Thank you for the very objective and detailed report. You seem to be one of the few menopausal experts that leads with caution and is completely honest with the studies limitations.
Thank you for tackling this study. As usual, your talent for distilling complexities to digestible explanations is a big help. Now if only I could convince my CRNP…At least I am better armed now. Thank you.
I am anxiously awaiting your impressions from the estrogen/progesterone results. How can progesterone and E2 alone be protective of breast but combine increase the risk??
I think the best answer is either this is an observational study, and this is one of the flaws, or there is something about combining the two, meaning one preps for the other to trigger cancer.
I was trying to figure out the number of women on E2 + P as I know this is often low as this combo of prescription hasn’t been around as long. Were the numbers lower and if so - what are the actual differences - 4 more cases per 10000? Is this reported in relative risk?
Yep, I too am looking forward to your part 2 as I have been so confused/concerned about this study's takeaway on medium/low dose transdermal estrogen + micronized progesterone, since I thought that was now considered best practice, and micronized progesterone actually had breast protective effects.
Like Christine, I really wonder if this is one of those percentage increases in studies that is actually quite meaningless when you see the raw numbers? Like one additional person out of thousands got breast cancer? Like they mentioned, is there just not enough longterm estrogen + progesterone users in this study since it's only been the standard for a short time? Or is this a weird outlier thing like the 19% reduction in lung cancer from vaginal estrogen, which seems truly bizarre?
Dear Dr. Gunther, thank you for your in-depth report. I so appreciate all your research and info for us!! I am still confused though: Due to family history of ovarian cancer and several cysts, I have had a profilactic BSO nine years ago at the age of 51, but kept my uterus. I was advised not to take HRT. Due to vaginal dryness and pain, I have now been put on Premarin vaginal cream 0,625 mg, which I use 2 x weekly, very sparingly and it has helped a lot. Is Premarin Vaginal Cream included in these findings, or in other words: does "low dose vaginal" mean "cream"? Is there an expiration date on safely using Premarin vaginal cream? And does it provide the same percentage health benefits as discussed in your report?
We consider vaginal Premarin at the dose you are using to be safe. The creams are usually not considered a low-dose vaginal option; the tablets and ring are low-dose. There is more on them here. https://vajenda.substack.com/p/a-deeper-dive-into-vaginal-estrogens There wasn't a safety signal from vaginal Premarin in the dose you describe in this study.
Good breakdown and explanations, thank you! I was wondering about the effects of having been on hormonal contraception prior to MHT, presumably not something this study could capture?
As someone who has been on either the combined or mini pill all my adult life, I am a little concerned about what will happen when I stop....
Thank you for this excellent analysis and summary. What about absolute length of time on MHT? Say, for someone who started taking it in their early 40s for vasomotor symptoms and thus may have many more years on it than someone starting in their 50s.
Such an informative read. I feel scared and like a failure for not being able to take mht at 53. I’m still having light symptoms and some nightsweats 4 years post menopause. I feel like I amsending myself to an early grave with all the mht push. I get so many side effects from it. Debilitating progesterone intolerance. I feel defeated but appreciate everything you share with us. I feel like you are the only logical source anymore.
We don't recommend MHT to prevent other diseases besides osteoporosis. And there are non-hormonal medications for hot flashes. Many women live long, wonderful lives without MHT!
I took the time to read the recent study. The one issue that is not presented however is the impact all forms of estrogen (including vaginal delivery) has on women who are on a thyroid replacement. You have stated,"In the main analysis, the investigators grouped low-dose transdermal and low-dose vaginal therapies together, meaning a 25 mcg estradiol patch was in the low-dose category, but so were vaginal estrogen tablets and rings. However, one of these delivers estrogen into the blood (patch), and the other does not". Since vaginal estrogen does to a small degree enter the bloodstream (which I have proven by using it TSH does increase) why is the Menopause Society not addressing this issue since more women are impacted by thyroid issues especially during midlife? The study does recognize through statistics that vaginal estrogen impacts bone health (to a lesser degree than transdermal patches) lung cancer et al which suggests that the impact of this form of therapy is systemic. The product monograph as well as the information from the manufacturer of vagifem (and yes I did reach out to them) can impact TBG proteins in women who are on a suppressive or replacement of levothyroxine. I have accessed JAMA, the Journals from the Endocrine and OB/GYN societies as well as PubMed and cross referenced all of the information with the product monographs (and was told by the pharmaceutical companies they are published for medical doctors to access for additional information) and all support that any form of estrogen will impact TBG proteins (increase). How many doctors are up to date on this? The information in the latest study means women who have been waiting for help should be able to access it. Some women on a replacement of levothyroxine require two specialists, one for menopause issues as well as one to assist with adjustments in doses.
