Estradiol levels with AI

Posted by cashemire @cashemire, Dec 5, 2022

Since a recent study (May 2022) found that estradiol was lowered similarly whether the AI (exemastane) was taken daily or every other day, does anyone know what is the aimed at level of estradiol when taking AI ? And can they confirm a blood test would allow one to know this?
Thanks!

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Some information that I found:
Not all generics are the same. Its about the fillers used. The manufacturer that I settled on for her was made by Accord. ALL AI`s cause discomfort, but there can be a lessening of this. She has mild joint aches that I treat with message and she seems to do ok. She is post menopausal so hot flashes (power surges) are regular for her, but minimal intensity. I keep her cool at night so that makes it easier for her to sleep.

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@windyshores

Again, the study above says side effects were the same for all doses tested. Not sure how this relates to the other comment in the study about toxicity.

The insert that comes with Femara states that 20% of the dose reduced estradiol below detectable levels. My doc okayed every other day.

The question would seem to be, is estrogen suppression the only reason for side effects? If the study found similar side effects at all doses tested, it would seem so, but that is the question I wondered about.

I don't know if side effects would be better on a lower dose. I didn't have bad ones on the full dose so I stuck with it for 5 years.

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Wondering if possible reduction in side effects might be related to those we dont experience everyday such as bone loss or elevated cholesterol. Less med might be less problems for bones.

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@anjalima

Wondering if possible reduction in side effects might be related to those we dont experience everyday such as bone loss or elevated cholesterol. Less med might be less problems for bones.

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Again, if a dose is "effective," meaning it reduces estradiol below detectable levels, the side effects of bone loss or elevated cholesterol or whatever, would be the same I would think. The side effects are from estrogen suppression and estrogen is suppressed if the dose is effective. That is the whole point of the med.

In other words, I don't see any reason why a lower dose, if effective, would cause fewer side effects.

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@windyshores

Again, if a dose is "effective," meaning it reduces estradiol below detectable levels, the side effects of bone loss or elevated cholesterol or whatever, would be the same I would think. The side effects are from estrogen suppression and estrogen is suppressed if the dose is effective. That is the whole point of the med.

In other words, I don't see any reason why a lower dose, if effective, would cause fewer side effects.

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I’m in agreement with you and I am grateful to have this med available to me; I am counting on it to be of great value for my 98/99% ER+. I feel safer taking it. What you say stands to reason and makes perfect sense. That said, the medical and research establishment is looking into lowest possible dose/effectiveness ratio. They mention the reason is because side effects account for significant non-compliance. This does make one wonder what is under consideration because, as you say, the side effects are BECAUSE of estrogen reduction… which is what is needed for treatment.

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@anjalima

I’m in agreement with you and I am grateful to have this med available to me; I am counting on it to be of great value for my 98/99% ER+. I feel safer taking it. What you say stands to reason and makes perfect sense. That said, the medical and research establishment is looking into lowest possible dose/effectiveness ratio. They mention the reason is because side effects account for significant non-compliance. This does make one wonder what is under consideration because, as you say, the side effects are BECAUSE of estrogen reduction… which is what is needed for treatment.

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It is a mystery! And it is a mystery why the dose is set where it is when the Femara drug info says 20% of that dose is effective.

I do wonder if there is some other mechanism in the medications that causes side effects, besides estrogen suppression. My doc didn't seem to think so.

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@windyshores

It is a mystery! And it is a mystery why the dose is set where it is when the Femara drug info says 20% of that dose is effective.

I do wonder if there is some other mechanism in the medications that causes side effects, besides estrogen suppression. My doc didn't seem to think so.

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Tamoxifen suppresses estrogen without affecting bone integrity.

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@anjalima

Tamoxifen suppresses estrogen without affecting bone integrity.

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Generally, we are told that Tamoxifen does not suppress estrogen. It affects estrogen receptors, not the actual estrogen level in the body.
https://www.webmd.com/breast-cancer/guide/tamoxifen-for-breast-cancer-treatment-and-prevention
Does tamoxifen reduce estrogen?
"It blocks estrogen from working on cancer cells that are sensitive to the hormone. "

Though it's a little more complicated than that:
https://pubmed.ncbi.nlm.nih.gov/7214366/

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@windyshores

Generally, we are told that Tamoxifen does not suppress estrogen. It affects estrogen receptors, not the actual estrogen level in the body.
https://www.webmd.com/breast-cancer/guide/tamoxifen-for-breast-cancer-treatment-and-prevention
Does tamoxifen reduce estrogen?
"It blocks estrogen from working on cancer cells that are sensitive to the hormone. "

Though it's a little more complicated than that:
https://pubmed.ncbi.nlm.nih.gov/7214366/

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Good information. Thank you.

