Science Friday - Hot flashes, hormone therapy, and the science of perimenopause

Episode Date: September 17, 2026

Perimenopause affects more than 4 billion people, but has historically been neglected by medicine. It’s the time before menopause when hormones start fluctuating wildly, leaving women with brain fog, hot flashes, dropping bone density, and mood changes. Thanks in part to social media, it’s more prominent in public discourse than it used to be.But it’s not just awareness that’s blown up: It’s also the promise that you don’t have to suffer like those before you, thanks to hormone therapy. After decades of controversy over prescribing estradiol and progesterone due to concerns of increased breast cancer and heart disease risk, new research has many providers reconsidering their approach.Joining Flora to sort out the science are reproductive endocrinologists Nanette Santoro and Genevieve Neal-Perry, who are both running some of the biggest long-term studies on perimenopause and the effects of hormone therapy. Guests:Dr. Nanette Santoro is a reproductive endocrinologist at the University of Colorado Anschutz and is the president of the Endocrine Society.Dr. Genevieve Neal-Perry is a reproductive endocrinologist and the OB-GYN department chair at the University of North Carolina at Chapel Hill.Transcripts for each episode are available within 1-3 days at sciencefriday.com. Subscribe to this podcast. Follow our show on Instagram, TikTok, Facebook, and Bluesky @scifri and sign up for our newsletters. Got a science question that’s keeping you up at night? Call us: 877-472-4374 Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Hey, it's Flora and you're listening to Science Friday. We're talking about a condition that affects more than 4 billion people on this planet, but historically has been pretty neglected by medicine. Any guesses? Perrymenopause, the window before menopause where hormones begin fluctuating wildly, leaving women with brain fog, hot flashes, dropping bone density and mood changes. Now, thanks in part to social media. perimenopause is way more in the public discourse than it used to be. But it's not just awareness

that's blown up. It's also this promise that you don't have to suffer like those before you, thanks to hormone therapy. And testimonials abound. This week marks my first week being on estrogen and progesterone. In the past week, my energy levels go up, my sleep's gotten better, and I'm not as moody or crabby. After decades of controversy over prescribing estradiol and progesterone due to concern of increased breast cancer and heart disease risk, new research has many providers reconsidering their approach. Here to sort out the science are two pioneers of this field. They're both running some of the biggest long-term studies on perimenopause and the effects of hormone therapy. Dr. Nanette Centoro is a reproductive endocrinologist at the University of Colorado Anshoutes. She's the lead

investigator on a three-decade study following 3,000 women to better understand the menopause transition. It's called the Swan Study. And Dr. Genevieve Neil Perry is a neuroendocrinologist and chair of UNC OBGYN. She's also a co-investigator on many large studies studying the effects of hormone therapy, and she researches how the brain changes in response to peri menopause and menopause. Welcome both of you to Science Friday. I'm so excited to talk to you about this. Thanks. Pleasure to be here. Absolutely. You both have been studying this since before it was cool. Do you feel like we're in a moment for perimenopause?

And how would you describe it? Well, we're definitely in a moment. And while I think it's wonderful that there's this much attention being paid to this life passage since I and Genevieve now are both survivors of perimenopause, it's a bit of a touchy time because we do lack information. So as you've said, you know, we don't have all the information we need to proceed. And some directions in which the field is going are a little concerning. Let's talk about the information we do have. Just the basics, what's happening under the hood during perimenopause? Well, there's this impression that, you know, women are just sort of like Whistler's mother,

just sitting quietly in a rocking chair while their hormones just peter out. And that's not what's happening. So as you said in the beginning, you know, hormones are up and down. So there's a period of fluctuation, but as we've also learned from the Swan study, really is a bodywide set of changes that are dramatic for some, but for many, they're inconvenient, annoying, and there's probably few women who don't really notice much of anything. You mentioned that symptoms aren't the same for everybody. We actually, we asked listeners to call in, and we got a bunch of responses with some people saying,

perimenopause totally altered their personality and other saying they barely noticed it. I don't like it. I don't like it at all. I ran into my doctor's office and literally yelled to say, please help me. I feel like I'm going to lose my mind. Never had a single symptom or problem. The thing that was so shocking to me on top of the hot flashes, the sleep disturbances, is I wasn't myself. I didn't call people back. Everything seemed harder than it should be. But of course, I'm on the other side now, and I'm considered menopausal. And I would say the skies have cleared a bit, but it was really hard for a long time.

