Hormonal therapy doses and outcomes, and post-menopausal status
Has anyone encountered research (or hypotheses or observations from clinicians about this): Given that after menopause, women's bodies produce vastly less estrogen than the bodies of younger fertile women-- is there any data suggesting that dosages for hormonal therapy might be varied according to the amount of estrogen a patient has?
Has anybody run across anything like this, even as an informed opinion or idea?
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I had a total hysterectomy due to endometrial cancer in 2008 at age 58. I hadn't hit menopause yet, and even after surgery, except for a few night sweats the first month, I had no menopausal symptoms. I've never taken HRTs. When I had breast cancer in 2018, the estrogen receptor was 98%, so my body was (and probably is) still cranking estrogen out at a high rate even with no ovaries. My purpose in life seems to be as an exception-to-the-rule example 🤪!
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Elizabeth - I can't answer your direct question, and I have wondered the same thing. Age, diet, exercise, weight, and natural genetics seem to all play a part in how much estrogen we individually produce. My understanding is that while we produce less after menopause, there is still so much produced in other areas of the body (breast tissue, liver, etc) that it remains a breast cancer threat. When I asked my oncologist why they don't measure individual levels, she only said, "We just don't do that." I've also seen where some say that what is measured in a blood draw reflects what is circulating in the blood, and not necessarily what is in other body tissue, so that it would be irrelevant. I have no idea and haven't seen any clear answers on here or anywhere.
What I have found are a few studies that suggest that doses lower than the standard for Letrozole (2.5 mg per day) can lower estrogen levels to the same numbers as the standard dose. The problem here though, is that lower doses don't necessarily mean "lower" side effects, because once our estrogen levels are low, we get the side effects, so even if a lower dose will produce the same decreased level of estrogen, it will likely produce the same amount of side effects too. Some on here have said, however, that they think their side effects are milder if they take it every other day or cut the pill, or whatever.
I opted to take my Letrozole every other day, contrary to the oncologist's wishes. I have justified it to myself by reading just a few small studies, some of which I am giving links to here:
This one talks about how older women likely don't clear the drug as quickly as younger women, hence lower doses might be in order.
https://cancerres.aacrjournals.org/content/75/9_su...
This one shows a study in which various doses and dose schedules were tested with just about everything above .5 mg a day producing the same level of lowered estrogen. It was done by some people at the Mayo Clinic and other good institutions, so I think it carries some weight. The authors concluded that lower and intermittent doses can provide the same level of protection as the full 2.5.
https://pubmed.ncbi.nlm.nih.gov/26667449/
This is the 2020 Novartis package insert. Section 12-2 "Pharmacodynamics", Novartis themselves mention that 2.5 mg per day might be a "borderline" dose that becomes too much for some; a point where serious side effects could occur. (I don't have a citation for this now, but I did read something about how Novartis, when they were first testing all of this, also determined that .5 mg and above, seemed to do the job, but they indicated that they wanted to max out the dose on purpose to cover all possibilities or something like that.)
https://www.accessdata.fda.gov/drugsatfda_docs/lab...
Additionally, the half life of the drug is usually noted as being 48 hours, although some sources extend that to 72 hours. If that is the case, and anything above .5 mg a day will do the job, it seems to me (I'm no scientist or expert here), that you could take half the pill (1.25 mg.) every other day and still be getting good coverage with .60 mg. on the second day. I haven't ventured that far off track, because I know this is scant evidence and that I'm no expert, but for me at least, I'm willing to do the 2.5 mg every other day. I have a lot of side effects which suggests to me my estrogen levels have been significantly lowered. Even if the side effects were no worse with the full dose, I just like thinking that I am putting less of that drug in my body overall, because it can cause some very serious side effects (ocular, cardiovascular, and more). Also, it's only slight, but I do think that on the afternoon of the second day (the day after I take the pill), my side effects to improve for that last half day before I need to take it again. Not a lot at all, but it is slightly noticeable and consistently so.
I realize this isn't exactly what you were asking about, but I think it is highly interrelated. Hope it helps in some way.
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Three Tree - THANK YOU for your post. I have found those studies plus one on three dosing patterns for exemestane (one "normal", one is 1/2 dose daily and the other is full dose every other day) BUT they have not posted results yet.
