Does Estrogen Cause Breast Cancer or Build Bone?? What the research got WRONG!

welcome to the Dr Doug show your resource for bone health hormone optimization and Women's Health span through midlife and Beyond today I've got a big topic for you so we're going to talk about estrogen and we're going to talk about breast cancer because we are now seeing a second generation of women millions of women who have been impacted by this strong belief in the medical community that estrogen causes breast cancer and real quickly if you haven't heard of this the Women's Health Initiative which is a very large trial that was published initially one of their the Publications in 2002 single-handedly changed the landscape of hormone optimization and replacement what I want to do here today is critically review this study I want to review subsequent Studies by both the Women's Health Initiative research group and other researchers and come to a conclusion to make you feel comfortable about the idea that estrogen plays a role in breast cancer but how strong is the actual causation I want to talk about what the studies show let's talk about how causitive it is or is it actually protective what are the other factors that you can consider so stick around because this is a really really important topic and if you are in these two generations of women that have been affected by this belief that estrogen causes breast cancer you're going to want to listen to this 3 2 1 here we go so prior to the early 2000s estrogen was used for a lot of things so it was hailed as the answer to menopause symptoms but it was also sold as sort of an anti-aging drug it was given for heart disease prevention and for cancer prevention and there were a lot of concerns around the way that estrogen was being sold to the public and so there was a need to do some well-designed studies so one such study called The Women's Health Initiative which is very well known in the space in addition to a number of other studies that were done in other countries like the million women study um and other studies were aimed at looking at the role of estrogen or hormone replacement with combined estrogen and some form of progesterone um and the risk of heart disease for one but also for other things like breast cancer colon cancer blood cot stroke fractures because it had been talked about in the in context of all of these things so now the Women's Health Initiative was a massive study so specifically though with hormone replacement there were two arms to this study so this is a placebo controlled trial and there were two groups of uh hormon related intervention so there was an estrogen group and then a combined group but important to point out here that the estrogen group that we're talking about here we're using an oral estrogen that was derived from horses so this is called Premarin and Premarin was very popular at the time it was sort of the standard of care so it makes sense that that's what they would use it has since fallen out of favor some but it is certainly still available and then uh the progesterone product that they used was not progesterone they used uh medroxy progesterone acetate or MPA which is known as one of many now progestin so as I move forward through this I'll talk about presten those are synthetic progesterones those are not the same thing as micronized oral progesterone which is a bioidentical form of progesterone so there was a group that had both of those things for women that still had a uterus and then there was a group that had undergone hysterectomy that was given estrogen alone and that was that oral Prine alone now the entire Women's Health Initiative again was a massive study over 160,000 women costing over $625 million so when people ask you know they say well what when am I going to see the double blind placebo trial for this supplement or this you know lifestyle thing and the truth is is that you're not because they're extremely expensive and to have a big enough study to show small differences like this study shows um it's going to cost hundreds of millions of dollars you know and somebody has to be able to make that money back or it's funded by the federal government um and they have only you know so much money and only so much interest all right so specifically this group of uh combined hormone replacement so the progestin and the oral EST was run for a little over 5 years and it was stopped early because they met some endpoints that were concerning for an increase in uh risk associated with the intervention and this was built into the study so some people took this as oh there was some emergency and there unexpected findings that's not true these termination points are kind of built in and so they reached one of these termination points and thought okay well we're not seeing the benefit that we think we're seeing and it is unethical to continue we need to stop this trial but if you dig into the data it's kind of interesting how this was built in and so if you look at what they said in the 2002 study uh publication they said that all cause mortality was not affected so that's good and then there were certain things that they were concerned about so coronary heart disease or CHD did go up just slightly so there was a mild increased risk of CHD U which was listed as a 29% increase and that's a statistical relative increase and then in invasive breast cancer so that's a big one so I'm going to say that again invasive breast cancer was increased but not statistically significantly relevant meaning that the uh statistics showed a 26% increase in the intervention group meaning those were on hormone replacement but it did not reach statistical significance in other words the confidence interval still was right at one and so it did not reach statistical significance easy for me to say um stroke and Pulmonary embolism another type of blood clot were also elevated and that was significant a couple of good things though hip fracture was reduced by 34% and colal cancer additionally by 37% so some big reductions in some good things like colal cancer and hip fracture