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Just want to share something that was written by Dinoiii (3 parts).
If this is old news to you, sorry for repost.
DHEA is of NO use to the average non-aged male! PART I
May 10, 2007
Author’s Note: We have had sincere discussions on DHEA use in the Post-cycle realm and otherwise over on DA in on-going debates but wanted to open this up over here. This post was therefore inspired by those interactions…my thoughts are summarized in the opening conglomerate below though this will be a multi-part addition over here on bb.com to get them all copied in here. Some questions/comments/concerns from other board members have also been included for completion’s sake to allow for an easier read.
——————————————–
————————-
Question: How would one dose DHEA at max does and what type of gains should be expected? How long can 1 run it? etc etc?
dinoiii’s retort:
I thought I had time-warped back to the late 80’s/early 90’s.
Hmmmmmm….I really can’t believe people are using this outside of the anti-aging realm. For those that are trying to combat age-related decline, it has likely some benefit.
Early research reports that muscle mass is NOT increased when adding DHEA supplements to compensate, however some small uncontrolled studies suggest otherwise. There may be some benefit in cases of adrenal insufficiency, but those too have been poorly controlled. I don’t like too much supplemental DHEA myself - PERIOD.
Based on data from studies in humans, DHEA may also increase blood sugar levels. In post-menopausal women, DHEA (1600 mg orally for 28 days alone) has been shown to cause INSULIN RESISTANCE and while this hasn’t adequately been tested in regular test subjects, the blood-sugar raising properties alone disuade me from recommending it in conjunction with the post-menopausal data.
Lab studies actually suggest that DHEA use may contribute to TaMOXIFEN RESISTANCE in breast cancer and one could easily extrapolate the same data for those that wonderfully execute suggestion that DHEA belongs in a PCT regime which it DOES NOT…as I have said for years…DHEA IS TOO FAR UPSTREAM.
Bottom Line…dinoiii does NOT think male bbers should use DHEA and in PCT:ACV, I actually suggested that I think DHEA should BE REMOVED FROM THE MARKET and it is unfortunate it didn’t get banned in 2004.
Sorry to be the bearer of bad news all the time though, for real.
D_
——————————————–
——————–
Question: Then how do you explain this?
Patent summary abstract:
Google Patents
Patent description:
Google Patents
DHEA + 6-OXO is already patented and proven to increase T and decrease E.
dinoiii’s retort:
There is a reason the patents were issued in the late 80s and 90s and nothing has really gone to market in the pharmaceutic world, even clinical trial.
Just getting a patent issued certainly doesn’t mean anything is “proven” - this is a complete pet peeve of mine, the “proven” in science thing. Here SERMs + DHEA have actually shown the contrary and 6-oxo in and of itself is partly pro-estrogenic.
It’s something about trading abstracts with one another on bb forums - oh well, I will oblige:
Am J Surg. 2003 May;185(5):411-5.
The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression.Calhoun K, Pommier R, Cheek J, Fletcher W, Toth-Fejel S.
Oregon Health & Science University, Division of Surgical Oncology, 3181 SW Sam Jackson Park Rd. L223A, Portland, OR 97201, USA.
BACKGROUND: We investigated the stimulatory potential of dehydroepiandrosterone sulfate (DHEA-S) on tamoxifen-treated cells and assessed its effect on cancer progression in the adjuvant setting. METHODS: Mean serial serum levels of sex hormones from 44 patients receiving tamoxifen were correlated with follow-up status. T-47D (ER+/PR+) and HCC1937 (ER-/PR-) breast cancer cells were pretreated with 100 microM anastrozole, with or without tamoxifen, and stimulated with 22.8 microM DHEA-S. Rapid colorimetric assays allowed calculation of growth percent change. RESULTS: Clinically, development of metastatic disease correlated only with > or =90 microg/dL DHEA-S (P = 0.005). In vitro, T-47D cells stimulated with DHEA-S after anastrozole showed 35% increased growth. Addition of 0.01 nM tamoxifen demonstrated -7% inhibition. Increasing the DHEA-S/tamoxifen ratio reversed suppression to +25%. CONCLUSIONS: DHEA-S > or =90 microg/dL is a risk factor for recurrence in the adjuvant setting. In vitro, although tamoxifen inhibits cell growth at high doses it can be circumvented by DHEA-S. These results indicate that DHEA-S contributes to tamoxifen resistance and disease progression.