I am on both vaginal estradiol and transdermal. My TSH has actually lowered to where it was flagged as Hyperthyroidism however my T4 and T3 are normal so my doctor is not concerned.
Was your TSH suppressed to begin with? That happened to a person I know her TSH was lower and her Frees were normal as well. Try to access labs before you started estrogen. My TSH doubled and Free 4 dropped which means FT3 drops too.
No it was not suppressed. I had labs done about 4-5 months before starting HRT and TSH was in the normal range and then just re-did them last week which was a little over 3 months on HRT. I have been on Synthroid for 35+ years and have had times when TSH was below range so it is hard to say if was related to HRT or not. Some doctors have called for lowering dosage based on TSH while others have not providing the Free T4 and T3 are normal. Opinions seem to vary on that. I see my endo next week and curious if she will want to adjust my dose or not.
Also if you were not told you should tae thyroid meds same time of day and have labs done at the same time each time they are ordered as TSH and Frees move around during the day, half life of T3 is very short.
Yup. After 35 years on thyroid medication, I know the drill. I also got lazy and stopped waiting to eat or drink coffee but it has had absolutely zero impact on my levels.
If you are on a supplement (your own thyroid is not working well without meds, subclinical) the portion of your thyroid that does work may be adding in to compensate. When on a replacement like me I can not make more T4. Estrogen of any kind can increase the TBG proteins (created in your liver) which will impact TSH levels. When I use any form my TSH goes up considerably. The endocrinologist I go to has confirmed my research is sound. There are not many menopause endocrinologists so someone like me has to go to two different specialists as an OB/GYN does not prescribe synthroid type medications. The GP's I have been to have no idea, look only at the WHI study. I have waited 9 years for any help (COVID 3 years of that meant no specialists were accepting new patients here) then before that I was over medicated with synthroid. The symptoms of meno, post meno are the same as thyroid either high or low. I have taken thyroid meds since 2003. Higher Frees are indicative of overmedicated as well as a low TSH depending on your scale for TSH (here .32-4) it shoul dbe under 2.5 so that the conversion process from T4 to T3 is within the ratio.
I am lucky to have a great Endo who is of peri/meno age herself which I have found to be very helpful overall. Not to say a younger doctor or a male doctor can't be informed but when you have experienced perio/meno first hand I think they do more research. My general doctor who is post menopause was the one who pushed me to find a new GYN after mine (who is younger) told me "We don't treat menopause" when I told her about my 20+ hot flashes a day. My T4 and T3 are in normal range. I take Synthroid and Cytomel for the T3. Years ago that was added and made me feel better so I continue with it. I am curious what she will say about my low TSH but it has been low before and since I feel fine (and T4/3 is normal) I just stay on the same dosage. I have always wished I would have some weight loss benefit when TSH is low but never have experienced that LOL
I gain weight over medicated. I also have finally found and endo who listens to me. He saw my TSH double but rerally was not putting 2 and 2 together. I have gone off all estrogen for now re test thyroid in 4 weeks (he told me 6 not required at this point) if TSH is below 2.5 then e now 100% it was the estrogen right now I am hypothyroid over range. I still get the night sweats which can last for life so I was told by one gyn, one male gyn not a meno expert told me I am too old to help. My new endo says I need it at one gyn as well but she retired. He did suggest taking cytomel and I new T4 meds have to be reduced to take it, perhaps that is the issue with you your T4 meds do not require more T3?? worth asking. I now my limits for T4 meds 100 over medicated and 50 undermedicated..I can ot sip doses either without my TSH going up. I was told I need both vag. and patch as well. I now wait once again for a meno expert (wait times here can be 2 plus years) and not paying out of pocket for help again.
