Neha Pathak, MD, FACP, DipABLM: Welcome to the WebMD Health Discovered Podcast. I'm Dr Neha Pathak, WebMD’s chief physician editor for health and lifestyle medicine. For decades, many women have navigated perimenopause and menopause without clear information, effective treatment options, or even validation that what they're experiencing is real. Add to that the lingering fear and stigma around hormone therapy, and it's no surprise so many women feel stuck, untreated, or afraid to ask questions.

Today, we're sharing part one of a two-part podcast series with Dr Sharon Malone on perimenopause, menopause, and hormone replacement therapy. We're talking about what actually happens during the menopausal transition, how long that transition can last, why symptoms can feel chaotic and unpredictable, and how outdated interpretations of past research have shaped—and in many cases, limited—women's care.

This episode is going to provide a lot of context, clarity, and hopefully empowerment. Our goal is for you to better understand your body, evaluate hormone therapy with accurate information, and have more informed conversations with your healthcare provider about what support looks like now, not based on information from 20 years ago.

If you're in your thirties, forties, or fifties and feeling confused by changes in your sleep, mood, memory, weight, or cycles—or if you've been told by your doctor that, well, this is just aging, or your labs are normal, so there's nothing we need to do—this episode is for you.

First, let me introduce my guest, Dr Sharon Malone. Dr Malone is the chief medical advisor for Alloy Women’s Health. She brings decades of clinical and real-life experience to her treatment of women in the menopausal transition and the post-reproductive years. She's the author of Grown Woman Talk and podcast host of The Second Opinion. Welcome to the WebMD Health Discovered Podcast, Dr Malone.

Sharon Malone, MD: Thank you for having me.

Pathak: I'm so excited to have you again because you always help clarify so much for us. But before we jump into our discussion for today, I'd love to ask about your own health discovery in your research or your work with patients around hormone therapy.

Malone: When I started this over 30 years ago, hormone therapy was very much a part of our conversation and how we counseled postmenopausal women. Then there was sort of a break in 2002, when the Women’s Health Initiative—a large, pivotal study—changed how we look at hormone therapy, the risks, and benefits.

And so there was sort of a break between the first 10 years of my practice and the second two-thirds—I would say the next 20 years. In that time, it has been very difficult trying to get women to see that hormone therapy is not as bad as it has been portrayed.

There’s also the point in these 20 years post that study where women just have gotten nothing. They've gotten no information about what's upcoming, what to do about it. And so there's been this sort of void for the past 20 years that we're finally seeing the ice breaking on. And now we're in a different era, and that's good news.

Pathak: Well, that's great, and I'm really looking forward to digging into the good news. I'd love to take a step back and help our audience understand perimenopause, the menopausal transition—what is happening with hormone levels and hormone cycling during this period.

Malone: In the life cycle of women, we go through various phases. As children, we are what we call pre-pubertal. Then you go through puberty—12, 13 years old—and you make that transition into your reproductive years. Everybody understands that. That's what you learn in health class, most of us, and that's what your parents and your mother really prepare you for as you transition from being a child to being a woman. We get that part.

Then there are your reproductive years, which start at puberty and usually go until about your mid-thirties—your peak reproductive years. People kind of understand what menopause is, and menopause is the permanent end of your reproductive years, which usually happens around 51.

But there’s this huge expanse in between, and this is where people get a little fuzzy—that’s perimenopause. I use the terms interchangeably: perimenopause and the menopausal transition. It’s the transition from your reproductive years to your post-reproductive years.

The issue is that it doesn’t happen orderly. It doesn’t happen to all women at the same age. It can happen anywhere from your mid-thirties to your early fifties.

Hormonally, you’re leaving that orderly production of hormones from your reproductive years, and then there are wild fluctuations. An analogy I like is this: imagine there’s an ongoing conversation between your brain and your ovaries. Your brain gives instructions, and your ovaries respond accordingly.

In perimenopause, the ovaries don’t hear as well, so the message doesn’t always get through. When it doesn’t, your brain responds by talking louder—it sends a stronger signal. Sometimes it works, sometimes it doesn’t. That’s where the fluctuation comes in.

Once you reach menopause—around 51 in this country—the ovaries have gone completely deaf. No matter how loud your brain is talking, they can’t respond. That’s a metaphor for what’s happening.

