Title: HRT and the FDA

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Brigid Bergin: It's The Brian Lehrer Show on WNYC. I'm Brigid Bergin, senior reporter in the WNYC and Gothamist newsroom, sitting in for Brian. Welcome back, everyone. Have you seen the news that the FDA is calling to remove warning labels from hormone therapy products used for treating menopause? Currently, all menopause treatments containing estrogen carry warning labels noting increased risk of strokes, blood clots, probable dementia, and breast cancer, regardless of formulation.

Last week, the Food and Drug Administration held a panel in which a dozen physicians and researchers advocated for this change, but some advocates are concerned that the FDA commissioner, Dr. Marty Makary, and the panel of experts at Thursday's meeting underplayed the risks associated with hormone treatments. With me now to talk about the risks and benefits of hormonal menopause treatments and what the possible removal of warning labels could mean for patients and their doctors is Dr. Jen Gunter. She's an OB/GYN and pain medicine physician, and author of the books the Menopause Manifesto and Blood: The Science, Medicine, and Mythology of Menstruation. Dr. Gunter, welcome to WNYC.

Dr. Jen Gunter: Thank you for having me.

Brigid Bergin: Before we get into the debate unfurling in Washington, can you just start us off with the basics of this issue? We're talking about hormones here, so it might be useful to explain the science of menopause, what's going on in the body when we enter menopause, and why does this happen.

Dr. Jen Gunter: Sure. Menopause is the end of ovulation. Puberty is the start of ovulation. Menopause is the end. We say that a woman is in menopause when she's a year from her final period, if she's over the age of 45, because obviously, we don't really know it's your final period until it's really your final period. There's a time leading up to that final period that we call the menopause transition, that many people call perimenopause. That is associated with changes in cycles, and symptoms can also start then.

In addition to just irregular cycles, people may have symptoms of menopause starting in their menopause transition, hot flashes and night sweats being the most common, but brain fog and depression, joint pain, or some other common symptoms that are described, vaginal dryness as well. Some people may develop those symptoms after their final period. Some people will have worse symptoms. Some people have no symptoms. I think the best explanation for the range in symptoms is if people think about pregnancy, people have a range of symptoms in pregnancy. Some people have terrible nausea and vomiting. Other people have no nausea and vomiting. It's this range of symptoms that's really quite common.

Brigid Bergin: What are some of the hormonal products on the market, and how are they intended to treat some of these symptoms?

Dr. Jen Gunter: I think it's really important to distinguish between therapies meant for the vagina that are supposed to just treat vaginal symptoms, and symptoms that therapies that get into your blood to treat widespread symptoms. This is actually part of the concern about how the reporting on the panel occurred, because the people who were, for example, Dr. Pinkerton, was calling to have the warning label removed from the vaginal estrogen, which is really, I think, supported by almost everybody. The American College of OB/GYN, The Menopause Society recommends removing the black box warning from vaginal estrogen, but that's been conflated to mean all estrogen, and that's a very different discussion.

Brigid Bergin: Talk a little bit about what those differences are. What is the research that exists on the risks and benefits of both of these types of therapies, and how did this conflation take place?

Dr. Jen Gunter: If we're talking about vaginal estrogen, vaginal estrogen is a local treatment for a local problem. Changes in the vagina associated with menopause include vaginal dryness, vaginal itching, decrease in lubrication, pain with sex, and also can encompass some bladder symptoms, for example, increased risk of urinary tract infections, which for some women can really be catastrophic. When we're talking about antibiotic stewardship and making sure that we're not overprescribing antibiotics, if we could prevent people from getting bladder infections, might that be a good thing?

We now have a lot of observational data on vaginal estrogen. It's important to point out that we don't have clinical trials that go longer than a year for safety, but we do have a ton of observational data. That's been increasing over the years. Now we can say with really high confidence that vaginal estrogen, when dosed appropriately, is a very safe local treatment for these symptoms. It wouldn't be appropriate to have that black box warning, because what happens is people get the prescriptions, they see the black box, and they think, "Oh, my God, my doctor's trying to kill me," or maybe their partner reads it, and then they don't take it. It's very scary.

