Risks and benefits, side effects, and costs of anti-estrogen medications. Note: Please remember that there are good experiences and bad with ALL treatments and this is a safe place to share YOUR experience, not to be influenced or influence others.
Posted on: Dec 31, 2008 12:22PM - edited Nov 15, 2017 01:04PM by Moderators
Posts 9511 - 9540 (10,290 total)
Mar 18, 2018 10:00AM - edited Mar 18, 2018 10:04AM by Icietla
Hi Mudd. I take mine at 7 pm. That is nearly always a while after my dinner.
I have memory challenges -- especially with but not only with short-term memory. My husband has a daily reminder alarm function set on his cell phone to remind us that it is time for my Letrozole. As I take the pill, I put a little mark on a date planner calendar there to signify that I have taken my Letrozole for that day. My husband observes and reminds me (as I may need it) to mark the calendar. Soon after that time, I start wondering whether I remembered to take it, so I have to check the calendar for that indication. I make other marks on the calendar to signify dosing with other medicines with which I need to follow my dosing.
N.B.: My memory issues are unrelated to and had long preceded my Letrozole treatment.
Mar 18, 2018 10:09AM gkbuser wrote:
i take my letrozole in the morning with my calcium, vit K, and vit D. At night I take melatonin and magnesium. I(because I heard magesium can be a mild muscle relaxer). I dont know if taking it at night leads to better tolerance. I am interested to see what others say about that.
Mar 18, 2018 11:29AM Lula73 wrote:
I take all my pills at bedtime with a snack. Vit D, calcium + mag, synthroid (yes I know AM 30 mins before eating but I’d never remember it), letrozole, curcumin, etc.
Mar 18, 2018 03:41PM NotBrokenJustBent wrote:
Lula, I don't have the brain power or the patience at the moment to read all your links but I will and I thank you for your efforts. I will be curious to know after menopause how much the ovaries release. Perhaps that is contained in the links but I would rather get my ovaries out than live on these blockers for a total of ten years. As to estrogen being stored in fat, I am good in that regard and actually very thin.
I take my letrozole around 8pm. I had started taking it in the morning and because of my fatigue I thought if it was related to the letrozole best to take it at night. Sadly it made no difference.
Icietla, I am quite sure I double up on the letrozole or believe I took it when I didn't quite often. I need a better system like you. It just has become such a mindless routine at this point it is hard to keep track.
Mar 18, 2018 04:20PM marijen wrote:
Yes Lula, thank you for all your work. I looked at the links, two didn't work for me, and it's just too much information. I was hoping for one link that put it all together, rather than needing a medical degree to sort things out. I'm not up to it. I'm confused on the 20% of estrogen that AIs reduce, that is the leftover amount after accounting for 80% estrogen reduction after menopause or ovary removal? I'm concerned that we are suffering with side effects for such a small amount. I did read that AIs decrease estrogen 90 - 95% but there wasn't a study referenced. And I did find out that ovary removal or tubal ligation has negative affects. I was sorry to read that as so many jump into oophorectomy without being advised or those side effects. I for one don't believe my ovaries just shut down immediately after menopause either.
Mar 18, 2018 05:11PM NotBrokenJustBent wrote:
And the other thing that has been discussed on these forums is that estrogen is stored in the fat so then why this one size fits all dose? I weigh approximately 123 but some weigh less and others more. I would think the heavier people might need a higher dose? And with weight loss then the estrogen is being released into the body in high dose surges? Ugh...I hate to overthink things but these days I question everything and just when I have an understanding science shakes things up. I was floored to read that the removal of positive nodes is now being questioned.
Mar 18, 2018 05:38PM NotBrokenJustBent wrote:
HapB, my MO said she does not test hormone levels but because of facial hair and oily skin associated with a hormone imbalance I went to an endocrinologist. I was found to have very high corizone, DHEA and other hormonal issues but was relieved to see my ER levels were low so the assumption was that Femara is doing it's job. I would like my ER to be monitored because I understand they can fluctuate throughout the day. I would think over time an average could be established. Why start a woman on these blockers if ER levels are already low? After five years why not come off the blockers and see if they rise and then continue drug treatment if deemed necessary instead of this haphazard guessing game? I don't get this either. It is frustrating and often it seems like BC is a newly discovered disease. I would think some of these basics would have already been established.
