By Emma Bascom, Michael Monostra, and Andrew Rhoades, November 10, 2025

HHS has announced changes to estrogen hormone therapy black box labeling for menopause treatment in a move that it said corrects misleading warnings.

HHS Secretary Robert F. Kennedy Jr. said in a press conference on Monday that women have been “told to fear the very therapy that could have given them strength, peace and dignity through one of life’s most difficult transitions, menopause,” but “that ends today.”

“We’re challenging outdated thinking and recommitting to evidence-based medicine that empowers rather than restricts,” he added. “When prescribed responsibly and started early, hormone replacement therapy transforms the lives of women.”

The details

The role estrogen replacement should play in menopause treatment has long been controversial. Concerns about menopausal hormonal therapy stem back to the publication of findings from the Women’s Health Initiative in JAMA in 2002.

The study found women receiving estrogen plus progestin had a significantly increased risk for total CVD, stroke and pulmonary embolism, and a nominally increased risk for breast cancer. The trial was stopped early due to “health risks that exceeded health benefits over an average follow-up of 5.2 years,” and its results led to a large decrease in the use of hormone therapy among women.

In July, the FDA convened an expert panel to discuss the safety and efficacy of menopausal hormone therapy, and some members stated the boxed warning should be changed to better reflect the published evidence. In the press conference, FDA commissioner Martin A. Makary, MD, MPH, said the move is based on “a robust review of the latest scientific evidence” and the July panel.

“After 23 years of dogma, the FDA today is announcing that we are going to stop the fear machine steering women away from this life-changing, even life-saving, treatment,” Makary said. “We are also approving two new drugs for the treatment of menopausal symptoms. We are listening to doctors who have been waving the flag in the air saying, ‘Hey, we have this wrong.’”

[….]

In a viewpoint published today in JAMA, Makary and colleagues wrote that the revisions to the labels “signal a meaningful shift toward more nuanced, evidence-based communication of hormone therapy risks — one that prioritizes clinical relevance, distinguishes between different formulations and patient populations, and balances the narrative to reflect both safety and therapeutic value.”

According to the viewpoint, the label updates specifically include:

• removing boxed warnings for CVD, breast cancer, probable dementia and stroke, but not the warning in systemic estrogen labels for endometrial cancer with unopposed estrogen, since “it is important to remind health care practitioners and patients that this serious risk can be mitigated by adding a progestogen”;
• removing the recommendation that hormone therapy be prescribed at the lowest effective dose for the shortest possible duration, since “treatment decisions are individualized and fall within the clinical judgment of a clinician in discussion with a patient”;
• updating timing information to include new guidance on treating women aged younger than 60 years or within 10 years of menopause onset “to optimize the benefit-risk balance”; and
• tailoring safety information that reflects the risks most relevant to each specific type of hormone therapy product.

[….]

According to Makary and colleagues, current evidence suggests that starting hormone therapy within 10 years of perimenopause onset has long-term health benefits. It has been associated with a reduced risk for fatal cardiovascular events, bone fractures cognitive decline and Alzheimer’s disease, they wrote.

Expert insight

In a statement, Steven J. Fleischman, MD, MBA, FACOG, ACOG president, commended HHS, saying “the modifications to certain warning labels for estrogen products are years in the making, reflecting the dedicated advocacy of physicians and patients across the country.”

[…]

The Menopause Society also released a statement saying it agrees with the decision since “the boxed warning may have been a deterrent to the use of the low-dose vaginal estrogen, which is a safe and effective therapy for a condition that affects most menopausal women.”

“However, systemic estrogen still comes with potential risks that should be reviewed in detail with women initiating therapy,” the organization said. “Risks are greater when initiated in older women and in those who are further from menopause onset. Medical comorbidities, personal and family histories, symptoms, and personal preferences all need to be considered and reviewed with patients considering the use of hormone therapy for management of menopause symptoms or prevention of bone loss.” 

Diana Zuckerman, PhD, the president of National Center for Health Research, told Healio that “the warnings on hormone products for menopause had become outdated and it was time to update them.”