That process can last anywhere from four to 10 years. It’s not just a point in time. What confuses women is that we think menopause is just the end of your period, plus some symptoms. But so many things happen during perimenopause that create confusion.

Some women have IUDs and don’t get periods. Others are on birth control pills and don’t know which periods are theirs. So we can’t use just the end of your periods as the marker for completing the transition.

The other confusing part is that the symptoms we associate with menopause—hot flashes, mood swings, sleeplessness, brain fog, depression, anxiety, sometimes weight gain—don’t happen in any particular order. They can start even when periods are still relatively regular.

What I want women to understand is that this isn’t a bright line separating one phase from another. It’s a years-long process. And believe it or not, women are often more symptomatic during the transition than after menopause, which leads to confusion for women and for doctors trying to make the correct diagnosis.

Pathak: So I’d like to dig into several of the threads you’ve laid out. First, let’s start with those messages coming from your brain, because we’re going to dig into hormone therapy. What are those hormones—the messengers—that are coming from your brain, and what response is meant to come from your ovaries?

Malone: Okay, we’re going to get a little nerdy for a moment, because that’s what we do. It’s called the hypothalamic axis. The signal comes from your hypothalamus, a part of your brain, to your pituitary gland at the base of your brain.

Those signals go back and forth, with feedback telling you when to stop and when to start. The pituitary makes hormones that direct the ovary—when to mature eggs, when to ovulate, when to stop and start over if conception hasn’t occurred. That’s the cyclical nature of the monthly cycle.

There’s also feedback from the ovary to the brain. If conception occurs, estrogen feeds back to the brain to say, “Stop. Mission accomplished.”

That ongoing conversation between the brain, pituitary gland, and ovary isn’t one-directional—it goes back and forth. That’s all upended during perimenopause. That’s why we see so many menstrual irregularities.

The regular 28-day cycle may become every two weeks or every 60 days. Irregularity is more the rule than the exception during that period.

Pathak: And so then let's get to another question that a lot of my patients come in with. And you mentioned this, that there is no bright line, but often patients will come in and say, “I need you to do a test and test me to see if I am in perimenopause.” So talk to us a little bit about how we can sort of dispel some of the confusion and talk about what we can and cannot do with labs in the office.

Malone: Remember when I said that what's happening in perimenopause is that the hormones wildly fluctuate. They may be normal today. Your estrogen may be normal next week. It may overshoot the mark by a lot, or it may undershoot, and all of those hormones. That's why I said it's not helpful in making the diagnosis, because just because it's normal one week doesn't mean it's out of whack the next week or even the week previously.

So we don't really use blood tests to confirm whether or not you're perimenopausal. However, a blood test can be helpful when you are trying to decide whether or not you are menopausal, which means you have had your last period. Because remember that signal where the brain is talking to your ovaries is to tell it to do something.

That hormone that it's sending out from your pituitary is called an FSH, and as that signal gets louder and louder and louder, that will rise. Well, it rises and it will stay at that level once you are postmenopausal. That's the only time that a blood test is sometimes helpful. It's helpful for women who've had hysterectomies, because remember we don't always have periods to go by to say, “Oh, the definition, the medical definition of menopause, is when you have had the moment that you have had your last menstrual period.” Because that means you are forever menopausal. But how do you know when you've had your last period?

You don't until you look back. It's confirmed by having had a year of no further periods. So that's kind of a diagnosis in retrospect. That's not helpful in the moment. So that is a case where sometimes we will use that blood test when we think someone is truly menopausal and we don't have the period marker to go by.

So that's why, when I say confusion, there's a lot of confusion in perimenopause because, you know, even though menopause means the end of your fertility, perimenopause means there is a change in your fertility. It is usually less. You are less fertile in your forties than you were in your thirties.

But because of that chaotic ovulation pattern, it is also a time when women think, “Oh, well, I haven't had a period in three months. I must be done.” And there are a lot of unintended pregnancies, because remember I said your fertility is diminished; it's not gone. And I can speak to that because my mother was almost 45 years old when I was born, and I would hazard a guess to say that she probably wasn't saying, “You know what I need? Another child. I already have seven. One more—make it eight.”

