‘Black box’ safety warning to be removed from hormone therapy for menopause

By Jacqueline Howard, Brenda Goodman, CNN

(CNN) — In a pivotal move, the US Food and Drug Administration said Monday that it is taking steps to remove the lengthy “black box” warning on many hormone treatments for women with menopause symptoms, a shift expected to give women more options for treatment and generate a flood of new prescriptions.

Hormone therapy has long been on the market, but prescriptions plummeted after 2003, when the warning described increased risks of cardiovascular disease, stroke, breast cancer and dementia.

“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,” FDA Commissioner Dr. Marty Makary said in announcing the change.

Prescribing requires nuance, FDA officials said, especially around when women start hormone therapy. Some women still face some risks from hormone therapy, including those at increased risk of blood clots or who have previously had breast cancer.

But for many women, the benefits may far outweigh the risks.

“With the exception of vaccines or antibiotics, there’s no medication that can improve the health of women on a population level more than hormone replacement therapy,” Makary posted on X Monday morning.

It could take months for the labels to change, but drugmakers are “very excited” to make the update, Makary said. Label changes will include updated guidance that hormones should be initiated in women who are younger than 60 or within 10 years of menopause to optimize benefits and risks, and removal of guidance to use the lowest effective dose for the shortest amount of time — clearing the way for women to stay on the treatments for years.

“We want people to talk to their doctors, and we want doctors to have the right information, and part of that means removing these scary black box warnings and putting the nuanced discussion in the package insert of the medications,” Makary said.

Women’s health experts praised the move to update the boxed warning to reflect newer scientific evidence around menopausal hormone therapy but said individualized discussions of risks and benefits will still be needed.

Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women’s Hospital and a past president of the Menopause Society, said the labeling change was overdue.

“As a bottom line, I think given more than 20 years of class-wide labeling of hormone therapy, it is time to get the labeling right, and some of these changes that are proposed are very well-supported. Others may be controversial, but overall, it is a step in the right direction,” said Manson, who was one of the original investigators on the Women’s Health Initiative study that spurred the initial label change.

“Right now, this box warning is a one-size-fits-all summary that hormone therapy increases the risk of all these conditions,” Manson said. “It doesn’t take into account whether it’s local estrogen or systemic estrogen, the age of the woman, the type of the formulation.”

Dr. JoAnn Pinkerton, a professor of obstetrics and gynecology at the University of Virginia School of Medicine, said she is among many doctors who advocated for label changes for years.

“Removing the scary boxed warning from local vaginal estrogen is a victory for women’s health and for those who care for and about menopausal women,” Pinkerton said in a statement. “Regarding the removal of the boxed warning for systemic hormone therapy, which is absorbed into the bloodstream and has systemic effects throughout the body, we appreciate the FDA’s thoughtful, nuanced approach. Discussions will be more complicated and need to be individualized, as different menopause therapies differ in potential risks.”

What changed around hormone therapy

The black box warning is the strongest type of alert the FDA puts on a drug label. Since 2003, labels of menopause treatments that contain estrogen – including pills, patches, sprays and creams – have warned that their use can increase the risk of uterine and breast cancers, as well as strokes and blood clots. The labels also warned about an increased risk of dementia for women over the age of 65.

The black box warning, or boxed warning, was added after a large government-funded study, the Women’s Health Initiative, found in 2002 that women taking estrogen pills after menopause had some higher health risks compared with women who took a placebo. The study participants had an average age of 63, so many were past menopause when they started the therapy.

After the study and the label change, doctors became reluctant to prescribe them, and prescriptions for hormone therapy for menopause dropped by more than 70%. In the late 1990s, more than 1 in 4 postmenopausal women were taking hormones to manage symptoms such as hot flashes, mood swings and night sweats. By 2020, that number had dropped to about 1 in 25, one study found.

The result has been undertreatment of symptoms that can be debilitating for women in midlife.

“It’s been a total horrible tragedy that so many millions of women have been deprived,” said Dr. Erika Schwartz, a New York-based internist and author of the books “Don’t Let Your Doctor Kill You” and “The New Hormone Solution.”

“Hormone therapy is important because for about 10 to 15 years before you go into menopause, your hormones start leaving you. As your hormones start leaving you, you need more hormones. And you don’t need hormone replacement; you need hormone supplementation,” Schwartz said.

“Chronic illnesses like heart disease, Alzheimer’s, osteoporosis, cancer, they are diseases of aging, and one reason is the loss of hormones.”

More recent analyses of the Women’s Health Initiative, as early as 2010, have since shown that hormone therapy started in women younger than 60, or within 10 years of starting menopause, can more safely help manage menopausal symptoms such as hot flashes and poor sleep as long as the women don’t have specific contraindications such as a history of hormone-sensitive breast or uterine cancer.

“To this day, I still have patients coming in telling me their obstetricians or gynecologists have said to them they shouldn’t be taking hormones, because they’re going to get cancer. And not only will they not get cancer, the hormones will protect them from cancer,” Schwartz said. “We have the data.”

In July, the FDA convened a panel of experts to discuss the benefits and risks of hormone replacement therapy for women. The panelists urged the agency to remove the warning label.

In October, Makary told CNN Chief Medical Correspondent Dr. Sanjay Gupta in an episode of the “Chasing Life” podcast that the agency was in “serious discussions” about what to do with the black box warning.

“It’s really a tragedy. It’s maybe one of the greatest screw-ups of modern medicine,” Makary said. “It’s resulted in 50 million women being denied this incredible therapy.”

Changing views on menopause

The FDA action follows a wave of policies introduced across the country to improve menopause care at the state level. Most of the legislation has been related to insurance coverage for menopause care, awareness and education, clinician training or menopause in the workplace.

“When we think about the timing of this announcement, it’s not just the FDA making a move. It comes in the good company of now 19 states, red and blue alike, introducing more than 35 bills to improve menopause care,” said Jennifer Weiss-Wolf, executive director of the Birnbaum Women’s Leadership Center at the New York University School of Law, who has been tracking menopause legislation.

“All these things are happening at the same time, and that’s in part because there is a loud and proud movement making these demands now, insisting that menopause care be equitable and treatments accessible, that menopause no longer be in the shadows and that we not be subject to misinformation,” said Weiss-Wolf, author of the forthcoming book, “When In Menopause: A User’s Manual and Citizens Guide.”

The removal of the warning on hormone for menopause has long been in the making, experts said.

“Back in 2014, the Menopause Society and other leading menopause experts had actually started a petition to the FDA to remove the label,” Weiss-Wolf said. “This is something that the menopause medical community has been asking for.”

The action will change the landscape of care to make hormone therapy, especially estrogen, more accessible for midlife women, said Dr. Jayne Morgan, an Atlanta-based cardiologist and vice president of medical affairs at Hello Heart, an app that specializes in women’s health and cardiovascular research.

“The fact of the matter is, estrogen is one of the primary drivers of the heart. There are estrogen receptors on the heart, on the brain, in the bones, so it’s like the fuel that drives our body. Once that fuel runs out, it’s just like a car, the car begins to sputter,” Morgan said.

“Women live about six years longer than men, but we spend about 25% of our lives in lower quality of life,” she said. “That’s where hormone therapy can help.”

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