I have Rheumatoid Arthritis which is apparently a bad combination with AI. I started on ARmidex 6 months ago, briefly tried exemestane (Rapid increase in BP and tenonitis in one arm that still persists and may be nerve related - also attributed to the AI). I am taking a trip late May that I have waited years for, so with the MO blessing, I will stop AI for 2 weeks. But it's a bear. I am very very lucky that my cancer was mucinous, small , early, very low KI67 (3.5%). So I don't have a 5 year goal on the AI - based on my understanding of the ONCOTYPE report (with Duke U. MO consult), my risks are pretty low and I was so happy to hear that the benefit of the AI is not even over the 5 years - it is front end loaded, so much benefit in Year One, then diminishing returns. So she and I did the math and I will do everything I possibly can to make it one year with an 'aspiration' for a second year. I had hoped to take full dose for the entire Year One, but I don't think I can make it. It is (on top of the RA) debilitating joint/tendon/muscle pain accompanied by a 'fatigue wall' each day around 3pm. With the blessing of my Rheumatologist, I take 5-10 mg prednisone ONE DAY each week - for a physical and psychological break - I count on that day, plan for that day, etc.
But still, I have decided to half the pill. In my heart of hearts, without data, I believe the dosing of AI will end up being like Birth Control pills - my generation of women took something like 20-30x the dose of estrogen in the PILL b/c "they" were slow to seek lowest effective dose. I believe that is exactly what we have with AIs. And I will, like you, track the very very few studies being done on that question.
THANK YOU.
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Alice - I went hunting for studies that would look at lowest effective dose as measured by estradiol levels. Unfortunately, what I found (none) was that the easy, inexpensive test for estradiol level that one can get anywhere won't tell us what we want to know. (apparently, it is not granular enough so we'll see close to zero with or without AI post menopause). The test that DOES tell us that is expensive and not regularly done (though I plan to ask my MO to do it).
My idea was that maybe I could "self-titrate" my dose of AI tracking an estradiol test available at "Any Lab Test Now". But as an old friend once said "It wasn't a bad idea, darlin', it was a good idea that just didn't work out".
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Thank you all for this focused discussion. I list the pill as Femara, the generic name. My pill is also 2.5. I have been on it for 2 months. One pill a day. As to side effects, i had surgery Feb 9th for a left mastectomy and ovaries and fallopian tube removal. I am ER + and PR -. I knew so little about estrogen production, that i did not know other body parts produce it! I had menopause at 41 years ago, 20 years ago.
I just started Perjeta and Herceptin 3 weeks ago. I have Brac2 as well, so treatment is different. Hormone suppression is not. I see the breast oncologist on May 2nd and my MO in early May. I am going to ask them about hormone treatments. What i believe their main goal has been is to stop the HER+ enzyme from galloping aggressively forward and to suppress any estrogen produced that could find a cancer cell in my body that wants to grow. My older sister had said after my chemo was done that i would be fine. The surgery would remove the tumor. Really sis? Do you know the Brac2 mutation ups my chances for reoccurrence? Removing my unaffected breast is necessary. How much estrogen is produced elsewhere in my body?
The oncologist went to school, she has a round table of doctors that cover different issues. I am only 2.5 months into these hormone blockers. Likely the side effects at the moment may also be part of the Eloquis pill i take twice a day for my blood clot. For right now, i get up daily and say God let's do it. What symptoms today? Can i take a walk? Drink all my water? Eat healthy? Wear a mask if i go out? Call friends! Reach out to 2 sisters. Do it all a day at atime.
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thanks for your research! I am an 89 yr old woman -had first mastectomy in 1984- other breast developed tumor, so had radical last Oct. It was not malignant - but they wanted to do hormone therapy, and put me on Letrozole. F;irst few weeks, no problems, but am now having bad side effects. Oncologist told me to stop med for a week, and call them . I am thinking at my age, why take the RX - if there was no malignancy and drug made me miserable, why not just stop it!
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paisleysmom
I would make certain to tell the doctor how you feel.
My Mom found out in 2014, that she had breast cancer, along with chronic lymphoma and a spot on her lungs. She left a doctor's form in her nightstand marked cancel, as she did not want to make appts. for further treatment. I found this form after she passed 2 years later.
