FDA Removes Black Box Warning from Menopausal Hormone Therapy Products

The U.S. Food and Drug Administration has approved drug labeling changes to six menopausal hormone therapy products, removing boxed warnings related to cardiovascular disease, breast cancer, and probable dementia. The warnings, which had been the agency's most prominent safety-related alerts, were removed following a comprehensive review of the scientific literature.

The updated labeling impacts four categories of hormone replacement therapy products: systemic combination therapy (estrogen and progestogen), systemic estrogen-alone therapy, systemic progestogen-alone therapy for women with a uterus using systemic estrogen, and topical vaginal estrogen therapy.

"This decision reflects our commitment to follow the science wherever it leads and to correct course when the evidence demands it," the Secretary of Health and Human Services said in the press release. "By removing these boxed warnings, we ensure that women receive accurate information about hormone therapy—free from exaggeration or fear. A health care system worthy of public trust tells the truth, updates its guidance as science evolves, and respects women's ability to make informed choices about their own health."

The black box warnings were originally implemented in January 2003 following results from the 2002 Women's Health Initiative Randomized Controlled Trial. That study reported major clinical outcomes with HRs for coronary heart disease, 1.29 (95% CI, 1.02-1.63) with 286 cases; breast cancer, 1.26 (95% CI, 1.00-1.59) with 290 cases; stroke, 1.41 (95% CI, 1.07-1.85) with 212 cases; pulmonary embolism, 2.13 (95% CI, 1.39-3.25) with 101 cases; colorectal cancer, 0.63 (95% CI, 0.43-0.92) with 112 cases; endometrial cancer, 0.83 (95% CI, 0.47-1.47) with 47 cases; hip fracture, 0.66 (95% CI, 0.45-0.98) with 106 cases; and death due to other causes, 0.92 (95% CI, 0.74-1.14) with 331 cases. The composite outcomes were 1.22 (95% CI, 1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (95% CI, 0.90-1.17) for total cancer, 0.76 (95% CI, 0.69-0.85) for combined fractures, 0.98 (95% CI, 0.82-1.18) for total mortality, and 1.15 (95% CI, 1.03-1.28) for the global index.

In July 2025, an expert panel of Menopause and Hormone Replacement Therapy for Women was hosted by the FDA. The goal of the meeting was to focus on the risk/benefits of these therapies, including the potential risks of breast cancer, uterine cancer, and certain cardiovascular risks versus potential benefits on bone, genitourinary, cardiovascular, and cognitive health. The panel also focused on the results from the Women's Health Initiative study, and spoke about the risks/benefits on the age of hormone initiation, formulation, and dose.

The FDA initiated the removal of these warnings in November 2025. At the FDA's request, 29 drug companies have submitted proposed labeling changes. This first batch of six products with approved labeling changes includes products from each of the four categories of HRT for menopausal women.

Randomized studies show that women who initiate HRT within 10 years of the onset of menopause (generally before age 60) have a reduction in all-cause mortality and fractures. However, as of 2020, there were 41 million women in the U.S. who were aged 45 to 64 years, and approximately 2 million women in that group were receiving hormone replacement therapy. Just a small fraction of women who could benefit from these treatments are using them. In 2020, only about 2 million women ages 46–65 received a hormone-therapy prescription.

Menopause is a normal life stage, but its symptoms can significantly reduce quality of life. Common symptoms include hot flashes and night sweats (called vasomotor symptoms or VMS); vaginal, vulvar, and urinary tract changes caused by lower estrogen levels; and osteoporosis (thinning bones), which increases fracture risk. The FDA has approved multiple hormone therapies for moderate-to-severe hot flashes, vaginal dryness and discomfort, and preventing bone loss.

"With today's action, we are delivering on our promise to make sure women have accurate, scientifically grounded information about the potentially life-changing benefits of HRT," the FDA Commissioner said. "Women face symptoms of menopause that can last for years, and our efforts will help these women make well-informed medical decisions."

Women are encouraged to consult the drug label for more detailed information about the benefits and risks of these products.