We believe that there's a lot of data that would support removing that. A really good point that was brought up at the panel is that there's another medication that we use for the same symptoms, these vaginal symptoms of menopause, called DHEA, and that doesn't have the warning because it's not an estrogen. The estrogen warning is like a class thing. Everything with estrogen has to have this. It doesn't seem fair that a drug that achieves the same very low estrogen levels, the DHEA, would not have the black box warning, but the low-dose vaginal estrogen does.

That's important to discuss as one issue, that black box, vaginal estrogen. It's very important that this happen, I think, to remove the black box warning, but it's also important that it happens with the normal process. Not just after hearing a panel and making a unilateral decision. This needs to go to a formal scientific committee where they take public input, they have a formal process, and then after that, making the decision because if you give the FDA commissioner the ability to unilaterally make a decision on one medication, what might happen with another, or something like mifepristone?

Brigid Bergin: Sure. Listeners, we have time for some of your calls and texts on the subject of hormonal treatments for menopause and the FDA's call to remove warning labels from these products. Are you currently undergoing treatment for menopause and using either an oral medication or transdermal alternative? How do you weigh the risks for versus the benefits? Have you experienced relief or side effects from your hormonal medication? Doctors, what's your take on the FDA's claim that the risks are overstated? How do you decide who to administer hormonal medications to, and what could it mean for your practice if these warning labels were removed?

We can also take questions for our guest, Dr. Jen Gunter, OB/GYN and pain medicine physician. You can call us at 212-433-WNYC. That's 212-433-9692. Dr. Gunter, you were talking about how this process needs to involve more than just the commission's decision. Some of the confusion and some of the coverage has raised the fact that the FDA's commissioner, Dr. Marty Makary, as well as some of the experts on last Thursday's panel, have claimed that women are being harmed because physicians and patients are being dissuaded from using hormonal treatments by these warning labels. Is there a cost-benefit analysis of hormone therapy as you see it?

Dr. Jen Gunter: When we talk about systemic hormones, hormones that go throughout your body, that when they're dosed appropriately, in the studies that we have, there is no doubt that they are highly beneficial for many of the symptoms of menopause, particularly hot flashes and night sweats. We have less good data on other symptoms, for example, brain fog, and we have some pretty good data on using it for depression in the menopause transition. We have pretty good data that shows that menopause hormone therapy can reduce the risk of osteoporosis, although we don't have good data about who we should be recommending it to for that reason.

We have some data, but we don't know if we should be screening people earlier. That's an open area. I think that some of the concerns about the older warnings, which are appropriate to revisit, are this concern about causing cardiovascular disease. I think that we have a lot of data now that we didn't have at the time. We have a lot more randomized trials. We have other data, and I think that we can say with really high confidence that the cardiovascular risk of an appropriately-dosed menopause hormone therapy just isn't there. That we don't have to be concerned about people harming their hearts.

It's possible there could be a benefit, but it's really important to say that because there's so many different types of estrogens, formulations, and also people who need a progesterone or progestin because they have a uterus, that also changes things. We sometimes see different results when we just give estrogen by itself or estrogen with these other things. The best that we can say for the heart is maybe there's a signal for benefit, but we really don't have enough data to say for sure from a cardio protection standpoint, but we can, I think, reassure women that this is a very safe medication.

Unless they have very high risk of cardiovascular disease or they're more than 10 years or so from their last period, then in these situations, we maybe have a little bit more concern from a cardiovascular risk. From this standpoint, we think that the medication is really very safe. From a breast cancer standpoint, if we look at the combination therapy with estrogen plus a progesterone or progestin, the risk is in what we would call the rare to very rare range. Between 1 in 1,000 and 1 in 10,000. You're talking a rare risk.

Whether that's going to mean different things to different people, and there is a little bit of data that suggests that people who have a much higher baseline risk, that might be a different discussion, but it's also important to point out that some of the estrogens, for example, Premarin, which was in the Women's Health Initiative, if you take it by itself without a progestin, there's actually a lower risk of breast cancer. It's a different molecule. There's a lot of, I wouldn't say confusion, but complexity. It's not fair, especially when we're talking about things like breast cancer or the heart, to lump all these things together and say hormone therapy, because there's actually some nuances here.