Do we know why perimenopause hits some people harder than others? We have some evidence that there are some people who are a little more vulnerable than others to it. And there's some racial and ethnic differences in severity of symptoms that can erode your well-being. People with heightened symptom sensitivity, people who have more aches and pains going into the process, people who struggle financially to get by, the people who are the most socially stressed, I would say, in our current environment with the worst social determinants of health, tend to have the worst symptoms. And tragically, these are the ones who tend to be treated less. Hmm. We're a very nerdy show, and I know you're both endocrinologist, so I want to get into the details. Let's talk about hot flashes. How are they linked to hormone changes? What's the mechanism? Genevieve? Yeah. So this is actually when I become nerdy because I am truly a neuroscientist at heart living, you know, in an OBGYN world. What triggers hot flashes, it is related to the way changes.

and hormones actually affect neurons that are located in the brain that actually regulate how we experience our environment, like whether we feel hot or cold. Do they name these neurons? They do. The neurons are called candy neurons. And the way that I like to think about them is if you remember the hot tamales, they're like these old hot tamales that become super active in the absence of estrogen. And these neurons increase this peptide called neurokinin.

And that is what will connect with neurons that actually regulate how we sense our environment. And it's because of these neurons become hyperactive. They stimulate the neurons who are located in an area that control heat, and then they stimulate themselves. So it's like this kind of self-stimulation and stimulating these other areas that trigger hot flashes. And that's what happens. There's two parts of hot flashes that are really sort of mysterious and still remain to be understood. And how does the brain adapt?

I mean, we know the brain adapts to so many things. It's what makes us human. So the brain does eventually adapt for 85 to 90 percent of women. And there's this 5 to 10 percent that their hot flashes never go away. And they're just as bad as they were in the menopause transition. The other part of this that's also very fast. is that we think of hot flashes in association with low estrogen. But during the menopause transition, estrogen is up, it's down, it's up, it's down, it's variable. And that is when

hot flashes peak in a woman's life. So that's when they reach their highest level then and the year or so after the final menstrual period. So why they're still happening with full force when estrogen is there is also not known. So there's something more dynamic going. on. You know, Nanette, on social media, I feel like so many symptoms get blamed on perimenopause. Like, if you're having a bad hair day, it's pari menopause. Do you feel like some symptoms are unfairly attributed to perimenopause? Absolutely. You know, there's, it's very difficult to sort out right now looking at hormones alone. So if I were to look at your reproductive hormones, as you're entering the menopause transition, I would see very, very tiny differences between,

what you are maybe doing in your 30s. And sometimes we see no difference at all. So in the absence of hormone changes, it's hard to attribute this to hormones. It may be a variation of sort of a PMS type of symptom or a hormone intolerance. And it definitely deserves to be, you know, assessed and treated. So I don't want to dismiss it. But when you look at the symptom experience of women in their 35 plus, there's high symptoms for many, many things, the things that really tick up with a menopause transition, are hot flashes, sleep, some mood changes. And at what age do those happen for most people? In their mid-40s to late-40s, that's the average person.

But we don't want to just dismiss people who may be having symptoms earlier. And that's where there's such a gap in knowledge, right? In understanding who's at risk for earlier symptoms, we do know that there's some racial and ethnic differences. so we do know African-American women have symptoms earlier and well before there is evidence of menopause. There is something that's related to aging in general. And in our animal models,

neurons that typically respond to estrogen don't respond the same way. So they start to become like they're desensitized. Now, you know, whether or not that's what's happening in humans, we don't know. But we do have data that that's what we're seeing in non-human models. I have to take a break, but when we come back, we have to talk about the wild ride that is hormone therapy and its history. Are you all up for that? Absolutely. Okay, buckle up, everybody. Don't go away.

Prescribing hormone therapy for perimenopause has been such a huge journey over the last few decades. Genevieve, can you give me a sort of short version of why it was taboo and what's changed in the last couple years? Ooh, that's, you, you asked for a lot there. So, you know, the Women's Health Initiative, the WHOI study was a really important study. And it was designed to help us understand whether estrogen hormone therapy was associated with breast cancer, whether we had improvement in terms of neurocognition, and whether we had a heart benefit. And it was, it was a It was designed to look at women who were older, right? And it did what it was intended to do in terms of the study.

And we found that it wasn't cardioprotective because for many years women were told, even if you, you know, you've been menopausal for 15 years, you should start estrogen because it's cardio protective. So it found that that wasn't a case. And you know, we found that... It wasn't helping heart health. It wasn't helping heart health. Yeah.

And it wasn't helping cognition in old. older women, and there was an increased risk for breast cancer, which, by the way, was not the first time this was demonstrated. However, what happened is that that study was extrapolated to a completely different population. And so there was this conflation, right, that, oh, all women should never have estrogen because estrogen is bad. And it was just, it was misapplied. The information was misapplied to a group that wasn't studied. The concern was that there was cancer and, you know, there was more cognitive dysfunction in women who used it. So it was just assumed that it was bad for everyone.