This has been a tremendously helpful review with great discussion points of your interpretation as I often have this question posed to me—“is there a reason to preventatively be on hormones?” I look forward to more studies. Thank you!!!
It's very common to see the suggestion on social media that everyone needs hormone therapy to protect their bones, heart, and brain. It's pervasive and I think leads to what Dr. Gunter calls estrogen FOMO. I wish women were not turning to Facebook for medical advice, but I think the problem is there is often a lack of quality information offered to women from their doctors. I really appreciate the effort Dr. Gunter puts into these blogs.
It is all over doctor accounts on social media. These are real MD's not "functional medicine" people or supplement companies. I see it frequently that everyone should be on MHT to prevent cardiovascular disease and dementia. The authors of Estrogen Matters state it frequently.
The pill is only helpful for anemia if someone is having menstrual periods, but if you have POI, then menstruation is not likely a cause of your anemia. If you have had thyroid cancer and POI and a bone scan with a T score of -2, most people would suggest speaking with an endocrinologist. The standard starting hormone replacement for POI is 100 mcg estradiol patch and 100 mg progesterone a day, but of course, there could be reasons to pick another regimen.
Thank you for the very objective and detailed report. You seem to be one of the few menopausal experts that leads with caution and is completely honest with the studies limitations.
Thank you! I actually get attacked for this on Instagram, and I just don't get it.
Huge thanks for this information, I read this avidly. They didn’t look at bone health?
No they were looking at risk attributed to hormones, so what to I risk by staying on them (if that makes sense)
This is the clearest synopsis of a complicated subject and everyone should read it.
Thank you!
Thank you for tackling this study. As usual, your talent for distilling complexities to digestible explanations is a big help. Now if only I could convince my CRNP…At least I am better armed now. Thank you.
This was...complex. I really did feel like I was living that meme.
Wow! Thanks for this!. Can’t wait for part 2. I really appreciate your work!
I am anxiously awaiting your impressions from the estrogen/progesterone results. How can progesterone and E2 alone be protective of breast but combine increase the risk??
I think the best answer is either this is an observational study, and this is one of the flaws, or there is something about combining the two, meaning one preps for the other to trigger cancer.
I was trying to figure out the number of women on E2 + P as I know this is often low as this combo of prescription hasn’t been around as long. Were the numbers lower and if so - what are the actual differences - 4 more cases per 10000? Is this reported in relative risk?
Yep, I too am looking forward to your part 2 as I have been so confused/concerned about this study's takeaway on medium/low dose transdermal estrogen + micronized progesterone, since I thought that was now considered best practice, and micronized progesterone actually had breast protective effects.
Like Christine, I really wonder if this is one of those percentage increases in studies that is actually quite meaningless when you see the raw numbers? Like one additional person out of thousands got breast cancer? Like they mentioned, is there just not enough longterm estrogen + progesterone users in this study since it's only been the standard for a short time? Or is this a weird outlier thing like the 19% reduction in lung cancer from vaginal estrogen, which seems truly bizarre?
Dear Dr. Gunther, thank you for your in-depth report. I so appreciate all your research and info for us!! I am still confused though: Due to family history of ovarian cancer and several cysts, I have had a profilactic BSO nine years ago at the age of 51, but kept my uterus. I was advised not to take HRT. Due to vaginal dryness and pain, I have now been put on Premarin vaginal cream 0,625 mg, which I use 2 x weekly, very sparingly and it has helped a lot. Is Premarin Vaginal Cream included in these findings, or in other words: does "low dose vaginal" mean "cream"? Is there an expiration date on safely using Premarin vaginal cream? And does it provide the same percentage health benefits as discussed in your report?
