FDA removes warning label from hormone-based menopause drugs, sidestepping usual process

Hormone-based drugs used to treat hot flashes and other menopause symptoms will no longer carry a bold warning label about stroke, heart attack, dementia, and other serious risks, the Food and Drug Administration announced Monday.

U.S. health officials said they will remove the boxed warning from more than 20 pills, patches, and creams containing hormones like estrogen and progestin, which are approved to ease disruptive symptoms like night sweats.

The change has been supported by some doctors—including FDA Commissioner Marty Makary, who has called the current label outdated and unnecessary. But some doctors worried that the process, which led to the decision, was flawed.

Health officials explained the move by pointing to studies suggesting hormone therapy has few risks when started before age 60 and within 10 years of menopause symptoms.

“We’re challenging outdated thinking and recommitting to evidence-based medicine that empowers rather than restricts,” Health Secretary Robert F. Kennedy Jr.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

The 22-year-old FDA warning advised doctors that hormone therapy increases the risk of blood clots, heart problems, and other health issues, citing data from an influential study published more than 20 years ago.

Many doctors—and pharmaceutical companies—have called for removing or revising the label, which they say discourages prescriptions and scares off women who could benefit.

Dr. Steven Fleischman, president of the American College of Obstetricians and Gynecologists, said the warnings have created a lot of hesitancy among patients.

“I can spend 30 minutes counseling someone about hormone-replacement therapy—tell them everything—but when they fill the prescription and see that warning, they just get scared,” Fleischman said.

Other experts have opposed making changes to the label without a careful, transparent process. They say the FDA should have convened its independent advisers to publicly consider any revisions.

Debate over the health benefits of hormone therapy continues

Medical guidelines generally recommend the drugs for a limited duration in younger women going through menopause who don’t have complicating risks, such as breast cancer. FDA’s updated prescribing information mostly matches that approach.

But Makary and some other doctors have suggested that hormone therapy’s benefits can go far beyond managing uncomfortable midlife symptoms. Before becoming FDA commissioner, Makary dedicated a chapter of his most recent book to extolling the overall benefits of hormone therapy and criticizing doctors unwilling to prescribe it.

On Monday, he reiterated that viewpoint, citing figures suggesting hormone therapy reduces heart disease, Alzheimer’s disease, and other age-related conditions.

“With few exceptions, there may be no other medication in the modern era that can improve the health outcomes of women at a population level more than hormone replacement therapy,” Makary told reporters.

The veracity of those benefits remains the subject of ongoing research and debate—including among the experts whose work led to the original warning.

Dr. JoAnn Manson of Harvard Medical School said the evidence for overall health benefits is not “as conclusive or definitive” as what Makary described. Still, removing the warning is a good step because it could lead to physicians and patients making more personalized decisions, she said.

“The black box is really one size fits all. It scares everyone away,” Manson said. “Without the black box warning, there may be more focus on the actual findings, how they differ by age and underlying health factors.”

Hormone therapy was once the norm for American women

In the 1990s, more than 1 in 4 U.S. women took estrogen alone or in combination with progestin on the assumption that—in addition to treating menopause—it would reduce rates of heart disease, dementia, and other issues.

But a landmark study of more than 26,000 women challenged that idea, linking two different types of hormone pills to higher rates of stroke, blood clots, breast cancer, and other serious risks. After the initial findings were published in 2002, prescriptions plummeted among women of all age groups, including younger menopausal women.

Since then, all estrogen drugs have carried the FDA’s boxed warning—the most serious type.

“That study was misrepresented and created a fear machine that lingers to this day,” Makary said.

Continuing analysis has shown a more nuanced picture of the risks.

A new analysis of the 2002 data published in September found that women in their 50s taking estrogen-based drugs faced no increased risk of heart problems, whereas women in their 70s did. The data was unclear for women in their 60s, and the authors advised caution.

Additionally, many newer forms of the drugs have been introduced since the early 2000s, including vaginal creams and tablets that deliver lower hormone doses than pills, patches, and other drugs that circulate throughout the bloodstream.

The original language contained in the boxed warning will still be available to prescribers, but it will appear lower down on the label. The drugs will retain a boxed warning that women who have not had a hysterectomy should receive a combination of estrogen-progestin due to risks of cancer in the lining of the uterus.

FDA sidestepped its usual public process in reviewing warning

Rather than convening one of the FDA’s standing advisory committees on women’s health or drug safety, Makary earlier this year invited a dozen doctors and researchers who overwhelmingly supported the health benefits of hormone-replacement drugs.

Many of the panelists at the July meeting consult for drugmakers or prescribe the medications in their private practices. Two of the experts also spoke at Monday’s FDA news conference.

Asked Monday why the FDA didn’t convene a formal advisory panel on the issue, Makary said such meetings are “bureaucratic, long, often conflicted, and very expensive.”

Diana Zuckerman of the nonprofit National Center for Health Research, which analyzes medical research, accused Makary of undermining the FDA’s credibility by announcing the change “rather than having scientists scrutinize the research at an FDA scientific meeting.”

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—By Matthew Perrone, AP health writer