PMID: 12727558 [PubMed - indexed for MEDLINE]
Well, tamoxifen resistance + support of upstream ability of DHEA converting to estrogen and tumor progression in ER (+) breast cancer.
1: Arch Surg. 2003 Aug;138(8):879-83. Links
Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant.Calhoun KE, Pommier RF, Muller P, Fletcher WS, Toth-Fejel S.
Department of General Surgery, Oregon Health and Sciences University, Portland, OR 97201, USA.
HYPOTHESIS: Dehydroepiandrosterone sulfate (DHEA-S) causes a proliferation of estrogen receptor (ER)-positive breast cancer cells, even with tamoxifen citrate blockade. The ER antagonist ICI 182780 (fulvestrant) will more effectively stop the proliferative effect of DHEA-S on breast cancer cells. DESIGN: Examination of in vitro breast cancer cell growth in the presence of fulvestrant and DHEA-S. SETTING: Surgical oncology research laboratory. INTERVENTIONS: The ER-positive and ER-negative breast cancer cells were pretreated with fulvestrant and stimulated with 900 microg/dL (22.8 micromol/L) of DHEA-S. MAIN OUTCOME MEASURES: Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet
razolium bromide, thiazolyl blue, were performed on the third, fifth, and seventh days poststimulation and permitted the calculation of growth percent change. RESULTS: The ER-positive and progesterone receptor-positive cells demonstrated universal proliferation of 107% by day 7 when treated with fulvestrant, regardless of the dose. The ER-negative and progesterone receptor-negative cells demonstrated growth inhibition. CONCLUSIONS: The DHEA-S circumvented fulvestrant inhibition and caused ER-positive breast cancer cell growth.
Oh ….and yes, I understand these were breast cancer cells…not what I am describing here - first is the ludicrousy of putting abstracts on message boards to support a plight, but these two DO show a couple of things…the overriding breast specificity of Estrogen in light of Tamox (which should be a select antagonist at the breast) when putting DHEA up to the charge AND offers further support for estrogen increases with DHEA administration.
D_
——————————————–
——————-
Please stay tuned for the conclusion of these debates….they get BETTER!!!
D_
DHEA is of NO use to the average non-aged male! Part II
May 22, 2007
Author’s Note: I am going to do this a tad out of order from its original context to offer a Q&A to follow. Remember that this was in response to the significant outcry of DHEA users everywhere - sucks to figure in realization, and I understand this. It’s usually imperative to not kill the messenger as the infamous “they” would like you to believe…let’s make them proud on this one, shall we?
Let’s review the literature rather than get into abstract wars becuase that is what other forums do and I would encourage us to be different for a moment.
Reviewing the literature on what we have already discussed and what you and I seem to agree on:
[1] DHEA taken as a supplement gets converted to androgens and estrogens in a gender-specific way.
a. women: increase androgens, NO sig. increase estrogens
b. men: increase estrogens, NO sig. increase androgens (essentially the opposite)
[2] Erectile dysfunction research: some people are speculated to have low DHEA and the sulfate ester (DHEA-S) levels to begin and thereby contributing to erectile dysfunction. If there is organic rationale (i.e. - low DHEA to begin), there is some evidence to support improvement (but it will only make the 2-minute man, say the 3-minute wonder…is this great considering other evidence?)…
Other erectile dysfunction populations have shown mixed review:
a. ED + Hypertensive: some benefit
b. ED + Diabetes: NO benefit
c. ED + Normal DHEA levels: NO benefit from preliminaries
* in NONE of the ED cases did Testosterone increase!!! (and this is despite DHEA administration and in some instances as described marginal difference in ED positive exchange)
[3] Side effects are sometimes not that great from tox studies for something that may give us marginal benefit (say increased wood or what have you):
a. insomnia
b. hepatic dysfunction (can we say NO to those using C17 alkylated; and then combine it with tamox, another hepatotoxic…Good God, what are “authorities” thinking?)