I am on femora, letrozole, and so far, not much in SE. Yet, we are all different. At 89. I agree with you. You got nearly 40 years more after the first treatments!!! Wow. No cancer now found. Why do they want you to take hormone therapy?
Please check and give us their suggestions please. Take care of you, no matter what!
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Sigh, katg, to find that doctor's note in your mom's nightstand. Thank you for sharing.
paisleysmom, I can understand your feelings. I am curious to follow your journey,. On another thread, a person mentioned that side effects should get better after 6 months. I wonder how often that is true. I am so miserable with constant aches and tiredness that I would like to stop. Before this medicine I had no real body problems daily. I am 65.
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oldladyblue, unfortunately it is not true for everyone, not for me. I've been struggling in pain for almost 2 years. And there is another thread similar to this one with a lot of people that feel the same.
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Paiselymom, boy are you brave to take these drugs at 89. Honestly, what oncologist would not have had a good heart to heart with you and not just "protocol up" your situation with their lecture of how you should be on these? I will be 70 later this year and had an early stage BC but it was HER2+. I did chemo, rads and herceptin. I really had to decide to try these AI drugs as before this journey I was in pretty good shape. I started Letrozole one month ago. I dread these for five years which I think I will never make.
I am taking Letrozole every other day and that may be the best they will get out of me short of stopping these toxic pills. It will be my choice. I read into the pharmacology as much as I could and it appears they do have a long half life up to 48 hours. I still do not "feel right" on these. I experience tiredness, sleepiness at times, but worst of all a "brain fog" and cognition issues which there are definitely articles about! My eyes feel drier and vision off, although I am at that age of eventually needing cataract surgery. Chemo must have sped that up too.
I feel like I cannot even plan days ahead anymore not knowing how I will wake up and feel which is not bringing me back to moving forward to the former "me." Has anyone else had cognition decreased on these? Vision?
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Hi lrng Thanks for your reply, gosh, struggling in pain for years, I never imagined that kind of scenario.
Racheldog I have increased insomnia, constant pain, mental (thinking) and emotional (anger) issues, vision (blurriness) issues, all pretty "light" BUT I didn't have such trouble 2 months ago. I feel foggy, and even worry about my driving right now. And this is on 1/2 dose, since I'm taking it every other day right now. The "good old me" is a much higher quality than I have right now. Ugh.
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Racheldog - I've pretty much given up posting on this site due to the epic failure this organization has turned this discussion board into, but when I saw your post about your Letrozole side effects, I really wanted to reply.
I can relate so very much to what you have described. You are not alone, and I'm glad to learn that I'm not either. I too will be 70 later this year and I take it every other day, after doing some reading. Maybe not ideal, but like you, I think my only other alternative would be to not take these drugs at all. At least this keeps me somewhere in the mix. I will have taken them for 2.5 years come the middle of June. I don't buy this business that many people mention about how the side effects supposedly improve after 6 months. I think you just gradually get used to, and come to ignore and/or live with some of them.
You described so much of what I experience: tiredness, sleepiness, brain fog, cognition problems (big time!), dry eyes, and other weird ocular symptoms to where I get real worried about my vision. I also cannot plan for something days ahead and have to tell people, I won't know if I can attend a meeting or social event, etc. until the actual day of. This is causing all sorts of work problems in particular. Also, like OldLadyBlue mentioned above, I too worry about my driving. I am super anxious now when I drive and I am afraid to go places I haven't been in awhile. It's really hard, because I need to drive as part of my job. During the first week I took Letrozole I actually almost ran a red light and it was only because the oncoming car wanted to turn left right in front of me, and I thought they were crazy (yeah, right), that I stopped and then realized it was me who was in the wrong and that my light was red. It scared the daylights out of me, because I realized there had just been a missing hole in my brain and thought processes at that time. It was short and sweet, but could have been deadly. So far, I have not had any other close calls like that, but I do experience all sorts of situations while driving that involve things I should see and noticed way before I actually do, and I have to hyper concentrate and focus to drive anywhere.
