Episode #138: Will Hormone Replacement Therapy Help You Lose Weight?

Menopause often brings weight gain, especially around the abdomen—but can hormone replacement therapy (HRT) help?

In this episode of Conquer Your Weight, Dr. Sarah Stombaugh reviews what real clinical trials say about HRT and weight. HRT isn’t a weight-loss drug, but it may slow fat gain, help maintain muscle, and possibly enhance results with GLP-1 medications. Always discuss risks and benefits with your healthcare provider.

Are you looking for a doctor who can help you with menopausal weight gain? Visit www.sarahstombaughmd.com to learn more and get started today. 

Transcript

Dr. Sarah Stombaugh 0:00

This is Dr. Sarah Stambaugh, and you are listening to the Conquer Your Weight Podcast.

Announcer 0:09

Welcome to the Conquer Your Weight Podcast, where you will learn to understand your mind and body so you can achieve long-term weight loss. Here's your host, obesity medicine physician and life coach, Dr. Sarah Stambaugh.

Dr. Sarah Stombaugh 0:29

Hello, everyone, and welcome to this week's episode of the Conquer Your Weight podcast. We are talking about a so, so important topic, which is hormone replacement therapy. And can hormone replacement therapy have an impact on weight, on weight loss goals? And this is a very controversial topic. We today are going to dive into what are the sex hormones, estrogen, progesterone, testosterone, what roles do those have in our body in general? How do those change during perimenopausal and menopausal years? And then especially if you've been dealing with perimenopausal, postmenopausal weight gain, what, if any, is the role of hormone replacement therapy in supporting your health and weight goals? This is a topic that I think we could talk about probably for 10 hours, so I'm going to do my best to talk about it in a single episode and to give you some of the great data you need. What is absolutely going to be true is that this is going to be ongoing. I think we'll likely have some updates to this as well as maybe a part two coming down sometime down the road, either just myself again, or perhaps bringing in a guest speaker in this area, because this is a conversation that amazingly has been happening more and more, recognizing that very commonly women are gaining weight in their perimenopausal and postmenopausal years. And they're frustrated and they're fed up with it. And let's talk about this. How can we support them? So let's take a step back and look at what are the sex hormones? What are the roles that those play in our body? And you know, does decreasing those, does increasing those, how can we, how do those impact our health? So today we're going to be talking about the role of estrogen, progesterone, and testosterone, but we're primarily actually going to be focusing on the estrogen piece. So when we think about all of these hormones, the estrogen, progesterone, testosterone, a lot of times we think of estrogen and progesterone as woman's hormones and testosterone as man's hormones. But the reality is Women also have testosterone. Men also have estrogen. And so both genders, both sexes do have these hormones naturally. Now for all women, there's estrogen, there's progesterone, and there's testosterone, and all of these levels decrease during the perimenopausal and postmenopausal years. During perimenopausal years, there's often this sort of crazy up and down rollercoaster that happens. So sometimes those levels are surging, sometimes they're dropping back through the floor, and those rapid changes in hormones day over day or week over week can create some of the really big challenges in terms of major menopause and perimenopausal symptoms. So estrogen, like I said, we think about it in the context of our sex hormones. We think about it in helping us to perhaps ovulate or to get pregnant or to have a baby and the roles that it may play in our menstruation cycle month over month with the goal of thinking about from a fertility standpoint. But the reality is estrogen does so, so much more than that. Estrogen signals throughout the entire human body their There are over 3,600 estrogen receptors in the human body, and we know that it plays a really significant role in things like our cardiovascular health. So having estrogen in our body helps to reduce the risk of cardiovascular disease. plays a really significant role in bone health. So certainly decreasing bone density with things like osteopenia or osteoporosis become much more common in later years of life for other reasons as well. But this estrogen deficiency can be one of the main reasons that happens. It plays a role in our metabolic health. And so this is related to the weight gain that we often see in the peri and postmenopausal years. And it's not just weight gain it's an insulin resistance that can lead crease lead to not just weight gain but actually visceral adiposity so when we think about that central weight gain we think about weight that comes on that sort of tire or softness that happens in the abdomen a lot of times people think about the weight that's sitting on the sort of on the outside the subcutaneous fat subcutaneous fat is the fat that you can pinch it's fat that you could grab with your hands it might be kind of jiggly where a visceral adiposity is a fat tissue that accumulates in and around our organs. Now, While subcutaneous fat may not be desirable for someone, they may still wish to lose that weight as well. It's not necessarily dangerous, doesn't come with increased metabolic health disease risk, where visceral adiposity, that fat that is in and around our tissues, does have an increased risk of cardiometabolic disease. And so this is why sometimes we'll notice, even if there's not that soft, loose or grabbable fat on the outside of the body, there still may be an increasing waist circumference. A very classic example, if you think of sort of the middle-aged