High Estradiol (Estrogen) levels on Tamoxifen

BCAE

So I'm on my 4th year of Tamoxifen to prevent DCIS. Recently my MO wanted to see if I was pre-menopausal, so she ordered a blood test. The test reported that estradiol levels were very high at 715. I messaged my Ob/Gyn who seemed concerned, especially because I have a history of ovarian cysts (removed pre-cancer with one of my ovaries), and last year US revealed thickened uterine lining and a new uterine fibroid. My Ob/Gyn says the estrogen might feed the uterine lining and fibroid and that I should talk with my MO more about it. I missed my MO's call, but she left me a message basically stating that the high estradiol levels are normal with Tamox, which causes ovarian overstimulation...but I'm concerned. I'm wondering if anyone knows if extra estrogen in my blood will remain after the Tamox. If so, doesn't that increase my risk for breast cancer...which is what the Tamox was suppose to prevent in the first place? I'm thinking of asking about lowering my dose of Tamox, as I've read recent studies to show that a lower dose is as effective. Does anyone have similar experiences to share? Thank you!

flashlight

Checking your estrogen levels while on tamoxifen isn't going to tell you anything. Tamoxifen doesn't suppress estrogen in your body. Tamoxifen works by attaching to the hormone receptors in any cancer cells, blocking estrogen from attaching to the receptors. Estrogen levels can be much higher on tamoxifen. That is why most MO's do not check the level, unless they do a baseline before treatment starts. I don't think decreasing your dose would have a big affect on your levels. Even at 10mg Tamoxifen enlarged my fibroids. Are you finished after 5 years? I would think your levels would drop after being off Tamoxifen for 6 weeks.

jhl

I agree with Flashlight. The way tamoxifen works is by being a competitive inhibitor of estradiol binding to estrogen receptors. Tamoxifen has a higher affinity for these receptors than estradiol. To be frank, your OB-GYN was a bit of an idiot to draw an estradiol level on you because it would be expected to be high. Please, do not lower your dose. Your dose is doing exactly what it should & that is to sit on the receptors so estradiol will not. As long as your estrogen receptors are being occupied by tamoxifen, your ER+ breast cancer will not be responsive.

The half life of tamoxifen in the blood is 7 days. The active metabolite has a half life of 14 days. So, it may take 100 days (about 5 half lives) to have the drug be metabolized out of your system. You will NOT be able to evaluate if you are menopausal based upon estradiol for 4 months after you have discontinued tamoxifen.

BCAE

Thanks for the info! Actually my MO wasn't testing for estrogen specifically, but FSH and LH. And she said that it is not uncommon for the estrogen levels to be even higher than mine for Tamox patients. She said that as long as the uterine thickening is going downward (which it is), than it's okay to stay at my 20 mg dose. (Now I just need to talk to my Ob/Gyn to see what she thinks.) Maybe one of you could explain...wouldn't increasing estrogen be a bad idea for cancer that feeds off of it? I guess it is because the Tamoxifen binds itself to the receptors to block estrogen. But doesn't that increase the level of estrogen it's competing against? How do I know that the Tamox is really doing its job?

Veeder14

Hi

I don’t think there is a way to tell if Tamoxifen is doing it’s job except for getting clear Mammograms, ultrasounds and MRI’S. That’s one thing that really bothers about blindly taking this med without a way to measure the effectiveness.

What I understood was the blocked estrogen circulates in your blood because it doesn’t go into breast tissue. That’s the reason for concern about blood clots or strokes. I might be all wrong so anyone feel free to correct me

flashlight

jhl, I didn't realize it was 4-months. Good to know. I'm on the 20mg now and doing well. BCAE, Have you had this talk with your MO?

BCAE

Sorry I should have said that I did end up talking to my MO, but I was waiting to hear back from my Ob/Gyn. My MO said a known side effect of Tamoxifen is to cause hyper-stimulation of the ovaries to produce high levels of estradiol. Apparently some women have levels as high as 1000 (mine only being 700)! But even with high levels of estrogen, because Tamox is a competitive inhibitor and blocking estrogen from feeding the cancer cells, it is still working....the high estrogen in my blood doesn't negate the effectiveness of the Tamoxifen. Thus, she doesn't think I need to stop taking it. She also said that the estrogen levels in my blood should go back to normal levels once I'm off Tamoxifen. (However, I did tell her that I've seen at least one study that seems to indicate that my levels may go down, but not completely back to normal...to which she said that she hadn't heard that.) That being said, she said she'd be willing to reduce my dosage if I'd prefer it...it's just that there hasn't been a ton of long-term data (beyond 3 years) to show the lower dosage's effectiveness.

