Decoding Your Hormone Support Questions with Siobhan O’Connor

00:00:17
Speaker 1: Pushkin.
00:00:24
Speaker 2: This show is not a substitute for professional medical advice, diagnosis, or treatment. It is for informational purposes. Please consult your healthcare professional with any medical questions. Also in this show, we use women as shorthand for people with XX chromosomes. We understand sex and gender are more complex and acknowledge the experiences we describe reach beyond that word.
00:00:54
Speaker 1: Welcome to Decoding Women's Health. I'm doctor Elizabeth Pointer Today on the show. I'm joined by my colleague Shavon O'Connor. She's a long term health and science journalist who works closely with me on this show. She's also the chief content officer at Atria. We're very excited to be here and thrilled that many listeners reached out for this episode with super smart questions related to menlife hormone support what most people refer to as HRT, but it is also now called in our modern women's health world menopausal hormone therapy or MHT. We received dozens of questions. We want to answer as many of them as possible, so let's get started, get into it. Excellent, Welcome to the show. Cheven, great to see, so happy to have you in person here in the cocoon of the recording studio.
00:01:46
Speaker 3: Thank you.
00:01:47
Speaker 1: So, I think we're going to start a little bit about the different types of HRT and the most effective forms of HRT and some of the differences between the different forms. This is a question from a listener who writes, I just found your podcast and absolutely love it, and then she goes on to ask which BHRT is most effective transdermal creams gels or vaginal creams answerts or oral pills.
00:02:09
Speaker 3: Okay, first, before we get into it, can you explain or define b HRT.
00:02:14
Speaker 1: BHRT usually refers to bioidentical hormone replacement therapy, which is largely a marketing term. These are non FDA approved preparations. Indeed, the hormones that you get that are FDA approved, many of them are bioidentical, and indeed the ones that we certainly recommend now or all bioidentical. All of the hormones are really produced, or all of the estrogens are really produced from either of some plant based sources or chemically synthesized in the laboratory. They're no more safer, They're really not different. All of our modern hormone support now is biodentical. The estradial is biodentical. The progesterone that we recommend now is bioidentical, and that's relatively new over the past like twenty five thirty years, actually interesting bioidentical.
00:02:54
Speaker 3: So if you hear someone sort of hawking bioidentical hormones, there is not a huge meaningful difference between now.
00:03:00
Speaker 1: I mean only that the bioidentical the compounded hormones are actually not FDA approved, right, so there's more consistency and the dosine and the absorption with an FDA proved medication because they go through testing, pharmacokinetic testing, so more reliable in their absorption. It would say that we need to look at how we monitor levels and such with the compounded hormones closely Interesting.
00:03:24
Speaker 3: Now, I know we're going to get into some of the benefits of menopause hormone support. I do have a question though that I think a lot of people are going to be wondering. So when it comes to estrogen, I know that you've said that topical application, either gels or patches, are the preferred method today, the safest method today. When we talk about the systemic benefits heart health, brain health, some of which we're going to get into today. Is it the same as if you use the vaginal application of topical estrogen.
00:03:54
Speaker 1: No, totally different. Our vaginal preparations are low dose and they really don't get systemic absorption. If they get a systemic absorption is like minute, and it's many times when you first start the hormone as the tissue is getting healthier, So you don't get what we call systemic effects or blood effects from the topical estrogens. And that allows women who may have a history of breast cancer or a recent history of breast cancer to get topical estrogens for the vagina. So systemic means that the estrogen is through the blood. Local means it's just in the vagina or where it's being delivered. The THEM ring is a great example of one where we actually do provide a systemic level of hormone through the vagina. However, it's a much higher dose. And it's important to understand too, just because you're on systemic hormones doesn't mean that your vaginal health is actually protected because our systemic hormones are many times dosed to a level that they don't get enough to penetrate the vaginal epithelium to get health of the vagina. So many people will come to us asking us, well, I'm on a systemic estrogen. It's going to be too much if I use this vaginal estrogen and actually that it could be further from the truth. You can be on both and many times you need both, and if you have had a history of breast cancer, the low dust vaginal estrogens are super safe actually and been demonstrated in many studies to be safe.
00:05:09
Speaker 3: Fantastic, All right. Next question is from a fifty three year old woman who writes, I'm taking HRT. I started taking these when I was still perimenopausal about two and a half years ago after working with a naturopath. My new male doctor doesn't seem to know much about HRT, welcome to the club, and hasn't changed my prescriptions. My question is do the HRT medications differ for perry and menopausal women totally different?
00:05:32
Speaker 1: So, perimenopausal transition are the years leading up to menopause, which can start anywhere between thirty five and early forties, basically because there are those eight to ten years before menopause actually starts. So during that transition, our ovaries are starting to not work as well, and so two things happen. One, estrogen can become very erratic, meaning swinging up and down. And I actually liken it too. You take a mirror and put it on the floor and it shatters and it's all shattered glass, And so it becomes Estrogen becomes a little bit unpredictable during perimenopause. For many people, this is the case. Some people estrogen just tapers down. But really, I think it's much more common to see these erratic, wild fluctuations in.
00:06:12
Speaker 3: Estrogen, not like a slow decline.