c. insulin resistance (yeah this is great for those seeking body comp change; more in a minute)
d. hair loss
e. hypertension
f. abdominal pain (though suggested in case report, the rationale was left at spontaneous association and could not be cause-effect linked, but MUST be noted when talking completion’s sake)
g. mania - 3 cases to date for people with no history of mania or bipolar
h. women - duh? androgenic sides have been reported
[4] Research mixed on cancer growth (some pro-cancer, one study has yielded regression of tumor, but admittedly may be specific to the tumor type and these are non-ER(+) tumors).
[5] DHEA continues to lower HDL levels AND increases levels of macro****e foam cells contributing to the atherosclerotic environment (NOT NEEDED in a time of recovery like PCT).
[6] Insulin Reistance is well-documented and I would be hard-press to suggest this good for anyone looking for optimal body comp. Could you imagine coming away from a cycle and making yourself potentially insulin-resistant? I wouldn’t recommend anyone in their right mind trying it to be honest.
[7] Now, I want to make a comment on how it can be conceived “good” for some steroidal AIs. DHEA inhibits cytochrome P450 3A4, which could theoretically heighten the effect of the AI through this mechanism…however, I MUST note that we only have documentation for this mechanism with concurrent use of triazolam, so it is suspect whether this would work, however given all the other effects and namely the increases in estrogens…I am inclined to suggest that you still NOT use it.
DHEA stinks and always has - I think I have offered up adequate debate, but hey I will offer you attempt to combat my rationale…and I eagerly await continued discussion. Until next time…
D_
DHEA is of NO use to the average non-aged male! Part III
May 31, 2007
ABSTRACT AFFIRMATION – THE OPENING SET
Author’s Note: With the release of the first couple parts to this series, young males everywhere have joined one of two groups – those who triumphantly allow their DHEA to reach their garbage can or their granddads or, alternatively, the group that has united against me and sent death threats while calling my mother names.
In any event, the truth hurts and DHEA remains worthless for the non-aged male when the dust settles. We will further explore this topic in a bit more depth citing specific research examples of DHEAs failure during times males like to employ this because the local internet “guru” told ‘em so!
One research group combined the most commonly employed PCT anti-estrogen (SERM), tamoxifen in combination with DHEA administration to find that the DHEA negated effects of the tamoxifen. My newfound hate-driven brethren who are aligning themselves as pro-DHEA are quick to point out that tamoxifen is pro-estrogenic in certain places while antagonistic in others and these studies were done in females and breast cancer patients to boot (yes, I have read the hate mail affectionately). Well, I can’t blame them for trying.
See, the point is that this suggests negating effects of a purported anti-estrogen at the level of the ER in breast tissue. This contradicts it and while no you cannot suggest that breast cancer equals gyno, negation of effects at what we are trying to prevent gyno with doesn’t make much sense to me, but alas I digress.
Without further adieu in the world where everyone loves abstracts…
[1] Am J Surg. 2003 May;185(5):411-5.
The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression.
Calhoun K, Pommier R, Cheek J, Fletcher W, Toth-Fejel S.
Oregon Health & Science University, Division of Surgical Oncology, 3181 SW Sam Jackson Park Rd. L223A, Portland, OR 97201, USA.
BACKGROUND: We investigated the stimulatory potential of dehydroepiandrosterone sulfate (DHEA-S) on tamoxifen-treated cells and assessed its effect on cancer progression in the adjuvant setting. METHODS: Mean serial serum levels of sex hormones from 44 patients receiving tamoxifen were correlated with follow-up status. T-47D (ER+/PR+) and HCC1937 (ER-/PR-) breast cancer cells were pretreated with 100 microM anastrozole, with or without tamoxifen, and stimulated with 22.8 microM DHEA-S. Rapid colorimetric assays allowed calculation of growth percent change. RESULTS: Clinically, development of metastatic disease correlated only with > or =90 microg/dL DHEA-S (P = 0.005). In vitro, T-47D cells stimulated with DHEA-S after anastrozole showed 35% increased growth. Addition of 0.01 nM tamoxifen demonstrated -7% inhibition. Increasing the DHEA-S/tamoxifen ratio reversed suppression to +25%. CONCLUSIONS: DHEA-S > or =90 microg/dL is a risk factor for recurrence in the adjuvant setting. In vitro, although tamoxifen inhibits cell growth at high doses it can be circumvented by DHEA-S. These results indicate that DHEA-S contributes to tamoxifen resistance and disease progression.