And then recently my Ob/Gyn messaged me that she is willing to defer to my MO regarding taking Tamoxifen for my overall health, but from a gynecological perspective she is very concerned about my estrogen levels especially given my history of thickened endometrium. She is open to reducing the dosage if it can be just as effective, and wants to do an US at 6 months (usually we do yearly US).

My thought is that since MO said that it is likely my ovaries have been hyper-stimulated since I started taking Tamox, I'm wondering what the issue is now for my Ob/Gyn...except that they gave me the blood test and know it is for sure happening. Don't get me wrong...I too am concerned that the estradiol levels are high...but shouldn't my Ob/Gyn know that was one of the issues with it? Honestly, I'm wondering if she doesn't have much experience with Tamoxifen patients or if she is just *that* concerned! I'm a bit confused as to what to do now.

jhl

Hi BCAE,

Your OB-GYN is right to be concerned with tamoxifen. There is a higher incidence of uterine cancer and blood clots in patients who have used tamoxifen. However, it is the drug of choice for BC patients who are pre-menopausal. I don't believe a dose reduction will reduce the risk of uterine cancer or blood clots. So, this is a risk/benefit discussion you need to have with your providers.

flashlight

BCAE, your Gyn might want to keep an eye on the cysts and fibroid. Did she say you might need a D&C? Do you finish Tamoxifen at 5-years? My Gyn would only do an ultrasound yearly because of the known side effects of Tamoxifen. When I had the D&C one of my fibroids was large throwing off the thickness of my lining. As it turned out my lining wasn't as thick as they thought. Your MO treats your BC so it would be a conflict of interest for your Gyn to change your dosage. That being said she can always call your MO and discuss it with him/her. Unless you have irregular bleeding or increased pelvic, lower abdominal pain I think you are being monitored for any signs of uterine cancer.

ShetlandPony

I did a lot of research on this topic after my premenopausal breast cancer diagnosis, and I took tamoxifen for about three years. I had very high E2 levels on it. It stopped my periods, but I was not postmenopausal.

I disagree that checking estrogen levels on tamoxifen won't tell you anything. E2 (estradiol) level, along with FSH (follicle -stimulating hormone) level, will show if a woman if premenopausal or postmenopausal. High E2 and low FSH says not in menopause. Low E2 and high FSH means postmenopausal. When tamoxifen stops menstruation, this is how you know which it is. The blood test tells you what is going on behind the scenes. (There are panels of labs done because the interaction of various hormones is important, and the doctor must interpret the whole picture.)

As far as the reason for high E2, Tamoxifen can raise estradiol levels by stimulating the ovaries in women whose ovaries can be stimulated; that is, in premenopausal women. Postmenopausal women have ovaries that are no longer responsive.

Regarding fibroids, my experience was that my uterine fibroids got very large when I was taking tamoxifen. When I stopped tamoxifen due to recurrence, I had Taxol, which shut my ovaries down -- permanent chemopause. Then I took aromatase inhibitors, a different kind of anti-estrogen that is not estrogenic on the uterus. My fibroids shrank and are now small.

Another note, my onc said they worry about uterine cancer and tamoxifen in postmenopausal women, but for women who menstruate, the lining is shed regularly so endometrial cancer is not so much of a concern. Ask your onc how this applies to you.

Is it safe to take tamoxifen if it raises your estrogen to high levels? The idea is that tamoxifen is there to block any extra estrogen, and that is why it is ok. And we know that studies show that as a group, premenopausal women who take tamoxifen after a diagnosis of ER+ breast cancer do better than those who do not; that is why it is standard of care. However, it appears that some lobular cancer (which is NOT the kind the OP had) can be resistant to tamoxifen from the start, and I believe this may have been part of what happened with me -- lots of estrogen and tamoxifen not doing the job. Do-over, I would have ovarian suppression, but all the medical oncologists said I did not need to do that.

Bottom line, fact-check everything in this discussion (including mine) with your oncologist, and find out what is accurate and how it applies to you. And get your gynecologist and oncologist to have a conversation about you. I also suspect the gynecologist may need some more information about tamoxifen.

https://labtestsonline.org/tests/follicle-stimulating-hormone-fsh

https://labtestsonline.org/tests/estrogens

https://ascopubs.org/doi/full/10.1200/JCO.2007.11.1633