00:06:14
Speaker 1: No, it would be so much easier to manage if it were a slow decline, but it's not. And the other hormone though that changes, is actually progesterone, and progesterone does have a slow decline, And so as we transition through perimenopause into menopause, we naturally have lower progesterone production in the second half of our cycles. So many times in perimenopause, in those earlier perimenopausal transition years, we'll start with progesterone alone because many times the symptoms are I can't sleep, or my mood is off with anxiety, and that's really can be remedied quite nicely with progesterone, so that our initial hormone that we usually use is progesterone. We may use it in what we call a cyclical fashion, only in the second half of the menstrual cycle, so in the luteal phase when it would normally be produced, we would just give you a little bit more to help support it. We then begin to add estrogen when we start to see maybe hot flashes at night, maybe cognitive issues. We're finding difficulties, memory issue, things like this. Maybe estrogen is a little bit better for this. We'll sometimes start with progesterone that situation too, but then add estrogen quite rapidly. So perimenopause is a little bit of a dance with your own hormones, right, We're supporting what you're missing actually in that perimenopausal transition. And then as you get closer to menopause, naturally, our estrogen dosage is increase because our ovaries are aging, they're they're declining, and our estrogen is beginning to fall off. We check a lot of levels in our practice. A lot of people don't do that, so you have to listen really carefully or to really see where people need support, so totally different, totally highly personalized, and everybody is a little bit different. But generally perimenopause pgesterone first cyclical over every day of the month, and then as we transition into menopause we add more estrogen, and estrogen levels naturally that we need to add will increase as somebody transitions into menopause.
00:08:03
Speaker 3: So presumably this woman should find another doctor.
00:08:07
Speaker 1: This is nuanced, it's hard to teach in a way. I was speaking to somebody the other day and they said, it's so messy, you know, And I'm looking at this going I don't think it's that messy because I've been doing this for thirty forty years now and listening to people. But this is a great opportunity to get everybody up to speed so they understand this conversation actually can and can help women. And so that's one of our missions actually is to help with education.
00:08:31
Speaker 3: Amen. All right, so we've talked a little bit about dosage, what about timing and duration? So first of all, when should women switch from getting hormones from a birth control pill for instance, to actually taking HRT or midlife hormone support. And then we have another question which is sort of like the opposite, which is like when, if ever, is it too late to start?
00:08:50
Speaker 1: We could talk an hour on both of those. Let's talk about the birth control PELP. So, the average age of menopause in the United States is fifty one, and by the age of fifty five fifty six, about ninety percent of women have actually transitioned through menopause into their final menstrual period. So generally, one algorithm or one way to look at this is to have a conversation with are you feeling well on the birth control pill and do you need contraception? Right? Because you can still get pregnant during this time period. And indeed, twins are even more common because of a phenomenon where the ovaries kind of ovulate twice in one month. So if you need contraception, it's nice to be on a birth control pill. Some people feel a little bit better mood wise, some people don't feel well. I think where we have to really start looking at is it right for you? Is looking at other medical features of the birth control pill, right, And it's not clear to me that just giving ethanyolestra die, which is much stronger and synthetic, does the same thing, and is certainly also the progestins and a birth control pill are very different than natural progesterone. Stroke risk actually naturally increases with age. Elevated risk means more strokes as we stay on the pill later in life. Cardiovascular disease as plaque builds up or blood pressure can start to go up, right, and the pill can exacerbate high blood pressure, so you have to be very careful with that, and then plaque formation and cardiovascular disease. The concern that I have with the birth control pill is actually over a brain health and brain protection. This is like the new leading edge I think of women's health. We know that oral preparations of estrogen and ethanial estra dil, which is in a birth control pill, actually increases a flammatory compound called see reactive protein. So we're increasing inflammation, and some brain health issues are directly related to inflammations. It's not clear that you're getting the same brain health protection when you're on a birth control pill. Now you have to believe that estrogen gives you brain health protection, right, which I do believe. There are options for women though, who can't take a birth control pill in terms of clotting risk or cardiovascular risk and that type of thing. They're progestin only pills that somebody can use if they're at clouting risk or have some other issues. I usually try to taper people off the pill at age fifty to fifty one. I truly think that we get so much support from regular estra dil, and we're replacing what our body is naturally making. It's not clear to me that just giving ethanil estradye, which is much stronger and synthetic, does the same thing. Well, you have to look at your medical history. Maybe they have irregular bleeding, maybe they just don't feel well, And those people will opt to stay on a birth control pill, and we'll try to taper them off maybe or you know, once every year after that, or certainly by the age of fifty five. Actually people should be off.
00:11:27
Speaker 3: All right, let's move on to the late onset estrogen support question. I know this is a controversial one, and I know you're kind of hot on the topic.
00:11:35
Speaker 1: So this is my favorite topic. I'd love to read an email excerpt from another listener who shared this. I rarely lead with my age. I'm seventy one, my uterus is intact and I'm pretty lively, but I'm also mourning. My role is the go to person. I feel ditsy, spacey, insecure. This all feels like a betrayal sometimes. Why is everything getting wider except my bandwidth powerful? I'm still working, still active, and hopefully have travel on the horizon. I have very contained high blood pressure, have had one incident of a FIB three years ago, and I assumed that I'm too old to start hrt am I. So we have an entire generation of women that was denied estrogen based on using the Women's Health Initiative trial data, which was a well designed trial at the time, using two drugs that we were using at the time, Premarn, which is an estrogen from pregnant mayre's urine composed of estrone, which is a very inflammatory, not the best estrogen. I won't to say it's the worst estrogen, but it's not the best estrogen. Estra dialeas and Provera, which is synthetic progestin that is associated with an elevator risk of developing breast cancer and maybe even more clotting risk too. So we took this trial and we said we saw that there was a slightly elevated risk of developing breast cancer one point two five times the baseline risk, and we basically told women that you can't be on hormone support, but we ignored the fact that we were really no longer using premarin and provera in modern practice. We were at using transdermal estradial, so that bioidentical estradial and natural progestrum and natural progesterone was just being FDA approved at the time that the Women's Health Initiative trial was kind of ongoing, So it kind of just crisscrossed right that we have safer alternatives now, but we use this old data to really deny women hormone support. When I was a young surgeon, I would take out your O reason give you a prescription for a prempro. It was like, here's your prescription, Like in the recovery room, it's like here you go start. Because we thought we were protecting against cardiac disease. And indeed, in this study and the Women's Health Initiative study, they showed that there was an elevator risk of breast cancer and if you started hormone therapy late, you actually increase your risk of cardiovascular disease. But we didn't interpret the data properly, we didn't use our newer preparations, and we also said that well, if you start early, it must be bad for you, so we can't give it to anybody.