Part of my job also involves creating reports that have deadlines, and having to organize and order my thoughts accordingly. It is almost impossible for me to do that since starting Letrozole and I think it is forcing me into retirement. I am really torn and sad about this, because I would bet my last dollar that if I was not taking Letrozole, I would be able to continue with routine driving and report writing for years to come. I hate to think that Letrozole is forcing me into retirement. All of this when there is really no guarantee that will actually even work.
Like you, Racheldog, I wonder if I will even make the 5 years and if I do, knowing the oncologist I have, I'm pretty sure she will suggest I go on for that 7 and 10 years they are now recommending to people. I just dread taking this pill every day that I do and long for the day when I can stop. Some doctors suggest that the side effects I complain of are related to aging and I really think that would only be a minimal chance. I had very mild arthritis before this, but immediately after starting Letrozole, all the aches and pains and all the other stuff described above started happening, and I am absolutely convinced it is the drug and not aging.
Since starting Letrozole almost two and half years ago now, it seems like everything I do is harder. It's harder to get up and get dressed, it's harder to brush my teeth, it's harder to prepare food, do the dishes, etc. Just everything! When it's time to brush my teeth, instead of just doing it without a second though, like before, I actually stand in front of the bathroom sink and go through a mental "Ok, here we go.. sort of thing like I have to think this job through, roll up my sleeves, and take it all step by step. It is no wonder I get so fatigued! Everything I do seems to take more effort and thought than ever before.
I really feel for you Racheldog and I just wonder how many of us are how there.
There's got to be a better way!
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Yes, I am convinced that there should be a better way than the side effects from these hormone suppression drugs. Ugh. I am so sorry that you might have to retire before you want to - threetree.
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Threetree, I too, go on this site far less that I had been checking in. Just tired of the sluggishness, glitches, and I have even given up putting in my profile. Have done that twice and it does not stick. I used to check in way more frequently, not now.
Yes, I still am plugging along with these drugs. I hate having to take this Letrozole. I doubt I would ever try anastrozole because I believe in my heart it would have the same side effects. I absolutely will not go on Tamoxifen with my history of retinal issues and I need a left knee replacement and will not risk a DVT.
I hope other women jump on this and qualify their cognition issues. I feel like I want to bonk myself in the head to clear out my brain on some days. I used to be a master at multitasking and zipping around and the new me is now no where close to the old me. If I have something important I need to do (like a funeral mass next week) I will not take the Letrozole because I want to feel as good as I can to not embarrass myself. I think these drugs are just toxic.
On the other hand, any new ache or pain makes me think of mets and the days where my brain seems more foggy I worry about brain spread. Will I stay on these 5 years? Hard to say at this point but doing the Letrozole every other day may be the best they will get out of me. My choice. The other choice is quitting all together and at 69, near 70, I guess I feel lucky that I have truly done everything I needed to do career wise even thought this diagnosis brought me into retirement. My life is in slow mode and I really do not like it.
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I was reading all your posts and thought my experience with letrozole is way shorter. Only 2.5 months or so. Not nearly enough time to build up a side effect i can state for sure comes from Letrozole. I just started the Perjeta and Herceptin 5 weeks ago. What side effect with which? Toss in blood thinners and a blood clot too. The fun road of breast cancer. So, i would say i am 61 and i too am a multitasker and am finding if i do not make a list, I do not remember. When i think i need to call someone and i start to call and think who was i going to call? Where did that come from? My eyes are not worse. I am at that age seeing close is rough. Will my side effects slowly get worse?
Funny.... not really, but my younger sister called to say she tested and has Covid. She has her shots and booster and is feeling pretty bad. A cold with a stuffy nose and some other symptoms including fatigue. She then told me to not tell my sister i know, but my older sister with no vaccine had covid a month ago. Really? She cannot tell me it seems. I visited her 2 weeks ago and she said nothing. This sister is not doing genetic testing to see if she carries BRCA2. Since she got Covid like the rest of us even after being uber careful. Really? For me, there are no secrets in health care. I am being reminded to tell my doctors about my side effects.
Thanks for sharing the details....fills in the gaps of care and how it all works for you.
