Hormonal medications used to treat hot flashes and other symptoms of menopause will no longer carry a bold warning label about the risk of stroke, heart attack, dementia and other serious risks, the Food and Drug Administration (FDA) announced Monday.
U.S. health officials said they will remove the boxed warning from more than 20 pills, patches and creams containing hormones such as estrogen and progestin (the synthetic form of progesterone) approved to relieve bothersome symptoms such as night sweats.
The change has received support from some doctors, including FDA Commissioner Marty Makary, who has called the current label outdated and unnecessary. However, some specialists worry that the process that led to the decision was flawed.
Health authorities explained the measure by pointing to studies that suggest that hormone therapy has few risks when started before age 60 and within 10 years of menopause symptoms.
“We are challenging outdated thinking and recommitting to evidence-based medicine that empowers rather than restricts,” Health Secretary Robert F. Kennedy Jr. said in presenting the update.
The 22-year-old FDA warning advised doctors that hormone therapy increases the risk of blood clots, heart problems and other health problems, citing data from an influential study published more than 20 years ago.
Many doctors — and pharmaceutical companies — have called for the label to be removed or revised, which they say discourages prescribing and scares away women who could benefit from it.
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, telling them everything, but when they go to fill the prescription and see that warning, they just freak out,” Fleischman said.
Other experts have opposed making label changes without a careful and transparent process. They stated that the FDA should have convened its independent advisers to publicly consider any review.
Debate continues over the benefits of hormone therapy
Medical guidelines typically recommend these medications for a limited period in young women going through menopause who do not have complicated risks, such as breast cancer. The FDA’s updated prescribing information largely aligns with that approach.
However, Makary and other doctors have suggested that the benefits of hormone therapy may go far beyond controlling uncomfortable symptoms. Before becoming FDA commissioner, Makary devoted a chapter of his most recent book to extolling the general benefits of hormone therapy and criticizing specialists who are unwilling to prescribe it.
On Monday he reiterated that view, citing figures suggesting that hormone therapy reduces heart disease, Alzheimer’s and other age-related conditions.
“With few exceptions, there may be no other drug in the modern era that can improve women’s health outcomes at a population level more than hormone replacement therapy,” Makary told reporters.
The veracity of those benefits remains the subject of research and debate, even 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 that described by Makary. Still, removing the warning is a good step because it could lead doctors and patients to make more personalized decisions, he said.
“The black box warning is really the same for everyone. It scares everyone,” Manson said. “Without the black box warning, more attention may be paid to the actual results, how they differ by age and underlying health factors.”
Hormone therapy was once the norm for American women
In the 1990s, more than one in four American women took estrogens alone or in combination with progestins, hypothesizing that in addition to treating menopause, they would reduce rates of heart disease, dementia and other problems.
However, a landmark study of more than 26,000 women challenged that idea, linking two different types of hormone pills to higher rates of strokes, blood clots, breast cancer and other serious risks. After initial results were published in 2002, prescriptions plummeted among all age groups, including younger people going through menopause.
Since then, all estrogen medications carry the FDA’s most serious boxed warning.
“That study was distorted and created a fear machine that persists to this day,” Makary said.
The following analyzes have shown a more nuanced picture of the risks.
A new analysis of 2002 data published in September found that women ages 50 to 59 who took estrogen-based medications were not at increased risk of heart problems, while those ages 70 to 79 were. The data was not clear for those between 60 and 69, so the authors recommended caution.
Additionally, many new forms of medications have been introduced since the early 2000s, such as vaginal creams and tablets that deliver lower doses of hormones than pills, patches, and other medications that circulate through the bloodstream.
The original text contained in the boxed warning will still be available to prescribers, but will appear lower on the label. The medications will keep a boxed warning stating that women who have not had a hysterectomy should receive a combination of estrogen and progestin because of the risk of cancer in the lining of the uterus.
The FDA bypassed its usual public process in reviewing the warning
Instead of 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 are consultants to drug manufacturers or prescribe the drugs in their private practices. Two of the experts also spoke at Monday’s FDA news conference.
Asked Monday why the FDA did not convene a formal advisory panel on the issue, Makary added that such meetings are “bureaucratic, lengthy, often confrontational and very costly.”
Diana Zuckerman of the National Center for Health Research, a nonprofit that analyzes medical research, accused Makary of undermining the FDA’s credibility by announcing the change “instead of having scientists examine the research at an FDA scientific meeting.”