00:14:03
Speaker 3: How long did that last?
00:14:05
Speaker 1: Well, it's still last. I mean, it's still ongoing, but I mean thanks to movements that are going on right now and the women is health movement that's actually beginning to dissipate a little bit. But still there's practitioners that are concerned about prescribing hormones. And even if you look at AI, they lump and put together oral oral estrogen with transdermal estrogen, and indeed the safety profile is so much different. So oral estrogens have a twofold elevated risk of developing blood clots with them, and transdermal estrogen the risk of development and blood clot is not elevated. Inflammation is higher with oral estrogen. See reactive protein goes up, which is super important for cardiovascular disease and brain health, and with transdermal estrogen it does not go up. So that's just too big examples actually, so beginning now to really obviously prescribe more hormones. But it's like, what do we do with this group of women who were actually denied hormones.
00:14:58
Speaker 3: Like a past woman right, was probably denied right.
00:15:00
Speaker 1: So we then have to look at again, so what are the risks. Stroke is a risk, Cardiovascular disease is a risk, and then we have to look at cognitive health or a risk of dementia as we age. These are major concerns for women. So if we look at stroke risk, we know that with oral estrogen, right, your risk of stroke is elevated, but with transdermal estrogen given at a kind of a mid range dose, it's not elevated at all. We have lots of data to support that, so we're not going to increase your stroke with transdermal estrogen. Cardiovascular risk is kind of the same thing oral estrogenen is inflammatory, but with transdermal estrogens, the feeling is in the literature is that it certainly it's not inflammatory, doesn't increase your sea reactive protein, so safer from the cardiovascular risk. But then we move into the dementia risk, and this is an area that has had a lot of controversy behind it. It's been very difficult to tease out, but we do know that there's this window of opportunity of starting estrogen really within one to three years of the final menstrual period, and I would argue we need to start way before that in terms of protection against dementia. Two thirds of dementia patients with Alzheimer's disease are women, and it's thought that it has something to do with estrogen and declining estrogen, that this elevated risk is exist. So if you look at us types of studies called meta analysis, which are studies that look at all the studies together and say what can we glean from this data. If you look at these large meta analysis that if you start estrogen, your risk of dementias decreases, then we look at some other studies now that show that if you start estrogen later in life we may increase risk of dementia. But these are largely done with our bad estrogen and our bad progestine, so there recent it's.
00:16:38
Speaker 3: Been done on the good.
00:16:40
Speaker 1: In our group, we do have an investigator, Richard Isaacson, who is really looking at this in a very logical manner and looking at brain biomarkers on our patients that we do late start estrogen, and what are those biomarkers showing and I think that he has reported that their brain biomarkers are surrogate biomarkers of what we look in the blood actually look better when somebody is on estrogen. So this really opens up the question that we really need to begin to look at surrogate markers for cognitive health, whether that's functional MRI imaging of the brain, whether it's serum biomarkers, so markers for amyloid TAO and Alzheimer's disease in the blood and pre impost transdermal estrogens, and we really need to drill down on that and get that answer for women because we can't afford to wait for two or three more generations and doing phase three randomized control trials. And we have all this great technology now where we can do all this biomarker data and look at it and analyze it. I think that's personally the next frontier. But definitely I think this is where shared decision making comes in. What are your symptoms? Why are you taking it if it's for vitality and brain health, or is it for I can't sleep and I have headaches that are bothering me. Do I still have drenching night sweats and so it's a balance. And this is again where you really need a really informed women's health hormone specialist, of which there's not that many I don't think in the United States right now, and hopefully we'll get these answers soon by looking at some of these surrogate biomarkers for cognitive health. Then this is what I'm looking forward to. Is what keeps me up thinking at night.
00:18:15
Speaker 3: Actually, I know you love this. I love it.
00:18:19
Speaker 1: Coming up, we're answering more of your questions about hormones and ADHD, about what low dose really means, and we'll get into what options you have if you don't tolerate progesterone well or have underlying health risk. All of that and much more. Stay with us. Will be right back.
00:18:50
Speaker 3: Okay, We're going to go back to progesterone for a second. So I have a question about this. I've heard you say that about ten percent of women don't tolerate progesterone. So you know, you did talk about what the role is of progesterone and hormone therapy, but what do you do if you're in that ten percent?
00:19:05
Speaker 1: Yeah, So progesterone and the perimenopausal transition is largely supported of progesterone when used in menopausal hormone therapy after menopause, is protective of the uterus, so the uterine lining. If you take estrogen alone, you have an elevator risk of developing and demetrial cancer of like anywhere between two and tenfold. It's like significantly elevated. It takes years to develop though it doesn't happen overnight. And also if you take estrogen for a period of time without progesterone, a significant number of women will go on to develop indmetrial hyperplasius, which is just a proliferative and demetrium estrogen.
00:19:42
Speaker 3: On estrogen, you need the progestin.