Brigid Bergin: Sure. We have a lot of callers who want to weigh in and potentially ask their questions. I want to go to Jen in Montclair, New Jersey. Jen, you're on WNYC.

Jen: Oh, hi. Thanks for taking my call. I wanted to just say that I understand the nuance and the science, and I know it gets really complex, and I totally appreciate this segment. I started the transdermal patch and progesterone six months ago, and literally within three days, about 80% of my arthritis pain went away, and I found myself running up a staircase and I sleep like a baby. I just want to tell that to all the women out there. I'm 52. I'm two years into menopause, and it has been utterly life-changing. I just hope women don't get mired in the complexity of the science and just speak to their doctors, because it's really, really, really life-changing.

Brigid Bergin: Jen, thanks for that story and that call. Dr. Gunter, I guess, what that caller makes me think of are two things you were saying. One, that we don't have the data to be able to answer some of the questions about these different types of medications, and forgive me as a journalist, not a scientist, but asking the dumb but obvious question. Why don't we have that data yet? Menopause itself is not exactly a new thing. I also think I could probably help answer some of that question. Also, how are women supposed to navigate these conversations with their doctors, given all the nuance that you've described? Is there a good starting point for that kind of conversation?

Dr. Jen Gunter: Yes. I think that it's important to point out that we really were hampered, obviously, by not having a lot of basic understanding of menopause. It wasn't until we started, I think, in the early '90s, getting studies like SWAN, Study of Women's Health Across the Nation, the Penn Ovarian Aging Study, I think the Seattle Midlife Women's Health Study, where women were being followed. We were collecting data so we could actually understand what symptoms are happening, because you also have to understand or remember that menopause is happening at the same time as aging.

There actually are two big bumps in aging at age 40 and age 60, which is the start of the menopause transition, and at the end, when symptoms tend for many people to be dissipating. We need to sort out what's what, and that's important while that's happening. Of course, it hasn't happened because people have rolled their eyes at menopause, they rolled their eyes at understanding, they're systemic patriarchy. I could go on and on, the systemic underfunding of gynecology. I think everybody gets that point. I think that while we're sorting that out, that we can say that this is a really low-risk therapy when dosed appropriately and used in the appropriate way.

If somebody is having symptoms, and especially if they are having sleep disturbance, because here's the deal, sleep disturbance impacts many other things in your life. If you're sleeping better, how many of those other things are going to get better? It's very valid to say, "Look, I have this constellation of symptoms. Some of them may or may not be menopause. Should we do a trial of the medication to see if I feel better?" Sure. That's a really valid thing. It's also important to point out that there are people who don't feel good on hormones. Who feel worse. You can try and see, and I think that's a very valid thing.

Brigid Bergin: Let's go to Deanna in Morristown, New Jersey.

Deanna: Hey. Hi. Thanks for having me on. I am 58, just started taking the patch and the pill and the cream this past year. It took me-- I'm 10 years out of menopause, 10 years since ending my period. It took me three different practitioners to be able to help me, who were willing to help me, could give me some straight information. My main question is if they're going to make this black box change, where's the education piece for doctors, and how is that going to reach us? Because we have to practically become doctors ourselves to get the information we need.

Brigid Bergin: Deanna, thanks for that question. Dr. Gunter, how do doctors stay abreast of some of this changing environment?

Dr. Jen Gunter: Well, I think that there's, again, a couple of things in play. First of all, the average gynecologist gets very little time in the office with their patient. That's related to the way the healthcare insurance industry, the way Medicare, Medicaid, and everything is structured. There's this systematic underfunding and underappreciation of what we call office gynecology. That's an issue, and with more and more private equity, this is just going to get worse because they're shuttering the gynecology components of many practices.

The other thing is that, for many people, menopause is not well taught in residency. It's not well taught in medical school, but I'm also going to push back a little bit on that. I didn't learn anything about pain with sex during medical school or really, residency in OB/GYN. In my first week of practice, I had a patient with pain with sex, so I learned about it very quickly. When we go to medical school, we learn how to learn. It is really our duty, if we have people coming into our office and they're having symptoms, to look those up, to see what's happening with the available literature.

