hello and welcome to another episode of The Dutch webinar Series this webinar is presented by Dr Tori Hudson and we're very excited for her to share her expertise in regard to debunking Common myths and misconceptions surrounding menopause per menopause and MHT which stands for menopausal hormone therapy Dr Tory Hudson a naturopathic physician graduated from the National University of natural medicine in 1984 and has served the in several capacities including medical director associate academic Dean and academic Dean she is currently a clinical Adjunct professor at nunm Southwest College of naturopathic medicine baser University and the Canadian College of naturopathic Medicine Dr Hudson has been in practice for more than 40 years and is the clinical or the medical director of her Clinic a woman's time in Portland Oregon she's also the co-owner and director of product research and education for vitanica which I'm sure a lot of you know about that supplement comp company it's wonderful and the program director for The Institute of women's health and Integrative Medicine which they have really great conferences she is also the founder and co-director of nerk a nonprofit organization for accredited naturopathic residencies in 2021 she received the 2020 American Botanical council's prestigious Freddy Cronenberg excellence research and education in Botanicals and Women's Health award for 2020 she's a nationally recognized author she wrote women's Encyclopedia of natural medicine which I actually have right here on my desk and she's a speaker educator researcher and clinician Dr Hudson serves on several editorial boards advisory panels and as a consultant to the natural products industry she also writes monthly columns and freelance articles for several Publications Dr Tory Hudson it's great to have you with us today I'll hand the floor over to you hi everybody welcome glad to be with you and glad to be in collaboration with Dutch uh and they have asked me to share some content uh about Miss and misconceptions of prescribing menopausal hormones to per menopausal and menopausal women which I'm thrilled to do because this is a menop is having a moment out there in case you haven't noticed uh and it's taken a long time to get here um but we want to make sure we're doing things not just effectively but safely and so we're going to spend some time talking about that I am do have some disclosures I'm not only on the speaker Bureau for precision analytical but a few other speakers bureaus there you see there I'm co-owner uh and director of research and education for Banica and on the scientific advisory Boards of several several companies so when I was uh thinking about this presentation uh just these this little mini flood of medical myths came to my mind from my childhood some of them the first one definitely from my childhood I always remember my mother saying you gota can't go in swimming until you haven't been eating for an hour uh and so that you don't cramp and you don't die right so this turns out is not true uh this myth is false and you can consume a normaliz meal right before swimming and it will not cause cramping now there might be some caution if someone is oving uh they tend to feel a little more tired and you know groggy so maybe avoid swimming right after a super heavy meal but other than that this myth this uh statement is a myth and then uh there's this one I remember this from my teenage years as well uh she told me m uh that I shouldn't be so eager to start shaving my legs because the the hair that grows back is going to grow thicker and darker well that also is false uh but because the hair is newer it may not have been bleached out yet by the Sun and so it does appear thicker and darker but it is not really thicker and darker and then there's this one I still kind of I think have this one in my head and I'm mindful of it when I'm out camping and swimming and such so the myth is if you go outside with wet hair in a cold day you'll catch a cold false we know colds are caused by viruses you can't get a virus just from being outside in the cold uh we may feel sick if we're outside all day in the cold or rain you know runny nose chills fatigue but it's not because we have a virus uh but those symptoms are the same or similar symptoms to having a cold and I think that's why that myth got some traction okay what about cracking your knuckles causes arthritis not true 30-year studies showed this is not the case but if we do crack our Knuckles it can lessen our grip strength over time because of just repeated stretching of those tendons so that's another fun one here's here's my uh here's one that lingers on today and patient after patient uh says I drink eight glasses a day um so that's the longstanding generation standing I would say that we need to drink eight glasses of water every day in order to stay hydrated Well turns out that is also a myth and is not true not you know obviously being dehydrated isn't great um but the idea that we need to drink eight glasses has no real scientific backing uh so I do not advise people to drink eight glasses of water a day in fact uh many women would especially postmenopausal women with nocturia uh you can improve their nocturia by decreasing their water intake to something a bit more reasonable but then there are let's move on now that we've covered our childhood and at least um let's talk about these menopausal hormone therapy myths and MHT does stand for menopause hormone therapy that's a fairly you know more recent term and terminology that's that's being used rather than ER r t or HRT um so these are to me is the top myths that I uh run into you might say with patients and with colleagues and with students and such so this is these are the ones that I wanted to Target today is that estrogen therapy causes breast cancer that estrogen and progestogens significantly increase the risk of breast cancer that screening mammograms must be done prior is prescribing menopausal hormone therapy that women should stop taking hor menopausal hormones at the age of 60 or by the age of 60 uh another myth postmenopausal women can safely initiate or start taking systemic menopausal hormone therapy at