Eric, so glad I found your substack. This post on HRT and the appalling WHI had special relevance for me--thank you for citing our book! The WHI story gets worse as we learn more about how the WHI manipulated their data into getting the scare stories they sought. e.g., Av Bluming and others found that the WHI knew as early as 2006 that HRT did NOT increase risk of breast cancer. Instead, difference between the HRT group and the control group was that the controls had a LOWER than average rate of BC. Why? Many had been on estrogen before joining the study and of course had to stop on entering. When they were removed from comparison, there was no difference btwn the control group and the women on HRT. Changing doctors' minds is often like turning around a battleship in a swimming pool. But women are persisting -- bringing evidence with them. Thank you so much for this splendid contribution to the challenge.
Wow! So great to hear from you as the author of the definitive book on this subject. And your posting about the WHI back story is so poignant. I'm vey impressed with the new data on organ clocks, particularly the effects orfestrogen for promoting a youthful immune system. I haven't seen any evidence for that previously. Have you? Thanks very much, Carol.
Eric, thank you and a counter wow! Avrum Bluming, the medical half of our team (I'm the social psychologist) offers these papers you might find relevant. He'd love to be in direct touch with you, as would I, at info@estrogenmatters.com.
Kelly -- I missed out too! Neither Avrum nor I would presume to advise anyone he has not seen personally. But, as others have said, the data show-- even the WHI--that vaginal estrogen is safe and effective for genitourinary symptoms and dryness. Our book explains the reason for the small but real risk of starting estrogen after the ten-year window: ten years after last menstrual period.
Carol and Eric - It is not surprising that women don’t trust western medicine and are turning to functional medicine, the supplement market and online apps for health care. I am not sure turning the battleship will be enough unless we acknowledge the shortcomings of womens medicine and science to this point and agree to work in a more patient centered framework. As precision genomics and tests like the ones that Eric discusses in this article become available to all, maybe we will see things change?
I’m very glad you wrote about this. I am one who missed out, with breast cancer in my fifties, at a time when estrogen therapy was completely ruled out for people in my situation. Now, at 76, it is too late for me, but hopefully, thanks to you, Carol Tavris, and others who are writing and speaking about this with clarity and knowledge, this will not be the case going forward.
While I had no trouble getting on hrt, when I moved and had to find a new doctor, encountered great resistance. Luckily my primary doc continued my prescription.
The data for estrogen was in a table in the WHI publication: reduced incidence of invasive breast cancer in women without a uterus who took estrogen without a progestin. This indicated to me that the progestin, medroxyprogesterone acetate was the bad actor. I began using transdermal estradiol and oral micronized progesterone in 1998 for bone health when I was in perimenopause. Because I was a research scientist in cell and molecular biology, I was able to track the research on female hormone replacement back to the studies in monkeys that showed that timing of initiation relative to menopause affected the cardiovascular benefits/harm. I also knew that I did not want to take a bisphosphonate to preserve bone density as this class of drugs can make bone more brittle.
This is such an important article! When I was in my mid-40’s, perimenopause hit with a vengeance. Thankfully, my OB/GYN was well versed in the flaws of the study you mentioned, and didn’t hesitate to put me on HRT. It was an absolute game changer. I’m now 67, and still on a low dose of estradiol because titrating off causes a resurgence in some symptoms. My doc continues to be comfortable with this because I’m so healthy. Next month, I’m doing a 500-mile bike trip with almost 20K of climb, so I have no complaints about my aging trajectory. I am also still working FT as a psychotherapist and feel as cognitively sharp as ever. While this is all anecdotal, I’ve watched so many clients, relatives and friends endure years of misery as they journey through perimenopause and beyond, complaining about cognitive fog, experiencing devastating losses in bone density, and succumbing to far more issues related to poor immune health. Either they heard about the study and decided HRT was dangerous, or they received poor medical guidance, but the outcome was the same.
As a footnote, now that gender-specific studies are not allowed under the constraints of the “big beautiful bill,” I do wonder what will happen to women’s health care. I’d love to have you address this at some point!
Fantastic to learn of your experience with long term estrogen and your vigorous physical activity. If only more physicians were like yours. Thanks for posting and subscribing!