00:19:43
Speaker 1: You need the progesterone. Estrogen makes the endometrium grow, progesterone halts it from growing. So if you have a uterus and you are on menopausal hormone therapy, you need something to protect the uterus. And we always try to use natural progesterone R because that helps your sleep. For many women, it helps mood, helps them feel better. Progesterone is the feel good hormone in terms of it relaxes us. But ten percent of women have like this idiosyncratic reaction of sorts to it where they don't respond well. They actually instead of sleeping, they have insomnia. Instead of feeling good, they actually feel depressed. There was a study that came out that was really cool that showed that lower doses of progesterone, women who were what we call progesterone resistant, they didn't respond well to progesterone. That if they had lower doses they were okay. Mid range doses they went down they did not feel well, but higher doses they felt better. So this is the transaction between PMDD, which is treated with this progesterone metabolite called allopregnant alone. They think of it as PMS on steroids. And so this is a severe form of depression right that now is treated with a high dose of something that some people react in a depressive way with. Right, So this is where you have to get creative. Sometimes actually, so some people will respond well to an IUD. We can put in a progestine releasing IUD actually at a higher dose called a marina IUD, which is leave an agesterol. Sometimes some people will respond okay to a synthetic progestine. In this situation, this is one of the instances of where you might want to use a synthetic compound. And then there's some regimens where you only use progesterone or progestines every three months and you don't take them every day, and you can get a little more creative with the delivery. Sometimes you can use a vaginal progesterone. And indeed, this is where compound and hormones can come into play, actually, because you can actually compound some different ways to deliver progesterone at different dosages that maybe help people who are what we call progesterone resistant or who don't respond well to progesterone.
00:21:38
Speaker 3: I have another somewhat related question. Let's say a patient comes to you and, putting aside family history and risk, she just doesn't want to go on hormones. Yeah, but she has symptoms, Yeah, what can we do for her?
00:21:51
Speaker 1: So certainly this is a highly personal decision, and we have to be inclusive of everybody. And some people feel very strongly that they want their body to do everything that their body's going to do, and they just want to support it. And I totally respect that, and I always just want people to realize that if you don't feel like you're being supported well or your physiology is being supported. Well, you can always bail out and use hormones, but if you don't, that's great too, And that's going to really segue into lifestyle, nutrition, exercise, mindset, sleep, partnership, a sense of purpose, all of these really big concepts. Right, So if we just talk about nutrition, what happens when your estrogen starts to go down. As we accumulate visceral fat, that fat around our abdomen, we become insulin resistant and we put on weight. For many of us, not everybody does, but many of us put on weight, and that increases risk of cardiovascular disease and of course insulin resistance and pre diabetes and diabetes. So in that situation, then when we begin to look at, okay, what are the nutritional things that we should do at midlife to counterbalances and support Even if you're going to use hormone support, like you know, taking estrogens, not just to just take a pill or bessage nood paants, So you still have to do all the lifestyle stuff. And so that's a logo singic index diet, So knocking down sugar, focusing on protein, making sure that you have kind of mid range a gram of protein per pound of body weight. Some people argue that that's a little bit high. But one thing that we haven't spoken about is something called sarcopenia that can develop at the time when our estrogen starts to go down, and sycopenia's muscle loss, so we lose a significant amount of muscle starting in our early forties. Actually it starts far before menopause. So you want to counterbalance that with protein, and you want to counterbalance the insulin resistance with a loglycemic indix nutrition plan. With that also comes exercise strength training. I talk about strength training all the time because I totally believe. I totally believe that muscle is the organ of loungetiviety. The more data I read, the more I learn, the more I do. Actually, it is our organ of longevity. We have to build it and maintain it. And that's where that one gram of protein per pound of body weight comes into along with strength training, because you really need to build muscle. We need to We're not just trying to maintain, we're trying to build also, So strength training I argue for four times a week, three or four times a week, but at least two times a week.
00:24:09
Speaker 3: Cannot be like twenty minutes, it's thirty minutes.
00:24:12
Speaker 1: Generally we recommend about forty five minutes. But anything is better than nothing. So if you can only if you start with ten minutes, then fifteen. Like I always tell my story my gym at the end of my bed, I started with push ups and sit ups and like so these old dumb bells I had left over from college, and I felt so good, and I just kept feeling better and better and better that I ended up in the gym now every morning between five and six am. So muscle is great because it consumes our glucose right, so it helps us with insulin resistance, It helps us with mood. It actually improves serotonin and dopamine. Some of the mood issues that you can get at perimenopause are actually really well managed with exercise. In addition, we need to support our cardiovascular health, so definitely aerobic exercise one hundred and fifty minutes of zone two every week, maybe doing some hit. Also, we're now learning for brain protection that maybe some of this interval training is better for brain protection, but that's evolving right now. Then, in terms of sleep, making sure that we have good sleep, hygiene, making sure that we are getting sleep, and if we're not, what can we do. And we can support with some supplements if we need to with that, especially if you're having hot flashes but you don't want to use hormones. There's certainly some phytoestrogens that you can use, pollen extracts in a number of things that you can do. Mindset super super super important to help with mental health in terms of having insight into what makes you happy in life and what is your purpose in life. But these are all really important things that I actually don't think we talk enough about mindset in midlife women's health. We talk about depression, anxiety, but we don't talk about mindset.
00:25:38
Speaker 3: And we loved your episode with Glory Synth.
00:25:40
Speaker 1: Yeah, it was great. I learned a ton from her. These were all things that contribute to helping in midlife and beyond with or without estrogen, and if you ought not to take hormone support, this is where lifestyle interventions really come into play. But I'm obviously a fan of estrogen. I've been on it for many years and I think it's really helped me and many, many, many, many of our patients. But again, this is an area of medicine and women's health and just health and wellness overall. That is super highly personalized, and everybody brings their own concerns and owned philosophies to the table, and we as physicians especially have to be respectful of all of those and work with people on their terms in terms of how they want to manage their health moving forward.
