98: Menopause, Hormones, & GLP Weight Loss Shots

 In this episode of Your Checkup, we explore a new study from the Mayo Clinic examining whether menopause hormone therapy enhances weight loss outcomes in postmenopausal women taking tirzepatide. Menopause is a major metabolic turning point — with rising visceral fat, declining muscle mass, and increasing cardiovascular risk. Researchers found that women using hormone therapy while on tirzepatide lost significantly more weight — nearly 5% more total body weight — and experienced additional cardiometabolic improvements compared to women not using hormones. We break down what this means, why estrogen may play a synergistic role, what the study does not prove, and how to think about personalized obesity treatment during midlife. 

Transcript

SPEAKER_00 0:06

Hi, welcome to your checkup. We are the Patient Education Podcast, where we bring conversations from the doctor's office to your ears. On this podcast, we try to bring medicine closer to its patients. I'm Ed Delesky, a family medicine doctor in the Philadelphia area.

SPEAKER_01 0:20

And I'm Cole Ruffo.

SPEAKER_00 0:21

I'm a nurse. And we are so excited you were able to join us here again today. Um, it's been a uh this has been an awesome weekend, I gotta say.

SPEAKER_01 0:30

It really has. Really has. Well, first of all, your man cold has seemed to be resolving itself. So thank God for that. All is right in the world.

SPEAKER_00 0:42

Yeah, I've looked the the mucus has given way to clear stuff, and there's a little bit of a cough. A little bit of a couple.

SPEAKER_01 0:53

You do that on purpose.

SPEAKER_00 0:54

Yeah, right on cue. Usually it's like every 12th word, which is tough during the day. But no, I'm feeling great. We've like gone to the gym three out of the last four days to lift. We do exercise almost every day, but like going to the gym for actual lifting. You looked like you were gonna say something. No, and yesterday we went on our little gym date and then executed our very highly anticipated Valentine's Day plans.

SPEAKER_01 1:23

Yeah, that was so great. Our Valentine's Day plans were going to the gym and having a nice long workout. And then we rotted all day, and we watched Love is Blind, the new season that just came out, and we ordered poly G's that we had for lunch and dinner. And you made chocolate covered strawberries.

SPEAKER_00 1:48

Yeah, it was the whole thing was great. How are you feeling about Love is Blind this season?

SPEAKER_01 1:55

I'm feeling good about this season.

SPEAKER_00 1:57

Me too.

SPEAKER_01 1:58

It's in Ohio, and I don't know, they just seem like more wholesome out in Ohio. And they're all like a little bit older. Not like older, but like sometimes people will be like 24.

SPEAKER_00 2:14

That's a good point.

SPEAKER_01 2:16

And they're like, oh my god, I'm like ready to get married, married, and like they're not.

SPEAKER_00 2:21

Also a good point.

SPEAKER_01 2:22

Yeah.

SPEAKER_00 2:22

Especially when you're going on one of these shows to see if you're ready to get married. No, I like it. I think I find like there's more people who are actually sincerely looking for love on this season than there were maybe last season or other seasons in the past. So that's good. There's no one particularly well, who's problematic that you can think of?

SPEAKER_01 2:46

Emma.

SPEAKER_00 2:47

Emma.

SPEAKER_01 2:48

Yeah.

SPEAKER_00 2:50

Which one's Emma?

SPEAKER_01 2:52

The one that was adopted with the arm.

SPEAKER_00 2:55

Yes. Yeah. She really did blossom though once she started talking about you know, like once she like opened up a little bit. She was very reserved and she was well, I don't know. What do you what did you think?

SPEAKER_01 3:13

I feel like I don't know. I just feel like she's gonna be problematic.

SPEAKER_00 3:18

Time will tell. Time will tell. Um any other big feelings about the what you're looking forward to? We did six episodes.

SPEAKER_01 3:28

We did. I'm looking forward to the next three episodes that are coming out.