Thank you so much for writing about this issue, especially as women’s health research is discontinued in the U.S.
I got Covid 5 years ago at 33yo, now 39, and severely disabled with Long Covid. Previous athlete turned bedridden. I have spent the last 18mo begging doctors to address my adrenal dysfunction and plummeting hormones - everything from estrogen to testosterone to cortisol, but none would listen - gynecologist and endocrinologist alike.
Finally, I found a gynecologist willing to treat me as if I’m in perimenopause. Not only due to low hormones, but also because the high dose estrogen in my birth control ring was causing 24/7 debilitating cramping, affecting the smooth muscle fibers tied to our autonomic nervous system.
Now, I am on a low dose estradiol patch and progesterone. Not only has the cramping stopped, but my Long Covid symptoms are improving! Less flu, less orthostatic intolerance, less body pain, less temperature dysregulation, less fatigue, less anxiety. Also, without a period my Long Covid symptoms don’t ramp up anymore at “that time” of the month.
HRT has improved my Long Covid baseline. I credit this gynecologist; she saved my life.
Thank-you for sharing your experiences. My daughter has long-covid, too.
She has found lymphatic massage by a practitioner using the Perrin Technique has been very helpful. She is in the UK, where many doctors are better informed about hormone replacement than in the U.S.
From the BMS website: The British Menopause Society (BMS) is the specialist authority for menopause and post reproductive health in the UK. Established in 1989, the BMS educates, informs and guides healthcare professionals, working in both primary and secondary care, on menopause and all aspects of post reproductive health.
I wish there were more Perrin practitioners in the U.S.! The only one remotely close to me seems to be no longer practicing. Well wishes to your daughter.
Thanks for writing this piece. I still find probably half my doctors are worried that I’m on HRT. I have two questions. You mention that there is no benefit for those who start 10+ years post menopause. For those who do start shortly before or after menopause, how long should women take estrogen? One of my doctors says forever. Another says for 10 years. My second question is about the role of progesterone in HRT. Progesterone is required to minimize the risk of endometrial cancer, but it does seem to be a mixed bag with the results you shared. Should one take the lowest effective dose to minimize negative effects?
I haven't seen any good data to support stopping estrogen (re: risks/benefit). My review of the data suggests progesterone is the bad actor so the lowest does or avoiding it completely seems prudent.
I am on ht because I insisted and have had to fight toaintain until recently. As an OBGYN it has been clear to me for decades that women who take ht age better. Now we know why.
Thank you for this IMPORTANT article. Those 3 books are EXACTLY my favorites for peri/menopause. If people want expert 100% doctor care for peri/menopause, check out pandiahealth.com/menopause, the ONLY #WomenFounded #WomenLed #Doctorfounded #DoctorLed birth control + menopause, asynchronous telemedicine + pharmacy company.
Important for people to know that there are FDA approved/tested bioidentical hormones (e.g. estradiol patch, ring, spray, gel and micronized progesterone aka prometrium) vs supplements which are NOT FDA tested/approved and compounded which are not tested/approved.
Drs. Yen and Topol, as one who was left behind, is there anything that can be done for the 65YO woman with intact quiescent ovaries? I can’t even find supportive help for bone loss other than to take supplements. I had heard that older women in the US were treated as if invisible, now I’m living that truth. Devastating
If you are within 10 years of your last menstrual period, and you have hot flashes, night sweats, genitourinary symptoms, or "at risk for osteoporosis" then you could consider systemic HRT. If more than that past your last menstrual period, then it's "shared decision making" and you need to find a doctor comfortable with that. if you have a good cardiac CT calcium scan, then most doctors would be OK with that.
And anyone at any age peri/post menopause are OK for vaginal NON systemic estrogen to prevent recurrent UTIs, urosepsis, and genitourinary symptoms.
Thank you for another excellent article, Dr. Topol. Is it possible to say what the practical implications of your article might be regarding treatment for a generally healthy woman who had a complete hysterectomy at age 30 and began HRT that continued for decades, and then *discontinued* HRT at age 70 on the advice of a primary care physician due to the health concerns (e.g., heart [EDIT JUL 6: sorry, the concern might actually have been about strokes]) cited in this article?