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Hello ladies, Just read through this thread again. Been awhile. Hope you are all well as can be! Life for me has returned to a "new normal" without the daily pain, cognitive trouble, and emotional issues as I stopped taking the AI a few months ago. The short time I was on it was enough for me. Recovery back to where I am now was steady. God only knows if I will be in the 85% or so who have no recurrence or if I will be in the 15% who will. Either way, what happens will happen. I am 1000% happier daily without the side effects from anastrozole and have stopped worrying about my choice. I am going to concentrate on good nutrition and exercise and things good for my soul. The Predict model says I have a 24% chance of dying of something other than breast cancer by 15 years from now. So I hope God grants me what I hope for: many more good years. I wish that for all of you too. I will be 66 this November.
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OldLadyBlue - I'm jealous. I'm just too chicken to do what you've done, but I want to.
I'm so glad to hear how much better you are feeling!
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Oh threetree you made me laugh. I don't know if I'm brave, stupid, or what. I just know that I was in the worst shape of my life outside of chemo, and haunted by the knowledge of what the AI was doing to me. Getting off of it, and no longer beating myself up mentally for my decision, I am at peace in my own head and body again finally.
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OldLadyBlue - Glad to hear you got a chuckle out of my comment. I'm really glad that you are at peace with your decision. Unfortunately, assuming that your stats here are right (can't believe much that BCO posts these days), you have a much less serious situation than many, and mine in particular. I had a pretty large tumor (5.5 cm, stage 3) and am like 98%+ ER/PR positive, so I think I am the "perfect" candidate for these AI's, sadly.
I'm actually not taking the letrozole right now, because I had a bad uti and the antibiotic they gave me for it made me even more sick - one of those "cure being worse than the disease" kind of things. I stopped putting anything in my body until these side effects from the antibiotic clear up. I'm thinking I might just take the rest of the month of of the AI, just so my head can clear for awhile. I have a late court report due as part of my job and I just haven't been able to get it done due to al of the letrozole side effects, and then the uti, etc. As long as I haven't taken the AI for a few days now, I think I'll continue and try to actually get that report in. I'm losing my job over these AI side effects and am just going to have to retire (I am almost 70, but was hoping to continue a bit longer). I've got some final things to clean up though, before I can actually call it quits.
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Hello All
I just started letrozole again. First try didn't go well.
Im on my feet all day at work, I worry about not being able to continue.
I'm ER+100%PR+84%. Oncotype 14. Even though I didn't have to do chemo because of the low number. Those other two numbers have me probably taking this forever.
Im 63 yr old. What I don't understand is why they give everyone the same dosage.
Younger, older ,some weigh more some weigh less. Probably same side effects. But if there is a chance it wouldn't be as bad it would be worth looking into. Why put more in our systems than it needs
It's nice reading your comments ,I don't feel as alone.
You all have a good day.
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Dear nahhey,
Welcome to the BCO community. We are very glad that you reached out to share your story and join with our members. Please keep us posted as to how we can assist you with finding your way around to the support and information that will continue to be helpful to you.
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three tree - looks like I missed answering your post, I am so sorry. I didn't mean to ignore you. Yes, my stats are correct, and yes, my situation is very different from yours. I wish that the side effects weren't bad from these pills, but my oncologist told me that they all have side effects. I am jealous of the few who don't feel them. Wow, you said you are having to retire from your job because of the AI, oh gosh, how disappointing for you. I still work from home, it is a pleasant part time job and I feel very lucky that I held onto it all through surgery, chemo, rads, covid and recovery. I hope maybe after your break from the AI your side effects will be less.
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I was diagnosed in May 2022 that I had invasive breast cancer in my left breast, I am a 61 year old women that went every year for my mamo and a ultra film because I have dense breast. I have been on HRT for 10 years due to my menopause, I had a mastectomy in July of my breast and am now in the process of reconstruction. My Oncatype score came back low so no chemo is needed. The oncologist put me on Letrozole and after 5 weeks I had to stop, the effects of this medication was starting to really effect me. The insomnia, the joints and muscle pains, tiredness, nausea, headache, sweats, very down mood, having to urinate in the middle of the night, which I never had to do Being on HRT would suggest that I was low on estrogen and that is the reson for this medicine . After really doing some research on this medication the side effects and the damage it can cause long term to your body is terrible. I am thinking of not going on any medications because they all seem to have these awful side effects. I was just fine and feeling great before all of this. I can not even think of 5 years of this. and after reading that it can have a reoccurrence even after taking these medications. My thoughts of coarse are conflicted, If my cancer was removed and no chemo needed then this medicine is just for a "just incase" measure but no guarantee. Has anyone stopped or opted out of this treatment.