And that's why there was this huge drop-off. And patients as well as providers became afraid to give women hormone therapy for hot flashes because they thought what they observed in WHA applied to all women who were menopausal as well as perimenopausal. No, no, anything to add to that piece of the history? It was known at the time of the WHA that there probably was going to be a small increase in the risk of breast cancer. That's been known. It's been supported. There was nothing new. There was no new risk uncovered. Exactly. Exactly. So if you were prescribing it for heart disease, you needed to stop. The breast cancer risk doesn't go away. The blood clot risk doesn't go away. But these are small.

And they were never balanced or meant to be balanced in the Women's Health Initiative against the benefit of making your symptoms go away. So doctors and prescribers were left with nothing because that was the only tool in the toolbox. So the furor that came out over this was just was such a hunk and mess. You know, now doctors are prescribing hormone therapy again. And of course it's like all the buzz on social media. what has changed? Sure. Well, for me, as the women's health initiative was followed up, there was 10-year follow-up, there was 18-year follow-up, and as you saw the follow-up of these women

who took it for about six to seven years, what you saw was a nothing burger. You saw no net change in mortality. People were not dying. There was no huge change in disease risks on any, there was some tiny differences. And then when you broke it down by age, you saw something that's a little more favorable for women ages 50 to 60, which is the prime hot flesh years. So it became far less scary, although I would pose it that it really never should have been anywhere near as scary as it was. To see, you know, hormone therapy dropped from 25% to 2.5% and never recover was just craziness. You know, Nadet, you said at the top you had some concerns about where the field is going

what do you mean? I have concerned about hormones being the answer to everything. Much as I love hormones and have dedicated my life to studying them, they're not the answer to everything. So we need to really keep our toolkit, you know, keep as many things as you can available to help your patient. And some of the influences that are happening in the social media world, there's a lot of commercialization. Midlife women have now been recognized as a fantastic market to sell stuff to.

So lots of stuff is being sold to women. They're being bombarded with information. And that makes it difficult to partner with my patient to work through her symptoms and use all of the modalities at hand if the promised, you know, fantastic treatment of hormone therapy isn't the answer for her. I want to just add to that because I am concerned, like Nanette, and I'm concerned because I feel that women are being taken advantage of, right? This is a very vulnerable time. You're tired because you're waking up at night, right, from sleep disruption. You know, you're not feeling your best, and they're looking for things to help them feel better. And there are people who are taking advantage of this and selling women things that we're doing.

There's absolutely no evidence to support it. Such as? Such as some of the peptide stuff, right? You know, there is an evidence that bioidenticals are better than our standard hormone therapy where we know that there's been an appropriate testing in terms of the dosing and safety, right? Women are being told, you know, that estrogen is the fountain of youth. right if you use estrogen and hormone therapy you're going to stay younger it feels like we're back

in the 50s and early 60s when women were told you need estrogen to stay young and and there is just you know it's the data isn't there um you know there are things that just happen as we get older and estrogen is not going to change that i like to tell my patients you know uh your estrogen was very low when you were nine years old. Your estrogen was nine and your skin was really great, right? So there are some beliefs that are very hard to shake. I call them zombie ideas. We're also at a time where I think there's a virtual crazon for testosterone as being an incredible fantastic treatment. And again, data just aren't there to support it. And it isn't that there's no data. There's actually negative data. There's data. Some studies have been done and do not support

some of the indications that my patients will bring in saying, you know, I must have testosterone for XYZ. And I think one one thing that's misconstrued is that there's this idea that, you know, testosterone levels are so low as you get older. And actually, if you look at the ratio of estrogen to testosterone, it's actually higher in the postmenopause. And people, you know, don't recognize that. And, you know, I tell my patients, I'm like, look, you know, you're concerned about hair growth on your face now. What do you think is going to happen if I give you androgens? So, you know, I think it's so important for people to be really, if it sounds too good to be true, it is. It is.

It always is. This has been such an informative conversation. Thank you both for walking us through today. It's our pleasure. Could talk about it all day. Thank you. Dr. Nanette Centoro is a reproductive endocrinologist and president of the Endocrine Society. And Dr. Genevieve Neil Perry is a reproductive endocrinologist and department chair of UNC OBGYN. This episode was produced by D. Peter Schmidt.

Thanks to everyone who called in for this and you can always call us. We're here. We're listening. 8774 sci-fi is our number. Thank you for listening. I'm Flora Lichten.