Hormone therapies for menopause will no longer carry a black box warning about serious risks such as breast cancer, heart attack and stroke, the Food and Drug Administration announced Monday.
In the announcement and an accompanying editorial in the medical journal JAMA, FDA Commissioner Marty Makary and other agency officials said the warnings are based on outdated science and have discouraged women from taking hormone therapy.
The medications are commonly prescribed to treat menopause symptoms such as hot flashes, mood swings, difficulty sleeping, urinary tract infections and vaginal dryness, and to reduce bone fractures. They replace estrogen and progesterone — hormones that decline during menopause — and come in the form of pills, patches, gels and creams.
“We are going to stop the fear machine steering women away from this life-changing, even lifesaving, treatment,” Makary said in a news conference. “The FDA is taking action to remove the black box warnings from estrogen-related products. This is based on a robust review of the latest scientific evidence.”
In the JAMA editorial, Makary and three other FDA officials wrote that the warnings — which appear on medication packaging — will be removed from products that contain estrogen or progestogen only, as well as the two combined.
“With the exception of antibiotics and vaccines, there may be no medication in the modern world that can improve the health outcomes of older women on a population level more than hormone therapy,” they wrote.
Many doctors have similarly argued that the black box warnings on hormone therapies are unnecessary and that the benefits of the medications outweigh potential risks.
“Our big concern about the black box warning is that a lot of women are excited about walking out the office and then go home and read the black box and then never start it, because they get scared,” said Dr. MargEva Cole, an obstetrician-gynecologist at Duke University School of Medicine.
The warnings were a response to a 2002 clinical trial that was halted after it detected an increased risk of breast cancer, heart attack and stroke in women receiving hormone therapy. The trial looked at a particular formulation of progesterone that is not commonly used today. Doctors say it was also biased toward women in their 60s and 70s, whereas women typically start hormone therapy in their 40s or 50s.
Hormone therapy prescriptions decreased after the trial was halted.
Studies done more recently have not found the same increased risk of adverse events with the current formulations of hormone therapy.
Nonetheless, Dr. Samantha Dunham, director of the Center for Midlife Health and Menopause at NYU Langone Health, said hormone replacement therapy is not a panacea.
“I would just reassure people going through menopause that they will not die sooner if they don’t take hormones,” Dunham said.
There are other options to treat menopause symptoms, she added, such as cognitive therapy or antidepressants for mood changes, and non-hormonal medications for hot flashes.
The FDA said Monday that it is adding a recommendation to the label of systemic hormone therapies — forms like pills and patches that typically contain more hormones — to start the treatment in women younger than age 60 or within 10 years of the onset of menopause (when symptoms are usually most pronounced).
Information about a risk of adverse events will still appear on the package inserts, the agency said.
Several doctors said that for women considering these medications, it's important to understand differences between various types of hormone replacement therapies.
Dr. Steven Fleischman, president of the American College of Obstetricians and Gynecologists, commended the removal of the black box warning for low-dose vaginal estrogen, which is used to treat symptoms like vaginal dryness or urinary tract infections. But he said in a statement that systemic estrogen medications have a different safety profile; long-term use may still carry a slightly elevated risk of breast cancer, depending on a person's age and medical history.
“Their use should be based on an individualized conversation between patients and their clinicians,” Fleischman said.
Dr. Tiffany Troso-Sandoval, a New York-based oncologist, said some of her patients quickly reached out with questions on Monday, since the FDA did not offer specific guidance for those with a history of breast cancer.
“In general, medical oncologists should be well comfortable with giving vaginal estrogen to all patients,” she said. “The systemic estrogen, despite the removal of the black box warning, still requires a fairly nuanced expert discussion.”
The FDA also announced on Monday that it is approving two new drugs to treat menopause symptoms: a generic mixture of estrogen hormones and a nonhormonal treatment for moderate to severe hot flashes.
In July, the agency convened a panel of experts who were pro-hormone replacement therapy. During the panel, Makary highlighted the potential for the treatment to reduce cognitive decline and the risk of Alzheimer’s. More research is needed, however: Dunham said there haven’t been long-term studies to demonstrate that hormone therapies benefit heart health.
Beaux Abington, a 51-year-old in Florida, said she is among the women who have struggled to obtain hormone therapy. Her mood suddenly started to sour when she turned 48, she said, and she suspected it was due to perimenopause. But Abington said three doctors declined to treat her with hormone therapy before she was eventually prescribed it at an anti-aging clinic.
“I was not in a good place. I couldn’t get out of bed,” she said.
After receiving the medication, Abington said, her mood started to improve: “It just was like all of the parts of my brain coming alive again.”