00:26:21
Speaker 3: Beautiful, we haven't talked about HRT and its effect on ADHD. It's one of those hot topics at the moment, and we received a great question about it. Is you want to read it, Elizabeth.
00:26:32
Speaker 1: I work with many women entering perimenopause and menopause who are seeking ADHD diagnoses for the first time in their adult lives. What existing research has been captured about the influence of HRT on dopamine production and ADHD. So a couple of issues here. One brain fog, which is super common at the time of perimenopause with hormone fluctuations. Many of the symptoms of brain fog overlap with the symptoms of ADHD in terms of yeah, go figure, executive functioning issues, loss of organization, memory issues, word finding difficulties. Maybe more specific to brain fog, but dopamine. Actually, ADHD is actually influenced by dopamine, and estrogen influences dopamine, so estrogen gives you more dopamine, so less estrogen, and fluctuating estrogen gives you like more radically changing dopamine levels. So for the first time, a diagnoses may be uncovered for a woman actually who never was really diagnosed with ADHD in the past. And as we learned on our pilot episode, women are frequently not diagnosed with ADHD to the same extent that men are actually and that there's probably just been there and then the perimenopausal transition has made it worse or fluctuating hormones have made it worse. Anecdotally, we all i think, have stories of people who have gotten much better with hormone support. But also it hasn't been a lot of study, right, I mean, this is the interesting thing about hormone health and women. Just because the data doesn't exist doesn't mean that it doesn't work or doesn't have an impact. It just hasn't been looked at. And so there are so many questions now that we need to ask and answer, and this is really one of them. The impact in terms of brain fog or ADHD and hormone support, but always realize if you have a history of ADHD, or you have a history of depression or any type of mood disorder anxiety and it's getting worse and your perimenopausal maybe considers a meestrogen support before trying to change around all of the SSRIs and having them not work. So if something that has worked for a long time is suddenly not working for you, whether it's your organizational ability right, maybe you've compensated for ADHD in the past with sticky notes or something, or you've been on SSRIs when something stops working for you and you're impairmentopause or you're after the age of thirty five, check it out, think about hormones actually and talk about them. What a pleasant surprise to hear from so many listeners, including this next one, who writes from New Zealand, was sort of a two part question. My wife is a trans woman. As such, she takes especially estrogen but also progesterone at doses that would be quite high compared to what is used here in news Zeline for HRT associated with perimenopause or menopause. My overall questions are number one, why are CIS women restricted to low doses of these hormones as treatment for perimenopause when trans women can take the same medications at higher levels.
00:29:27
Speaker 3: Genuine speaking, how do you know if your HRT needs adjusting?
00:29:30
Speaker 1: So your HRT needs adjusting if your symptoms are not controlled. You know, we've had this dictum that people should be on the lowest dose of hormone that controls our symptoms. And I think a lot of times practitioners here the lowest dose of hormone. So we certainly see people coming to us who are on low doses of hormones who still have symptoms, And I'm kind of like, you should increase your dosing, right, If you have symptoms and you're on a medication to treat a symptom, you should have the symptom treated. But more importantly, or just as important, is the physiologic protection that you get from hormone support. So when we look at hormone support, just in the trials that have been done, we decrease your risk of cardiovascular disease by thirty percent if initiated within ten years of the final minstrual period. Those studies have all been done with dosages of estrogen oral estra dial at one milligram or premarin at point six two five milligrams, so a point of two five miligram patch, which is low dose. Whether it's controlling your symptoms or not, it may not be controlling your physiology right and helping your physiology, because there's two things that we need to look at, right, we need to look at symptom control, but we also need to look at how do we impact your physiology and brain health is another one.
00:30:43
Speaker 3: Right, So to go back to this reader's questions, why are CIS women restricted to lower doses and why don't we use HRT to increase hormone levels to just at or above pre menopausal.
00:30:55
Speaker 1: So the levels fluctuate right when you when your premenopausal levels are going to fluctuate, they're going to go anywhere between you know, low levels. Can't measure estrogen right right after you have a period or right before you you know, right as your episation is starting to go up to mid level ranges of anywhere between two hundred and five hundred and then back down to like a luteal range of one hundred eighty to one hundred. And we don't have data on this I mean, we have no data on this. It's what I call a data free zone. But it's interesting because we definitely have some women who feel better with higher dosages of estrogen. There's some of our patients that just like I need more estrogen, I need more essergin and you get their estrogen level up around one hundred and they feel great, and if their estrogen level is like around fifty, they feel like not well. So again, this is all information that we need and we don't have to restrict people. This is just coming from this guideline of the lowest, you know, give the lowest dose possible. And I think that again we worry a little bit though about maybe stroke risk and older women of course, because we do have data that shows that when we have transdermal estrogen over a point oh five milligram patch dosing that the risk of stroke does go up in older women. So there is some dose response in terms of we don't want higher levels necessarily that are going to be detrimental to somebody, and we want to keep it kind of in a good zone. But if you're still having symptoms and you're on a like a low dose patch, right, you should probably increase and if you don't feel well, you should increase into a reasonable zone for you. And again this all needs to be defined. This is all data free zone, policy free zone, and it's all information that we need to collect. We check levels to make sure that you're at least in a range where you have a physiologic protection right anywhere between you know, fifty and eighty, we get some physiologic protection right in terms of cardiac risk and brain health and metabolism too. We know that insulin resistance goes down actually when we have good levels of estrogen.