PMID: 12727558 [PubMed - indexed for MEDLINE]
[2] Arch Surg. 2003 Aug;138(8):879-83.
Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant.
Calhoun KE, Pommier RF, Muller P, Fletcher WS, Toth-Fejel S.
Department of General Surgery, Oregon Health and Sciences University, Portland, OR 97201, USA.
HYPOTHESIS: Dehydroepiandrosterone sulfate (DHEA-S) causes a proliferation of estrogen receptor (ER)-positive breast cancer cells, even with tamoxifen citrate blockade. The ER antagonist ICI 182780 (fulvestrant) will more effectively stop the proliferative effect of DHEA-S on breast cancer cells. DESIGN: Examination of in vitro breast cancer cell growth in the presence of fulvestrant and DHEA-S. SETTING: Surgical oncology research laboratory. INTERVENTIONS: The ER-positive and ER-negative breast cancer cells were pretreated with fulvestrant and stimulated with 900 microg/dL (22.8 micromol/L) of DHEA-S. MAIN OUTCOME MEASURES: Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet
razolium bromide, thiazolyl blue, were performed on the third, fifth, and seventh days poststimulation and permitted the calculation of growth percent change. RESULTS: The ER-positive and progesterone receptor-positive cells demonstrated universal proliferation of 107% by day 7 when treated with fulvestrant, regardless of the dose. The ER-negative and progesterone receptor-negative cells demonstrated growth inhibition. CONCLUSIONS: The DHEA-S circumvented fulvestrant inhibition and caused ER-positive breast cancer cell growth.
——————————————
Until Next time….
D_
If this is old news to you, sorry for repost.
DHEA is of NO use to the average non-aged male! PART I
May 10, 2007
Author’s Note: We have had sincere discussions on DHEA use in the Post-cycle realm and otherwise over on DA in on-going debates but wanted to open this up over here. This post was therefore inspired by those interactions…my thoughts are summarized in the opening conglomerate below though this will be a multi-part addition over here on bb.com to get them all copied in here. Some questions/comments/concerns from other board members have also been included for completion’s sake to allow for an easier read.
——————————————–
————————-
Question: How would one dose DHEA at max does and what type of gains should be expected? How long can 1 run it? etc etc?
dinoiii’s retort:
I thought I had time-warped back to the late 80’s/early 90’s.
Hmmmmmm….I really can’t believe people are using this outside of the anti-aging realm. For those that are trying to combat age-related decline, it has likely some benefit.
Early research reports that muscle mass is NOT increased when adding DHEA supplements to compensate, however some small uncontrolled studies suggest otherwise. There may be some benefit in cases of adrenal insufficiency, but those too have been poorly controlled. I don’t like too much supplemental DHEA myself - PERIOD.
Based on data from studies in humans, DHEA may also increase blood sugar levels. In post-menopausal women, DHEA (1600 mg orally for 28 days alone) has been shown to cause INSULIN RESISTANCE and while this hasn’t adequately been tested in regular test subjects, the blood-sugar raising properties alone disuade me from recommending it in conjunction with the post-menopausal data.
Lab studies actually suggest that DHEA use may contribute to TaMOXIFEN RESISTANCE in breast cancer and one could easily extrapolate the same data for those that wonderfully execute suggestion that DHEA belongs in a PCT regime which it DOES NOT…as I have said for years…DHEA IS TOO FAR UPSTREAM.
Bottom Line…dinoiii does NOT think male bbers should use DHEA and in PCT:ACV, I actually suggested that I think DHEA should BE REMOVED FROM THE MARKET and it is unfortunate it didn’t get banned in 2004.
Sorry to be the bearer of bad news all the time though, for real.