“However, these products still have clear risks, and the benefits are mostly for hot flashes and related symptoms,” Zuckerman said. “They are not the fountain of youth that some people claim, they absolutely are not proven to prevent dementia, and they are definitely not safe for everyone.”

Barbara DePree, MD, NCMP, MMM, director of the Women’s Midlife Services at Holland Hospital in Michigan, told Healio that the decision will likely increase hormone therapy uptake, which is “a win.” Yet she wondered how exactly HHS will tailor the safety information to reflect the most relevant risks for each type of hormone therapy.

“I’m not opposed to that, I’m just curious what data they’ll be using to tailor that information,” she said. “When the FDA panel happened, it felt like some of the benefits were cherry-picked from data.”

DePree was also concerned about claims that hormone therapy can prevent some very serious noncommunicable diseases.

“I’m fine with maybe taking some of the blinking red lights out of it. That gives women some more ease,” she said. “But I also think we’re not in a position to promote its use to prevent some conditions that we just don’t have the data to support, and I’m worried that it’s headed in that direction. With social media and what’s being overstated, I think this will maybe be another step in that direction, which is a little concerning.”

But she said this will likely give providers more confidence in offering the therapy as a safe alternative.

“We’ve had a whole generation of providers who’ve only grown up with data from the WHI, which basically put it completely in a risk category, and I think this brings it back to the middle for those people who’ve not really had the confidence or the understanding to properly screen women who can very safely and appropriately be using hormone therapy,” De Pree said. “We just don’t want it to say it’s the right option for every woman or just because it’s available everybody should do it because we’re going to save brains and hearts because I just don’t think we have the data to support that.”

Nanette Santoro, MD, professor and the E. Stewart Taylor Chair of OB/GYN at the University of Colorado School of Medicine told Healio that the changes “are a positive step for menopausal women and their physicians,” but was “a bit surprised the black box was completely removed.”

“The changes reflect current data, and it’s great that the route and types of hormones will be dealt with separately as the risks and benefits of estrogen alone compared to estrogen plus progestin are different. These changes should reduce physician anxiety about prescribing hormones, which is important because they are under-prescribed in general,” Santoro said. “And best of all, removing the black box from topical vaginal estrogen is a big relief, because the tiny incremental increase in circulating estradiol that occurs when women use these preparations should not be compared to the systemic dosing regimens and should not be considered to have the same risk.”

However, “some assumptions and statements made here that go way beyond the data that we have available,” which “raise a bunch of red flags for me.”  

“While hormone therapy can indeed be life-changing for symptomatic women, there is not randomized clinical trial evidence that it reduces heart disease, or immune and cognitive decline. There just isn’t,” Santoro said. “And when hormone therapy prescriptions abruptly dropped after the primary WHI publication in 2002, the only population health change that was seen, when hormone therapy went from about 25% of women to less than 2%, was a decrease in breast cancer mortality. There has not been any kind of massive morbidity or mortality as a result of this drop in hormones, although many women suffered with symptoms unnecessarily because of the fear.”

Overall, she said it is “a very good thing that women don’t have to try to decipher the estrogen black box warning (which includes the phrase ‘probable dementia’ and which confuses my patients who read it because they think it means they will probably get dementia if they take estrogen!) and their prescribing clinicians don’t have to have excessive fear of doing harm.”

“[But] the rebirth of the concept that estrogen and hormone therapy are a fountain of youth for women and will extend their lives feels a whole lot like a sharp swing of a pendulum back into the ‘feminine forever’ days.”
[….]

To read the entire article, click here 

Politico Prescription Plus

BY DAVID LIM AND LAUREN GARDNER, OCTOBER 11, 2025

MAKARY’S PRIORITY — In the Hubert H. Humphrey Building’s atrium in front of a crowd of HHS officials, doctors and journalists Monday, FDA Commissioner Marty Makary declared the agency is
urging companies to remove black box warnings for hormone replacement therapy for menopausal women.

[….]

“With few exceptions, there may be no other medication in a modern era that can improve the health outcomes of women on a population level than hormone replacement,” Makary said. “After 23 years of dogma, the FDA today is announcing that we are going to stop the fear machine steering women away from this life-changing, life-saving treatment.”