any age and then last but not least progesterone cream is an adequate delivery method to provide endometrial protection in women who are taking systemic estrogen all those are this and now we get to the details uh I wanted to have these next two slides really show you the the prim I I would consider essential studies that have been done on this issue T not all within some precede the last 20 years but a majority of it is the last 20 years um so these are Landmark studies on menopausal hormone therapy important essential studies to be familiar with so you could just look up any of these v stands for um Venus anthrop embolism or Strokes or clots um and and that should be VTE by the way uh didn't catch that one typo that was why I was stumbling there but the Pepe trial the keep study the million women study the all the the many now dozens of wh spin-offs from the Whi study uh all these are uh you could look them up and get cliff notes and uh if you don't want to read each and every study in detail you can often read the the uh the introduction the results the discussion and you're in in good shape a second whole slide on key Landmark studies uh on this topic uh the Rejoice study replenish all these are in the last few years I'm going to talk about a few of these in uh relationship to our myths so hopefully uh giving you the names of these code names of these studies will help you enhance your education even more so and then I highly recommend uh some of these position statements and consensus guidelines ultimately if you could read all of them great but we have some now that are moving forward into more recent years rather than back to 2015 but for example the latest um position statement on menopausal hormone therapy from the North American menopause Society was published in 2022 and that is a excellent excellent document of the review of the literature with citations and in a sort of a cliffnote version um but breaking it down you know hormone therapy and breast cancer risk hormone therapy and metrial cancer risk hormone therapy and cardiovascular risk hormone therapy and osteoporosis I shouldn't just say risk you know benefits and risk and it really dials it in um there also the most recent publication was their position statement on non hormonal therapy for per menopausal and menopausal women this is you know you talking about ssris Gabapentin uh Etc and um uh some of the newest drugs uh that are like the viza and Botanicals and nutrients and that's certainly not the document you want to rely on for your education on Botanicals neutrals and nutrition as it relates to menopause symptoms but it's they certainly do highlight the the what they consider the highest quality studies that have been done and it's and but it's limiting it's if you just went by that it would be very limiting in terms of Botanicals um but they also have an excellent position statement that's not too old on genital urinary syndrome of menopause and osteoporosis so I highly recommend um these position statements and then the consensus guidelines on testosterone is also extremely good so before we get to the menopause hormon Miss I just thought it would be good to start with some of the symptom issue myths um and the myth is really that you have to have basom motor symptoms to be diagnosed as per menopausal vasomotor symptoms are hot flashes and or night sweats so that is a myth that is not the determining diagnostic criteria for par menopause the diagnostic criteria is this it is an IL defined period of time individual for each woman that surr rounds the final years of a woman's reproductive life it begins with the first onset of the menstrual irregularity which could be very subtle by the way and we'll talk a bit more about that and then ends per menopause ends after one year of 12 consecutive months of No period uh at the age appropriate time obviously if you have 12 consecutive months at age 25 um there might be in other words there are other causes of secondary amenorrhea there are two stages to the per menopause or menopause transition there's the early transition phase where the Cycles are mostly regular with a few interruptions and that's the subtle part I was talking about and then the late transition part of per manopause where amena becomes more prolonged and then and last for at least 60 days that's the late perimenopause transition up to the final menstrual period and then like I said 12 consecutive months without a period and an FSH of greater than 25 this is something called the straw data and this is just I want to show this slide just to highlight you can see this minus two this is the early uh menopause transition or par menopause I was talking about and then here's the late uh um phase of perimenopause the hormone markers are not reliable and Par menopause what I mean by that they're reliable for that day but they're not reli they they are very changeable very much influx and uh it's very difficult to conclude uh useful prescribing information from uh those kind of test results that are so variable uh and then the late per menopausal phase you know might last one to three years in total that transition phase could be kind of four to seven years is think think about that which may or may not include any other symptoms other than a change in the menstrual cycle that's the defining criteria although in the late perimenopause vasomotor symptoms are likely but in the first two years of postmenopause that's when vasomotor symptoms are most likely but the average duration of vasomotor symptoms uh and according to a study that was done not too long ago is uh 7 years and not everybody's happy to hear that number okay let's talk about some also just just to make sure we're all on the same page you might say what are symptoms of per of per menopause and menopause there are classic ones these are the classic symptoms whether you're Perry or postmenopausal a change in the men cycle is going to happen to everybody one way or another and obviously it can happen by removing the uterus but removing the uterus is not menopause removing the ovaries is surgical menopause um um or you know obviously having a hormone IUD is going to alter the menstrual cycle pattern