uh but some concern for some things that reach statistical significance around blood clot and then again breast cancer was not statistically significant but was certainly a trend so okay let's stop the study but then my concern was after reading this you know later of course I was I was in medical school and this came out um and the takeaway was well estrogen causes breast cancer but I didn't read the study because I was studying to be an orthopedic surgeon and I didn't care um never thought I'd be in this place but the takeaway certainly for most of my peers and for doctors that were practicing is estrogen causes breast cancer but the truth is that they didn't really say that it also wasn't statistically significant and so what I wish would have happened is I wish the study would have come out and it have said hey we need to ask additional questions and we have this second arm of this study that hasn't come out yet that we are still ongoing let's wait for this to come out before we jump to any conclusions around estrogen cuz remember the second arm of the study had over 10,000 women who were enrolled and were either on Placebo or on an oral estrogen without the synthetic progesterone so this study went on for about another two years stopped at an average of 6.8 years and this one was also stopped early but it was stopped early because they weren't it didn't look like they were going to achieve statistical significance on an improvement in coronary heart disease which which was their primary uh endpoint they realized hey it's not going to be ethical for us to continue the study we need to terminate it not because there was too much increased risk but they weren't seeing the benefit that they that the study was designed to see so they stopped it early then they looked at all the data and what they found is that the risk of coronary heart disease was not increased but it was not decreased the risk of Choral cancer was similarly decreased in this group as it was in the other and the risk of hip fracture again similarly decreased so great reduction in hip fracture great reduction in coloral cancer and then as far as blood clot goes there was uh a trend towards an increase but there was nothing statistically significant there and then there's the breast cancer data so the breast cancer data are really interesting so the breast cancer data would show that there was a protection from this estrogen I'm G say it again the estrogen is an oral estrogen in premine was protective of breast cancer now it was not statistically significant but it was nearly as statistically significant as the increase of breast cancer and the combined group in the other study so again what was the takeaway here well the takeaway cuz again I was in medical school and the takeaway was estrogen causes breast cancer um but that's not what the data show the data shows that estrogen was as protective on this side as it was potentially risking in the combined side and so to a thousandth of a point statistically they were similar in protection and uh at risk so if that were the case then wouldn't you think that we would at least want to ask more questions or potentially it wasn't the estrogen at all it was probably the the synthetic progesterone the progestin so there's a lot more to talk about here because again this was in the early 2000s The Fallout here though was dramatic so millions of women across United States and then ultimately across the world were taken off of hormone replacement and what I've seen in my practice because now I am working in the space of working with women with osteoporosis and hormone challenges in their 50s 60s and 7s this is a group of women that were denied hormone therapy because they thought there was too much risk around estrogen and breast cancer yet this single study really didn't show that in fact if anything it showed that the synthetic progesterone was likely the culprit but that wouldn't bear out in the literature until later and yet millions of women were ripped off of their hormone replacement there was so much undue suffering as a result of the misinterpretation of these data so we're going to go through the newer studies because a lot of Studies have come out since 2004 so we're going to go through the newer studies compare those to the women's health initiative and come up with the conclusion here at the end but before we do that if you are interested in seeing how I put together a bone health program or how we look at hormone replacement as a comprehensive solution consider our master classes we have two free master classes one specifically for bone health one specifically for Hormone Health uh look in the description if you're watching this on YouTube if you're listening to this uh on a podcast then just go to drd lucas.com for more information on those again totally free resources for anybody who's listening to these uh messages so let's fast forward to 2023 so almost 20 years after the well over 20 years after the first publication but almost 20 years after the second publication of the Women's Health Initiative there have been a number of studies published there have been over 30 critical reviews of the women's health initiative and how the data was interpreted that have been published in peer-reviewed journals so we're going to look at this study so this study from 2023 kind of lumps all of these things together um and they look at uh and they really do this as sort of like a meta analysis and they look at the collaborative group on hormonal factors in breast cancer and they look at the million women study and they go through all of the data and what's really challenging about this Bas is when you're dealing with a study like the Women's Health Initiative there is so much data you can statistically manipulate those data in a lot of different ways and so a lot of these commentaries and these studies that have been published subsequently took the data set because they're publicly available they took the data sets looked at them in in various ways and different authors come to different conclusions but this is the