D_
——————————————–
——————–
Question: Then how do you explain this?
Patent summary abstract:
Google Patents
Patent description:
Google Patents
DHEA + 6-OXO is already patented and proven to increase T and decrease E.
dinoiii’s retort:
There is a reason the patents were issued in the late 80s and 90s and nothing has really gone to market in the pharmaceutic world, even clinical trial.
Just getting a patent issued certainly doesn’t mean anything is “proven” - this is a complete pet peeve of mine, the “proven” in science thing. Here SERMs + DHEA have actually shown the contrary and 6-oxo in and of itself is partly pro-estrogenic.
It’s something about trading abstracts with one another on bb forums - oh well, I will oblige:
Am J Surg. 2003 May;185(5):411-5.
The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression.Calhoun K, Pommier R, Cheek J, Fletcher W, Toth-Fejel S.
Oregon Health & Science University, Division of Surgical Oncology, 3181 SW Sam Jackson Park Rd. L223A, Portland, OR 97201, USA.
BACKGROUND: We investigated the stimulatory potential of dehydroepiandrosterone sulfate (DHEA-S) on tamoxifen-treated cells and assessed its effect on cancer progression in the adjuvant setting. METHODS: Mean serial serum levels of sex hormones from 44 patients receiving tamoxifen were correlated with follow-up status. T-47D (ER+/PR+) and HCC1937 (ER-/PR-) breast cancer cells were pretreated with 100 microM anastrozole, with or without tamoxifen, and stimulated with 22.8 microM DHEA-S. Rapid colorimetric assays allowed calculation of growth percent change. RESULTS: Clinically, development of metastatic disease correlated only with > or =90 microg/dL DHEA-S (P = 0.005). In vitro, T-47D cells stimulated with DHEA-S after anastrozole showed 35% increased growth. Addition of 0.01 nM tamoxifen demonstrated -7% inhibition. Increasing the DHEA-S/tamoxifen ratio reversed suppression to +25%. CONCLUSIONS: DHEA-S > or =90 microg/dL is a risk factor for recurrence in the adjuvant setting. In vitro, although tamoxifen inhibits cell growth at high doses it can be circumvented by DHEA-S. These results indicate that DHEA-S contributes to tamoxifen resistance and disease progression.
PMID: 12727558 [PubMed - indexed for MEDLINE]
Well, tamoxifen resistance + support of upstream ability of DHEA converting to estrogen and tumor progression in ER (+) breast cancer.
1: Arch Surg. 2003 Aug;138(8):879-83. Links
Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant.Calhoun KE, Pommier RF, Muller P, Fletcher WS, Toth-Fejel S.
Department of General Surgery, Oregon Health and Sciences University, Portland, OR 97201, USA.
HYPOTHESIS: Dehydroepiandrosterone sulfate (DHEA-S) causes a proliferation of estrogen receptor (ER)-positive breast cancer cells, even with tamoxifen citrate blockade. The ER antagonist ICI 182780 (fulvestrant) will more effectively stop the proliferative effect of DHEA-S on breast cancer cells. DESIGN: Examination of in vitro breast cancer cell growth in the presence of fulvestrant and DHEA-S. SETTING: Surgical oncology research laboratory. INTERVENTIONS: The ER-positive and ER-negative breast cancer cells were pretreated with fulvestrant and stimulated with 900 microg/dL (22.8 micromol/L) of DHEA-S. MAIN OUTCOME MEASURES: Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet
razolium bromide, thiazolyl blue, were performed on the third, fifth, and seventh days poststimulation and permitted the calculation of growth percent change. RESULTS: The ER-positive and progesterone receptor-positive cells demonstrated universal proliferation of 107% by day 7 when treated with fulvestrant, regardless of the dose. The ER-negative and progesterone receptor-negative cells demonstrated growth inhibition. CONCLUSIONS: The DHEA-S circumvented fulvestrant inhibition and caused ER-positive breast cancer cell growth.
Oh ….and yes, I understand these were breast cancer cells…not what I am describing here - first is the ludicrousy of putting abstracts on message boards to support a plight, but these two DO show a couple of things…the overriding breast specificity of Estrogen in light of Tamox (which should be a select antagonist at the breast) when putting DHEA up to the charge AND offers further support for estrogen increases with DHEA administration.