taking or hormonal birth control pills with estrogen and progestins is going to be CL in the picture of when is this woman in menopause you have with the hormone IUD and birth control pills you have to figure you have to learn how to diagnose menopause uh so when she no longer needs contraception if that's why she's using those for example a marina IUD you can check an FSH level at any time and get the number that you're looking for and you want above 30 two months in a row one month apart to determine okay yeah that hormone IUD is no longer needed if she's on birth control pills you have her and and if she hope and you need to have her be off the pill for six or seven days and on the sixth or seventh day you take her FSH and it again has to be above 30 two months in a row and we're trying to cover our bases here that's why we don't use above 25 we're trying to cover our bases uh so we don't risk someone who getting pregnant if they're having a sex life that could lead to that so classic symptoms change in the menstrual cycle vasomotor symptoms Volvo vaginal symptoms that that can include itching dryness burning disper peronia um sleep disturbances so common in all sizes and shapes and psychological symptoms are more come in per menopause you get an either a recurrence of depression an xiety is uh more likely a or a new onset or a worsening any of those three things can happen uh in per menopause a little bit more likely than than before or in than in postmenopause there's no one universal symptom or syndrome it's very very individual it's a really uh beautiful example of treat the individual know the individual there are and I those classic symptoms are really in the US because there are things that look a little bit differently elsewhere um which is interesting if you look around the world in South Africa for example women are pretty unhappy with their mood disorders their sexual dysfunction and their joint and muscle pains um but in um vasomotor symptoms and joint and muscle pains are particularly highly reported uh in Australia Vaso motor symptoms and genital urinary dysfunction is the most common in the US it's vasomotor symptoms and body aches and pains remember that little tidbit in Asia more depressive disorders Europe sleep in depressive disorders so uh good to know about what happens in women who are living in other places or perhaps coming from other places but we don't just have our classic symptoms we have a laundry list of things that can occur they're not enough necessarily occurring in a problematic way I mean every woman is going to have skin changes Dental changes um likely changes in body weight uh but not every woman is going to have aching joints or palpitations or brain fog or fatigue or sexual dysfunction but there are changes that are just actually occurring because of that decline in estrogen in particular um even and I don't even have it on here I don't think but the voice can get a little deeper a little more ho voice horse because of decline in estrogen so there's all these other changes to be aware of and symptoms to be aware of that need perhaps if depending on the degree of bothersomeness it is for her we our treatment strategies need to include addressing those symptoms as well okay now let's get to the the main event which is what are the main myth about menopausal hormone therapy and we got to start with breast cancer and the two myths that I'd like to address are here is that number one estrogen causes breast cancer and number two estrogens and progestin significantly increase the risk of breast cancer so those are both myths and I want to I'll make my case with a few key uh studies and scientific evidence let's start with uh one in eight breast cancer effects about one in eight women in the United States so it's important to have an accurate understanding of the potential effect of menopausal hormone therapy on breast cancer risk and we need to understand the differences between estrogen alone estrogen and a progestogen the difference between uh an estrogen plus bioidentical progesterone versus estrogen plus a progestin which is synthetic because they have a little bit different effect on breast tissues and I'm going to highlight some research on that the different types of formulations uh timing of initiation is more related to other issues not so much breast cancer but duration is definitely related to the slight breast cancer risk and then all kinds of Select patient characteristics play a role in breast cancer risk um and they play the most dominant role and we'll come back to that as well okay in the original Whi women's health iniu study published in 2002 to continuous combin Prem and pra that's what those two two CE and MPA mean resulted in an increased risk of breast cancer but it was a rare absolute risk and so let's go into that a little bit what that really meant was nine additional breast cancer cases per 10,000 women per year and the increase in breast cancer risk was found after 5.6 years when they stopped the study but it started to occur kind of in the late part of year three so by year four there was this ever so slight increase but this was considered uh nominal in statistical terms and it was actually nonsignificant when adjustments were made for multiple risk factors but this was what the all the Holo was about and even they because they had a cut off I believe it was 1.28 in their uh in their setup of the study and their safety analysis and once it exceeded 1.28 they stopped the study and it got to 1.29 but is not actually considered uh statistically significant in the big picture of all their risk factor the risk like I said appears to start somewhere late in year three of using Prem and Pera and it remained elevated at 20 years post intervention in the post-publication analysis that increased instance of breast cancer this is a key point was limited to women who had prior exposure to menopausal hormone therapy whereas women without prior exposure these are menopausal hormone therapy naive women breast cancer instance was not significantly affected by premin Vera in this same time frame for a total of 20 years the attributable risk of breast can since the study the