Mar 18, 2018 06:46PM marijen wrote:
HapB, I was under the impression you had stopped Femara because of the side effects. Is that not true?
I asked at the very beginning why our estrogen levels aren't checked and I was given this answer - Femara is a very strong drug. Huh? I changed MOs after that but still most of us aren't getting these hormone tests. I have read that hormone levels fluctuate too much and that's why, but I'm not buying that. I only wish that I had gone and got it tested myself when I started all this. I may still do that. So I agree it doesn't make sense to not find out where we are estrogenwise (new word : ).
Mar 18, 2018 11:29PM - edited Jul 13, 2018 08:43PM by Lula73
Here's a basic rundown of how all this works:
Before menopause, most of the estrogen in a woman's body is made by the ovaries.
After menopause, the ovaries stop producing estrogen (and there is some data showing they may actually start releasing androgens)
Smaller amounts of estrogen are still made in the body - Androgens produced by the adrenal glands are made into estrogen in fat tissue through a process known as aromatization (the aromatase enzyme is the key to the androgens being converted to estrogen by our fat cells).AIs inhibit the aromatase action.
Everyone of us, regardless of BMI, size, weight, etc. has subcutaneous fat (the layer of fat that lies between the skin and musc)
and some level of visceral fat (the fat behind the abdominal muscles that surrounds our organs), so aromatization will happen regardless of how thin or heavy you are.
It has been hypothesized that heavier women may have a higher risk of breast cancer with all other factors being equal compared to thinner women because of this process and the possibility of greater amounts of estrogen production. (key words: hypothesized & possibility). One would think though that since it all starts with the adrenals releasing androgens, that it would go back to how much androgens are released. This hypothesis would only apply to ER+ breast cancers. Anyway that's a whole other topic with no definitive evidence either way. On a side note, being overweight or obese is a risk factor for developing any type of cancer and is true regardless of gender.
There is a lot of discussion on various boards in multiple disease states about why a thin person takes the same dosage as a heavier person. Dosing of medications depends on several different factors and weight isn't always one of them. (Weight is usually a factor for children's dosing as their bodies are not fully developed and so much smaller with far less blood volume than an adult.) Let's take ibuproen or tylenol as an example: dose is based on weight in children but not adults for this very reason. We also know from phase 2 trials that there is an overdose threshold for both. But you likely don't think twice about popping 2-4 ibuprofen/2-3 tylenol at a time for a headache even though the bottle says to take 1-2. Very similar to pain relievers, when it comes to AIs and tamoxifen, weight is not considered a factor based on results from clinical trials. The AIs (as well as practically every other med on the planet) have been tested to find the dose that delivers the greatest efficacy with manageable side effects. Dosing tests are done in phase 2 clinical trials. This is where they test different doses for efficacy and analyze differences in dose vs weight, vs severity/duration of disease, etc. Phase 2 trials can be harder to come across in the public domain and may have to be requested from the pharmaceutical manufacturer. Phase 3 trials are the ones where you really see just how effective a given dose is as that's when they test for efficacy, safety and longer term outcomes. If it makes it through Phase 3 trials then you know the med is as effective/as safe as or more effective/safer than the gold standard drug that was first developed to do what the particular drug does and/or compared to placebo. If there is no gold standard drug in existence then its studied vs placebo for the desired effect with manageable side effects.
Another thing on the side effects listed in the prescribing information of a medication. All the side effects listed may not be caused by taking the drug. You always have to look at the difference compared to placebo. The reason is study participants can experience a placebo effect. (Have you ever noticed how headache, nausea, GI issues and fatigue are listed as a side effect for just about every medication on the planet?) Additionally, if you're in a clinical trial and lets say you get the flu (headache, body ache, nasal/chest congestion, fever, sore throat, body aches, nausea, etc), you have to report those symptoms as side effects to the research doctor even though you know they were caused by the flu and not the drug. The size of the trial hopefully evens out the numbers when the side effect incidences are averaged.
They don't test for hormones when you're on an AI because what will you do with the information? You're already doing all you can do by being on the AI. Additionally its a complex and very expensive set of labs that are done and unless you've got something like precocious puberty or growth hormone disorder going on insurance typically will not pay for it (even then they don't like to pay for it). When you have your "hormones" tested by the OB/GYN they are usually just testing for the FSH (follicular stimulating hormone) results. Its kind of a backwards way of testing - the FSH levels go up as the estrogen levels go down. If your FSH levels are elevated that is an indicator of menopause. No need then to order the much more expensive test for estrogen levels. On an AI, your FSH numbers would be high and if we pulled an estrogen level it would be low.