or a middle-aged man who maybe has skinny arms and legs, but just has a large belly, but it looks kind of taut. It's this firm, large belly. While that can be associated with certain alcohol conditions, for example, it can also be associated with metabolic health. And so that taut abdomen, there's not necessarily fat that you could grab. It's not just but it's that visceral adiposity, the fat tissue that accumulates in and around our organs. And this is the type of fat tissue that is very metabolically dangerous and can increase the risk of heart attacks, of strokes, can increase the risk of other metabolic diseases like type two diabetes. And so this is the type of fat that during peri and postmenopausal years, we may experience both of those, a both subcutaneous fat that sort of saw or looser fat as well as that visceral adiposity, but it's that visceral fat that is most dangerous. And both of these can increase during the period and post-menopausal years because of decrease in estrogen. We also know that we have estrogen receptors in our brain. And so when it comes to risk of dementia, for example, the decreasing estrogen receptors and decreasing estrogen stimulation on those receptors increases the risk of dementia, for example. And those are just a few specific call outs, you know, certainly in terms of things like the vulvar tissue, the vaginal tissue can get more dry, which can increase risk of urinary tract infections. And so estrogen plays many, many more roles even beyond these, but that cardiovascular health the risk of osteoporosis, the metabolic health, the brain health, the urogenital system health, all of these things are very directly tied to estrogen. And what very commonly happens is that when we look at women's health in their perimenopausal years where their estrogen is going crazy, and then in their postmenopausal years where that estrogen level is reaching lower levels, we start to see a significant increased risk of many of these different conditions. What I very commonly see for women is in terms of metabolic health and weight gain, for example, is they have gone their whole life through their 30s, maybe even their early 40s, and weight has been pretty stable. They know their body, they know their routine, they know that if they eat a certain way and they move a certain way that their body will stay at a stable weight. And then all of a sudden that changes in a drastic and frustrating way because they're doing the exact same thing, yet they're starting to accumulate weight around their body. around their midsection. And a lot of times starting to see lab changes as well. We'll see a lot of times increase in cholesterol levels. We'll see increase in blood pressure. We'll see increase in blood sugar levels and a hemoglobin A1C. Both of those things are closely related to one another. Women may have gone from having fasting blood sugar levels in the seventies or eighties, and now they're seeing levels in the nineties or the low one hundreds kind of flagging either just barely above the normal range or in that at the very high end of the normal range. Similarly, their hemoglobin A1c that looks at the blood sugar over three months period of time. may have lived in the 5.3, 5.4 range and been totally stable there. And now as they've gone through menopause, they see that level 5.6, 5.7, 5.8, or even higher. We know that the risk of insulin resistance with decreasing estrogen levels is significant and the risk of type two diabetes can certainly come up. And so these changes are frustrating. From a weight perspective, we see it generally pretty, obviously we see it pretty quickly, But some of those other changes with cardiovascular disease, with bone health, with brain health, with all of these other pieces, a lot of times those are just sort of simmering underneath the surface and may not be apparent till many years later. Now, one of the biggest challenges is there's been this big swing in the pendulum of how we view hormone replacement therapy. A few decades ago, we were pretty pro hormone replacement therapy as a society, as a medical community, the women's health and came out in the early 2000s that said, whoa, whoa, whoa, there's a huge increased risk of breast cancer and ovarian cancer and heart disease and blood clots and all of these things just instantaneously and abruptly stopped the use of hormone replacement therapy for many women who were doing just fine on their hormone replacement therapy. And what we've seen is really an entire generation of women who have gone through menopause without the support of hormone replacement therapy or even when they were given it, were given this idea of taking the lowest dose possible for the shortest amount of time possible. And so women for whom maybe did do it begrudgingly, sort of fearfully being afraid of, oh my gosh, how is this increasing my breast cancer risk, for example. And then even if that medication was working really well for them and they felt really good on it, being discontinued on that medication, maybe prematurely or before they wanted to. What will be beyond the scope of Thank you so much for joining us. We as a medical community have been re-evaluating that data. They've looked at subgroup analysis. So if you look at 50-year-old women versus 60-year-old versus 70-year-old versus 80, there's a very different risk based on age, also based on other medical conditions, based on things like family history. And so when they have done subgroup analyses, it has actually shown that, oh, things aren't as bad as we thought. And oops, actually, there may be quite a bit of benefit in hormone replacement therapy. given to the right people at the right stage. What we do know is that when estrogen receptors are not stimulated constantly, that they may downregulate. And this is true for a If the receptor is not being stimulated, that the receptor may not have a need and they may decrease