So I can tell you for a fact, it does happen. And because of that chaotic nature of what's happening with your hormones, believe it or not, for women who are in perimenopause who do conceive, there is also a higher risk of twins and multiple births in women who are in their forties. And that is because, again, you're not ovulating one egg at a time. Sometimes you overshoot and your hormones are too high, and now you’ve got two.

So I say that to all my perimenopausal ladies: be careful. Just be careful if that's not what you choose.

Pathak: So I'd love to then dig into really the focus of our discussion today, which is hormone therapy. So help us understand—what does that term encompass in today's world?

Malone: Well, hormone therapy is the overarching umbrella that sort of hangs over all of the different therapies that we have. And remember, because we say that perimenopause and menopause are basically hormonal disruptions or the end of hormone production, that is really what triggers so many of the symptoms that women have.

It makes sense that our solution is a hormonal solution. Now, most women will say, “Oh no,” they're so afraid of hormone therapy. And these will be women who've taken birth control pills for 25 years. And believe it or not, birth control pills are one of the options for hormonal therapy as well.

And they work really well for women who are in that perimenopausal transition, who not only need relief of their symptoms but sometimes regulation of their menstrual cycles, because that also can be terrible. Cycles are either too heavy, too long, or too infrequent. We use birth control pills for that. And we also need them, obviously, for contraception, as we just talked about before.

So again—fearful of hormone therapy, not so fearful of birth control pills. But understand they are the same basic components in birth control pills that are in hormone therapy, which basically is an estrogen and a progestogen, which are just the two hormones that your ovaries would make in the course of a normal menstrual cycle.

The difference is there are different types. We use a different type of estrogen in a birth control pill than we use in hormone therapy. And basically, for hormone therapy or menopausal hormone therapy, it is usually far less than you would ever take in a birth control pill. So if you're taking hormone therapy or menopausal hormone replacement therapy, you're taking anywhere from a third to a quarter of the dose of what's in even a low-dose birth control pill.

So I think the fear of hormone therapy is something that has been generated—not because people don't understand what hormone therapy really is. It's simply an estrogen of some type or another, and it is a progestogen. You need far less in menopause to control your symptoms than you do when you're trying to control cycles and contraception when you're perimenopausal or even in your premenopausal years.

So those are the basic components of it. And we can talk, if we have time, about why that sort of misperception of hormone therapy—and how that's dangerous—and why birth control pills aren't. And that's not made up. That's something that really came as a result of bad press from over 23 years ago.

Pathak: Let's dig into the fear and some of the stigma around hormone therapy. So part of it relates to what you were talking about with regard to the media attention around the study that came out around 20 years ago, and also the black box warnings. So talk a little bit about both of those things and myths you'd like to dispel around hormone therapy.

Malone: This is a good point to sort of have a little historical context. Hormone therapy as a treatment for menopause is not new. The first hormone was approved by the FDA in 1942. Okay, so here we are—we have almost 80 years of experience using hormones for the treatment of menopause.

So fast forward. Women had been taking hormones, and we learned certain things along the way about, “Oh, perhaps we shouldn't just give estrogen by itself to women who have a uterus.” That was probably around the seventies, when we said, “Oh, we're seeing a higher incidence of uterine cancer in women who use estrogen alone.” It did great for the symptoms—now that says nothing about the efficacy for treating what it was given for—but we started to see a higher spike in endometrial cancer.

That's when progestin, or that second hormone, was added to the hormonal regimen, and there we sailed along beautifully. Until 2002, we were using estrogen alone for women who had hysterectomies, who didn't have a uterus, and estrogen and a progestogen for women who did have a uterus. Things were going great. Women were happy. Probably, by the time I started in practice, about 30 to 40% of women who were symptomatic in menopause were given prescriptions for hormones because it did wonderful things. It relieved your menopausal symptoms—hot flashes, night sweats, irritability went away like magic with hormone therapy.

Here is the problem. Because we had all of this observational data—50 years of women who had taken hormone therapy—we observed that, in addition to relief of symptoms, women who were taking hormone therapy had a decreased risk of osteoporosis. Oh, that's a good thing. We also observed that they had about a 50% decrease in the risk of cardiovascular disease. And that was huge, because believe it or not, and I know you know this, but most people don't realize that the number one killer of women in this country then and now is cardiovascular disease, not breast cancer.