SPEAKER_00 3:31

Unfortunately, it's on a Wednesday, so we're probably not gonna watch it in real time.

Gym Form Fail And Neutral Spine

SPEAKER_01 3:36

No, unfortunately not.

SPEAKER_00 3:40

I have something I have to share that I just learned yesterday. What? So we we did a nice leg day at the gym, and I think maybe you you stopped me at one point and you were like, why are you doing it that way? Why are you squatting that way? Why are you squatting that way? And I, for the longest time in my life, have squatted as I was taught when I was a young lad in Jackson, New Jersey, and a teacher of some sort. I might have been like a like physical education teacher, wrestling coach. I didn't wrestle, so I don't know why he was why I was interfacing with him. But he told me to pinch my shoulders back, which I think is good form, stick my butt out like I'm an exotic dancer. That's not the wording he used, but for the purposes of this podcast, that's what I'll say, and get to work and bring my butt to the floor, and that's how you squat. And it stuck with me every day. I don't know why. So my tuckis has always been a little small, but when I was, and my legs and my thighs always big, and in college, I like did my did a fine job squatting. So it was in track athlete, so we were always lifting. And through all of my 20s and now my early 30s, I've squatted with this like gigantic arch in my back. And I think you looked at me as painful.

SPEAKER_01 5:07

Like my back hurts watching you squat.

SPEAKER_00 5:12

And I and you know, last year I I talked to people a lot about their form during the day, or like I tell them about like squats and stuff, and I tell them about back exercises a little bit if they have low back pain. And you should probably stop telling people. I probably should. And then yesterday, last year you taught me about a neutral spine, which I do tell people, and I'm like, oh, whenever you're doing these back exercises, you need to use a neutral spine. That's what they're gonna teach you at PT. It's a tricky thing, unless you have a Nikki at home. Then you told me that I need to use a neutral spine when I'm squatting. And my I'm his head exploded. Yeah, I feel like I've lived it's my parent, I my parents are my parents, but it's as if I found out I was adopted. Like that my life when it comes to leg day is a lie.

unknown 6:08

Yeah.

SPEAKER_00 6:09

The entire time. And I've always wondered like I squat so much, why is my booty a little small?

SPEAKER_01 6:16

Because you are squatting with your back.

SPEAKER_00 6:18

Because you're squatting with my back and my quads.

SPEAKER_01 6:21

Which is so then I text like my med school friends, and they're like, Yeah, I was very validating that you're he like texted his other friends who are also like very into like fitness and working out. And they were like, Yeah, bro.

SPEAKER_00 6:38

What are you doing?

SPEAKER_01 6:39

Shouldn't be doing that.

SPEAKER_00 6:42

That got me. I was they're like, Yeah, duh, of course, what are you doing? I'm like, are you kidding me?

SPEAKER_01 6:49

You're like loading, like doing like a back squat, you're loading all this weight on your back, straining your, you're like arching your lower back, so you're just like straining and putting more like pressure on your lower back. Yeah, not embracing your core whatsoever.

SPEAKER_00 7:07

No, not so not what not at all. No support. But this is how he taught me, and now it's all wrong. And why is this only coming up now? Is the question. Like, I worked out with Justin all the time. Did he notice this? Did he not tell me anything? Like, why did no one say anything up until now? Is my question.

SPEAKER_01 7:34

That's because for some reason everyone thinks you walk on water and I'm here to humble you.

SPEAKER_00 7:40

No, but this isn't even anything to do with that. I think you just have that luck and loading my wifely duty. But like be humble. That's so wrong. I was so, so wrong. And I I think in the summertime I did hurt my back a little bit when I was squatting, and I didn't understand why. And now every time I'm in the middle of the street, we're walking Ollie, and I'm in the middle of the street, and I'm trying to squat with a neutral spine. And then there are people walking up behind me on the sidewalk. Like I'm obsessed now that I can't do this. I mean, there are a couple tools, and um, you know, our close personal friend at the gym, Paul, showed us the the one incline thing to do the squat with.