But the push to remove the warnings of breast cancer, cardiovascular disease and possible dementia isn’t clear-cut, and the process will likely take several months. Makary said the updated package inserts accompanying the treatments will include a nuanced discussion of the recommended ages for HRT use.

An HHS fact sheet released Monday says the FDA will advise women to start hormone replacement therapy within 10 years of menopause or before 60 years old for use of systemic HRT, which delivers the hormone throughout the body instead of a single area. And the FDA is not seeking to change its black box warning for endometrial cancer for systemic estrogen-alone products.

The background: The Women’s Health Initiative — a National Institutes of Health-backed study that looked at the treatments’ benefits and risks — halted a clinical trial in 2002 after researchers said breast cancer, blood clot and stroke risks outweighed the treatments’ benefits in relieving menopausal symptoms. The action prompted many women to stop the therapy.

But Makary slammed the study, saying it was misrepresented and created a “fear machine” around HRT for menopausal women. He argued the study did not show a significant link to breast cancer.

Diana Zuckerman, president of the National Center for Health Research, said it is “well established” that menopausal hormone therapy can increase heart disease and cancer risks in some circumstances.

“I am glad that the Commissioner admitted that there are risks of some types of hormone therapy for some women, but his claim that hormones for menopause is the best way to improve the health of women sounds like a PR statement,
not a scientific one,” Zuckerman said in an email.

Makary dinged advisory committees on Monday as “bureaucratic,
long and often conflicted, and very expensive” when asked why the

FDA did not opt to convene a panel of its outside advisers before making the recommendation.

[….]

To read the entire article, sign up for Politico Pulse Newsletter at politico.com

AFP (Agence France Presse); November 11, 2025

Hormone Replacement Therapy (HRT) replaces estrogen that the female body stops producing during menopause with the aim of alleviating symptoms including hot flashes, brain fog, insomnia, night sweats and joint pain.

Previously used routinely, prescription and use of the therapies have plummeted worldwide since a landmark trial in the early 2000s pointed to risks associated with specific HRT formulations.

Since then “black box warnings” — the strongest warning the US Food and Drug Administration can require on prescription drugs — have sounded alarm over increased HRT risks including of certain cancers, cardiovascular conditions and probable dementia.

But critics have pointed to flaws with the early 2000s Women’s Health Initiative, whose trials were halted as risks appeared: namely it focused on women who were a decade-post-menopause and in their 60s, when cardiovascular risks increase regardless.

Today guidance generally indicates that healthy newly menopausal or perimenopausal women — people broadly in their 40s or 50s — are among potential candidates for treatment.

There also are newer, more localized or lower-dose forms of the therapies available.

“We’re challenging outdated thinking and recommitting to evidence-based medicine that empowers rather than restricts,” US health chief Robert F. Kennedy Jr said in introducing the measure.

Many experts had urged revisiting the black box label, which they say can scare women for whom benefits may outweigh risks.

Others have voiced concern that changes shouldn’t come without a rigorous review process.

“The warnings on hormone products for menopause had become outdated and it was time to update them,” said Diana Zuckerman, president of the nonprofit National Center for Health Research.

But she told AFP “these products still have clear risks and the benefits are mostly for hot flashes and related symptoms of menopause, not for general health.”

FDA head Marty Makary dismissed that notion of an independent review committee, saying they are “bureaucratic, long, often conflicted and very expensive.”

Over the summer Makary convened a panel of experts overwhelmingly in favor of HRT, which included people with ties to pharmaceutical lobbying.

Adriane Fugh-Berman, who directs a project that promotes rational prescribing at Georgetown University, told AFP that Monday’s announcement was “embarrassing” as it was ahead of any consensus and was “not how regulation should happen.”

There could be benefits of HRT for some people, she told AFP, but cautioned that real risks remain, and more high-quality study is needed.

But the president of the American College of Obstetricians and Gynecologists, Steven Fleischman, commended the FDA’s move, saying “the updated labels will better allow patients and clinicians to engage in a shared decision-making process.”

[….]