in number. And so what happens with estrogen receptors is that as we go through menopause and those early postmenopausal years where the body is seeing less exposure to estrogen, that it may decrease the number of estrogen receptors such that if a person has been without estrogen stimulation, sort of the general rule of thumb is about a decade, but there's some for specific indications, maybe a little more, a little bit less, that even in giving them hormone replacement therapy, if they haven't had stimulation of those receptors in a while, that giving the hormones may not actually unfortunately do much. And so you can find yourself in a position where even if you're taking hormone replacement therapy for heart health or for bone health or for some of these other conditions, there may not be the same benefit compared to if you had continued estrogen. Now, again, that's sort of a general statement that won't apply to every single health condition. So it's valuable to have that conversation with your own physician. Also, even to read and educate yourself about it. One of my favorite books on the topic is a book called Estrogen Matters by a There's also a podcast recently that my good friend, Dr. Rachel Rubin did with Peter Attia, where they're talking about hormone replacement therapy and safety. And honestly, whether you're a patient or whether you are another provider who is listening to this podcast, those two resources, Estrogen Matters book and the podcast with Dr. Rachel Rubin on Peter Attia, those are really good starting places to see people talk about estrogen in a very evidence-based type way. So that being said, we are going to get into a little bit about what does it mean to use estrogen replacement therapy or hormone replacement therapy, and does that have an impact on our weight? What does the data show? Now, what I will tell you is there's not a lot of data out there. There are certainly many case studies. There's a lot of good retrospective data studies, meaning they look at patient charts, look back at things that have happened, and we're just starting to get some prospective type studies where patients are being randomized to receive either or types of treatments and then looking at what happens. So when we look at using estrogen in weight and how does that actually work? Does that actually help? Here is what we know. So again, I'm speaking about estrogen, but this will be sort of encompassing of estrogen alone versus estrogen with progesterone. What we know is that for women who still have a uterus, so women who have not had a hysterectomy, that they will need some sort of progesterone replacement also to help promote the safety and health of the uterus. We know that giving estrogen by itself without any sort of progesterone will grow and thicken the lining of the uterus. This is part of the normal menstrual cycle. It helps to grow and stimulate the lining of the uterus. And then later in the menstrual cycle, when progesterone levels to Wrap off. and estrogen levels drop off, that we would have a period, a menstrual cycle where all of that would shed. Now, after menopause, there's not going to be any sort of menstrual cycle. And so you want to make sure that someone who still has a uterus does have some sort of progesterone therapy in addition to their estrogen, because we want to make sure to protect the lining of the uterus because thickening the lining of the uterus could increase the risk of endometrial or uterine cancers. So... This is referring to both estrogen and estrogen progesterone. So it'll be dependent on the individual. Progesterone therapy can look like a lot of different things, whether it's progesterone pills, whether it's an IUD, lots of different ways that people may take progesterone. So what we know about the role in estrogen, we talked about how there's this major metabolic effect that happens. And it's very common that this change in metabolic effect changes our fat distribution, may also contribute to muscle loss. And so when we look at body composition and we think about not just what is your weight on the scale, but what is your muscle mass versus what is your fat mass, declining levels of estrogen can contribute to those changes of body composition where we have an increase proportionally of fat mass and a decrease of muscle mass. And so even if the weight on the scale stays the same, a lot of people may notice that the size of their body, the way their clothing fits, for example, is very different compared to before menopause. So estrogen absolutely plays a role with that. For women, an average weight gain... of about one and a half pounds per year attributed to that estrogen decline alone. Now, certainly other things in our life can also contribute to weight gain and people may be experiencing that alongside of their perimenopausal journey with decreasing estrogen, but about a pound and a half per year, specifically due to that hormonal decline. Now, there are some clinical trials with hormone replacement and weight. There was one called the PEPI trial, P-E-P-I the postmenopausal estrogen and progesterone intervention. And this was a randomized placebo controlled trial about 875 women over three years. And what they did is looked at women who were taking estrogen now with or without progesterone compared to women who were taking placebo. So women taking hormones versus women who were taking a placebo and the women who were on hormones gained one kilogram less weight and had 1.2 centimeters less waist circumference compared to the placebo group. So we're not talking huge numbers here, but this is just that hormonal piece alone. There's also been body composition trials where we've seen that patients taking estrogen plus or minus progestin therapy may help to mitigate fat gain and help to preserve lean muscle mass. And so hormone replacement may slow weight gain, even if it doesn't cause weight loss, especially