We consider vaginal Premarin at the dose you are using to be safe. The creams are usually not considered a low-dose vaginal option; the tablets and ring are low-dose. There is more on them here. https://vajenda.substack.com/p/a-deeper-dive-into-vaginal-estrogens There wasn't a safety signal from vaginal Premarin in the dose you describe in this study.
Good breakdown and explanations, thank you! I was wondering about the effects of having been on hormonal contraception prior to MHT, presumably not something this study could capture?
As someone who has been on either the combined or mini pill all my adult life, I am a little concerned about what will happen when I stop....
Not captured in the study. The pill isn't associated with accumulative long-term risks, so I don't see there would be any concern.
Thank you for reporting on this research. Looking forward to part 2.
Whenever I have a question about anything related to female health, my search includes your name.
Thank you for this excellent analysis and summary. What about absolute length of time on MHT? Say, for someone who started taking it in their early 40s for vasomotor symptoms and thus may have many more years on it than someone starting in their 50s.
Great analysis. I too, am looking forward to Part 2.
Such an informative read. I feel scared and like a failure for not being able to take mht at 53. I’m still having light symptoms and some nightsweats 4 years post menopause. I feel like I amsending myself to an early grave with all the mht push. I get so many side effects from it. Debilitating progesterone intolerance. I feel defeated but appreciate everything you share with us. I feel like you are the only logical source anymore.
We don't recommend MHT to prevent other diseases besides osteoporosis. And there are non-hormonal medications for hot flashes. Many women live long, wonderful lives without MHT!
I took the time to read the recent study. The one issue that is not presented however is the impact all forms of estrogen (including vaginal delivery) has on women who are on a thyroid replacement. You have stated,"In the main analysis, the investigators grouped low-dose transdermal and low-dose vaginal therapies together, meaning a 25 mcg estradiol patch was in the low-dose category, but so were vaginal estrogen tablets and rings. However, one of these delivers estrogen into the blood (patch), and the other does not". Since vaginal estrogen does to a small degree enter the bloodstream (which I have proven by using it TSH does increase) why is the Menopause Society not addressing this issue since more women are impacted by thyroid issues especially during midlife? The study does recognize through statistics that vaginal estrogen impacts bone health (to a lesser degree than transdermal patches) lung cancer et al which suggests that the impact of this form of therapy is systemic. The product monograph as well as the information from the manufacturer of vagifem (and yes I did reach out to them) can impact TBG proteins in women who are on a suppressive or replacement of levothyroxine. I have accessed JAMA, the Journals from the Endocrine and OB/GYN societies as well as PubMed and cross referenced all of the information with the product monographs (and was told by the pharmaceutical companies they are published for medical doctors to access for additional information) and all support that any form of estrogen will impact TBG proteins (increase). How many doctors are up to date on this? The information in the latest study means women who have been waiting for help should be able to access it. Some women on a replacement of levothyroxine require two specialists, one for menopause issues as well as one to assist with adjustments in doses.
I am on both vaginal estradiol and transdermal. My TSH has actually lowered to where it was flagged as Hyperthyroidism however my T4 and T3 are normal so my doctor is not concerned.
Was your TSH suppressed to begin with? That happened to a person I know her TSH was lower and her Frees were normal as well. Try to access labs before you started estrogen. My TSH doubled and Free 4 dropped which means FT3 drops too.
No it was not suppressed. I had labs done about 4-5 months before starting HRT and TSH was in the normal range and then just re-did them last week which was a little over 3 months on HRT. I have been on Synthroid for 35+ years and have had times when TSH was below range so it is hard to say if was related to HRT or not. Some doctors have called for lowering dosage based on TSH while others have not providing the Free T4 and T3 are normal. Opinions seem to vary on that. I see my endo next week and curious if she will want to adjust my dose or not.
Also if you were not told you should tae thyroid meds same time of day and have labs done at the same time each time they are ordered as TSH and Frees move around during the day, half life of T3 is very short.
Yup. After 35 years on thyroid medication, I know the drill. I also got lazy and stopped waiting to eat or drink coffee but it has had absolutely zero impact on my levels.
I imagine you were told when taking T3 meds you have to test in the middle of the two doses per day. If you take 2 then test at noon.