00:32:45
Speaker 3: An estrogen level between fifty and eighty.
00:32:47
Speaker 1: Between anywhere between fifty and eighty, and you could even maybe go down to forty, right, And it's important to measure levels because transdermal estrogens are not reliably absorbed across every woman at every level. Right, So you can have a woman on a point one milligram patch, which is a higher dose, have an estrogen level of fifty or sixty because she's absorbing it differently. Yeah, she's absorbing differently than somebody's on a point of three seventy five milligram patch who you know has an estrogen level of sixty. And you're like how's that happening. But and it's also important to realize too that when you start to check levels that less than fifty, if you're still having symptoms, you should probably go up on the patch and that or your transfermal estrogen, maybe a cream or a gel, And you should make sure that your levels are checked on a somewhat regular basis, just to make sure that you're actually getting the dosages that you think that you're getting.
00:33:38
Speaker 3: Yeah, so I'm hearing two things that I think are interesting. One is pay attention to how you feel. If you're being treated and you're not getting the benefit, then talk to your doctor about raising the dose. And then also this was important, This is new to me, but the idea of like if the dose is too low, you're not actually going to get the system wide benefits that come from estrogen, like the radiac benefits in the brain.
00:33:59
Speaker 1: So we don't have data. We have data to support that you do get benefits at these levels. We don't have data to say that you don't get level at lower levels, and we'll never have that data necessarily data unless you know, we get the brain biomarker data. Right.
00:34:11
Speaker 3: Okay, So we received some really great questions from a number of listeners about HRT and risks involved when managing a serious illness and other health issues. One of the listeners shared this with us. Everyone seems to think that hormone therapy is the solution to so many things for women's health. I was diagnosed with er PR positive breast cancer this year at the age of forty two. So er and PR positive, for our listeners, means that breast cancer cells have receptors for both estrogen and progesterone, which means these hormones can fuel the cancer's growth. So the writer continues, I have no family history or genetic links. I'll be taking hormone blocking to moxifen for five years. Not only can I not take hormone therapy that will supposedly help my brain, wait, sleep, hot flashes, et cetera, but I need to be blocking the hormones I do still have what's a gal to do?
00:35:01
Speaker 1: I think that again, this is the frontier of women's health and hormone support. As we realize the benefits of hormone support, we're gonna be I think, more liberal in terms of how we use hormone support. Right because largely we've reviewed hormone support in the past of just controlling symptoms, right, and so now that we know that there's you know some obviously there's cardiovascular protection and where there's the thought process that we have brain health protection and such, and of course bone health protection. We haven't even talked about bones or touched on that, but you know, prevention of fracture risk and cycopenia. So I think as we realize the benefits and we get more information about the benefits of estrogen use, I think we'll be more liberal in terms of how we use. And we already see that in the breast cancer world a little bit. People are now having this conversation. Five years ago, you would not have had a conversation about hormone support after breast cancer. Now the conversation as well, if you're ERP ARE negative, you're probably okay at some point to consider it with a conversation with you're a medical oncologist. And if yeah, if you're many years out after an ERP R positive you know small cancer, that you're okay to talk to your oncologists and consider it. And those conversations are now start. You know, five years ago that was a resounding no, and so now we're being I think a little bit more liberal, and I think again, this is going to be the change in women's health and hormone support that we're going to have to just reassess the safety of it, because if you really look at the risk of breast cancer recurrence with hormone exposure. We allow young women right who have had ERPR positive cancers on TAM for two years go off and get pregnant. It's okay to get pregnant, but it's not okay to be on hormone support if you're older. That has never made a lot of sense to me necessarily, So if you're having significant symptoms, again, this goes back to shared decision making and why are you taking it? And certainly if you have significant symptoms and you're at low risk for recurrence or you have an EUPR negative cancer early stage, these are considerations and topics that you should review with you're a medical oncologist, and I think that there's going to be more medical oncologists in the future here a little bit more open to this.
00:37:05
Speaker 3: Okay, someone writing in from Boston wants you to talk about HRT and estrogen in the context of women who've experienced adverse side effects in the past. In this writer's case of pulmonary embolism after only six months of taking hormonal birth control, Do I have any viable options when I become menopausal?
00:37:21
Speaker 1: She asks, yes, So again, share decision making, Get a hematologist involved. If you had what we call a provoked pulmonary embolists mean there's a reason for it that is not an absolute contraindication to using transdermal hormone support. We have to look at was it provoked, was the embolist provoked? Were you on an airplane for a long period of time and a birth control pill something like that, or do you have a susceptibility? Do you have what we call a thrombophilia, meaning the clouding risk is just so high that you would never start anybody on a hormone support And there are some that are relatively elevated risk but are not super high risk. Right, get out of the silos, get the hematologists involved in the conversation. Get the hematologists up to speed on what the differences between transdermal and oral estrogen. Not at elevated clouting risk with transdermal estrogens, And there was actually a study that showed that people with the previous claw us who were given transdermal estrogen afterward did not have an increased risk of recurrent clots.
00:38:17
Speaker 3: Another great question from a forty eight year old woman. I'm forty eight years old. I've had a stroke caused technically unknown, but at least one doc thinks it was because of lime and otherwise in good health. Have no residual effects from the stroke. I have a mother with Alzheimer's, I'm in perimenopause, and I'd really like to consider HRT for both my symptoms and for brain protection. Does my medical history automatically rule me out taking so?