tributal risk of breast cancer in the wh is not only not quite nine additional per 10,000 but the number I like to use in my speaking and with my patients is it is that number is less than one additional case of breast cancer per 1,000 users annually so if they're on menopausal hormone therapy for four years or longer this uh let's say estrogen and progestogen of any kind for the moment um the worst we could say is one not quite one more case per 1,000 women annually and this risk is slightly greater get this than that observed with one daily glass of wine but it's less than two daily glasses of wine wi and similar to the risk reported with obesity and low exercise so put it in perspective and it's sort of like pow and not quite one out of a thousand even more pow so this is the original data of the 2002 e+ P the premum plus pra and you see that 3.8 and the placebo 3.0 this is the number I'm talking about not that calcul us to not quite one woman out of a thousand um a slight increased risk of clot Strokes heart uh disease those were all in the increase and the worst was claws uh so uh dvts and remember the prescription that was given was oral estrogen and uh oral progestin there was actually reduce uh and there was a reduced hip fractures and colon cancers in this group so we now have some benefits to cogitate on now what about the estrogen only so when they stopped the original whhi at 5.6 years they continued the estrogen only arm in women who did not have a uterus because that's typically the prescription if they need estrogen and they don't have a uterus they don't need to take the progestogen so now you see uh let's just track down to breast cancer because that's what we're talking about the less than 1.0 Haz a ratio this means that take the women on estrogen only had a lower risk of breast cancer than women who did not take estrogen only again maybe a pow to you again benefits to Bone um not quite uh a benefit on colar rectal cancer but really not an increased risk and really no increased mortality overall so these are data points estrogen only and the previous slide estrogen and the progestin in the original Whi so now let's look at uh make our case a little bit more detailed about estrogen only so in the Whi observational study this study directly compared different estrogen Doses formulations and route of delivery of the estrogen among women with a Hy who estrogen only and women who have hysterectomy in relations to invasive breast cancer incidents this was a large multi- Center prospective cohort they had 40 different sites around the United States and the results after 8.2 years followup indicate that invasive breast cancer risk did not differ in women with a hysterectomy using estrogen alone when directly comparing different estrogen doses formulations or deliveries so whether it was u a patch or oral it was the same lower than average doses so average dose of premine is 625 which is the same as an average dose of oral biodental estrad 1.0 milligrams which is the same as biodental estrad patches average dose 0.05 milligram patch so less than those average doses was associated with a similar risk when compared to the conventional dose so lower or the same dose didn't seem to really matter transdermal estradi May confer a slightly less risk of breast cancer than oral but the sample size was too small so and not powered so we can't really uh really assert anything about that uh we can assert things about transdermal estrad for Less stroke less DBT less ding on triglycerides less ding on liver enzymes Etc but in terms of breast cancer risk not really like I said so the oral maybe there was a trend a little higher than the transal but it was the sample size was too small so I wouldn't uh really take stock of that I would not assert that okay the in jamama 2020 we have now 20 years and even a little more than 20 years of data analysis and medium and this again was analysis of the estrogen only arm of the Women's Health Initiative estrogen alone They concluded after 20 years of followup reduced incidents of and mortality from invasive breast cancer while combining the estrogen and the progestin elevated the incidence slightly right less than one more woman out of a thousand but did not increase mortality from breast cancer so estrogen alone no increase after 20 years of followup estrogen and progestin confirmed that slight increase but not increase IM mortality love that and then but to be fair I wanted to just say yes there are some other data points the first bullet point there is a repeat of what we' already said from jamama 2020 there are smaller and that was a randomized controlled trial the Whi there are some smaller randomized controll trials again showing estrogen only reduced risk the nurse's health study which is observational estrogen only uh times 5 to n years no in of use no increased risk longer like 15 years or more observational data there is a slight Trend towards increase even with estrogen only in the collaborative Group which was fairly recent in the last five years uh five to nine years of estrogen only again very very slight increase risk and the the million women study is kind of an out outlier and it's but it's a survey study only uh but there was that increased breast cancer mortality in that reported study so but our best data the randomized clinical trials reduced risk with estrogen only that doesn't mean we should go out of our way to give women estrogen to to reduce their risk it's the matter of if we're having our compelling reasons and our analysis and criteria for prescribing uh estrogen only we can be pretty comfortable in assuring her hey this doesn't really seem to increase your risk of breast cancer at all um again this is a repeat uh uh just want to emphasize uh this study the jam study of 2020 after 20 years um estrogen only lower risk and lower breast cancer mortality and the rest is a repeat okay so the Whi summary to date as it relates to breast cancer Premarin alone significantly reduces breast cancer risk and cancer mortality so this is the whhi data the premine and the pra when initiated in menopausal hormone therapy naive women it does not increase breast cancer risk and it does not