conclusion of this study from 2023 and it says based on the randomized clinical trials estrogen therapy for women with prior hysterectomy meaning they've had their uterus taken out decreases breast cancer incidence and mortality in contrast estrogen plus progestin increases breast cancer incidence which persists through two decades women considering estrogen Plus progest use for Vasa motor symptoms should understand the breast cancer risk so what's the takeaway there the takeaway there is that estrogen according to this study is protective estrogen plus progestin increases the risk of uh of breast cancer and likely other things so let's look into this a little bit deeper because that's s of a big leap now to be fair that's actually how I looked at the women's health initiative to begin with and I think that should have been the takeaway but that certainly isn't what's happened over the last 20 years so then let's look at the a little bit deeper and understand how this could possibly be the case so if we look at this fourth study here this is a study that's looking at the gene expression and so for those who don't understand genetics so gene expression our genes are all the same person to person the genes that are expressed are based off of those things that we are exposed to whether it be nutrition stress the environment whatever so different people are going to express different genes uh different exposures are going to express different genes within the same person okay so this study looked at then the gene expression of 30 and posle woman exposed to different types of estrogen or combined estrogen in progestin therapy so the first one was the same Premarin as was in the women's health initiative and proa so again the same compounds that were in the Women's Health Initiative or a topical estrad and uh oral micronized progesterone which is the biogenic micronized progesterone and so this study looked at over 3,000 genes and what they found is that the combined Premarin and proa combo changed the expression of the genes related to breast cancer at a quote unquote very highly significant rate and much more so than the estrogen and micronized progesterone and their conclusion was that the combined therapy with primin and proa affected breast cancer related genes much much more than the estradi and micronized progesterone so then again it was it the estrogen well let's keep talking about it so this next study our fifth study here was a 2017 Swedish uh population study this is a massive cohort study 290,000 women in 7 years of hormone therapy exposure they looked at invasive breast cancer endometrial and ovarian Cancers and they saw that there was an increase of 31% increase in the odds of disease a 31% increase in odds of disease but they noted at the end that progestin combined therapy was really driving the increased risk but there was a little bit of increased um odds with estrogen only therapy so we'll talk a little bit more about that estrogen only therapy increased risk because we keep seeing this signal it just sort of keeps popping up every now and then but they also noted at the end of this study which I thought was kind of interesting as they said well that slight increased risk of breast cancer will be balanced by the significantly reduced risk of GI cancers which in countries like Sweden are actually more prevalent than in the US so then we can keep going and we can look at more studies so here's a 2022 case controlled study on 43,000 cases of breast cancer so now this is kind of a different way of looking at it because breast cancer even though it's common um if you were to study big parts of the population you wouldn't actually see that many cases right one in seven to one in8 women will develop breast cancer over the course of their lifetime but if you look at a large chunk of people over the course of you know five years 10 years how many cases will you actually see not that many and so doing a case study where you actually look at the cancers themselves now we can look at that group of people that cancer and then compare them to uh people that haven't developed cancer and look at the increased risk associated with hormone replacement therapy that way and so they did just that and hormone therapy was associated with an increased risk of breast cancer 12% increased odds of breast cancer but again formulation matters estrogen derived from animals the same thing Premarin or bioidentical estrogen the estradi alone was not associated with breast cancer the micronized progesterone was not assoc assciated with breast cancer but the synthetic progesterone the progestin were with a 28% increased odds and so their conclusion was is although uh menopausal hormone replacement therapy use appears to be associated with the overall increased risk of breast cancer this risk appears predominantly mediated through formulations containing synthetic progestins so again form matters and Route matters we'll talk about route for other things later topical versus oral so at this point you might be saying to yourself well clearly I don't want to use the synthetic progesterone but most of the studies have been done on that so if I use something else are they actually going to do what I want them to do that's a great question so our seventh study here was a 2022 metaanalysis that looked at 74 Publications comparing micronized progesterone to progestins and show that they are equally effective at preventing the endometrial hyperplasia which is in the traditional medical model the only reason why we give progesterone is so that you don't develop hypertrophy inside the uterus and potentially uh increased risk of uterine cancers um I think there are other reasons to use progesterone but they showed that in this case that micronized progesterone was similar and probably better uh than the synthetic progestin and not only for that not developing hypertrophy but also there were better outcomes from a cardiovascular and breast cancer perspective um they also noted that progestin uh was not as good as the micronized progesterone at preventing