Also if we look at the women taking tamoxifen, their circulating blood estrogen levels often go up on the drug because the estrogen is still being made but cannot enter the cells as tamoxifen blocks it's path. The body may at that point increase estrogen production in response to the lack of feedback from the cells. All this estrogen is now trapped in the blood. The liver will eventually metabolize it but sometimes the liver can't keep up and if you were to pull an estrogen level it would be elevated. FSH would also likely be high as well.
Why do we take AIs if its only addressing 20% of the overall estrogen levels? When we hit menopause (naturally, surgically or med induced), that 20% just became our new 100%. By stopping the aromatase conversion process, we effectively take that estrogen level down to 0 (or almost 0). Even though the amount of estrogen is lower than before, it does not change the fact that the ER+ cancer cells use it for "food". As long as they have food they will continue to thrive. Here's an analogy: lets say you had an ant infestation at your dog' or cat's feeding dish over the scattered kibble that your pet didn't eat/got pushed out of the bowl. Would it make sense to physically remove all the ants you can see right now knowing there is a possibility that there may be some more in the wall that you can't see (surgery), perhaps lay down some poison to hopefully take care of any strays/reduce the size of the population (chemo if warranted) and then just clean up 80% of the dog/cat's food which allows the remaining ants to survive & reproduce (menopause) if your intent is to eradicate them? That remaining 20% of food just became those ant's new 100% of food; keeping in mind that the demand for that food also went down with the reduction in the ant population from the removal and/or poisoning. Why do some women have recurrence/mets while on AIs? A lot of it goes back to the oncotype tests and recurrence rates. Some cancers are just more aggressive than others and they grow and replicate faster than the AI can starve them. Some cancers are PR+ but not 100%. This means there are other things that the cancer is using for food in addition to estrogen. Those that are PR- but ER+ are missing the protective factor of PR receptors on the cancer cells, increasing their risk.If the cancer is triple + then the HER2 component can come into play as well.
On the brain making estrogen. Here's a breakdown of the 3 arms of the trial and what they found (note that the studies were done in rhesus monkeys, not humans, but the researchers think it should be a similar process for humans): "In the first experiment, a brief infusion of estradiol benzoate administered into the hypothalamus of rhesus monkeys that had surgery to remove their ovaries rapidly stimulated GnRH release. The brain took over and began rapidly releasing this estrogen in large pulsing surges. In the second experiment, mild electrical stimulation of the hypothalamus caused the release of both estrogen and GnRH (thus mimicking how estrogen could induce a neurotransmitter-like action). Third, the research team infused letrazole, an aromatase inhibitor that blocks the synthesis of estrogen, resulting in a lack of estrogen as well as GnRH release from the brain."
I hope this helps clarify the process and answers some of the questions :-)
Mar 19, 2018 06:11AM Germangirl16 wrote:
Lula, thank you for posting the explaination on estrogen and AI's.
Mar 19, 2018 02:12PM KBeee wrote:
Thank you for taking the time to so clearly describe that. I wish there were a way to pin that to the top of the hormonal therapy board!
Mar 19, 2018 02:26PM Lula73 wrote:
you all are very welcome. I’m glad you found it helpful. It’s actually part of my job at work to take things from the clinical level and break them down into common sense language that most can understand. I’m happy to help. The more we know the better off we all are. Feel free to ask any questions to clarify further.
Mar 19, 2018 04:25PM NotBrokenJustBent wrote:
On any given day I can change my mind ten times about continuing this drug for five years never mind ten. And I thought chemo and reconstruction options were the tough choices.
Yes Lula, thank you much for interpreting these studies for us. That was a lot of work but know it is very appreciated. That has clarified much.
Mar 19, 2018 05:38PM honeybair wrote:
Lula, thank you for writing such a clear explanation of just what AI's do. I am scheduled to go off my letrozole in May of this year, reaching my five year anniversary. I have read recently that there is some thought that the drug should be extended by at least two years and up to five additional years. Do you have any information as to the research and though behind this? i believe that this drug has aged me more rapidly but I am also five years older as well. I have tolerated well, I think, and my MO has told me that I will feel much better once I am off of it.