increase breast cancer mortality even in women with a family history of breast cancer and we'll swing back to that so even if an estimated increase risk of breast cancer is accepted that slight increased risk with estrogen and progestin at four years or more one more not quite one more woman out of a thousand um that is a very very very very low risk I'm not you know trying to dismiss one woman but that it really puts it in perspective I hope the worst you could say again is this non not really statistically significant very very slight increase risk not even one more woman out of thousand I know I'm being repetitive but I'm trying to make some points and again put things in perspective uh I love that stuff about the alcohol obesity and inactivity um so I think all this is repeat except to say vaginal estrogens if you're prescribing vaginal estrogen for the purpose of GSM you know dryness burning itching leakage overactive bladder stress incontinence urinary incontinence dunia those are tiny doses they're the general maintenance dose is twice a week unless you're using the lowd dose ring that LE stays in for three months there is no incre this has nothing to do with breast cancer nothing to do with heart disease no benefit to Bones no benefit or harm to heart no benefit or harm in terms of stroke or DVT it's a local phenomenon it's like chapstick so let's look towards the bottom here there is no additive effect with menopausal hormone therapy with age or elevated personal breast cancer risk factors so if she has a breast cancer risk leaving genetic testing aside for a moment let's say just a family history of breast cancer or or obesity she has her risk of breast cancer and we are not there's not we're not adding to that by her going on menopausal hormone therapy and a lot of women just relax with that reassurance she's talking to me we're talking about her family history oh yeah her mother had breast cancer or her sister had breast cancer uh and we don't know anything about Brea testing there is no reason for her to not take menopausal hormone therapy if she has the indications to do so we are not adding to her risk very important concept um so let's talk though about uh the the genetic testing of it menopausal hormone therapy does not further increase the relative risk of breast cancer in women with the family history like I just said but also in it does not increase the risk if she's had her ovaries removed bilateral Singo ectomy because of a Brea one or two mutation if she's had has Brea one and or two if she has her ovaries removed menopausal hormone therapy is not contraindicated for her but you notice I said ovaries remove um what about if the genetic risk and she's less than 50 no increased risk of Young on breast cancer patient care of breast cancer with the use of an estrogen and a progestogen uh and estrogen alone actually reduce diagnosis of young onset breast cancer uh in people with a genetic risk so hopefully those highlight and clarify some things for you as well let's look at the role of progestogens and make some distinctions uh some but not all observational data suggest that bioidentical progesterone or oral micronized progesterone may have less effect on breast cancer risk versus that slight increase with the progestin we do need randomized control trials to confirm this and I am going to come back to some important data on some French studies and a recent one from the United Kingdom on this distinction between biodental progesterone and progestin on the breast but again even a progestin with an estrogen only ever so slightly after four at four years and more more not quite one more woman out of a thousand and estrogen alone not at all why not try try to take away the one out of a thousand and we might might be able to do that with progesterone with our estrogen versus a progestin and again I'll come back to that at the end clinical data from observation studies such as the collaborative group study report no difference in effects of Premarin versus estradi on Ault breast cancer growth it's the same there's no real difference both oral and trans dermal estrogens appear to have similar effects on the number of breast cancer diagnosed remember we did say earlier the trans dermal estra dial look there was a perhaps Trend uh in the in the in the favorable department but it was too small in numbers it wasn't statistically powered adequately and again lowd dose vaginal estrogens no effect on breast cancer risk um and it's considered safe in breast canc patients again we'll come back to that a little bit so sometimes uh there is this myth of that you need to do a screening mamogram before you start menopausal hormone therapy there is no guideline or standard of care that says so so that is a myth however might you make a judgment call and feel more comfortable doing that you might more importantly she might so I'm not arguing that uh perhaps perhaps is prudent um but it's not required it's not standard of care perhaps you would want to in the previous one to two years before initiating we'll talk a little bit about different recommendations uh for screening um and then there's also been a myth about oh if you you should maybe stop hormone therapy for two months before the screening mamogram but um because hormone therapy can incre inre you know breast density but brief hormone therapy suspension in this read study was associated with small changes in breast density but did not affect recall rates and there was no evidence to support this myth so I just kind of threw up this slide you might want to print this one out if you don't have it already just the I like to refer to it with patients sometimes just to share with them there are different guidelines for average risk women and that's a different guideline for women who are above average risk but average risk AOG now you see their guidelines the US preventive Services Task Force just updated their they kind of were the ones that threw a wrench in the system a few years ago but now they're back to uh every two years beginning at age 40 uh World health organizations every two years starting at age 40 American Cancer Society is even a little bit different depending