age related cognitive decline and bone fractures they also noted that estradi alone versus the conjugated equin estrogen the Premarin has similar or better risk profile for uh blood clot which also makes sense because we know the oral estrogens will increase the risk of blood clot over topical and then um also topical estrogen estradi may protect better related to cognitive decline in bone fractures versus the Premarin so that's really good to know so again this will show that not only are they likely safer but estradi and micronized progesterone are likely going to be as effective if not more effective for the things that we actually care about all right so here's another topic that people will bring up often when they discuss the literature and this is this is a totally valid concern which is the Woman's Health Initiative talked about cases of breast cancer now this is a different conversation than say uh mortality from gu breast cancer or dying from breast cancer now I wouldn't wish a case of breast cancer on anybody but understanding the difference between increased identification of cancer versus dying of cancer is an important thing to study so there was the study uh from 2016 um from Finland that looked at over 89,000 women on hormone replacement and followed them for 15 years and looked for breast cancer death now again this is a different type of study because now we're following not just um not just diagnosis because there are some potential bias and people that are on hormone replacement therapy getting more uh mammograms and there for the incidence of diagnosis might actually be higher just because of that it might have nothing to do with the hormone replacement um but if you follow them to death then now we're going to look and see what actually happened to these people that were identified as having breast cancer and what was interesting here is that mortality was actually reduced in all hormone therapy users regardless of the exposure duration uh but they saw that the people that were on the synthetic progestins actually had less uh benefit and there were also more cases some nice not notes Here is that age of initiation was not associated with breast cancer mortality meaning that it didn't matter if you started early or late so there were some interesting things to take away here but the biggest takeaway was that hormone replacement therapy did not increase the risk of breast cancer death but again I wouldn't wish a breast cancer case on anybody so all of that said you might be wondering but gosh my doctor still says that hormones cause cancer how could that be well let me run through a couple of the studies that they're going to hang their hats on if they're an anti-estrogen uh type of person um because there are some studies that show this and I want to talk about this so that we're not just presenting my biased perspective we're presenting all the evidence that is related to estrogen and um cancer risk all right so there are a couple of big studies actually that point these things out and one is this 2020 observational study this is our nth study and this was on almost 100,000 women and so they were age matched two controls and they compared users with never users of estrogen and looked at the association of the increased risk of breast cancer now estrogen alone was associated with a 15% increased risk of breast cancer estrogen and artificial progesterone was associated with an 80% increased risk so again the form matters um couple other points here is that past estrogen use was not associated with an increased risk of breast cancer meaning that if you've been on it and you came off of it you didn't need to necessarily worry about that past short-term use of both estrogen and progestin was also not associated with the an increased odds of developing cancer but past long-term use with progestin was associated with an increased oddo developing breast cancer so again the progestin seem particularly nasty but then they went on to say that yes it causes an increased uh odds of developing cancer but you would expect in this study if you were on estradi that or an oral estrogen that you would see three cancers per 10 th000 woman years for younger patients and eight for older patients um those same data in the uh synthetic progesterone group were nine and 36 another reason why I bring that up is that statistically that's not a lot of cases again every case matters but it's not a lot of cases and how clinically relevant is it if you're taking it for some reason that you really need to take it for like say osteoporosis something that you know that you have so this is where decision- making is really important and then the last study we're going to talk about is the million women study so this was a really big study and the timing of this was really really critical so it came out shortly after the women's health initiative so this was a study from the UK and again it included over a million women um and it just added fuel to the fire because the Women's Health Initiative came out and then this study came out and basically what they showed is that users of hormone replacement therapy were more likely to develop breast cancer with a 66% increase in uh an odd of developing uh breast cancer and a 22% increase odds of dying from it what so you know you could say oh my gosh this massive cohort showed these big increased risks um that's a big problem right they went on to say in this study that past users were not at increased risk and well that's a nice like takeaway I guess and then they went on to say that if you were on estrogen only there was a 30% increased uh odds of having a breast cancer diagnosis and then if you were on again the synthetic progesterone the progestins that you had a 100% increased risk so it seems like the the r the ratio between the two was similar as we've seen in other studies there were just bigger numbers and so how do I explain that you know when people ask me about this study which isn't very common but when people ask me about this study how do I explain it and the the truth is I am not smart