00:38:41
Speaker 1: Remote stroke does not actually relative contra indication, not an absolute contracation. Always would do a thrombophelia work up and evaluation, get the neurologist involved, get the hematologists involved. But not an absolute contraindication. Actually you would think that it is. But it's a relative contraindication and recent stroke absolutely not. But remote stroke maybe related to an inflammatory situation. It's a conversation to have with all the experts. We have to get everybody out of the silos. If you've been listening to this show for a while, you know that this is a common refrain for me. Let's get rid of those silos. We see better health outcomes from women when we bring all of these specialties together and treat the whole person. When we get back from the break, Chavon and I tackle more of your really excellent questions, including one from a former patient of mine.
00:39:51
Speaker 3: So here's an interesting one. We received a great email from someone. She's sixty years old, postmenopausal woman, and her family physician told me quote on my last annual visit that she was getting on her soapbox to advocate for vaginal estrogen therapy to prevent UTIs. Now, I have no history of UTIs, and I have no vaginal dryness and other such issues. I told her I would look into the matter, but have found no research yet to indicate widespread acceptance of this treatment with no history and no problems. What do you think?
00:40:18
Speaker 1: So, you know, this thought probably comes from some guidelines have been updated that if you do have recurrent UTIs, estrogen can be protective and preventive of recurrent UTIs. So in terms of getting everybody on vaginal estrogen who may not be having symptoms, I don't think that that's a current guideline actually, but there is a guideline that if you have recurrent UTIs or you have problems with UTIs, actually hormone support meaning vaginal estrogen. It's definitely safer than just oral prophylaxis with them antibiotics actually, which have their own side effects associated with them. And we've had great experience with using vaginal estrogen and prevention of recurrent UTIs, I mean, it actually really works well. And then there's some also there's some data that shows that older women who are on vaginal estrogen who have recurrent UTIs, the risk of sepsis or developing blood infection from a urinary tract infection of which you can die from, is actually decreased with the use of vaginal estrogen. So definitely, if you have recurrent UTIs, one hundred percent supporter of vaginal estrogen. If you don't have any problems, what are you trying to fix, Like, it's hard to palliate something or fix something that is not a problem. But also if you have any problems with what we call genitourinary syndrome amenopause meaning vaginal bulvar thinning of the skin, which changes the microbiome and can be very lead to microabrasions and be very uncomfortable. Definitely, vaginal estrogen in that situation, or discomfort with intercourse or sex, of course, but definitely if you're having issues, vaginal estrogen is great. If you're not having any issues, don't know what you're treating.
00:41:49
Speaker 3: Yes, So let's go for two more questions. I think we're going to go to you, Elizabeth.
00:41:54
Speaker 1: Okay, I was pleasantly surprised to learn that we've received an email from one of my former patients, and I'm smiling here, she writes, I remember when I started seeing you in two thousand and six. We talked about the idea of what was discussed, clearing out the precancerous weeds. So to speak with occasional treatment, are there studies that you know of where women can preventatively take occasional PARP inhibitors as suggested in the podcast, or take the DNA plasma vaccine.
00:42:22
Speaker 3: Okay, So before you respond, Elizabeth, what are PARP inhibitors? What about the DNA plasma vaccine? Can just give us a little bit more context, okay, so that we understand your answer.
00:42:33
Speaker 1: So, PARP inhibitors, they're a class of drugs and they're targeted cancer drugs that block an enzyme called PARP, which is the polyADP ribos polymerase. These enzymes help you repair DNA. So every time cells divide, DNA becomes disrupted and you actually have mismatches, right, and you need to fix that. So you have like these little pac Man enzymes that come up the DNA, they clear it out and they wreck the problem, so that these inhibitors actually inhibit that enzyme. And the concept of them is that if you already have mutations in cancer producerposition gene in which your cells already can't repair the DNA the same way, that this extra hit of the repair of the DNA will kill the cell. So these cells that are really super susceptible to cancer, right, they've lost two copies. Let's just talk about Brokko one. They've lost two copies of the Broca one gene. You inherit one copy. That's bad, so you've lost it. So you got one copy, you knock out the second copy, right, then that cell can go on to become a cancer more easily. And that's why you were at elevated risk develop cancers with these with these gene mutations and then the PARPs what they do is they just give a final blow to that cell so that cell. So normal cells won't be hit the same way because you know they can repair that DNA. And then the cancer cells though can't, and you just give them an extra hit so and then there's they become so damaged that they die. So there are studies now ongoing looking at PARP inhibitors right for individuals who are elevated genetic risk development cancer. And right now, if you're an elevated genetic risk to develop cancer, such as myself, you either have surgery, have mestectomies so we're talking about broco one here as a specifically for example, and have your ovares plus or minus your uterus out, or you undergo increased surveillance of the breast and plus or minus the ovaries depending on your viewpoint on a varying cancer screening. But the idea is for chemoprevention in the future or targeted agents to prevent, and the ways to do that are through these targeted compounds. The second way to do that is through a cancer vaccine, which is super cool, and what a DNA plasma vaccine is is we just put you inject basically a plasmid the cells, which is a little independent circle of DNA, right, so it can make its own proteins and such. So cells will take up this plasmid that triggers the immune system to react to a protein which may be only expressed on a cancer cell. So a unique protein expressed on a cancer cell, you ramp up your immune system so that it's pre programmed that if a cancer cell develops, your immune system kills it.
00:45:14
Speaker 3: Wow.