on those three different age groups there again these are all guidelines for average risk women um and it's can be a it is confusing for our patients it is confusing for us as well to keep up to date on this um but the latest is sort of most of the consistency is around starting at 40 and average or swiming every two years okay let's go to our next myth and about duration women who take menopausal hormones should stop by the age of 60 this is a myth there is no guideline or standard of care about that but I can't tell you how often women are told that and deprived of hormones the age of 60 has something to do with initiation and we'll come back to that so this is a brand new there's lots of of things to read on this topic but this is really quite new uh when did this this is like 2024 right around April early April this came out and it was made a big impression on me because it really kind of punctuated the important points so the the objective of this study was can menopausal hormone therapy be continued after age 65 that was what this one was about not 60 but after age 65 and here's what they found out estrogen monotherapy Beyond age 65 now these are women who were already on it we're not talking about initiation we're talking about women who were on it and should they stop or not at age 65 and Beyond estrogen monotherapy Beyond age 65 was associated with significant risk reductions in mortality breast cancer again lung cancer colar rectal cancer even uh CHF and even uh VTE aib acute Mis and dementia next bullet point estrogen and a progestogen combo therapy whether it was estrogen and a progestin synthetic or estrogen and bioidentical progesterone yes there was this increased risk of breast cancer by these same small numbers even tinier than before but such risk can be mitigated using lower dose transdermal that that's a new finding or a vaginal estrogen and a progestin so a vaginal estrogen for systemic purposes would be like the fem ring the E string or estring is low dose for just GSM but the femring comes in two different doses is a way to deliver it systemically but just through the vagina and then estrogen plus progestins exhibited significant risk reduction in endometrial cancer absolutely you have lower risk of endometrial cancer by staying on menopause the right doses of menopausal hormone e+ p versus none at all uh reduced risk reductions ovarian cancer esemicolonr a day of bioidentical progesterone with average doses of systemic estrogen or less than average that is considered safe for endometrial prot protection there's only two doses of bioidentical progesterone that are proven safe it's either 100 every day or 212 days out of the month and by the way if I go above average doses I do bump that up uh to 200 every day not just 100 every day but bio but bioidentical progesterone in this study plus the estrogen the only risk reduction was in CHF it wasn't in endometrial cancer does doesn't mean it caused it uh but it didn't wasn't associate with reduced risk compared to PBO conclusions among senior Medicare women menopausal hormone therapy continued use Beyond AG 65 varies by type dose type roots and strengths risk reductions appear to be greater with risk reduction is better with lower rather than medium or high higher Doses and then again the vaginal or transdermal rather than oral and a little bit this one called out a little bit better with the estrad than the Premarin when it comes to breast that is not confirmed in randomized controlled trials okay next myth any delivery route of estrogen is safe at any age not true any delivery rad is safe at any age no after the age of 65 you need to switch if she is on oral estrogen you need to switch to transdermal estrogen you don't doesn't have anything to do with the progestogen oral transdermal but oral increases uh clotting factors and and with age we don't metabolize hormones as well it's there's the phaco kinetics are different our risk because of plaque and uh uh stiffness our risk for uh dbts and strokes goes up so you got to switch to trans dermal estrogen and then we're always if we're whenever we uh have a woman on menopausal hormone therapy at any age minimally annually we're going to weigh what are the benefits and what are the risks for her but this is especially important as she gets older why are we doing this is it quality of life issue is it reducing in the risk of an illness for which you're at increased risk for and estrogen does that in certain doses like osteoporosis or are we treating something like osteoporosis that's the sort of the third bucket um by the way uh average or less I'm sorry h h less than average doses of systemic estrogen can slow bone loss but only average Doses and above reduce fracture rate so keep that in mind so if she has no contraindications and contraindications evolve and change over time so that's part of the annual update but are we why are we giving it to her if it's a quality of life issue the only way we know if she still needs it is if she has gone off and on her own and said oh I went off for two weeks because I didn't I forgot it on my vacation and my hot flashes came back miserably she's not going to be wanting to go off um but the only way you know if she still needs menopausal hormone therapy to resolve a quality life issue is if you stop there's no test to predict that or to know that or to understand that it's an experiment and she has to decide does she want to take that experiment or not and if there's a contraindication then we have to really say yeah we do need that experiment because you had a DBT last 6 months ago and uh and now we need to revisit this whole thing or your triglycerides are way up or any or now you have type two diabetes any number of things change so what's the quality of life issue what's the disease prevention issue and this get there's a lot of nuances here if she has ovaries or not and what age she was menopausal or not a lot of things here determine risk for cardiovascular disease osteoporosis and Alzheimer's dementia so that bucket is important to really become familiar with what are the risk factors for those three areas and then as I said what can uh what disease condition pathological