SPEAKER_01 8:25

Oh, yeah. I like that thing a lot.

SPEAKER_00 8:27

I do too. Oh man. So that's that was a big deal. Um, I was really bothered by that.

SPEAKER_01 8:35

Yeah. Eddie found out he was adopted this weekend.

SPEAKER_00 8:40

Wow.

SPEAKER_01 8:42

Maybe on Thursday.

Setting The Agenda: Menopause And Meds

SPEAKER_00 8:44

Yeah, maybe we'll go on Thursday. Thursday's today. We have a little bit more time together at home. So until the schedule changes, hopefully. All right, why don't we dive into it? We've given the people really good.

SPEAKER_01 8:56

We got ravioli to make.

SPEAKER_00 8:57

We got ravioli to make. So what are we gonna talk about today, Nick?

SPEAKER_01 9:02

Today we're talking about menopause, hormones, and weight loss shots.

SPEAKER_00 9:07

Yeah, there was a new study that came out from the Mayo Clinic, and I think the press grabbed onto this a lot, and it has some legs on social media. And so I figured what better venue than for us to take a little time outside of any big grand themes that we have and cover something that's very much in the health zeitgeist between the three of these topics themselves. So if you're in menopause and taking terzepitide, like zep bound or munjaro, does hormone therapy improve weight loss results? And I this is not meant to be headline grabby. This is meant to be an exploratory conversation that is not sexy. It's not gonna be headline-y, but it's gonna go over the study in light person terms so that you understand it and you walk out of here with a balanced perspective. Does it seem fair, Nick?

SPEAKER_01 10:08

I think so.

Why Menopause Changes Metabolism

How Tirzepatide Works

Mayo Clinic Study Design

SPEAKER_00 10:09

So the new study from the Mayo Clinic suggests, and I say suggests because that's an important word. Politicians use the word cause all the time, but suggests that post-menopausal women using hormone therapy lost a significant amount more weight on terzepatide than women who were not using hormones. And they also saw additional cardiometabolic benefits. So we break down why menopause increases weight gain and cardiovascular risk. That's a maddening thing for women, what terzepatide does in the body, how estrogen affects fat distribution, metabolism, and some muscle. The key findings from this new study, not to bury the lead, there needs to be more. What this study does and does not prove and investigate, and who should or should not consider hormone therapy. So if you were navigating midlife weight gain, vasomotor symptoms, or obesity treatment, I think this episode could be really helpful for you. So the first part we want to talk about is why menopause changes everything to set the stage. Between ages 40 and 65, obesity rates in women actually jump significantly. They go from about 37% to nearly 47%. That's not just aging. We would argue that menopause plays a major role. Because when estrogen declines, we understand that lean muscle mass decreases because of that, resting metabolic rate drops. Fat or adipose tissue shifts from the hips and the thighs to the abdomen. Visceral fat increases much faster thereafter. And in fact, visceral fat can increase by about 6% per year after menopause compared to 1% before. This is uh from a figure from a study cited within this study that we're reviewing today. Study within a study, if you will. So this shift isn't just cosmetic because it increases the risk for type 2 diabetes, high blood pressure, dyslipidemia, fatty liver disease, and also increases the risk of sleep apnea and cardiovascular disease, the number one cause of death in the world. So, in fact, after menopause, women's cardiovascular disease risk rises sharply, eventually matching or exceeding men's. So menopause isn't just a symptom phase, it is actually a cardiometabolic transition. So then we're going to transition into the second part of this. Where does terzepitide come in? Zeppebound or Munjaro? You know these names now if you've listened to us. It is currently the most effective FDA-approved medicine for the treatment of obesity. It works on two hormone pathways, GLP1. Everyone knows it, everyone loves it, and GIP, gastric inhibitory peptide. They added that in there. It makes for increased potency and also reduces side effects. Together, they reduce appetite, improve insulin sensitivity. For a period of time, they slow gastric emptying, but there's thought that that goes away, and improve blood sugar and promote significant weight loss. In clinical trials, people lost up to 20% or more of their body weight on average. But the interesting question falls in here does reproductive stage, specifically menopause, change how well it works? And then a layered question in there that the study was looking into is does adding hormone therapy make it work better? And that is what the researchers at the Mayo Clinic were looking at. They looked at postmenopausal women treated with trzeptide for at least 12 months, and they compared 40 women on systemic hormone therapy and 80 matched women not on hormone therapy. Right from the jump, I want to say, very small amount. They looked, when I say retrospective, I mean that they looked back. They found people in health records. They looked at many, thousands, and they found this many. So 40 and 80 is not a lot, but it's what we have that we can look at today. They carefully matched these two groups for age, BMI, age of menopause, onset, diabetes status, and prior obesity medication use. And in essence, what they tried to do is they tried to make similar groups to make comparisons. So, Nikki, can you tell us, starting off, what did they find?

