By Harshit | October 3, 2025 | Washington, D.C. | 1:00 AM EDT
The U.S. Food and Drug Administration (FDA) is considering changes to the long-standing black box warning on hormone replacement therapy (HRT) for women with menopause symptoms, Commissioner Dr. Martin Makary said in a recent podcast interview. The warning, the agency’s strongest label, alerts patients to potential risks of uterine and breast cancers, strokes, blood clots, and dementia for women over 65.
“We are in serious discussions now about what to do about the black box warning, and I think you’ll hear something on it very soon,” Makary told CNN Chief Medical Correspondent Dr. Sanjay Gupta on the “Chasing Life” podcast.
Origins of the Warning
The FDA added the black box warning in 2003 following results from the government-funded Women’s Health Initiative (WHI) study. The trial found that women taking estrogen after menopause faced higher risks of certain cancers, heart disease, and stroke compared to placebo. The average age of participants was 63, well past menopause, which critics argue limited the applicability of the findings.
After the warning was issued, prescriptions for HRT dropped by more than 70 percent, leaving many women undertreated for debilitating menopausal symptoms such as hot flashes, night sweats, mood swings, and vaginal dryness. In the late 1990s, more than one in four postmenopausal women used HRT; by 2020, that number had fallen to about one in 25.
Reassessing Benefits and Risks
Recent analyses suggest that HRT started before age 60 or within 10 years of menopause onset may safely alleviate symptoms while providing additional health benefits, including reducing bone loss, cardiovascular risk, and memory decline.
“Women live longer and feel better on hormone replacement therapy when started before age 60,” Makary said.
Experts have argued that the blanket black box warning may not apply to all forms of estrogen. Dr. JoAnn Manson of Harvard Medical School noted that low-dose estrogen delivered vaginally—via creams, rings, or tablets—does not significantly raise blood levels, and is unlikely to increase cancer risk. Yet, the warning may discourage women from using even these safer options.
“It scares them away. And even after they purchase the product, they just don’t take it,” Manson said.
Calls for Change
The FDA’s review follows a July panel convened to discuss the risks and benefits of menopause hormone therapy. Panelists, including Dr. JoAnn Pinkerton of the University of Virginia, urged the agency to remove or revise the warning.
“I am begging the FDA, and all of us are begging, please remove the box label, and please stop harming women,” Pinkerton said.
Dr. Leslie Cho, of Cleveland Clinic’s Women’s Cardiovascular Center, supports lifting the warning for vaginal estrogen products, calling it “never made sense on the cream.” However, she cautioned that some claimed benefits—like preventing heart disease or Alzheimer’s—are based on post-hoc analyses, not studies designed to examine those outcomes.
Safety Considerations
Even with potential changes, experts emphasize that HRT is not risk-free. Women with high blood pressure, obesity, high cholesterol, or a history of hormone-sensitive cancers should discuss therapy with their physician. Hormone therapy can also increase the risk of dangerous blood clots, even in younger women.
“Women have to talk to their physicians about hormone replacement therapy before they believe in all the hype that’s currently ongoing, because so much of it is hype,” Cho said.
Next Steps
The FDA has not yet announced a timeline for changing the black box warning, but discussions are underway. If revised, the move could improve access to HRT for millions of women, allowing them to manage menopause symptoms safely while reducing undertreatment.
Medical societies, including the American College of Obstetricians and Gynecologists, The Menopause Society, and the Endocrine Society, support using hormone therapy for symptom relief but do not recommend it solely for preventing chronic conditions like heart disease or dementia.
Experts say that if the FDA proceeds carefully, focusing on low-risk formulations such as vaginal creams, patches, or sprays, the change could restore confidence in hormone therapy for women navigating menopause.