that weight gain around the abdomen. And that's where we're talking about that visceral adiposity, that tissue in and around our organs that is particularly dangerous. Now, one of the questions we get all the time, especially as we're looking at the role of estrogen and metabolic disease, is as we're seeing new medications that come on the market that can be supportive of metabolic disease, things like the GLPs, medications like Ozempic, Wolgovi, Zepound, How can we use these medications and should we use these medications in combination with something like hormone replacement therapy to help support the weight and metabolic goals of postmenopausal patients? So There was a retrospective clinical trial recognizing, and trial is probably the wrong word, but a retrospective study that looked at about 100 postmenopausal patients who were on semaglutide. So that is the generic name for Ozempic and Wagovi. And they looked at the patients who were on semaglutide and also taking hormone replacement therapy versus the women who were taking semaglutide and were not on hormone replacement therapy. And over the course of a year, the patients taking both hormone replacement therapy and semaglutide lost an average of 16% total body weight over that year compared to women taking just the semaglutide alone. No hormone replacement therapy had a 12% weight loss. So 16% with hormone replacement therapy, 12% without hormone replacement therapy. And the hormone replacement therapy users also had a greater improvement in their cardiometabolic markers. So those are things like blood pressure and cholesterol. Now they also That retrospective study was done at Mayo Clinic. They also had a recent presentation where they looked at terzapatide in patients who were and were not using hormone replacement therapy, terzapatide being the same medication, the generic name for Zepound and Monjaro, showing a 17% weight loss in patients with hormone replacement therapy versus 14% weight loss in patients not using hormone replacement therapy. And what is interesting was that in this trial, the women who are using hormone replacement therapy, at least half of those patients with hormone replacement therapy and terzapatide actually lost 20% or greater of their total body weight loss. And so these studies are suggesting that hormone replacement therapy may enhance the response to anti-obesity medications like semaglutide and terzapatide. And this isn't totally surprising when we look at the effect of estradiol. We know that, as I said, there are 37 more than 3,600 receptors for estrogen in the human body. And many of those are involved in things like hunger, like appetite regulation. We think about hunger, we think about fullness. There are a lot of different neuro and hormonal signaling that go into what and how we experience hormonal or how we experience hunger and fullness. Interestingly, we think of hunger and fullness as the same pathway, but there's actually sort of two parallel pathways that run in the brain. One that is stimulating hunger and says, okay, now it's time for me to eat. I'm hungry. I'm ready to eat. Cravings can be associated with that pathway as well. And then there's a pathway that signals satiety. Okay, I'm full. I'm I should stop eating. I should end my meal. And we know that estrogen plays a role in both of these in terms of decreasing ghrelin, which is one of our hunger hormones that makes us feel more hungry, in terms of decreasing leptin or improving leptin sensitivity. Leptin is a hormone that helps our body to recognize fullness. And so many people with obesity, interestingly, actually have elevated leptin levels who would think they would experience fullness more rapidly, but have leptin resistance. So similar to how we talk about insulin resistance, leptin resistance being a condition where you have adequate or even surplus of leptin levels, but your body stops, sort of ignores the signal because there's so much of it. And so estradiol works in that pathway and can help improve leptin sensitivity. So it's very common in the perimenopausal and postmenopausal years that appetite regulation, both at hormone or both at hunger and fullness pieces may be off. And we know that estrogen plays a role in that. in the way that GLP certainly does as well. There's also estrogen receptors in our gastrointestinal system and may help to potentiate the effects of GLP in the system, both in terms of stimulating the receptor, helping to keep it active more longer. And so there's some belief that there's a actually synergistic effect between hormone replacement therapy and GLP medications. And so we've started using, and sort of as a community, we've seen more use in this space. I think one of the biggest things to caution, though, is that this is pretty preliminary data. As we talked about that pendulum swinging of nobody takes hormones to now there's lots of people interested in it. I think we do want to be really careful of how we are really intentionally approaching this. Both for physicians, you have someone who is experienced in this area, someone who has studied in this area, looking for a menopause certified provider may be one of the best options to find someone who is skilled, trained, and tested in perimenopausal symptom management. Additionally, though, looking for people who are board certified in obesity medicine, that skill set certainly really important as well, because we're talking about these two things in combination with one another. Now, the thing that really challenging is that hormone replacement therapy is not approved for weight loss. So when we look at FDA approvals of medication, it is very common that medications will have approvals for very certain indications and then other uses are off-label. So the FDA will say, yes, it's been studied for this indication and it's appropriate to use in that. That being said, we as clinicians use off-label medications all