enough to look at those statistics and and Po and poke holes at them but fortunately there are people that are and so this uh last uh kind of rebuttal study the study 11 is a a 2012 basically statistic iCal argument and this is a group of uh researchers that basically looked at some of these big studies and said the way that they're doing the statistics is silly and so what they said in conclusion is that despite the massive size of the million women study the findings for the progestin group and for the estrogen alone group did not adequately satisfy the criteria of time order information bias detection bias confounding statistical stability and strength of Association duration response internal con consistency external consistency or biological plausibility now this is why I say that I'm not smart enough to understand this because there's so many different ways to look at statistics especially in these really really big studies so they go on to say that had detection bias resulted in the identification in women aged 50 to 55 that there would be 0.3 additional cases of breast cancer in the estrogen group and um 1.2 in the estrogen plus progestin group and that's per 1,000 patients per year per 1,000 patients per year so 0.03% and it would have nullified the apparent risks reported and so they actually did a similar study on the Women's Health Initiative which we don't need to go through so the challenge here is there is evidence just support both sides of the argument I think clearly we can see from the data that progestins the synthetic progesterone sometimes called progestagens progestins do increase the risk of breast cancer and other complications of HRT but what about estrogen what about estradiol so estradiol has been found in these studies to be related both to an increased risk and a decreased risk uh you know if you were to look at all the studies and do the statistics I don't know where it would balance out but I think of it like this and this is what I tell my patients breast cancer occurs like I said earlier in one out of seven to one out of eight women during their lifetime if you were to do a study and apply estrogen to a large group of women and some of them are going to develop breast cancer no matter what that breast cancer if it's hormone sensitive is likely to grow faster so here's what I think is happening is that the population that is given a hormone that develops breast cancer anyway is going to see it faster on Imaging than the women who are not on a hormone replacement and not on hormones because they're just simply going to grow faster if they're hormone sensitive they're going to get bigger faster they're going to be seen on Imaging quicker so this is really hard to isolate and control for in a study and so that's why I think for me in my practice I tell my patients that I don't think estradi causes breast cancer I think progestins likely cause breast cancer but I don't think estradi causes breast cancer I think it will make a hormone sensitive cancer grow faster and if you are at high risk then this becomes this challenging conversation to say well is it worth it or not if you're already at high risk and that's where the conversation needs to really be focused on not just to say estrogen causes breast cancer what is their reason for taking estradiol do they have symptoms of menopause do they have osteoporosis what is the actual risk versus the actual benefit and if you don't understand the risks it's hard to have that conversation as a doctor so what we do then is for people that meet our criteria we use an estradi cream we use micronized progesterone capsules and we use testosterone cream because remember testosterone cream is also protective very protective of breast cancer and maybe that was the missing ingredient for all those studies studies we'll never know because I don't think we're going to see any big studies on the trio of hormone replacement like we recommend it so okay I think that's enough I think we beat this horse to death um this is a challenging topic and it's challenging to find the right type of Provider to have this conversation with because again most providers don't really understand the risks like somebody who is steeped in this data uh does so that's it for now remember my friends that you are created for greatness so seek optimal not average don't be afraid to be extraordinary because you are and that's what it takes couple of quick announcements if you haven't already please subscribe to this channel it will help other people looking for hormone and bone health related things to find this channel if you've already been to our master classes and you need more because let's face it you might just need more um consider joining our healthspan nation Health span nation is a u an inexpensive opportunity to chat with me and my team on a weekly basis to ask questions and a weekly Q&A Style zoom you also have access to our community of people in the health span Nation supporting each other and elevating each other having the same goals and the same challenges as one another and it's a really really beautiful community and then lastly you have access to our content Vault and our discount codes that come out of our um out of our podcast here in our YouTube channel so you would have access to those things above and beyond what you see on YouTube so you can check all of those things out at Dr douglas.com I'll see you in the next video this presentation is for General informational purposes only does not come constitute the practice of medicine nursing or other professional health care services including the giving of medical advice no doctor patient relationship is formed the use of this information and the materials linked to this presentation are at the user's own risk the content in this presentation is not intended to be substitute for professional medical advice diagnosis or treatment users should not disregard or delay obtaining medical advice for any medical condition they have and they should seek the assistance of their Health Care Professionals for any such conditions oh