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2022: 'Babytam' 1/4 dose as effective without adverse effects
https://ascopost.com/videos/2022-san-antonio-breast-cancer-symposium/andrea-de-censi-on-noninvasive-breast-cancer-10-year-results-on-low-dose-tamoxifen/Andrea De Censi, MD, on Noninvasive Breast Cancer: 10-Year Results on Low-Dose Tamoxifen
2022 San Antonio Breast Cancer SymposiumDisclaimer: This video transcript has not been proofread or edited and may contain errors.
Tam01 is a phase three trial of low-dose Tamoxifen in women with high-risk lesions, including DCIS, atypical ductal hyperplasia and lobular carcinoma in situ. These lesions have a five to 10 higher risk of developing invasive breast cancer compared to the general population. We reason that the dose that is given in the clinic of Tamoxifen 20 milligram per day was too high because of the adverse events which have prevented the uptake of Tamoxifen in the prevention setting, which is our main goal. We did a number of biomarker trials looking at the minimal effective dose, which is a very important concept, which has always been overlooked by pharmaceutical companies. The pressure to reduce the drugs and it's a leading team of this symposium is we are giving too much higher doses for this targeted drugs. We selected, based on a number of clinical trials, the dose of five milligram per day, one quarter of the standard dose to conduct this phase three trial. And we randomly assigned 500 women with high risk lesions to either five milligram per day for three years of Tamoxifen or placebo. And we are then following these women up to 10 years. The main results are that there is still a significant 42% reduction in the incidents of recurrence in women with high risk lesions with a nice carryover effect. Seven years after treatment cessation, there is still a significant reduction. And most of the recurrences were invasive, up to 77%. They were ipsilateral and stage one without differences between Tamoxifen or baby Tam or placebo in terms of staging or biological characteristics. There was a very significant reduction in the DCIS cohort, which represented 70% of the overall population. The other important finding is of course safety, because the baby Tam was not associated with an excess in any serious adverse event typically associated with Tamoxifen, including endometrial cancer, venous thromboembolism, and others. And also the patient reported outcomes, which are very important for prevention, because women do not tolerate having hot flashes or sexual disturbances. With a lower dose, we didn't see a difference in patient reported outcomes except for less than an extra hot flash per day in the baby Tam arm. The treatment is very well tolerated, it's safe, and seems to be very effective even seven years after treatment cessation. We will do ongoing follow-up up to maybe three, five more years if we manage. There are several clinical and research implications. Our study provides evidence that baby Tam can be the standard of care in women with high risk lesions. And as a matter of fact, in several prominent US centers like the Dana-Farber, the Brigham's Women's Hospital, the Mount Sinai Hospital, baby Tam has already become the most popular treatment strategies for women with high risk lesions because the women want baby Tam, want the low dose, and there is also a higher retention rate at one year compared with full dose Tamoxifen or Raloxifene or other drugs like their aromatase inhibitors. I think that was the most straightforward conclusion is you can give baby Tam for high risk lesions and this is very effective and nontoxic. Then I think baby Tam can reopen the door for primary prevention in high risk and affected women. The doors which has been closed because of the low uptake of the full dose as well as other drugs. But we desperately need some agent to prevent breast cancer, which is so common. And another very interesting research implication is the use of baby Tam to improve the sensitivity of mammography because baby Tam decreases mammographic density. And so it seems to reduce the risk of interval cancers among screening rounds, which is very important. That is another application which has been pioneered by the Swedish group using very low doses of Tamoxifen. We could also use baby Tam for young women who receive radiotherapy of the chest, and there is already some phase two trials showing a nice biomarker modulation with five milligram per day of Tamoxifen. Finally, the women who have gene carrier mutation like the BRCA two or other moderate penetrance genes like PALB2, CHEK2 or ATM. These women might benefit from baby Tam to reduce their risk of developing breast cancer.