That was the genesis of the big study started in 1991 by Dr Bernadine Healy, a cardiologist and the first female director of the NIH—which is why who's in charge matters. Prior to that, all we had was observational data. There had never been a rigorous, randomized, double-blind, placebo-controlled study that actually looked at hormone therapy for women postmenopausally, because in 1991, women weren't even included in most clinical trials.

So this was huge. The Women's Health Initiative was designed to look at whether hormone therapy decreased the risk of heart disease. We didn't need a study to know whether it relieved symptoms—we knew that for 50-plus years. Unfortunately, the average age of the women in the study was 63, meaning they were about 10 years postmenopause. The findings were therefore not applicable to the general population of women being prescribed hormones.

The results showed no decrease in cardiovascular disease, a slight increase in breast cancer—about one additional case per thousand women per year—which was not statistically significant, and increased risks of stroke, blood clots, and dementia, primarily in much older women. But that nuance was lost.

When the findings came out in 2002, it was seismic. Women stopped hormone therapy immediately. Even the 40,000 women in the study stopped their hormones. And from that data alone came the black box warning—the highest warning you can place on a medication.

So now, over 22 years later, the black box warning is finally coming off estrogen-containing products. The risks and benefits will still be in the package insert, which is where they belong. And I want to be very clear: that black box warning should never have been there in the first place.

This isn’t new information. Those of us in the medical field have been advocating for this correction since day one.

Pathak: So tell us a little bit more about this advocacy that has been ongoing since 2002. What has that entailed? What were the sort of ways that you really interrogated that study to make this shift again now?

Malone: Well, I tell you, context is everything. And there was so much drama when they announced the findings from the Women’s Health Initiative in 2002. And, you know, I mean, they held a press conference at the National Press Club here in DC and invited all the press in. That’s why it was such a big splash.

Now, that’s not the way study results are announced. You know, maybe if you were curing cancer, that would be worthwhile, but it wasn’t really an appropriate venue. So you have to say maybe there was an agenda about why you chose to report that way. So that’s number one.

But the other part about it—and for young people who realize there was a time before the internet—we didn’t have access to the journal. So they announced and put this out there, and it went on immediately across all the news media: Good Morning America, the Today show, The New York Times—everything, headlines everywhere.

We doctors didn’t get the journal for another 10 days, so we didn’t even know what to say. We’re like, “Oh my God, have we been doing this wrong all this time?” So you get it, you read it, and you go, “Okay, it didn’t say that. Oh, and that didn’t say that. And this doesn’t apply to that.”

And do you know how difficult it is to put that genie back in the bottle after it’s already been out there in the press for weeks? It went on and on. So those of us who really read it—and you’d be surprised how many people didn’t actually read the study; they just took the headlines. And I’m talking about doctors, not patients. They didn’t read it, and they didn’t get into it and understand it. So they were like, “Oh, you know, maybe this should stop.”

Well, when it stopped, it had several very pernicious effects. One, women stopped right away, even women who were doing well. Doctors stopped prescribing. And I think, more importantly, research into women’s health and hormones stopped—not just in the United States, but around the world.

So, you know, we’ve been living in this vacuum for all this time because nobody now wants to do a study about hormone therapy. They assume, “Well, we already know the answer. What’s the point of doing another study?” And so we’ve been at that place.

But there were so many people who objected in the room at the time—and I’m talking about the researchers who were actually collecting the data. Because there were 40 medical centers across the country, and there were 40,000 women in the hormone part of it. And the principal investigators who were conducting these clinical trials, they were not warned.

So imagine you’re sitting there and they announce it, and they say, “Well, oh yeah, by the way…” And the article’s already written. They did not involve any of the clinical investigators. I say that to say that’s been ongoing.

There have been a lot of us who are out there, and I will say Dr Jim Simon has been an advocate for reframing this. Dr Avrum Bluming. Dr Roger Lobo. I mean, these are all people who were heavyweights, who knew that this was wrong at the time. But we didn’t have social media, so we argued about it in medical conferences, and we tried to talk to our patients one on one in the room, but we couldn’t really make the headway that we needed to make.