D_
——————————————–
——————-
Please stay tuned for the conclusion of these debates….they get BETTER!!!
D_
DHEA is of NO use to the average non-aged male! Part II
May 22, 2007
Author’s Note: I am going to do this a tad out of order from its original context to offer a Q&A to follow. Remember that this was in response to the significant outcry of DHEA users everywhere - sucks to figure in realization, and I understand this. It’s usually imperative to not kill the messenger as the infamous “they” would like you to believe…let’s make them proud on this one, shall we?
Let’s review the literature rather than get into abstract wars becuase that is what other forums do and I would encourage us to be different for a moment.
Reviewing the literature on what we have already discussed and what you and I seem to agree on:
[1] DHEA taken as a supplement gets converted to androgens and estrogens in a gender-specific way.
a. women: increase androgens, NO sig. increase estrogens
b. men: increase estrogens, NO sig. increase androgens (essentially the opposite)
[2] Erectile dysfunction research: some people are speculated to have low DHEA and the sulfate ester (DHEA-S) levels to begin and thereby contributing to erectile dysfunction. If there is organic rationale (i.e. - low DHEA to begin), there is some evidence to support improvement (but it will only make the 2-minute man, say the 3-minute wonder…is this great considering other evidence?)…
Other erectile dysfunction populations have shown mixed review:
a. ED + Hypertensive: some benefit
b. ED + Diabetes: NO benefit
c. ED + Normal DHEA levels: NO benefit from preliminaries
* in NONE of the ED cases did Testosterone increase!!! (and this is despite DHEA administration and in some instances as described marginal difference in ED positive exchange)
[3] Side effects are sometimes not that great from tox studies for something that may give us marginal benefit (say increased wood or what have you):
a. insomnia
b. hepatic dysfunction (can we say NO to those using C17 alkylated; and then combine it with tamox, another hepatotoxic…Good God, what are “authorities” thinking?)
c. insulin resistance (yeah this is great for those seeking body comp change; more in a minute)
d. hair loss
e. hypertension
f. abdominal pain (though suggested in case report, the rationale was left at spontaneous association and could not be cause-effect linked, but MUST be noted when talking completion’s sake)
g. mania - 3 cases to date for people with no history of mania or bipolar
h. women - duh? androgenic sides have been reported
[4] Research mixed on cancer growth (some pro-cancer, one study has yielded regression of tumor, but admittedly may be specific to the tumor type and these are non-ER(+) tumors).
[5] DHEA continues to lower HDL levels AND increases levels of macro****e foam cells contributing to the atherosclerotic environment (NOT NEEDED in a time of recovery like PCT).
[6] Insulin Reistance is well-documented and I would be hard-press to suggest this good for anyone looking for optimal body comp. Could you imagine coming away from a cycle and making yourself potentially insulin-resistant? I wouldn’t recommend anyone in their right mind trying it to be honest.
[7] Now, I want to make a comment on how it can be conceived “good” for some steroidal AIs. DHEA inhibits cytochrome P450 3A4, which could theoretically heighten the effect of the AI through this mechanism…however, I MUST note that we only have documentation for this mechanism with concurrent use of triazolam, so it is suspect whether this would work, however given all the other effects and namely the increases in estrogens…I am inclined to suggest that you still NOT use it.
DHEA stinks and always has - I think I have offered up adequate debate, but hey I will offer you attempt to combat my rationale…and I eagerly await continued discussion. Until next time…
D_
DHEA is of NO use to the average non-aged male! Part III
May 31, 2007
ABSTRACT AFFIRMATION – THE OPENING SET
Author’s Note: With the release of the first couple parts to this series, young males everywhere have joined one of two groups – those who triumphantly allow their DHEA to reach their garbage can or their granddads or, alternatively, the group that has united against me and sent death threats while calling my mother names.
In any event, the truth hurts and DHEA remains worthless for the non-aged male when the dust settles. We will further explore this topic in a bit more depth citing specific research examples of DHEAs failure during times males like to employ this because the local internet “guru” told ‘em so!