Possible, but still haven't seen meaningful data that supports stopping HRT (without adverse effects of therapy) so I wonder if your primary care physician is extrapolating from the WHI trial?
Yes, the WHI trial was the main grounds for my wife's PCP (who'd only been her doctor for a year at that point) discontinuing the HRT. And to confirm, my wife had experienced *no* adverse effects from the HRT (and indeed has generally felt worse since discontinuing it).
Hi Eric, thanks for this excellent review of the data and studies on HRT! I am a mostly retired Internist but remember when the WHI study came out in the early 2000s and the recommendations for women completely shifted to STOP all HRT. It was heartbreaking for many women then and many refused to stop as they would tell me “I feel normal” taking them. In the year 2000 (Y2K), Premarin was the top selling drug in the US!
I would point out that the negative effects of HRT are mostly due to the progesterone component, not the estrogen part and that for women with a uterus (the vast majority) it is still a tricky decision to take HRT as the overall health benefits vs risks are difficult to assess. For women under 60 who have had a hysterectomy the overall benefits are clear. For women who have had breast cancer, HRT remains a significant risk and is not recommended.
Thanks for your great coverage of complex topics in the world of medicine. I invite you to read my first Substack post “The Best Prescription” and would like to offer you a copy of my new book of my life in medicine “Tales from the Trenches, A Life in Primary Care”. Cheers!
I’m 64, is it too late for me? I already have heart & kidney disease, never really thought of having HRT as my symptoms were not bad, now I know that my heart, kidney and stenosis’s would possibly have been helped by it 😔 I take it my organs have aged, I’m actually in good health now. Can I take it now? Would it improve my health? I will discuss with my doctor, thank you for highlighting this. Love reading your Substack, even more so now! 🙏
I’ve sent my GP (I’m in Australia) your article as I think he will find it interesting as he’s a gynaecologist originally so women’s health is of interest to him, I hope! I’ve known him for 30+ years so he’s been on my journey. I will chat with him next week. 🙏
Concerning the Science Advances study: I offer a quote that helps me clarify the study findings. I think this suggests that the studies show that late start of HRT is more closely linked with poor AD-outcomes. After this quote, the discussion goes on to suggest that the poor outcomes may be related to the longer term fluctuations in hormones.
[Quote] "It should also be noted that given the observational nature of the data, we are unable to definitively state a causal association between HT to drive AD biomarker accumulation; however, the Women’s Health Initiative (WHI) demonstrated clear evidence of an association between delayed HT initiation and greater dementia incidence rates. Our findings lend weight to the evidence suggesting that delayed initiation of HT, particularly in older women, is associated with poor AD-related outcomes."
Thank You for this article! I have found conflicting and confusing info on this subject for years. I was recommended HRT after an osteoporosis diagnosis. I started it at age 58 (1.5 years after menopause) and have been on it for 6 years. I use a reduced dose combi patch. My bone scores have improved/stayed the same since then, and the debilitating hot flashes have been non existent. My neurologist freaks me out every time i see her because I have migraines with aura and she is convinced i am setting myself up for stroke. Is there any research on bioidentical estradiol/progestin and increased stroke risk for migraine patients? I can only find info on horse estrogen which i believe was what was used in the WHI study. Again, thank you for this incredibly helpful article.
Thanks for your feedback. Glad you got an early start and it has been sustained. I don't know the data on HRT, migraines and any increased risk of stroke indexed to the preparation. You're right about equine estrogen used in WHI and there may be be something to the different preparations, especial transdermal
Eric, so glad I found your substack. This post on HRT and the appalling WHI had special relevance for me--thank you for citing our book! The WHI story gets worse as we learn more about how the WHI manipulated their data into getting the scare stories they sought. e.g., Av Bluming and others found that the WHI knew as early as 2006 that HRT did NOT increase risk of breast cancer. Instead, difference between the HRT group and the control group was that the controls had a LOWER than average rate of BC. Why? Many had been on estrogen before joining the study and of course had to stop on entering. When they were removed from comparison, there was no difference btwn the control group and the women on HRT. Changing doctors' minds is often like turning around a battleship in a swimming pool. But women are persisting -- bringing evidence with them. Thank you so much for this splendid contribution to the challenge.