I have gone by the book all these years only water 1 hour and most times more than an hour before I eat..never coffee in the am.
If you are on a supplement (your own thyroid is not working well without meds, subclinical) the portion of your thyroid that does work may be adding in to compensate. When on a replacement like me I can not make more T4. Estrogen of any kind can increase the TBG proteins (created in your liver) which will impact TSH levels. When I use any form my TSH goes up considerably. The endocrinologist I go to has confirmed my research is sound. There are not many menopause endocrinologists so someone like me has to go to two different specialists as an OB/GYN does not prescribe synthroid type medications. The GP's I have been to have no idea, look only at the WHI study. I have waited 9 years for any help (COVID 3 years of that meant no specialists were accepting new patients here) then before that I was over medicated with synthroid. The symptoms of meno, post meno are the same as thyroid either high or low. I have taken thyroid meds since 2003. Higher Frees are indicative of overmedicated as well as a low TSH depending on your scale for TSH (here .32-4) it shoul dbe under 2.5 so that the conversion process from T4 to T3 is within the ratio.
I am lucky to have a great Endo who is of peri/meno age herself which I have found to be very helpful overall. Not to say a younger doctor or a male doctor can't be informed but when you have experienced perio/meno first hand I think they do more research. My general doctor who is post menopause was the one who pushed me to find a new GYN after mine (who is younger) told me "We don't treat menopause" when I told her about my 20+ hot flashes a day. My T4 and T3 are in normal range. I take Synthroid and Cytomel for the T3. Years ago that was added and made me feel better so I continue with it. I am curious what she will say about my low TSH but it has been low before and since I feel fine (and T4/3 is normal) I just stay on the same dosage. I have always wished I would have some weight loss benefit when TSH is low but never have experienced that LOL
I gain weight over medicated. I also have finally found and endo who listens to me. He saw my TSH double but rerally was not putting 2 and 2 together. I have gone off all estrogen for now re test thyroid in 4 weeks (he told me 6 not required at this point) if TSH is below 2.5 then e now 100% it was the estrogen right now I am hypothyroid over range. I still get the night sweats which can last for life so I was told by one gyn, one male gyn not a meno expert told me I am too old to help. My new endo says I need it at one gyn as well but she retired. He did suggest taking cytomel and I new T4 meds have to be reduced to take it, perhaps that is the issue with you your T4 meds do not require more T3?? worth asking. I now my limits for T4 meds 100 over medicated and 50 undermedicated..I can ot sip doses either without my TSH going up. I was told I need both vag. and patch as well. I now wait once again for a meno expert (wait times here can be 2 plus years) and not paying out of pocket for help again.
Thank you for this information. Did the study address MHT and cholesterol levels?
No, this study only reported on death, 5 cancers, the 6 types of heart disease, and dementia
This has been a tremendously helpful review with great discussion points of your interpretation as I often have this question posed to me—“is there a reason to preventatively be on hormones?” I look forward to more studies. Thank you!!!
It's very common to see the suggestion on social media that everyone needs hormone therapy to protect their bones, heart, and brain. It's pervasive and I think leads to what Dr. Gunter calls estrogen FOMO. I wish women were not turning to Facebook for medical advice, but I think the problem is there is often a lack of quality information offered to women from their doctors. I really appreciate the effort Dr. Gunter puts into these blogs.
It is all over doctor accounts on social media. These are real MD's not "functional medicine" people or supplement companies. I see it frequently that everyone should be on MHT to prevent cardiovascular disease and dementia. The authors of Estrogen Matters state it frequently.
We don't currently recommend MHT to protect the heart or to prevent dementia
Ooh, and I just saw your subtitle “Part 1”!
The pill is only helpful for anemia if someone is having menstrual periods, but if you have POI, then menstruation is not likely a cause of your anemia. If you have had thyroid cancer and POI and a bone scan with a T score of -2, most people would suggest speaking with an endocrinologist. The standard starting hormone replacement for POI is 100 mcg estradiol patch and 100 mg progesterone a day, but of course, there could be reasons to pick another regimen.