JUANA SUMMERS, HOST:
For more than two decades, the Food and Drug Administration has warned women about the potential risks of using estrogen to treat menopause symptoms. And that's because early studies showed an increased risk of endometrial cancer, cardiovascular disorders and breast cancer. Well, those warnings are going away, and FDA Commissioner Marty Makary led the way on that decision, and he's here with me in studio now. Thanks for coming by.
MARTY MAKARY: Great to be with you, Juana.
SUMMERS: So, I mean, this black box warning that we're talking about, it's been in place on all estrogen treatments for more than two decades, since back in 2003. The timing - why remove it now?
MAKARY: Well, the fear machine did start in 2003, after a 2002 study that really hit the airwaves in the media with a big splash, scaring women out of hormone replacement therapy in the postmenopausal setting. Up to 1 in 4 Americans were taking it. Women lived longer and felt better. But then it got deemed a carcinogen based on this study. It turns out when the study results were finally released after the media announcement, there was no statistically significant increased risk of breast cancer. There was a lower rate of breast cancer in the estrogen-only group. And so it ends up being very nuanced. And the cardiovascular benefits are profound when hormone replacement therapy is started within 10 years of the onset of menopause. So there is some nuance here.
SUMMERS: Yeah.
MAKARY: But unfortunately, the fear machine has dominated the field, and women have been talked out of it. They've been denied or never offered hormone replacement therapy despite the profound short-term and long-term benefits.
SUMMERS: Well, let's talk about that for a second, because there is a lot of nuance here. Just spell out plainly for us some of the benefits of hormone therapy as you see them.
MAKARY: Yeah. So starting hormone replacement therapy around the time of menopause not only can alleviate the short-term symptoms of menopause - that is the hot flashes, night sweats, mood swings, weight gain, difficulty sleeping...
SUMMERS: Right.
MAKARY: ...Pain with sexual activity. There are 50-plus different symptoms, and every woman experiences them differently. You know, we were taught at medical school that some women have symptoms, but they're usually mild and last just a couple years - not true. Eighty-plus percent of women have symptoms. The average duration is eight years, and for many women, it is severe. They are debilitating.
The long-term benefits are remarkable and massively misunderstood. It reduces the risk of bone fractures later in life by 50- to 60%. That's a New England Journal study. It reduces cognitive decline by up to 64%. In one study, reduced the risk of Alzheimer's by 35%, and there are cardiovascular benefits when it's started within 10 years of the onset of menopause.
SUMMERS: Does it matter if a woman is taking a pill, which is systemic, or using a cream, which is a local treatment?
MAKARY: So there are pills. There are patches. There are creams and gels.
SUMMERS: Right.
MAKARY: And so all of these products had a black box warning from the FDA as a part of this pile-on, as a part of this bandwagon thinking in 2002, 2003. We are removing those and putting the nuances of the risks in the package insert. And the idea is to get better information in front of women.
SUMMERS: Spell out some of these risks for us, because there are still risks associated with hormone replacement therapy, is that right?
MAKARY: Yeah. When started more than 10 years after the onset of menopause, then you actually see some of these risks that are - have been attributed to all hormone replacement therapy products. And that's probably because the body naturally is making estrogen, and that increases nitric oxide. It keeps the blood vessels soft and the walls soft and healthy and dilated. And so when it started such that there's not a gap where your body is without it, then there are cardiovascular benefits where the reduction in heart disease has been noted to be 35 - 30- to 50%. That is a 30- to 50% reduction in heart disease, and in a study in circulation two years ago, a 48% decline in heart attack deaths. And so that is because of the effect of estrogen. So if it's started too late, the blood vessels are narrowing and the theory is that they're hardening and that aging and atherosclerosis can then result in a situation that is prone for a blood clot...
SUMMERS: Right.
MAKARY: ...With hormone therapy.
SUMMERS: Commissioner, are there women who should not be using hormone therapy?
MAKARY: Yes. Many doctors do identify some contraindications - a woman with an underlying risk for blood clots, a woman with active breast cancer or past breast cancer, depending on the practice style of the physician. But the vast majority of women who go through menopause, which is about 2 million women a year, are great candidates for hormone replacement therapy. If a woman has a uterus, it's important for them to also take progesterone to reduce the risk of endometrial hyperplasia and possibly uterine cancer. But women who have been taking this for a long time have reported tremendous benefits, and they're talking about it on social media now.
SUMMERS: Yeah.
MAKARY: So there is a bit of an awakening.
SUMMERS: I do want to ask you about the process here. Because in preparing to remove the black box warning, there's usually a formal, very detailed process. Things seemed to play out differently this time. Tell us why.
MAKARY: Yeah. We're getting things done. In this administration, at the FDA, we're getting things done. They were talking about removing or banning a food dye for 35 years before I got to the FDA. Within weeks, we took action to remove nine petroleum-based food dyes from the food supply. That's all artificial dyes. In this case, we are responding to a petition that was filed in 2016. It was basically blown off. It was refiled in 2025. We held an expert panel. We didn't go through the long, bureaucratic, expensive process of bringing in conflicted experts to talk about a product. We brought in a range of diverse medical experts who passionately made the case for stopping this fear machine by removing the black box warnings around cardiovascular disease, dementia and breast cancer.
SUMMERS: I mean, over the last several years in our society, I don't have to tell you this, but there has been this increasing recognition of the health challenges, the very real challenges that women face during menopause, and you and I were talking about the nuance in this conversation earlier. Do you worry at all that by removing this black box warning, that it might result in the pendulum tipping the other way, and there's now going to be an overuse of hormone therapy?
MAKARY: Well, tragically, over the last 23 years, 50 million women have been denied or talked out of hormone replacement therapy in part because of the fear machine that it - hormone replacement therapy is a carcinogen, it causes breast cancer. We can argue whether or not the old type of progesterone used, called MPA, in that original study may have slightly increased the risk of breast cancer in women who took that MPA. But no clinical trial has ever found that it increases the risk of breast cancer mortality. And if it did, that harm would be far eclipsed by the profound cardiovascular benefits. You know, early on in the 1920s, Mayo Clinic researchers noted that young girls who had their ovaries removed went on to have heart disease in their 30s and 40s, suggesting a profound cardiovascular protective effect. And so that's the nuance conversation that people need to have.
SUMMERS: We've been speaking with FDA commissioner Dr. Marty Makary, coming in to talk to us about the FDA's decision to remove black box warnings for estrogen treatments for menopause. Thank you so much for coming by our studios today.
MAKARY: Great to be with you, Juana. Transcript provided by NPR, Copyright NPR.
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