Wow! So great to hear from you as the author of the definitive book on this subject. And your posting about the WHI back story is so poignant. I'm vey impressed with the new data on organ clocks, particularly the effects orfestrogen for promoting a youthful immune system. I haven't seen any evidence for that previously. Have you? Thanks very much, Carol.
What can those of us who missed out do at 70?
Eric, thank you and a counter wow! Avrum Bluming, the medical half of our team (I'm the social psychologist) offers these papers you might find relevant. He'd love to be in direct touch with you, as would I, at info@estrogenmatters.com.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8870346/pdf/cancers-14-00909.pdf
https://pmc.ncbi.nlm.nih.gov/articles/PMC8573061/pdf/nihms-1702432.pdf
Kelly -- I missed out too! Neither Avrum nor I would presume to advise anyone he has not seen personally. But, as others have said, the data show-- even the WHI--that vaginal estrogen is safe and effective for genitourinary symptoms and dryness. Our book explains the reason for the small but real risk of starting estrogen after the ten-year window: ten years after last menstrual period.
Carol and Eric - It is not surprising that women don’t trust western medicine and are turning to functional medicine, the supplement market and online apps for health care. I am not sure turning the battleship will be enough unless we acknowledge the shortcomings of womens medicine and science to this point and agree to work in a more patient centered framework. As precision genomics and tests like the ones that Eric discusses in this article become available to all, maybe we will see things change?
I’m very glad you wrote about this. I am one who missed out, with breast cancer in my fifties, at a time when estrogen therapy was completely ruled out for people in my situation. Now, at 76, it is too late for me, but hopefully, thanks to you, Carol Tavris, and others who are writing and speaking about this with clarity and knowledge, this will not be the case going forward.
Great question. I don’t know the answer but I would think polygenic risk scores could help to make the call
While I had no trouble getting on hrt, when I moved and had to find a new doctor, encountered great resistance. Luckily my primary doc continued my prescription.
The data for estrogen was in a table in the WHI publication: reduced incidence of invasive breast cancer in women without a uterus who took estrogen without a progestin. This indicated to me that the progestin, medroxyprogesterone acetate was the bad actor. I began using transdermal estradiol and oral micronized progesterone in 1998 for bone health when I was in perimenopause. Because I was a research scientist in cell and molecular biology, I was able to track the research on female hormone replacement back to the studies in monkeys that showed that timing of initiation relative to menopause affected the cardiovascular benefits/harm. I also knew that I did not want to take a bisphosphonate to preserve bone density as this class of drugs can make bone more brittle.
That's great. Benefits of being a life scientist!
Yes!
And the benefits of life-long curiosity and access to the often free peer-reviewed science in our National Library of Medicine.
For example: https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed_citedin&from_uid=37323518.
Who could resist?
This is such an important article! When I was in my mid-40’s, perimenopause hit with a vengeance. Thankfully, my OB/GYN was well versed in the flaws of the study you mentioned, and didn’t hesitate to put me on HRT. It was an absolute game changer. I’m now 67, and still on a low dose of estradiol because titrating off causes a resurgence in some symptoms. My doc continues to be comfortable with this because I’m so healthy. Next month, I’m doing a 500-mile bike trip with almost 20K of climb, so I have no complaints about my aging trajectory. I am also still working FT as a psychotherapist and feel as cognitively sharp as ever. While this is all anecdotal, I’ve watched so many clients, relatives and friends endure years of misery as they journey through perimenopause and beyond, complaining about cognitive fog, experiencing devastating losses in bone density, and succumbing to far more issues related to poor immune health. Either they heard about the study and decided HRT was dangerous, or they received poor medical guidance, but the outcome was the same.
As a footnote, now that gender-specific studies are not allowed under the constraints of the “big beautiful bill,” I do wonder what will happen to women’s health care. I’d love to have you address this at some point!
Fantastic to learn of your experience with long term estrogen and your vigorous physical activity. If only more physicians were like yours. Thanks for posting and subscribing!
HRT & LONG COVID
Thank you so much for writing about this issue, especially as women’s health research is discontinued in the U.S.