The FDA said it is not seeking to remove the boxed warning for endometrial cancer for systemic estrogen-alone products.

[….]

To read the entire article, click here 

LAUREN GARDNER and DAVID LIM, Politico, October 28, 2025

OUT OF THE BLACK BOX? The FDA could announce as soon as this week a change to the black box warning on estrogen products used to treat menopause symptoms — a policy move that would be the first to stem from Commissioner Marty Makary’s “expert panel” series.

Makary told CNN’s Sanjay Gupta on a podcast earlier this month that the FDA was having “serious discussions” about the warning with changes coming “very soon.” He focused a chapter of his 2024 book “Blind Spots” on an NIH-backed hormone therapy clinical trial that was halted in 2002 amid concerns about cancer and stroke risks, blasting the study’s administrators for misinterpreting the data.

It’s unclear how far the agency will go, according to advocates monitoring the issue. Some of the speakers at Makary’s July panel discussion are medical advisers to a group petitioning the FDA to remove the boxed warning from vaginal estrogen products, arguing that it deters providers and patients from using them.

[….]

At issue: The FDA could opt to remove the warning for topical, nonsystemic estrogen creams or ointments that treat dryness and other genitourinary symptoms that some women experience while going through menopause.

Existing evidence suggests those localized low doses are safe, though Diana Zuckerman, president of the National Center for Health Research, said there’s a dearth of data from long-term controlled trials. Any changes to the black box warning should distinguish between local and systemic therapies, the latter of which she said pose some risks depending on the timing and duration of treatment and the patient’s health profile.

“There’s a lot of nuance in the research,” said Zuckerman, who criticized the July panel as being skewed in favor of hormone therapy. “But when it is presented as if there is no risk here of cancer or heart disease or anything else, that is just completely untrue.”

The opportunity: But Anne Fulenwider, co-founder and co-CEO of telehealth platform Alloy, said removing the warning will help “millions and millions of women” gain greater access to those therapies.

“Even if it is [removed from] just one of them, that is a huge step for all women,” Fulenwider said. “Everyone is afraid of estrogen to their detriment.”

[….]

To read the entire article, click here https://www.politico.com/newsletters/prescription-pulse/2025/10/28/fda-serious-about-hormone-therapy-changes-00623982

Arthur Allen, KFF News, September 12-16, 2025

Under President Donald Trump, leaders at the US Food and Drug Administration (FDA) are moving to abandon a decades-old policy of asking outside experts to review drug applications, a move critics say would shield the agency’s decisions from public scrutiny.

The agency “would like to get away” from assembling panels of experts to examine and vote on individual drugs, because “I don’t think they’re needed,” said George Tidmarsh, head of the FDA’s Center for Drug Evaluation and Research. He relayed the message last week at a meeting of health care product makers and to an FDA advocacy group.

In addition to being redundant, Tidmarsh said, advisory meetings on specific drugs were “a tremendous amount of work for the company and for the FDA. We want to use that work and our time to focus on the big questions.”

The FDA’s advisory committees were created in their current form by a 1972 law aimed at expanding and regulating the government’s use of experts in technical decisions. They’re periodically summoned for advice, including to review evidence and vote on whether the FDA should approve drugs, vaccines, and medical devices, often when FDA officials face a difficult decision.

FDA actions have traditionally aligned with committee votes. A departure can provoke controversy and public debate, as was the case with the split 2021 decision on whether to approve the Biogen drug Aduhelm to treat Alzheimer’s disease.

The FDA approved the drug despite a “no” vote from its advisory committee, whose members felt the medicine did little to treat the disease. The conflict over Aduhelm laid bare the FDA’s struggle to reconcile pressure from industry and desperate patients with its rigorous evaluation of drug risks and benefits.

Tidmarsh said the committees would still be consulted on general issues like how to regulate different classes of drugs. But meetings on specific drugs, in which experts plow through piles of studies and hours of testimony from FDA and company officials, were mainly useful, he said, because they allowed the public to see how the FDA worked.

