A panel assembled by the U.S. Food and Drug Administration (FDA) has unanimously called for the removal of a black box warning on certain forms of estrogen replacement hormone therapy (HRT) for menopause.
The warning — which has been on all estrogen-containing menopause treatments for over two decades — states that estrogen use may increase the risk of stroke, blood clots, and breast cancer.
However, most experts believe that the warning isn’t appropriate for all types of estrogen, particularly the localized kind, such as vaginal cream, and that for many women it overstates the risks.
The panel included a dozen physicians, researchers, and influencers, chosen by Dr. Makary, including JoAnn Pinkerton, MD, a professor of obstetrics and gynecology at the University of Virginia in Charlottesville and past president of the Menopause Society; Heather Hirsch, MD, a menopause care specialist; and Mary Jane Minkin, MD, of the Yale School of Medicine in New Haven, Connecticut.
Four panelists are members of Let’s Talk Menopause, an advocacy group supported by pharmaceutical companies including Pfizer and Bayer. Several panelists run exclusive practices that don’t take insurance and charge high fees.
Panel Process Breaks From Tradition, Prompting Some Criticism
While most experts agree that a review of the black box warning is a good thing, some question the FDA’s process.
Cindy Pearson, a longtime women’s health advocate, voiced concern that the meeting was unbalanced — heavy on personal anecdotes and supportive voices, light on dissent and rigorous data review. No members of the panel delved into whether removing the warning could have negative impacts and, breaking from tradition, no FDA scientists and drug safety experts gave presentations.
“This was a media event, not a scientific review,” says Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at the Northwestern University Feinberg School of Medicine in Chicago and host of the podcast Dr. Streicher’s Inside Information: Menopause, Midlife, and More.
While reviewing the data and removing the warning label for some types of estrogen replacement is appropriate, conducting a public hearing on YouTube attended by the media is not, says Dr. Streicher.
“The way that you do this is by having an expert scientific committee, beyond closed doors, that does a very, very careful analysis and statistical analysis of all the current literature to determine what modifications or changes need to be made,” she says.
Why Estrogen Replacement Ended Up With a Black Box Warning
In response, the FDA added a black box warning (indicating the highest level of risk) to all estrogen-containing products, regardless of their form or absorption rate.
Use of these medications plummeted. In 2000, roughly 20 percent of women over 50 were using HRT. By 2008, that number had dropped below 5 percent.
Later Research Suggests HRT Much Safer Than Previously Thought
The study findings have since come under intense scrutiny, with many experts now saying the results were skewed. For example, participants were 63 years old on average, which means those women already had a higher baseline risk for cardiovascular issues.
A follow-up study published in 2024 concluded that HRT is safe and beneficial for most healthy women with bothersome menopause symptoms, when started in the years shortly after menopause begins. Investigators found that hormone therapy didn’t increase the chances of death from all causes in any age group when compared with women of similar age taking a placebo.
Vaginal Estrogen Should Never Have Had a Black Box Warning, Experts Say
“When you’re talking about local estrogen therapy, there’s no controversy — the warning label is not appropriate,” says Streicher.
Local estrogen replacement is for women who have vaginal and vulvar dryness or urinary symptoms associated with menopause. Estrogen therapy comes in multiple forms — vaginal ring, tablet, insert, and cream — and delivers small hormone doses directly to genital tissue.
Hugh Taylor, MD, a menopause expert and chair of obstetrics and gynecology and at the Yale School of Medicine, agrees. “These forms don’t absorb much in the circulation, and the risks really are very different from other forms of hormone therapy,” he says.
“I think it’s important not to scare people about using the vaginal estrogen, which is really crucially important to have available. There’s really nothing else that can restore the vagina for people who have dryness and sexual dysfunction,” says Dr. Taylor.
Should Warning Labels Be Removed From Estrogen Patches and Pills? It’s Complicated
It isn’t clear if the panel aims to remove the warning label from other forms of menopause hormone therapy, including systemic hormone therapy such as estrogen patches or gels and pills taken orally.
Both Streicher and Taylor agree that decision isn’t as clear cut, because there are more associated health risks for systemic therapy, especially for some groups of women.
“The labeling for systemic therapies really needs to be done on a product by product basis, and it’s more nuanced,” says Streicher.
“This is a more complicated question and would require nuanced discussions about breast cancer risk with estrogen plus progestin regimens versus estrogen alone regimens,” agrees Stephanie Faubion, MD, director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida, and medical director of the Menopause Society. “Further, there remains a lack of randomized controlled trial data to warrant a different label for transdermal [skin patches] versus oral estrogen at this point,” she says.
Hormone Therapy Needs Be Started Within 10 Years of Menopause Onset
Hormone therapy remains the most effective treatment for classic menopause symptoms like hot flashes, night sweats, mood swings, and vaginal dryness. Beyond that, mounting evidence suggests broader benefits when women start HRT within 10 years of menopause onset.
“When a woman starts estrogen, or estrogen and progesterone, within 10 years of menopause, there is somewhere between a 25 percent and 50 percent reduction in fatal heart attacks and cardiovascular disease,” said Makary during the FDA meeting. “That is comparable to — or greater than — the risk reduction of a statin.”
“In younger women who have risk factors for heart disease, there is good data suggesting that estrogen has heart protective effects,” says Taylor. But for older women, estrogen appears to increase the risk of heart issues, he adds.
Women should understand that there are lots of ways to protect themselves against heart disease, including diet, exercise, and blood pressure management, along with other medications aimed to reduce heart disease risk factors, says Taylor.
“Estrogen is not the most efficient way to do that. I would never advocate using estrogen to prevent cardiovascular disease or to replace statins,” he says.
Risks of Hormone Therapy for Menopause Are Often Exaggerated
The conversation around hormone therapy for menopause symptoms should focus on each woman’s individual risks and benefits, says Taylor. “In general, [hormone therapy’s] risks have been exaggerated and overplayed, and the benefits downplayed,” he says.
It may be easy to underestimate a symptom like hot flashes if you’ve never had one, but they are highly disruptive and can have a major quality of life impact, says Taylor.
“There’s a surge of adrenaline that can come with heart racing, palpitations, sweating, and anxiety. These can be devastating and interrupt your job, your sleep, and your overall function,” he says.
So while the risks of menopause therapy shouldn’t be taken lightly, the overall risk for many women is low, and there could be a lot of benefit, says Taylor.
Bottom Line: Talk With Your Doctor
For women and doctors who may have been reluctant to consider vaginal estrogen therapy, “Removing the warning would certainly go a long way to eliminating a barrier to women using this safe and effective therapy,” says Dr. Faubion.
For systemic forms of hormone therapy, whether or not the warning is removed, women need to talk to a menopause expert to decide if HRT is right for them, says Streicher. “Go to an expert who understands the literature and who’s going to make recommendations based on what is backed by science,” she says.
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