change can systemic estrogen actually treat possibly osteoarthritis definitely osteoporosis in certain um doses okay myth uh post menop this is about initiation postmenopausal women no matter their age could start systemic menopausal hormone therapy by the way and I'll probably say it again she can start vulvo vaginal estrogen for the purpose of GSM or atrophic changes at any age this myth does not have to do with that this has to do with systemic you cannot start menopausal hormone therapy safely at any age that is myth and here's uh some data points um the the therapeutic window for initiating menopausal hormone therapy occurs shortly after menopause at which time the benefits of initiating hormones May outweigh the risk for many many many postmenopausal women and that therapeutic window is a period of less than 10 years from her last menstrual period in which or before the age of 60 either one is the therapeutic window and that is the ideal time to prevent eurogen atrophy dementia possibly cardiovascular disease although that's not an FDA approved or standard of care guideline for prescribing um and but for the prevention and treatment of bone loss the window is better in the first three to six years after the last menstrual period so women lose about 2% per year in the first four four years four to five years and if uh she had a family history uh of osteoporosis especially a hip fracture and if she has the quality of life at bucket is super bothersome symptoms um systemic estrogen could be a good strategy for her but we want to ideally start in the first three to six years but the numbers you should really keep especially keep in mind is the rule of thumb is is don't initiate systemic menopausal hormone therapy if she's P 10 years after last menstrual period or after age 60 because doing so increases the risk of DBT stroke cardiovascular disease and Alzheimer's dementia nothing to do with lowd dose vaginal but systemic now might there be a scenario where you have not solved her quality of life bucket by other means and she has severe vasomotor symptoms especially at night they're keeping her up she's now fatigued she's depressed she can't think straight other things have been tried and is not working and she maybe you would initiate systemic menopausal hormone therapy for her severe vasomotor symptoms because all the herbs the non- hormonal therapies nothing has worked and she's done trying I mean because there's probably always something else to try but she's done trying um so but that's the exception it's not all in this menopause moment that we're having in 2024 and you're getting this influx of inquiries and women reading something and they're coming in and they're they're 63 and they want to start menopausal hormone therapy because they read this this and that well our job is going to basically evaluate assess but likely discourage and tell her actually for you it's there's potential for harm that outweighs the potential for benefit and there are exceptions okay uh I think the last main myth is that progesterone cream is an adequate delivery method to provide endometrial protection in women taking systemic estrogen this is a myth and I know some of you might be getting squirmy in your seats but uh let me make the case there are very specific doses forms and deliveries of progestogens that are accepted methods of providing adequate endometrial protection based on adequate studies now I have only found five studies to date that have been identified investigating the impact of biodental progesterone on the uterine lining delivered as transdermal like a cream or a gel five all but one study were randomized controlled trials some of which had a placebo or a progestin as a comparator so hopefully you can see the problem already if you're looking ahead at the slides the studies were too small too short to conclude safety uh the estrogens were applied either orally or transdermally and the dosing R were ranges were from highend of normal to moderate dosing categories of the estrogen the transdermal progesterone creams were applied either sequentially or continuously they ranged from 16 milligrams even up to 64 some of you might be at thinking oh 40 milligrams a day we'll come back to that in one study trans vaginal ultrasound showed a significant increase in endometrial thickness that means she's going to have a biopsy all five studies had endometrial biopsies pre- and post treatment two studies indicated an adequate progesterone opposing effect by the same lead author but it was only 28 days in duration who cares 28 days the dose of progesterone was at 15 milligrams bid or 40 B in those two studies that was one problem then uh we have there was a study that was six months in duration and that was the 40 milligrams a day transdermal and this study did have 19% of the women acquired a proliferate endometrium granted there was no hyperplasia on biopsy but the remaining three studies did not have an adequate progesterone cream opposing effect meaning there was proliferate of endometrium there were two cases of complex hyperplasia there was no cancer yet one of the negative studies the one with complex hyperplasia was only 48 weeks duration two of the negative studies were 12 weeks duration so in general I'll come back to these studies are too short too few there's concerning cases of endometrial thicking of hyperplasia and even complex hyperplasia even in these short durations that were done keep in mind that endometrium stimulated by a systemic estrogen with inadequate progestogens in women with the uterus tend to get thicker and abnormal changes over time more proliferate more hyperplasia more atypia more cancers over time these were only 12 weeks 28 days 6 months and they were small numbers so even when you read this study of which is often the one that is cited as the rationale for using progesterone cream 20 milligrams twice a day with a systemic estrogen these were 26 women were in each wor of the 52 post- treatment biopsies 40 had the atrophic and demetrium 12 proliferative there was no evidence of hyperplasia but but there was and there was spotting but the problem again too small way too short we need to study this issue