For example, when the Women's Health Initiative came out and there was this whole shock and awe, and what does this mean, and the press coverage, I went to the Menopause Society and see what they wrote. I said, "Who were the mentors that I trained with who knew the most about hormones? Let me see what they've written on this." I very quickly got myself up to speed. While it is important to teach people and to emphasize it, we also have to remember that what you learn in medical school or residency may not be valid 15 years later, so you certainly can't rely on what you learn.

I think teaching about it underscores the importance, but it really needs to be embedded into everything. If you're a preventative cardiologist, for example, half the people you're going to see are probably women, or close to half, and a lot of them are going to be in menopause. That should be folded into understanding heart disease.

Brigid Bergin: One of the listeners just texted. "Both my mom and sister were on tamoxifen for five years for breast cancer. It blocked estrogen." How does this fit into the conversation?

Dr. Jen Gunter: The current guidelines from Menopause Society, from The American College of OB/GYN, from the Endocrine Society is that women who have hormone receptor-positive breast cancer, and women with breast cancer in general, we would be concerned about giving hormone therapy to that patient population. Is there a possibility that in some very select populations, it may be appropriate? That's a very individual one-on-one discussion with a provider for somebody maybe who has very, very severe symptoms. I think across the board that, generally, that's not indicated.

Tamoxifen is a very important drug for many women with breast cancer. It can also be an important drug to prevent breast cancer as part of a chemo reduction strategy. These are things that have to be individualized. A family history of breast cancer is itself not a contraindication to menopause hormone therapy, but obviously, a full history needs to be undertaken, and I would recommend that everybody do a breast cancer risk scoring system before they start menopause hormone therapy, there's the Gail Model and the Tyrer-Cuzick Model, both of them are available online.

This is important for a couple of reasons. It might change how you get screened for breast cancer. It might change the screening that we want to do before we start you on menopause hormone therapy, and people who score very high may be candidates for chemoprevention. These are just all other discussions so you can have an evidence-based discussion.

Brigid Bergin: Just to wrap things up, we touched on the politics of this issue. This call to remove the black box warnings is coming from the Trump administration and President Trump's appointed commissioner to the FDA. The New York Times was reporting that four of the physicians are members of the Let's Talk Menopause, an advocacy group supported by Pfizer, Bayer, and other pharmaceutical companies. Several of the panelists run exclusive practices that don't accept insurance and charge high fees. Do you see other financial or political motivators that are behind this call to remove the warnings?

Dr. Jen Gunter: I think that if you look specifically just at the black box warning for vaginal estrogen, that that's universally supported by expert societies and by as best observational data as we're going to get. I think once we start talking about veering into some of the other discussions of the panel where it was basically just like, "Tell us what you think about hormone therapy." I've also read Makary's book chapter on hormone therapy, and it's an egregious example of cherry picking the literature. Let's just call it what it is.

I think my concern is more from what I've heard Makary say afterwards on NewsNation or on the Megyn Kelly Radio Show or whatever her show is, is that there's a big propaganda tool that seems to be coming from this. I don't know how much of this is a distraction. I don't know how much of this is lip service, but he's repeating the disinformation on these shows about estrogen being proven to reduce deaths from cardiovascular disease, estrogen is being proven to reduce dementia, and that we do not have that data. In fact, at the 2024 Menopause Society Meeting last year, we had an amazing update on all of the data on dementia, and we do not have the data.

For him to go on news shows and say that we do, that's an ethical issue for me, and that's problematic. I would just have people think about the fact that if we set the precedent that the FDA commissioner can just start to unilaterally make changes with labeling, what could that also lead to? Dr. Makary has been on record on Fox News of saying that a fetus moves away from abortion equipment, which is a fantasy. That it's a purposeful movement. I just think people need to be aware of the entire picture, and I think that they need to understand that if the FDA commissioner is talking about all of menopause hormone therapy, systemic and vaginal, as if it's one thing, then he clearly doesn't understand it at all.

Brigid Bergin: Thank you so much for helping us better understand it. We're going to leave it there for now. My guest was Jen Gunter, OB/GYN and pain medicine physician, and author of the Menopause Manifesto and Blood: The Science, Medicine, and Mythology of Menstruation. Dr. Gunter, thank you so much.

Dr. Jen Gunter: Oh, thank you so much for having me.

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