SPEAKER_01 15:07

Sure. So after 15 months, women on hormone therapy lost 19.2% of their body weight, while the women who were not on hormone therapy lost 14%. So that's a solid 5% greater total body loss. Yeah. Total body weight loss. And 5% is something that's clinically meaningful. It is. 5%, not, you know, 5 pounds.

Physiology And Possible Synergy

Limits, Causation, And Caution

Who Should Consider Hormone Therapy

Personalized Care And Takeaways

SPEAKER_00 15:32

And what was so what was even more striking is that more women in the hormone therapy group hit greater than 20% weight loss, greater than 25% total body weight loss, or even greater than 30% total body weight loss. Some of these thresholds approaching bariatric surgery territory for some patients. There were also cardiometabolic improvements, which we talked about earlier. Both groups improved blood sugar, blood pressure, and liver enzymes. We've talked about this in previous episodes, how obesity can affect the liver, metabolic disease of the liver. But the hormone therapy group had additional improvements in diastolic pressure. That's interesting. That's a tough one to bring down. Triglycerides, that is a type of cholesterol that really is affected by meal-to-meal variations. And AST, which is a specific liver enzyme. So it is just more than weight loss, but probably better metabolic improvements as well in women who were on the hormone therapy. So they who, the researchers who did this study, kudos to them, they postulated why this might happen. And this is where the physiology gets exciting. They were suggesting that estrogen itself also might improve insulin sensitivity, enhance fat oxidation. Fat oxidation is, you can think of oxidation as a word to describe breaking down fat to use it for energy. That they could help preserve lean mass. We talked about that being so intimately related to resting metabolic rate. That it reduces, though estrogen may reduce visceral fat accumulation if it goes away during menopause. And then women experience an increase in visceral adiposity, that giving it back might reduce that, and improve lipid profiles. That's just the estrogen. Meanwhile, trisepatide, as we know and love, suppresses appetite through hormonal regulation with the brain, improves glycemic control by allowing people to be even more insulin sensitive, and overall just enhances metabolic flexibility. So it's possible that these mechanisms are actually complementary if you couldn't see what I was trying to connect there. You could imagine that estrogen helping to maintain muscle and metabolic rate while terzepitide reduces calorie intake and improves handling the body's handling of glucose. That offers a potential synergy there, but there's an important caveat to this because this study has a certain list of things it doesn't prove. So we're going to cover what this study does not prove next. This was a retrospective cohort study. So they took a population of people, they looked back at medical records, and they saw, all right, these people were on trazepatide and took hormones. These people were just on trzepatide. Let's compare them. That is not as scientifically rigorous as something else, like call they it was a randomized controlled trial. So in essence, this was not randomized, and therefore it cannot prove causation. So it can't tell us, this study that is, whether hormone therapy directly enhances terzepatite, or whether women on hormone therapy were more health engaged because they were going to the doctor, they, or whoever they were seeing, and they got these medicines, or whether unmeasured factors influenced outcomes just because of how the study works. It was also small. I mean, there were 120 women total. 94% of them were white. So that counts. That means something. That's a pretty limited scope of people to look at. And so overall, when we look at this, we have to be cautious. And the authors were were really great in their discussion section looking at that too. And they themselves called for prospective randomized trials, meaning you take large groups of people, you give one per and you go forward in time, and you give one group of people terzepatide, the other group of people hormones and terzepitide, and you follow them in the course of time. That's what they're calling for. And that hasn't been done yet because it's only been a couple months that there aren't significant black box warnings on hormone replacement therapy. So we just want to say out loud to answer a question that might come from this. Should every woman on trzepatide start hormone therapy? Absolutely not. Hormone therapy is not a weight loss drug. It is indicated for moderate to severe vasomotor symptoms. And there are some benefits of preventing bone loss in certain women. So that's good. But it does carry some risks. There are contraindications, meaning reasons that people have that they can't take the medicine, and individual personal goals. So this study suggests that if a woman already has clinical indication for hormone therapy, it may enhance weight loss and cardiometabolic response to terzepatide, which is a very different thing from prescribing hormones solely for weight loss. So the big takeaway is that this study highlights something that we talk about a lot. Obesity treatment should be personalized, and that menopause is not just a life phase, but it is a metabolic inflection point. We should be thinking about reproductive stage, symptom burden, cardiovascular risk, body composition changes, which we're going to be talking about soon, and the hormonal environment when we are figuring out treatment plans for people, and especially for women in midlife, a thoughtful combination of lifestyle, pharmacotherapy, and maybe hormone therapy, but who knows? We have to, there's more to be said. So if you're navigating menopause and struggling with weight gain, you are not imagining it. These are real physiological changes happening to your body. And the good news is that we are finally able to start taking these things more seriously. As always, please talk to your clinician about your individual risks and benefits. And don't go running around just slapping a headline saying, like, ooh, hormones and traceptide do this. That's not how science works. We tried to explain that here today. And yeah, so that's what we got for you. What do you think, Nick?