There were articles written about it—many articles—about how the Women’s Health Initiative got it wrong. Again, how many people read those? And imagine if OB-GYNs were not trained post-2002. Well then the falloff is steeper when you get to internal medicine, when you get to oncologists, when you get to cardiologists who were affiliated, but not really part of the core of women’s health.

And so it’s been stuck. But make no mistake about this: the information is not new. We’ve known it. The difference now in the advocacy is that we have increased the awareness. Now we’ve talked about it so much and have the ability to disseminate this information in a way that we never had before that now it is part of the general conversation. It’s part of social media. You see a lot of people talking about it. You see more doctors talking about it.

So that’s the point. It’s, you know, I always like to say, no, you didn’t just discover something, because there really hasn’t been that much more research done in this amount of time. But I think that when we look at that study, we don’t want to throw the baby out with the bathwater.

There have been several follow-ups. They did a 10-year follow-up, but now we’ve got a 20-year follow-up. And as we look at those women over time, they found that, wow—timing matters, huh? Don’t start hormone therapy at 75 years old.

When you parse the data and look at women who start hormone therapy either before age 60 or within 10 years of menopause, those women do have a decrease in the risk of cardiovascular disease. Those women do have a decrease in the risk of osteoporosis. And all the symptoms that we know are alleviated—hot flashes, sleeplessness, depression.

Type 2 diabetes is also decreased in women. And those things are independent risk factors for developing cardiovascular disease. So doesn’t it make sense that if you treat those symptoms early?

But we learned about the window of opportunity from the Women’s Health Initiative. So we did learn some things. Timing matters. We also learned that the type of estrogen may matter. We couldn’t say that definitively because the study only used one type of hormone—an oral estrogen. It only used one dose. It only used one progestogen.

So you can’t generalize and say, “Well, the effects of Premarin are the same as a transdermal estrogen.” We did, but we shouldn’t have.

We also learned—and I think this is a very important piece—that there were two groups. If you have a uterus, you have to take estrogen and progestin, because the progestogen protects the uterus. But there was a whole cohort of women who had had hysterectomies, and those women were on estrogen only.

And guess what they found? At 20 years of follow-up, the women who were on estrogen only had a 23% decrease in the risk of breast cancer, a 40% decrease in the risk of dying from breast cancer—even if you were diagnosed with breast cancer—and a 30% decrease in overall mortality. That’s dying from everything, not just breast cancer.

So had it not been for the Women’s Health Initiative, we wouldn’t know that. And I think it helps take out of the conversation the idea that estrogen is bad. Estrogen is not bad.

Pathak: Thank you so much for being with us today for part one of our two-part podcast series on perimenopause, menopause, and HRT. I’d like to close with my three key takeaways from this conversation.

First, perimenopause is a hormonal transition, not a single moment. This transition can take years, and symptoms can be all over the place for years before and after menopause. Because hormones fluctuate unpredictably during this time, blood tests are usually not helpful for diagnosis. Listening to symptoms and patterns is often far more clinically meaningful, particularly in that long stretch of perimenopause.

Second, we’ve come a long way in our understanding of hormone therapy. Dose, formulation, route of administration, and—most importantly—timing matters. When started in appropriate candidates and within the appropriate timeframe, hormone therapy can be effective in relieving symptoms and may offer potential benefits beyond traditional perimenopausal symptoms.

Finally, fear around hormone therapy has been driven largely by misinterpretation and oversimplification of older data. Estrogen itself is not bad, and decades of follow-up research have helped clarify who benefits most and how to use it appropriately.

The main takeaway for everyone listening is that you deserve nuanced, individualized care. Asking your healthcare provider questions about perimenopause, menopause, and hormone therapy is not only appropriate—it’s essential. It’s also important to realize that many healthcare providers need more education on this topic, so try to find someone who’s trained in menopause treatment and management.

To find out more information about Dr Sharon Malone, menopause, and HRT, make sure to check out our show notes. We’ll be back next week with part two of our conversation with Dr Malone. In the meantime, to find out more information about her, her work, menopause, perimenopause, and HRT, make sure to check out our show notes.

Thank you so much for listening. Please take a moment to follow, rate, and review this podcast on your favorite listening platform. If you’d like to send me an email about topics you’re interested in or questions for future guests, please send me a note at [email protected].

This is Dr Neha Pathak for the WebMD Health Discovered Podcast.