of the time. It is very very common that we'll prescribe medications that were initially thought of maybe for the treatment of depression. We'll use it for appetite suppression or smoking cessation. Medications that were for seizure prevention now are used for migraine prevention. Medications that are for seizures may be used for pain relief. And so we see this happen very frequently where medications are used off-label. So off-label is not a bad thing. but off-label sometimes will draw a little bit more skepticism from people. And it certainly needs to be done judiciously when we recognize, are you an appropriate candidate for this medication? Is it being done in a way that makes sense? Certainly you don't want to just take any medication for any indication. You want to know that there is some data, both in terms of safety, as well as in terms of efficacy or meaning, does that actually work? And so HRT, hormone replacement therapy with estrogen is FDA approved for a few specific. reasons. Specifically, when we think about the postmenopausal years, it does have FDA approval for vasomotor symptoms. So that is the classic menopausal hot flushes or hot flashes and does have FDA approval for that indication. It's also approved for the prevention of osteoporosis. And finally, in the menopausal patient population, also for vulvovaginal atrophy, which is the vaginal dryness that can happen in the postmenopausal years, increasing pain with intercourse, as well as increasing the risk for urinary tract infection. So estrogen is approved for those indications. It does also have other indications for a younger patient population. So people with hypogonadism, meaning that their ovaries aren't functioning properly, that their ovaries aren't producing the estrogen that they should be, or for women who've had total hysterectomy, including ovarian removal, which would decrease their estrogen levels, that it is approved in that patient population as well. So what you did not hear me saying is this medication approved for the use of weight. And so it is not at this time. There certainly are some downsides and some risk of using estrogen medication. So it's important to know What are your individual risk? Again, the book Estrogen Matters can be a really great resource. Dr. Rachel Rubin's podcast on Peter Tia, a great resource. As I'm saying all this thinking, okay, definitely we need an episode talking about the safety and some of the data on these medications. But risk versus benefits. Are there any potential risk or downsides or things that you are uniquely at risk for with using these medications? What are the things that you're at risk for for not using these medications? How long has passed since you've gone through menopause? We know that the longer period of time since you've gone through menopause, there may be less benefit from using these medications compared to people who've had similar estrogen levels or at least continual estrogen stimulation even beyond their perimenopausal years. And so it's challenging because there's not FDA approval from a weight reduction purpose. And I don't know that right now we really have the data for there to be. But what we do know is that estrogen signals in many of these pathways related to our metabolic health. We have some of the early data to show that estrogen in combination with GLP may be really helpful in from a weight perspective that continuing to stimulate estrogen may help not just to decrease weight, but to decrease that central adiposity, that visceral weight gain that can really increase the risk of cardiovascular disease. And so thinking about hormone replacement therapy may be a part of the picture for the right person. Now, as we're wrapping up this episode, like I said, I'm realizing I am leaving a couple of things hanging. And so if you're thinking about oh my gosh, what happens next? If you have been struggling with your weight, there's nothing better I could recommend than to connect with a board certified obesity medicine physician. You can do that at the ABOM, the American Board of Obesity Medicine. Look at a physician and providers who are certified in your area. Similarly, we mentioned the North American Menopause Society, which has recently changed their name to the Menopause Society, but looking at women or physicians rather who are certified in treatment of menopause, that can be really valuable to make sure that you're finding someone who is going to understand these pieces. There are physicians who are certified in both of those things who may be able to help you uniquely navigate the perimenopausal and postmenopausal weight gain. And then as a patient, or even as providers who aren't yet well educated in this field, and I don't say that in a derogatory way, but in a way that even as a physician, Thank you so much for joining us. The residents at your program need to know this because she had felt ill-equipped to be able to do that. And this is as a family medicine physician. So someone who was trained in primary care in the family medicine space, there's a really big emphasis on women's health. And this is not something that because there was so much controversy afterwards. controversy after the Women's Health Initiative, there is a whole cohort of women who are not treated and a cohort of physicians who have not been fully educated on this. And so my best advice for you is to start educating yourself, look at some of those resources to help understand what would this mean for me. And it may be appropriate to use hormone replacement therapy as part of your journey, depending on your symptoms. If you are in Charlotte's Virginia. We are enrolling patients for in-person care. I also see patients throughout the states of Illinois, Tennessee, and Virginia. You can learn more about me at www.sarahstombaumd.com. Thank you so much for joining me today. We'll look forward to seeing you all next week. Bye-bye.