I got Covid 5 years ago at 33yo, now 39, and severely disabled with Long Covid. Previous athlete turned bedridden. I have spent the last 18mo begging doctors to address my adrenal dysfunction and plummeting hormones - everything from estrogen to testosterone to cortisol, but none would listen - gynecologist and endocrinologist alike.
Finally, I found a gynecologist willing to treat me as if I’m in perimenopause. Not only due to low hormones, but also because the high dose estrogen in my birth control ring was causing 24/7 debilitating cramping, affecting the smooth muscle fibers tied to our autonomic nervous system.
Now, I am on a low dose estradiol patch and progesterone. Not only has the cramping stopped, but my Long Covid symptoms are improving! Less flu, less orthostatic intolerance, less body pain, less temperature dysregulation, less fatigue, less anxiety. Also, without a period my Long Covid symptoms don’t ramp up anymore at “that time” of the month.
HRT has improved my Long Covid baseline. I credit this gynecologist; she saved my life.
This is so good to see! Thanks for sharing your experience and the help it brought to your Long Covid condition
Thank-you for sharing your experiences. My daughter has long-covid, too.
She has found lymphatic massage by a practitioner using the Perrin Technique has been very helpful. She is in the UK, where many doctors are better informed about hormone replacement than in the U.S.
From the BMS website: The British Menopause Society (BMS) is the specialist authority for menopause and post reproductive health in the UK. Established in 1989, the BMS educates, informs and guides healthcare professionals, working in both primary and secondary care, on menopause and all aspects of post reproductive health.
https://thebms.org.uk/
I wish there were more Perrin practitioners in the U.S.! The only one remotely close to me seems to be no longer practicing. Well wishes to your daughter.
Thank-you, Pepper.
Hoping that you continue to feel better with time.
Thanks for writing this piece. I still find probably half my doctors are worried that I’m on HRT. I have two questions. You mention that there is no benefit for those who start 10+ years post menopause. For those who do start shortly before or after menopause, how long should women take estrogen? One of my doctors says forever. Another says for 10 years. My second question is about the role of progesterone in HRT. Progesterone is required to minimize the risk of endometrial cancer, but it does seem to be a mixed bag with the results you shared. Should one take the lowest effective dose to minimize negative effects?
I haven't seen any good data to support stopping estrogen (re: risks/benefit). My review of the data suggests progesterone is the bad actor so the lowest does or avoiding it completely seems prudent.
I am on ht because I insisted and have had to fight toaintain until recently. As an OBGYN it has been clear to me for decades that women who take ht age better. Now we know why.
Right!
Thank you for this IMPORTANT article. Those 3 books are EXACTLY my favorites for peri/menopause. If people want expert 100% doctor care for peri/menopause, check out pandiahealth.com/menopause, the ONLY #WomenFounded #WomenLed #Doctorfounded #DoctorLed birth control + menopause, asynchronous telemedicine + pharmacy company.
Important for people to know that there are FDA approved/tested bioidentical hormones (e.g. estradiol patch, ring, spray, gel and micronized progesterone aka prometrium) vs supplements which are NOT FDA tested/approved and compounded which are not tested/approved.
Thank you!
Drs. Yen and Topol, as one who was left behind, is there anything that can be done for the 65YO woman with intact quiescent ovaries? I can’t even find supportive help for bone loss other than to take supplements. I had heard that older women in the US were treated as if invisible, now I’m living that truth. Devastating
If you are within 10 years of your last menstrual period, and you have hot flashes, night sweats, genitourinary symptoms, or "at risk for osteoporosis" then you could consider systemic HRT. If more than that past your last menstrual period, then it's "shared decision making" and you need to find a doctor comfortable with that. if you have a good cardiac CT calcium scan, then most doctors would be OK with that.
And anyone at any age peri/post menopause are OK for vaginal NON systemic estrogen to prevent recurrent UTIs, urosepsis, and genitourinary symptoms.