00:45:15
Speaker 1: So there are studies ongoing right now, and hopefully in the future. The surgery that we're doing or undergoing right won't be done in the future because we'll have chemoprevention strategies and we'll have immotherapy strategies. Great time to be a curious doctor, because it's every day there's something to read. I'd love to read one of the emails next. Hello, doctor Pointer, here's my question. Would you recommend taking HRT only as a preventive measure. I'm a fifty year old, healthy and active woman. I do cardio four to five times per week. I do weights three to four times per week. I try to eat twenty grams of protein per meal. I don't know what you read, but you're doing everything right. I meditate, I have a strong group of friends. I work hard on being healthy, strong and happy. Ish. I went on a HRT to help with my menopausal symptoms itchy skin, sleep issues, anxiety six months ago. The HRT has no impact. My doctor last week suggested that I stopped taking HRT. I understand that HRT helps prevent bone loss and can have positive impacts on cardiac health. Should someone take HRT only as a preventive measure if it has no impact on current menopause symptoms?
00:46:27
Speaker 3: Great question?
00:46:28
Speaker 1: Great question. So the first thing that I would do is I would ask what are you taking? And has any mighty checked your levels? Because again this is one of these highly highly personalized areas that require a lot of management, a lot of narrative interpretation as such. But in terms of HRT as prevention and not just treatment of symptoms. So hormone support is going to definitely prevent bone loss, sarcopenia, and then you have to look at you know what symptoms you have and you have to drill down deep on them in terms of cognitive function, sleep and such. But the real question is should you be on it to protect physiology? I think that's where we're headed. Honestly, I hope that's where we're headed. We have all this data. I don't know how we ignore it. In terms of it's safe. I've never seen anything like this. It's safe. Most women can take it. It's going to help you, but don't take it right. And I don't understand that. And I can tell you that you know, we have great data to show that hormone support and I'm going to say it again, when initiated early right and that critical time period or that window of opportunity that we call it, can protect your brain actually by the current data that we have, protect your heart, protect your metabolism, protect your bones, protect your muscles. Like but and it's safe, but why aren't you taking it? And so I think this is the next we have to really we have to really question why we're making these recommendations. And so I am a fan of physiologic support. I'm on it myself right now. I think in the past I definitely had mood isshoes and started it for mood isshes. I'm not sure that I have them, although if you listen to last podcast, my husband to say that I do. But certainly the reason that I do stay on it actually is more so for physiologic support now than anything else.
00:48:07
Speaker 3: Something Rich Shapiro, your husband's that in a recent episode I thought was so interesting where he made the comparison to erectional dysfunction drugs, where they there used to be a stigma associated with them. Now it's pretty standard. I think a lot of men are on them. They're advertised on the subway. It's I mean, it's been completely destigmatized, and yet that still hasn't happened.
00:48:29
Speaker 1: No.
00:48:29
Speaker 3: With hormone therapy for women.
00:48:30
Speaker 1: No, No, And I think a lot of times too doctors and providers don't know how to use hormones and that, and sometimes what you're afraid of in medicine you don't recommend right. And I think this will be getting people up to speed on how to prescribe and that type of thing. But more so than that, too, we have to also change how we look at women's health, Like what are we really trying to accomplish here? I always said that women are much more than their breast cancer risk, hot flashes and baginal dryness. We're far more complex than that. We have brains, we have hearts, we have bones, we have muscles, we have jobs, we have families. To bring it down to like these basic, these basic, you know symptoms, is I think trivializing the health of women. And I think we really need to seriously look at the physiologic protection that we get from hormone support and preventive strategies, and that's our new forefront of preventive health and proactive health.
00:49:22
Speaker 3: All right, Well, thank you to all of the listeners who responded to our call, either by leaving us a voicemail or sending us an email. I mean, I think Elizabeth and I were both kind of blown away by the Todvelder of the question questions, great questions. Yeah, we're definitely going to be doing this again. Love it, tune in.
00:49:41
Speaker 1: Okay, So we covered a lot in today's episode, and I know that this topic can feel overwhelming, like you're lost in a sea of information, information that is often outdated and just not helpful when you're trying to make informed decisions about your health because there's no magic pill, no one size fits all approach. That's why I'm so happy that you all wrote in with your specific questions and criteria. I hope that you are leaving this episode, feeling better informed about the choices that are available to you. Few important basics to underscore low DOS. Vaginal estrogen is actually very safe. It's been demonstrated in many studies, so if you're experiencing vaginal dryness or any discomfort, this may be a good starting point to discuss with your doctor. Of course, it's essential to consider your health risk and your family history when making any changes, but as we discussed, there are ways to mitigate those risks and find solutions for almost every case out there. I never want women to think that this is a binary choice. It's so much more nuanced than that. I really do believe that there is a path for every woman out there listening that can improve your quality of life and align with your risk profile while supporting your overall health. Thank you again to everyone who wrote to us. We'll be responding to more of your questions in the coming weeks. We encourage you to send us any questions related to midlife women's gynecologic health, about PCOS, pelvic pain, painful sex and demetriosis, PMS, pmdd UTIs, or yeast infections, really just anything that you're wondering about and would like us to tackle on the show. If you'd like to submit a question, we cannot wait to hear from you. Are very smart listener. Just leave us a voicemail at four FI five two oh one three three eight five, or send us a message at Decodingwomen's Health at Pushkin dot fm. Decoding Women's Health is a production of Pushkin Industries and the Atria Health and Research Institute. This episode was produced by Kalaliah. It was edited by Amy Gaines McQuaid, mastering by Sarah Bugaire. Our associate producer is Sonia Gerwit. Our executive producer is Alexander Garaton. Our theme song was composed by Hannas Brown. Concept and creative development by Chabbaan O'Connor. Special thanks to Vicky Merrick, Alan Tish, David Saltzman, Doctor David Dodick, Sarah Nix, Jacob Goldstein, Leah Rose, Jordan McMillan, Morgan Ratner, Owen Miller, Eric Sandler, and Greta Cohne. I'm doctor Elizabeth Pointer. Thanks for listening. Until next time.