Why are dosages for estrogen suppression drugs one-size-fits-all?

Posted by gldilli @gldilli, Mar 28, 2023

Why is the dosage for Anastrozole (and any other AI) the same for everyone no matter your weight or size? Does this-one size-fits-all approach have an impact on side effects, risk of recurrence, etc. I’d like to know what the medical community has to say.

Interested in more discussions like this? Go to the Breast Cancer Support Group.

The members here are not medical professionals. We are patients like you, but I for one have seen this question many times. I am also interested in the studies you talked about.
Can you post a link to any of those studies?

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I am also very interested in this question. Any information would be helpful.

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The dosage for Letrozole was discussed here on another thread maybe a year or so back. Because of that discussion I asked my oncologist and he agreed to put me on a half dose. I will look for the research. In the meantime I found this research on Anastrazole. I'm providing the link, but I've also cut/pasted the most pertinent paragraph. The parenthesis content is my addition.
https://www.drugs.com/pro/anastrozole.html

(estradiol=estrogen)

Mean serum concentrations of estradiol were evaluated in multiple daily dosing trials with 0.5, 1, 3, 5, and 10 mg of Anastrozole tablets in postmenopausal women with advanced breast cancer. Clinically significant suppression of serum estradiol was seen with all doses. Doses of 1 mg and higher resulted in suppression of mean serum concentrations of estradiol to the lower limit of detection (3.7 pmol/L). The recommended daily dose, Anastrozole tablets 1 mg, reduced estradiol by approximately 70% within 24 hours and by approximately 80% after 14 days of daily dosing. Suppression of serum estradiol was maintained for up to 6 days after cessation of daily dosing with Anastrozole tablets 1 mg.

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Here's what I found on Letrozole which given dosage is 2.5 mg.
https://www.drugs.com/pro/letrozole.html
In postmenopausal patients with advanced breast cancer, daily doses of 0.1 mg to 5 mg Letrozole suppress plasma concentrations of estradiol, estrone, and estrone sulfate by 75% to 95% from baseline with maximal suppression achieved within two to three days. Suppression is dose-related, with doses of 0.5 mg and higher giving many values of estrone and estrone sulfate that were below the limit of detection in the assays. Estrogen suppression was maintained throughout treatment in all patients treated at 0.5 mg or higher.

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@auntieoakley

The members here are not medical professionals. We are patients like you, but I for one have seen this question many times. I am also interested in the studies you talked about.
Can you post a link to any of those studies?

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I am unable to find any studies regarding this topic hence my question. I did read that after menopause fat cells continue to produce estrogen which is why being overweight is a risk factor for developing ER+ breast cancer. It makes since then that women develop ER+ positive BC after menopause since that's when weight tends to increase. It seems logical, to my mind, that the dosage of your AI medication should be adjusted to fit your weight/BMI. It just seems that the treatment protocols are too regulated.
Will losing the extra 20 lbs I gained during menopause, eating better, drinking less, etc. impact my risk of recurrence? Who knows? But I'm counting on the Anastrozole being more effective at a normal BMI.

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I understand the questioning of BC after menopause, but I feel like there might be a flawed theory at play.
If this were a robust theory, how would it account for all the many women like myself who get estrogen positive breast cancer well before menopause.
Something like 80% of all breast cancer is ER positive.
That all being said, I gained weight 15 years after my breast cancer and forced menopause. I sure would like to take off a few of those pounds.
I think your theory of dosage by weight should have merit, and this is the thing I have seen others here questioning. Not all drugs are figured this way, but I do wonder why?

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Auntieoakley,
That is the best question yet! I am going to the doctor on the 17th and I will
bring that up. After I had surgery and radiation, I am to take the pill, but I didn't
to many side affects. My breeder where I got my small dog told me not to give
my dog a rabies shot, because there is no half size for small dogs they get the same
as a german shepard. I then read in the paper about it-----to stop giving small dogs
rabies shots. She is with me all the time or in her playpen in the house if I go on
errands.
Great job on your question!

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Very few medications are weight based. When initial drug studies are done, things like pharmacokinetics, distribution, etc are looked at very closely.
When you look at the clinical trials that are done prior to bringing a drug to market, look at the patient characteristics and you will see the wide range of body weights. Subgroups are then analyzed to see if efficacy in one group is diminished or increased, if the studies are sufficiently powered.
So, the answer to your question for any specific drug is to go back to the initial clinical trial and carefully look at inclusion and exclusion criteria.

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I came across a study specific to anastrozole dosage and BMI posted on sciencedirect.com in 2014.

Does Obesity interfere with Anastrozole treatment? Positive association between body mass index and Anastrozole plasma levels
Original study link is
https://www.sciencedirect.com/science/article/abs/pii/S1526820913003133#!

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@gldilli

I came across a study specific to anastrozole dosage and BMI posted on sciencedirect.com in 2014.

Does Obesity interfere with Anastrozole treatment? Positive association between body mass index and Anastrozole plasma levels
Original study link is
https://www.sciencedirect.com/science/article/abs/pii/S1526820913003133#!

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I wanted to read this study, but the address is ‘not found’. I too was prescribed an AI and declined, due to standard protocols and dosage. I am 74, weigh 108 lbs (with partial Osteopenia) and have good health (exception BC with recent lumpectomy followed by 5day rad) My Oncologist has been outwardly upset with me and my husband for refusing any AI. At the time of my surgery and post treatment, I was given a choice, radiation or AI or both. I choice radiation. I am closely monitoring my breasts and praying no recurrence. The standard protocols call for a one-size treatment for all BC sufferers.

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