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morkiemom - I opted out of AIs and tamoxifen because of other medical problems (osteoporosis, osteoarthritis, thyroid issues, family history of DVT and others.) I am currently 70 and had an intermediate Oncotype score so no chemo recommended at my age. The Oncotype report also gives a statistical risk of distant recurrence at 9 years if taking anti-estrogen therapy. From that percentage my MO told me I am increasing my risk by 7-8%. This, however, is only a statistical risk which considers large populations and will not tell you what your future holds. Some people who take these meds have a recurrence anyway and some who do not take them stay NED. Looking at a large group of people they have been shown to substantially lessen recurrence rates.
My rationale was that I already had symptoms similar to AI side effects which would probably get worse. I want to be able to walk three miles every day and sleep at night so as not to aggravate my other medical problems. My MO and BS were fine with this since they thought my reasons were valid and I was making the decision with my eyes wide open. My RO scolded me for doing this but he changed his attitude when I had serious pulmonary side effects from the radiation. Sometimes the side effects can be worse than the benefits of treatment.
Many people try different AIs to find one with fewer side effects or take additional meds to alleviate them. In the end it is a personal decision which depends on your own situation and medical advice. Best wishes sorting this out!
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Maggie15
Thank you for sharing your experience with me. I have decided to opt out of these medications. After 5 weeks I know I can not handle them. I to have thyroid issues and feel the same way as you, I want to be able to live my life not sick from these medicines. It is definitely our decision to stop what we put into our bodies only we know what we can handle. My attitude right now is to feel well, enjoy my loved ones, not look back and not to worry about the future. This is my choice, and I really commend the women that are coping with these medicines and I pray that they all live long healthy happy lives.
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Morkiemom: I just finished first week of three of radiation. I now have to decide on Hormone Therapy. I REALLY do not want to do it, I have Osteoporosis, OsteoArthritis and Rheumatoid Arthritis. Stage 1A Breast Cancer - no Chemo needed.
It just seems like the cure is worse than the disease and there is no guarantee anyway.
Anyone else feel this way?
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Yes, Trilogy, the treatments for breast cancer are not easy at all. I agree. I met a woman at a store whose response to me telling her I am now pretty much recovered from my cancer treatments, who came right back at me with "Oh you get mammograms every 6 months now! I don't get mammograms!, they CAUSE cancer, I'm sure I will be fine". Well I hope she stays cancer free but who knows? With no monitoring, I wouldn't have known I had it in 2021. Where I would be now without treatment, no one knows.
The AIs and I didn't agree at all. I stopped them. But then again, I had a far less invasive cancer than some women have had, so my choice was perhaps easier to make. It is a real risk. A friend emailed me recently that she has metastatic cancer now, 1.5 years after her earlier tumor, despite being on AIs as prescribed. As she said, "They obviously didn't help me."
All these choices and outcomes are so sobering.
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Trilogy, yes I feel that way. I've been struggling for 28 months in constant pain. But mentally I can't not take them. The thought of MBC is too frightening for me. Rock/Hard place. I have made progress on the insomnia and learned to manage night sweats and hot flashes a little, no more heave clothing, heavy pjs, crank the AC.
I would like people to realize, the Oncotype "assumes" you will take hormone therapy when it assesses need for chemo. It considers them overlapping. And it also isn't really accurate for node positive. I was borderline, 15, and went for several opinions and decided to do chemo because I had two positive nodes. Little did I know that would be the easy part.
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Thank you for the responses.
jrnj: Does the constant pain have to do with Osteoporosis, etc?
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trilogy, I don't know, I never thought of that. I thought it was muscle and joint pain. My feet and legs hurt the worst, and my whole-body aches all the time, sitting, standing, laying, and feels swollen. I wake up several times a night sweating and have to pee. My baseline dexa showed osteopenia. 2 years later, it is worse, borderline osteopetrosis, but not bad enough to medicate yet according to my doctor. I take celebrex. I've tried a million other things, nothing helps. I don't have back or hip pain.
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