SPEAKER_01 22:02

I think that sounds great.

Wrap Up And Listener Invitations

SPEAKER_00 22:03

Awesome. Any takeaways? Okay, great. So thank you for coming back to another episode of Your Checkup. Hopefully you were able to learn something for yourself, a loved one, or a neighbor. You could find us on Threads, where we are most proactive, probably too much. You can find us, you can send us an email, follow our Instagram, or you can just reach out to us. And if you have any questions, we'd love to do a mailbag episode at some point in the future at the suggestion of our friends, just going over some random things. We're going to try to set up another mini-series for you to keep things cohesive, as we, you know, sometimes the weekly episodes are disparate topics, and you know, thematically it just fits a little bit better into our life if we talk about one thing for a couple episodes. We're going to be coming up to our 100th episode in a c a little while. Isn't that something? And we're coming up on two years that we've been doing this, which is very cool. But most importantly, thank you for coming back. Stay healthy, my friends. Until next time, I'm Ed Delesky.

SPEAKER_01 23:07

I'm Nicole Rupo.

SPEAKER_00 23:08

Thank you and goodbye.

SPEAKER_01 23:09

Bye.

SPEAKER_00 23:15

This information may provide a brief overview of diagnosis, treatment, and medications. It's not exhaustive and is a tool to help you understand potential options about your health. It doesn't cover all details about conditions, treatments, or medications for a specific person. This is not medical advice or an attempt to substitute medical advice. You should contact a healthcare provider for personalized guidance based on your unique circumstances. We explicitly disclaim any liability relating to the information given or its use. This content doesn't endorse any treatments or medications for a specific patient. Always talk to your healthcare provider for a complete information tailored to you. In short, I'm not your doctor. I am not your nurse. And make sure you go get your own checkup with your own personal doctor.