This month, the FDA began publishing the “complete response letters” it sends to companies when it declines to approve their products. Releasing the letters, which previously required filing requests under the federal Freedom of Information Act, promotes a level of transparency akin to the advisory meetings’, Tidmarsh said.

Advisory committee meetings on individual drugs “are redundant when you have the complete review letters,” he told KFF Health News in a brief interview after appearing at the health care products conference.

Former FDA officials and academics who study the agency disagree. The meetings help FDA scientists make decisions and increase public understanding of drug regulation, and abandoning them doesn’t make sense, they said.

Tidmarsh’s reasoning is “hard to follow,” former FDA Commissioner Robert Califf told KFF Health News. “It’s extremely useful for people inside FDA to find out what other experts think before they make their final decisions. And it’s important to do that in a way that enables the public to understand the points of view.”

“Experts might ask questions of the company or FDA that neither of them thought of on their own,” said Holly Fernandez Lynch, an associate professor of bioethics and law at the University of Pennsylvania. “The public has few other opportunities to comment about FDA decisions.”

Spokespeople for FDA and the Health and Human Services Department did not respond to repeated requests for elaboration on Tidmarsh’s comments.

Califf at times disagreed with advisory committees as commissioner of the agency and once floated the idea that it might be better if they deliberated but did not vote on products. Still, while “maybe someone can come up with a better one, I always thought it was an amazing system,” he said.

[….]

The advisory committees are “an important resource” for the FDA, said Sarah Ryan, a spokesperson for the Pharmaceutical Research and Manufacturers of America. “They can play an important part of the rigorous human drug review process we have in the U.S.”

[….]

The changes Tidmarsh described are already playing out on the ground. The FDA has held only seven advisory committee meetings since Trump reentered the White House, compared with 22 over the same time frame last year. Officials say they will now release complete response letters as they are sent, and published a batch of 89 earlier this month.

Makary has, to some extent, replaced the advisory committees, whose members have traditionally been vetted for expertise and biases and are required to deliberate in public, with panels of handpicked scientists who support his views on subjects such as hormone replacement therapy and antidepressants.

Diana Zuckerman, an FDA watchdog, attended the July hormone replacement therapy panel that considered the FDA’s black box warning listing dangers of the treatment. Makary had wanted the warning removed and packed the panel with like-minded experts.

The event was hastily called with no opportunity for the public to review discussion materials or comment on them, she said.

“All that was transparent was that they didn’t want to hear from anyone who disagreed with them,” said Zuckerman, who leads the National Center for Health Research.

Before becoming commissioner, Makary pushed for more advisory committee meetings. In early 2022, he blasted the FDA’s decision to approve COVID-19 boosters for children ages 12 to 15 without consulting its Vaccine and Related Biological Products Advisory Committee. Makary posted on the social platform X at the time, “It is a slap in the face to science for @US_FDA to circumvent the standard convening of the expert advisory board.”

But Tidmarsh seems to disagree.

Instead of asking an advisory committee to vote in favor of or against a Duchenne muscular dystrophy drug, for example, he said the FDA would be better served by a committee studying the best way to evaluate such drugs, such as which outcomes, or endpoints, to measure. “Is this endpoint correct for Duchenne muscular dystrophy? That’s an important question that cuts across many different companies,” he told KFF Health News.

FDA official Vinay Prasad canceled a planned July advisory committee meeting to discuss a Duchenne drug made by the biotech company Capricor Therapeutics. The FDA later published its complete response letter to Capricor, which then published its own letter of response to the FDA. Prasad was later pushed out and rehired with fewer powers.

An advisory committee meeting could have worked through the drug’s risks and benefits in a calmer, public, less politicized atmosphere, Ramachandran said.

[….] 

That’s why Tidmarsh’s comments “come as a complete surprise,” said Genevieve Kanter, an associate professor of public policy at the University of Southern California, who wrote commentary accompanying the study. 

[….]

“Another theory is that this decision is strategic,” she said, “in terms of consolidating power in the agencies so that you are no longer accountable to outside experts or the public.”

To read the entire article, click here https://www.cancertherapyadvisor.com/news/under-trump-fda-seeks-to-abandon-expert-reviews-of-new-drugs/