like five years 10 years so in this dose the dose that's often referred to it's still not providing safe data on using it with a systemic estrogen for endometrial protection so don't do it is my strong advice if you want to do no harm so these are the doses of progestogens that are proven endometrial protection so here we have orom micronized progesterone either 200 milligram cycling it or with the estrogen every day or you can do it 100 or orally every day either of those two regimens is considered safe for average or less than average doses of systemic estrogen if you she doesn't tolerate this this because of nuisance effects from the oral micronized progesterone you could have a progesterone gel there's a big Pharma version you could have it compounded don't rely on just a capsule in the vagina that has not been proven so you'd either do 45 milligrams more than 10 days a month or 100 milligrams every other day is what that should that's a little confusing but every other day those these are and then you see others there that are proven doses the synthetics if it's continuous you can stay in this range if it's sick like you can go in that range okay there are other myths uh women with the history of breast cancer cannot use vulvo vaginal estrogen that should say GSM sorry we missed that typo and gestin and progesterone have the same effect on the breast so just uh kind of go through this a little more quickly I'm going to have you look these are the this is the position statement 2020 from the North American menopause society and their guidelines for genital urinary syndrome of menopause they encourage us to try lubricants with sexual activity and moisturizers three times a week that's the sort of first line therapies but uh moderate to severe GSM and non-responders to the lubricants and the moisturizers there's many options there's many lowd dose big Pharma vaginal estrogens there's all kinds of compounded vaginal estrogen options estriol estradi there's vaginal DHEA big PHA and compounded there's this newer drug emine um you can get a a genital effect by giving a systemic estrogen uh when she also has systemic symptoms so that might enough of that estrogen might find its way down to that tissue you might need both for some people um if she has a history of breast or endometrial cancer uh you might want to talk to oncologist but this is considered uh safe but first line recommendations and they have a separate position statement for breast cancer patients first line recommendations are again the moisturizer three times a week and then lubrica as needed but it lowd dose vaginal estrogen is generally considered safe in breast cancer and endometrial cancer patients it's better to use a ring or a tablet or suppository than a cream because a cream gets a tiny bit of systemic bump and estrogen if you're using just lowd dose Volvo vaginal estrogen uh then you don't at these low Doses and in two times a week you don't need um a systemic progestogen if she has a uterus any time someone has a post-menopausal spot or bleed obviously that requires an evaluation so here's the the there are three French studies that I observational studies that go to the point that biodental progesterone does not increase the risk of breast cancer and versus the progestin that only slight risk so these are kind of you can Ponder and look at but there are Bonafide three observational French studies that says the risk of breast cancer is slightly increased with the estrogen and progestin but not when it's the estrogen and progesterone the second French study estrogen uh again this is the uh this if you look at the E plus progesterone 1.0 is no increased risk now this observational study did have that ever so slight increase which is not which is out outside of our now 20 years of data from thehi that estrogen loone does not increase the risk of breast cancer but then this observational study very very slight but see that progestins more so at least well not that proest in but the Northend drone um mroy progesterone acetate this is a little higher than what we see in the Whi and most of the other data but the point in the fren study number two estrogen alone I mean estrogen plus Biden progesterone did not increase the risk of breast cancer this is a third French study also showing that estrogen plus progesterone biodental progesterone did not increase the risk of breast cancer that third bullet point there and then this is the brand new UK study in 20122 uh this was a populationbased case control study and and uh 50 women aged 50 years or older and it was of a course of almost 20 years um compared with women who never use menopausal hormone therapy its use was associated with a very slight increased risk of breast cancer compared with never users estrogen alone were not associated with breast cancer uh whether it was biod dentical or Premarin uh progestogen appear to be differently Associated meaning the bioidentical progesterone lower risk or at least not increase because it's not more than 1.0 and here we have that classic kind of 1.28 right around the same exact number as the Whi so Three French studies observational and one uh populationbased control study recently out of the UK say bodal progesterone with an estrogen does not seem to increase the risk at all of breast cancer and tracking back even if it was a progestin only not quite one more woman out of a thousand so we have come to the end of our time together I think we succeeded in about a 60-minute presentation few um and here's some resources if you want to access some things uh and I thank uh Precision analytical uh and their team a fabulous team to work with really appreciate the collaboration and the uh the trust thank you so much and hopefully everybody now understand the main myths and how we can proceed smartly wisely safely and effectively thank you for joining us today watch your inboxes tomorrow for a link to the recording and to access the resources we shared today you can learn more about the res search behind the Dutch test at Dutch test.com resesarch and make sure to be to visit the become a provider tab Dutch test.com to register 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