Mar 19, 2018 06:20PM NotBrokenJustBent wrote:
Honeybair, forgive me for jumping in but if I had your stats I would think long and hard about going off. Yes, I too have aged much in 4 years, it takes it's toll. Hoping Lula has some thoughts and insights to offer but with Stage 3 I would think that staying on blockers as long as they are tolerated would be recommended. Can you get a second opinion with another MO?
Mar 19, 2018 09:06PM - edited Mar 19, 2018 10:06PM by Lula73
So I've reviewed the studies, but I also found a really good synopsis of both femara extension trials on BCO. I've attached the link below.
Overall the bottom line is extending therapy reduces overall recurrence (by 34% in study 1), reduces risk of developing cancer in the other breast (by 34% in study 1) and reduces risk of distant recurrence/mets (by 28% in study 2), and may reduce development of other cancers (study 2).
Overall survival rate was equal between groups. Another way of staying that is the same number/percentage of women in each arm of the trial died during the timeframe of the trial. This was all causes of death whether BC related or not. If they died from BC, their numbers were already included in the recurrence numbers. It was noted that fewer women died of BC in the femara arm.I personally think it would be interesting if they redid the study looking at younger women only as i think they may show a difference in this respect.The median age in the trials was 65 which already puts those participants closer to the average end of lifespan in the developed world. Just my own hypothesis at the end there.
With all that being said, women who took femara for the additional 5 years had more bone fractures vs the placebo group and developed more blood clots than placebo (but still a very low occurrence rate). These side effects are serious as fractures/fragility of bones and blood clots can raise the risk of mortality as these things tend to snowball (ex you break your arm, heavy cast puts you off balance, you fall and break your leg, the two casts now have you very unsteady and relatively immobile/sedentary, muscle wasting occurs leaving you significantly weaker than before. This in turn can lead to further falls/injuries or even put you at increased risk of death from viruses/bacterial infection than a woman who hadn't had muscle wasting.) Not trying to scare anyone, but that's the possibility and we see it everyday.
Bottom line is that if you can manage the side effects of femara, your bones are good (or you're ok with taking bone building meds), and especially if you had an aggressive cancer and/or especially if you're young (let's face it-that term is relative) an additional 5 years would be beneficial and would outweigh the risk of SEs.
Mar 19, 2018 10:03PM Lula73 wrote:
very good question, HapB! Basically that statement just means that the same number of women died from any/all causes of death in each group. A lower percentage of women in the femara arm died of BC vs placebo. Or phrased another way, the femara group had a higher disease free survival rate vs the placebo group. This was determined in a separate analysis done after the trial ended vs being laid out as something they were tracking from the start. This is what you’d expect since the recurrence rate was lower with femara. However, it should be stated that the number 1 cause of death in both arms was BC recurrence, followed by another primary cancer and cardiovascular disease. It is confusing I know.
You’re not the only one pondering the benefit vs SE question. I’m 45 and I take curcumin to help with the hot flashes. Little did I know how much it was helping combat the fatigue until I forgot to take it this weekend. I was literally drained. Slept very late, took a nap, seriously considered cutting grocery shopping trip short when a huge wave of fatigue overtook me in the middle of the store. I didn’t want to scare my 13 year old so I pushed through. If I had to deal with that level of fatigue everyday I’d likely have to stop taking it. The memory issues are bad enough and the fatigue would do me in at work and home. However I’m 45 with a 13 year old and a wonderful DH. I would have to keep taking it for their sakes. Luckily the curcumin works for me and today was a much better day.
You’re 65. chronological age is just a measure of how many days we’ve lived outside the womb. You may be a young 65 or you may be an old 65 or a just right 65. If you’re an old 65 and due to other health issues don’t think you’ll make it another 5-10 years then quality of life would factor heavily into deciding whether to stop taking an AI early or deciding to only do the 5 initial years. On the other hand if you’re a young 65 or a just right 65 with 10-20+ years still ahead of you (barring any other unexpected health issues popping up), then dealing with the SEs may well be worth it to increase your odds of remaining disease free.
Mar 19, 2018 11:07PM MO-Beth wrote:
Lula, what IS your job? I looked at your profile, and boy, what you've been through! I'm so sorry, dear! And you are such a trooper and you are so knowledgeable! I'm asking about your job because my daughter is an LPC (clinical counselor, Master's level) and she's now going back to school to do a different career in cancer markers.