Thank you for your thoughtful and informative response! Also tremendous gratitude for founding Pandia - caring healthcare for the needs of all women 💕
Thank you for another excellent article, Dr. Topol. Is it possible to say what the practical implications of your article might be regarding treatment for a generally healthy woman who had a complete hysterectomy at age 30 and began HRT that continued for decades, and then *discontinued* HRT at age 70 on the advice of a primary care physician due to the health concerns (e.g., heart [EDIT JUL 6: sorry, the concern might actually have been about strokes]) cited in this article?
Possible, but still haven't seen meaningful data that supports stopping HRT (without adverse effects of therapy) so I wonder if your primary care physician is extrapolating from the WHI trial?
Yes, the WHI trial was the main grounds for my wife's PCP (who'd only been her doctor for a year at that point) discontinuing the HRT. And to confirm, my wife had experienced *no* adverse effects from the HRT (and indeed has generally felt worse since discontinuing it).
Hi Eric, thanks for this excellent review of the data and studies on HRT! I am a mostly retired Internist but remember when the WHI study came out in the early 2000s and the recommendations for women completely shifted to STOP all HRT. It was heartbreaking for many women then and many refused to stop as they would tell me “I feel normal” taking them. In the year 2000 (Y2K), Premarin was the top selling drug in the US!
I would point out that the negative effects of HRT are mostly due to the progesterone component, not the estrogen part and that for women with a uterus (the vast majority) it is still a tricky decision to take HRT as the overall health benefits vs risks are difficult to assess. For women under 60 who have had a hysterectomy the overall benefits are clear. For women who have had breast cancer, HRT remains a significant risk and is not recommended.
Thanks for your great coverage of complex topics in the world of medicine. I invite you to read my first Substack post “The Best Prescription” and would like to offer you a copy of my new book of my life in medicine “Tales from the Trenches, A Life in Primary Care”. Cheers!
I’m 64, is it too late for me? I already have heart & kidney disease, never really thought of having HRT as my symptoms were not bad, now I know that my heart, kidney and stenosis’s would possibly have been helped by it 😔 I take it my organs have aged, I’m actually in good health now. Can I take it now? Would it improve my health? I will discuss with my doctor, thank you for highlighting this. Love reading your Substack, even more so now! 🙏
A great question. I hoe your physical can weigh in for integrating your health status and the up-to-date data to help you decide. Thanks
I’ve sent my GP (I’m in Australia) your article as I think he will find it interesting as he’s a gynaecologist originally so women’s health is of interest to him, I hope! I’ve known him for 30+ years so he’s been on my journey. I will chat with him next week. 🙏
Concerning the Science Advances study: I offer a quote that helps me clarify the study findings. I think this suggests that the studies show that late start of HRT is more closely linked with poor AD-outcomes. After this quote, the discussion goes on to suggest that the poor outcomes may be related to the longer term fluctuations in hormones.
[Quote] "It should also be noted that given the observational nature of the data, we are unable to definitively state a causal association between HT to drive AD biomarker accumulation; however, the Women’s Health Initiative (WHI) demonstrated clear evidence of an association between delayed HT initiation and greater dementia incidence rates. Our findings lend weight to the evidence suggesting that delayed initiation of HT, particularly in older women, is associated with poor AD-related outcomes."
Thank You for this article! I have found conflicting and confusing info on this subject for years. I was recommended HRT after an osteoporosis diagnosis. I started it at age 58 (1.5 years after menopause) and have been on it for 6 years. I use a reduced dose combi patch. My bone scores have improved/stayed the same since then, and the debilitating hot flashes have been non existent. My neurologist freaks me out every time i see her because I have migraines with aura and she is convinced i am setting myself up for stroke. Is there any research on bioidentical estradiol/progestin and increased stroke risk for migraine patients? I can only find info on horse estrogen which i believe was what was used in the WHI study. Again, thank you for this incredibly helpful article.
Thanks for your feedback. Glad you got an early start and it has been sustained. I don't know the data on HRT, migraines and any increased risk of stroke indexed to the preparation. You're right about equine estrogen used in WHI and there may be be something to the different preparations, especial transdermal
Yes and
have been refuting WHI for years.
Have written HRT/ MHT for years and the strongest reasoning is exactly yours in Super Agers- find out what is your personal
Risk of breast cancer- 12 % for most women and for all the others consider MHT.