One research group combined the most commonly employed PCT anti-estrogen (SERM), tamoxifen in combination with DHEA administration to find that the DHEA negated effects of the tamoxifen. My newfound hate-driven brethren who are aligning themselves as pro-DHEA are quick to point out that tamoxifen is pro-estrogenic in certain places while antagonistic in others and these studies were done in females and breast cancer patients to boot (yes, I have read the hate mail affectionately). Well, I can’t blame them for trying.
See, the point is that this suggests negating effects of a purported anti-estrogen at the level of the ER in breast tissue. This contradicts it and while no you cannot suggest that breast cancer equals gyno, negation of effects at what we are trying to prevent gyno with doesn’t make much sense to me, but alas I digress.
Without further adieu in the world where everyone loves abstracts…
[1] Am J Surg. 2003 May;185(5):411-5.
The effect of high dehydroepiandrosterone sulfate levels on tamoxifen blockade and breast cancer progression.
Calhoun K, Pommier R, Cheek J, Fletcher W, Toth-Fejel S.
Oregon Health & Science University, Division of Surgical Oncology, 3181 SW Sam Jackson Park Rd. L223A, Portland, OR 97201, USA.
BACKGROUND: We investigated the stimulatory potential of dehydroepiandrosterone sulfate (DHEA-S) on tamoxifen-treated cells and assessed its effect on cancer progression in the adjuvant setting. METHODS: Mean serial serum levels of sex hormones from 44 patients receiving tamoxifen were correlated with follow-up status. T-47D (ER+/PR+) and HCC1937 (ER-/PR-) breast cancer cells were pretreated with 100 microM anastrozole, with or without tamoxifen, and stimulated with 22.8 microM DHEA-S. Rapid colorimetric assays allowed calculation of growth percent change. RESULTS: Clinically, development of metastatic disease correlated only with > or =90 microg/dL DHEA-S (P = 0.005). In vitro, T-47D cells stimulated with DHEA-S after anastrozole showed 35% increased growth. Addition of 0.01 nM tamoxifen demonstrated -7% inhibition. Increasing the DHEA-S/tamoxifen ratio reversed suppression to +25%. CONCLUSIONS: DHEA-S > or =90 microg/dL is a risk factor for recurrence in the adjuvant setting. In vitro, although tamoxifen inhibits cell growth at high doses it can be circumvented by DHEA-S. These results indicate that DHEA-S contributes to tamoxifen resistance and disease progression.
PMID: 12727558 [PubMed - indexed for MEDLINE]
[2] Arch Surg. 2003 Aug;138(8):879-83.
Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant.
Calhoun KE, Pommier RF, Muller P, Fletcher WS, Toth-Fejel S.
Department of General Surgery, Oregon Health and Sciences University, Portland, OR 97201, USA.
HYPOTHESIS: Dehydroepiandrosterone sulfate (DHEA-S) causes a proliferation of estrogen receptor (ER)-positive breast cancer cells, even with tamoxifen citrate blockade. The ER antagonist ICI 182780 (fulvestrant) will more effectively stop the proliferative effect of DHEA-S on breast cancer cells. DESIGN: Examination of in vitro breast cancer cell growth in the presence of fulvestrant and DHEA-S. SETTING: Surgical oncology research laboratory. INTERVENTIONS: The ER-positive and ER-negative breast cancer cells were pretreated with fulvestrant and stimulated with 900 microg/dL (22.8 micromol/L) of DHEA-S. MAIN OUTCOME MEASURES: Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet
razolium bromide, thiazolyl blue, were performed on the third, fifth, and seventh days poststimulation and permitted the calculation of growth percent change. RESULTS: The ER-positive and progesterone receptor-positive cells demonstrated universal proliferation of 107% by day 7 when treated with fulvestrant, regardless of the dose. The ER-negative and progesterone receptor-negative cells demonstrated growth inhibition. CONCLUSIONS: The DHEA-S circumvented fulvestrant inhibition and caused ER-positive breast cancer cell growth.
——————————————
Until Next time….
D_