Mar 19, 2018 11:25PM MO-Beth wrote:
HapB, that would be so glorious to wipe out BC!
I'm older, 58, and it seems BC has increased SIGNIFICANTLY in my lifetime. Maybe not, maybe I've just lived in la-la land and have just become aware as I've become older that it is so prevalent. When I was diagnosed, all of a sudden people came out of the woodwork, telling me that so-and-so have or have had BC, people who I knew, friends and relatives of people that I actually knew, that I never knew had BC. (And by the way, all but one of those people are still living...and the one who died didn't die of breast cancer.)
When I was 5 years old, my mom's friend, who was about 25 years old at the time, died of breast cancer. When I was about 40 years old, my mom's best friend died of breast cancer that she didn't get treatment for when she was diagnosed and it spread to her liver (long story) and then my mother-in-law had a uni-MX at age 30 or so before I knew her and never had any other treatment, had regular mammograms and never had a recurrence. Before then, those were all of the breast cancers I really knew about.
Mar 19, 2018 11:47PM MO-Beth wrote:
Lula, I'm just going to throw this question out there: I'm always freezing. Any research on Femara and "cold" flashes?
I'm 58, postmenopausal. Was thin most of my life and always cold most of my life. Gained 50 lbs. in the middle of life, but have recently lost it and am back to normal. I had hot flashes when I was peri-, pre- and menopausal, but they didn't last for years, I'd just say for "a year" (and now I know why, because I produced enough ER/PR probably?)
Mar 20, 2018 05:21AM 2FUN wrote:
I have read (sorry I can't find the article) that once going off AI s your BC risk returns to the same level before you took AI. In other words, your risk is reduced while u are taking it. Makes sence, you need constant estrogen blocking to keep it at bay.
Mar 20, 2018 05:53AM windingshores wrote:
Regarding dosing: the package insert for Femara, from the company, states that 20% of the dose we all take (0.5mg) is essentially effective. So the real question is why are we all taking 2.5mg?
The other question is, if 0.5mg reduces estrogen to below detectable levels, does 2.5mg do something more or are they the same effect? I mean zero estrogen is zero estrogen. If 0.5 means zero, then it is impossible for 2.5 to reduce it further!
I have talked with my oncologist about this and she is okay with me splitting the pill in half or alternating days. So far, I haven't. If she wants me off after 5 years (I am now in my 4th year) then I may take 1/4 pill each day!!
Mar 20, 2018 08:39AM NotBrokenJustBent wrote:
Lula, what dose of curcumin are you taking? Do you recommend a specific brand? I am taking many supplements and I stock up at my local pharmacy during these BOGO events but lately I am wondering about the quality and purity. Perhaps I am doing more harm than good.
Mar 20, 2018 03:06PM lala1 wrote:
NotBrokenJustBent---I have been on turmeric since about a year into my diagnosis when I couldn't stand the muscle and joint pain anymore and was contemplating quitting Tamoxifen. I went to see a holistic doctor who specializes in BC and he add tumeric to my arsenal (he also added ginger because he thinks the 2 are complimentary). Within a couple of weeks my pain was significantly decreased and I was easily able to complete my 5 years. I put my DH on it when he tore his ACL and meniscus and needed surgery. His doctors were amazed with his recovery and how quickly he returned to work (he rides horses for a living). They now recommend it to all their patients. My dad was told 2 years ago that he needed a knee replacement when he could no longer golf, hunt or ski. He's 81 years old. I told him about turmeric. A couple of months later I asked if he ever took it and if it worked. He said "put it this way....last week alone I played 5 days of golf!" I credit it with getting me through Tamoxifen and helping me feel so much healthier and alert. I take the Gaia brand based on my holistic doctor's recommendation. He said it's source out of NC and he's been to the plant. You can buy it at Vitamin Shoppe or I buy it from Amazon. Per my doc's instructions....take 1 capsule a day for a month. If that works, continue. If not, up it to 2 a day. If that works continue that dose for another month then start tapering off. If 2 a day doesn't work, then it won't work at all for you. And I said I take mine with ginger. I'm done with Tamoxifen but still take it because it makes me feel so much better. And latest studies show it may help prevent cancer. No brainer! (Thank god, since Tamoxifen pretty much turned mine to mush!!)