses (2mg - 3mg) each per dose (taken 1-3 times daily) would likely create a blockbuster anti-estrogen without the feminizing effects of progesterone for males." Does Idealabs have this combo for sale? I am on TRT (injectable test cyp 50 mgs e4d) and have follow up labs set in about 3 weeks. I believe I don't tolerate arimedex well so it would be great to find an effective alternative. I currently have a Rx for 1 mg / pill of arimedex that I try to split into quarters. I take a quarter e4d also and it just does not feel well... may still be too high? Guess I'll know more in about 3 weeks. Do you or anyone else for that matter know the optimal number for E1S in males? Thanks in advance...
 

haidut

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Haidut, thanks for this post..I have a special interest in the following part..."The other reason I like this study is that as you can see older studies clearly recognized the fact that estrone sulfate (E1S) is the true biomarker for estrogenic load/activity while newer studies use estradiol on purpose to show that postmenopausal women have estrogen "deficiency".

Finally, given progesterone's estrogen "receptor" antagonism and aromatase inhibition (but weaker than androsterone), and pregnenolone's aromatase inhibition - a combination of pregnenolone, progesterone and androsterone in about equal doses (2mg - 3mg) each per dose (taken 1-3 times daily) would likely create a blockbuster anti-estrogen without the feminizing effects of progesterone for males." Does Idealabs have this combo for sale? I am on TRT (injectable test cyp 50 mgs e4d) and have follow up labs set in about 3 weeks. I believe I don't tolerate arimedex well so it would be great to find an effective alternative. I currently have a Rx for 1 mg / pill of arimedex that I try to split into quarters. I take a quarter e4d also and it just does not feel well... may still be too high? Guess I'll know more in about 3 weeks. Do you or anyone else for that matter know the optimal number for E1S in males? Thanks in advance...

The E1S ranges will be provided by the lab. I think being in the bottom 25%, as Peat mentioned a few times for estradiol, is desirable.
As far as the combination, we sell StressNon (pregnenolone), Progestene (progesterone) and androsterone as separate supplements. But most males here seem to do best on a combination of Pansterone + androsterone. Look at the signature of all my posts and you will find the links to buy all of these supplements.
 

Wagner83

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Haidut, thanks for this post..I have a special interest in the following part..."The other reason I like this study is that as you can see older studies clearly recognized the fact that estrone sulfate (E1S) is the true biomarker for estrogenic load/activity while newer studies use estradiol on purpose to show that postmenopausal women have estrogen "deficiency".

Finally, given progesterone's estrogen "receptor" antagonism and aromatase inhibition (but weaker than androsterone), and pregnenolone's aromatase inhibition - a combination of pregnenolone, progesterone and androsterone in about equal doses (2mg - 3mg) each per dose (taken 1-3 times daily) would likely create a blockbuster anti-estrogen without the feminizing effects of progesterone for males." Does Idealabs have this combo for sale? I am on TRT (injectable test cyp 50 mgs e4d) and have follow up labs set in about 3 weeks. I believe I don't tolerate arimedex well so it would be great to find an effective alternative. I currently have a Rx for 1 mg / pill of arimedex that I try to split into quarters. I take a quarter e4d also and it just does not feel well... may still be too high? Guess I'll know more in about 3 weeks. Do you or anyone else for that matter know the optimal number for E1S in males? Thanks in advance...
Did you check what physiological doses of T for men are?
 

Texon

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The E1S ranges will be provided by the lab. I think being in the bottom 25%, as Peat mentioned a few times for estradiol, is desirable.
As far as the combination, we sell StressNon (pregnenolone), Progestene (progesterone) and androsterone as separate supplements. But most males here seem to do best on a combination of Pansterone + androsterone. Look at the signature of all my posts and you will find the links to buy all of these supplements.
Thanks I'll give them a try, and I may just get my labs sooner to see just what is going on with e2 since I may have driven it too low with arimedex taken too frequently.
 

Texon

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Did you check what physiological doses of T for men are?
@haidut
Many add in hcg injectable, but I have not tried it yet. If you guys want some interesting info to ponder, Google the word "justaskin" and you will find a string of posts from a 60+ y.o. guy who seems to have everything TRT dialed in in a pretty optimal way.
 

haidut

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@haidut
Many add in hcg injectable, but I have not tried it yet. If you guys want some interesting info to ponder, Google the word "justaskin" and you will find a string of posts from a 60+ y.o. guy who seems to have everything TRT dialed in in a pretty optimal way.

I am not interested in hCG in any shape or form. Even less interested in offering injectable products. The goal of our products it optimize health, not cater to the weight lifting market. Given that hCG is a biomarker for a number of cancers, especially in males, this latest craze of increasing its levels are similar to the HGH fiasco, which is now starting to unfold with so many of the athletes that abused it developing cancer, CVD, and blood clotting issues.
Google for "hCG cancer biomarker" if you want to learn more.
 
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