REPLY
@cashemire

2022: 'Babytam' 1/4 dose as effective without adverse effects
https://ascopost.com/videos/2022-san-antonio-breast-cancer-symposium/andrea-de-censi-on-noninvasive-breast-cancer-10-year-results-on-low-dose-tamoxifen/Andrea De Censi, MD, on Noninvasive Breast Cancer: 10-Year Results on Low-Dose Tamoxifen
2022 San Antonio Breast Cancer SymposiumDisclaimer: This video transcript has not been proofread or edited and may contain errors.
Tam01 is a phase three trial of low-dose Tamoxifen in women with high-risk lesions, including DCIS, atypical ductal hyperplasia and lobular carcinoma in situ. These lesions have a five to 10 higher risk of developing invasive breast cancer compared to the general population. We reason that the dose that is given in the clinic of Tamoxifen 20 milligram per day was too high because of the adverse events which have prevented the uptake of Tamoxifen in the prevention setting, which is our main goal. We did a number of biomarker trials looking at the minimal effective dose, which is a very important concept, which has always been overlooked by pharmaceutical companies. The pressure to reduce the drugs and it's a leading team of this symposium is we are giving too much higher doses for this targeted drugs. We selected, based on a number of clinical trials, the dose of five milligram per day, one quarter of the standard dose to conduct this phase three trial. And we randomly assigned 500 women with high risk lesions to either five milligram per day for three years of Tamoxifen or placebo. And we are then following these women up to 10 years. The main results are that there is still a significant 42% reduction in the incidents of recurrence in women with high risk lesions with a nice carryover effect. Seven years after treatment cessation, there is still a significant reduction. And most of the recurrences were invasive, up to 77%. They were ipsilateral and stage one without differences between Tamoxifen or baby Tam or placebo in terms of staging or biological characteristics. There was a very significant reduction in the DCIS cohort, which represented 70% of the overall population. The other important finding is of course safety, because the baby Tam was not associated with an excess in any serious adverse event typically associated with Tamoxifen, including endometrial cancer, venous thromboembolism, and others. And also the patient reported outcomes, which are very important for prevention, because women do not tolerate having hot flashes or sexual disturbances. With a lower dose, we didn't see a difference in patient reported outcomes except for less than an extra hot flash per day in the baby Tam arm. The treatment is very well tolerated, it's safe, and seems to be very effective even seven years after treatment cessation. We will do ongoing follow-up up to maybe three, five more years if we manage. There are several clinical and research implications. Our study provides evidence that baby Tam can be the standard of care in women with high risk lesions. And as a matter of fact, in several prominent US centers like the Dana-Farber, the Brigham's Women's Hospital, the Mount Sinai Hospital, baby Tam has already become the most popular treatment strategies for women with high risk lesions because the women want baby Tam, want the low dose, and there is also a higher retention rate at one year compared with full dose Tamoxifen or Raloxifene or other drugs like their aromatase inhibitors. I think that was the most straightforward conclusion is you can give baby Tam for high risk lesions and this is very effective and nontoxic. Then I think baby Tam can reopen the door for primary prevention in high risk and affected women. The doors which has been closed because of the low uptake of the full dose as well as other drugs. But we desperately need some agent to prevent breast cancer, which is so common. And another very interesting research implication is the use of baby Tam to improve the sensitivity of mammography because baby Tam decreases mammographic density. And so it seems to reduce the risk of interval cancers among screening rounds, which is very important. That is another application which has been pioneered by the Swedish group using very low doses of Tamoxifen. We could also use baby Tam for young women who receive radiotherapy of the chest, and there is already some phase two trials showing a nice biomarker modulation with five milligram per day of Tamoxifen. Finally, the women who have gene carrier mutation like the BRCA two or other moderate penetrance genes like PALB2, CHEK2 or ATM. These women might benefit from baby Tam to reduce their risk of developing breast cancer.

Jump to this post

Just to clarify the above:

"Tam01 is a phase three trial of low-dose Tamoxifen in women with high-risk lesions, including DCIS, atypical ductal hyperplasia and lobular carcinoma in situ."

Note the word "lesions." Some of these are now termed "pre-cancers."

So this study does not relate to invasive cancers that , it seems. Am I missing something?

Also most of us are told that after menopause, we should be on aromatase inhibitors, which are more effective for us than tamoxifen. Or that is what I was told.

I would like to see a study that proves baby Tam works for invasive cancers at this low dose and is still effective for these more severe cancers.

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