FDA Removes Boxed Warnings From Six Menopausal Hormone Therapy Products
The FDA approved labeling changes to six menopausal hormone therapy products on February 12, 2026, eliminating boxed warnings related to cardiovascular disease, breast cancer, and probable dementia.
The Story at a Glance:
- The FDA removed menopausal hormone therapy boxed warning language on cardiovascular disease, breast cancer, and probable dementia from six products — the first batch of an agency-wide relabeling effort.
- The six products span all four HRT categories: Bijuva, Divigel, Cenestin, Enjuvia, Prometrium, and Estring.
- The endometrial cancer boxed warning remains in place for systemic estrogen-alone therapies.
- Updated labels now recommend initiating hormone therapy within 10 years of menopause onset or before age 60.
- A total of 29 drug companies have submitted proposed labeling changes; additional approvals are expected.
What Happened
On February 12, 2026, the FDA approved drug labeling changes to six menopausal hormone therapy products, removing risk statements related to cardiovascular disease, breast cancer, and probable dementia from their boxed warnings — the agency’s most prominent safety alert. The decision represents the first tangible outcome of a comprehensive scientific review that the agency initiated in November 2025, according to the FDA.
The six products with updated labeling cover all four FDA categories of menopausal hormone therapy: systemic combination therapy (Bijuva), systemic estrogen-alone therapy (Divigel, Cenestin, Enjuvia), systemic progestogen-alone therapy (Prometrium), and topical vaginal estrogen (Estring). A total of 29 drug companies have submitted proposed changes to the FDA, and additional approvals are expected in the coming months.
The boxed warning for endometrial cancer risk associated with systemic estrogen-alone products in women with an intact uterus will remain in place. Safety information regarding venous thromboembolism, ischemic stroke, and gallbladder disease also remains in the updated labeling.
Why It Matters for Menopausal Hormone Therapy Prescribing
The original boxed warnings were added in 2003 following results from the Women’s Health Initiative (WHI) trial, which reported increased risks of breast cancer, cardiovascular events, and dementia among participants. However, the average age of women in that study was 63 — more than a decade past the typical age of menopause onset — and the hormonal formulation used (conjugated equine estrogens with medroxyprogesterone acetate) is no longer in common clinical use, according to the FDA.
The impact on prescribing patterns was substantial. According to the FDA, approximately 41 million U.S. women were aged 45 to 64 in 2020, yet only about 2 million women aged 46 to 65 received a hormone therapy prescription. Estimated use among postmenopausal women fell from approximately 27% to roughly 5% between 1999 and 2020, according to data published in JAMA.
Key Details: Menopausal Hormone Therapy Boxed Warning Changes
| Regulatory Action | Removal of boxed warning language for cardiovascular disease, breast cancer, and probable dementia |
|---|---|
| Effective Date | February 12, 2026 (first batch) |
| Products Updated | Bijuva (estradiol/progesterone), Divigel (estradiol gel), Cenestin (synthetic conjugated estrogens A), Enjuvia (synthetic conjugated estrogens B), Prometrium (progesterone), Estring (estradiol vaginal ring) |
| HRT Categories Covered | Systemic combination, systemic estrogen-alone, systemic progestogen-alone, topical vaginal estrogen |
| Warnings Retained | Endometrial cancer (systemic estrogen-alone products); VTE, ischemic stroke, and gallbladder disease information in labeling |
| New Labeling Guidance | Recommend initiating systemic HRT within 10 years of menopause onset or before age 60; includes WHI data from women aged 50–59 |
| Basis for Decision | Comprehensive literature review, FDA expert panel (July 2025), public comment period |
| Pending | Additional label changes from remaining 23 companies under FDA review |
What Experts Are Saying
The Menopause Society expressed support for the decision, particularly regarding low-dose vaginal estrogen products. The organization stated that the boxed warning had likely discouraged use of vaginal estrogen, which it considers safe and effective for genitourinary symptoms of menopause. However, the Society also noted that systemic estrogen carries potential risks in certain individuals that clinicians should review in detail before initiating therapy.
“It is time to get the labeling right.” — Dr. JoAnn Manson, Chief of Preventive Medicine, Brigham and Women’s Hospital; Past President, The Menopause Society; original WHI investigator
The European Menopause and Andropause Society (EMAS) also endorsed the FDA’s decision, calling it an acknowledgment of a structural gap in women’s health. EMAS cautioned, however, that the removal of a warning does not mean hormone therapy is appropriate for every woman, emphasizing that individualized prescribing — not maximal prescribing — should remain the standard.
What’s Next
The FDA is continuing to review labeling submissions from the remaining 23 drug companies that have proposed changes. Additional product approvals are expected over the coming months. Updated prescribing information for each of the six approved products is now available on the FDA’s menopausal hormone therapy labeling page.
Clinicians should review the updated labels carefully, as some safety language remains — particularly around venous thromboembolism and stroke risk. The transdermal route of estrogen delivery may carry lower thrombotic and stroke risk compared with oral formulations, a distinction that may factor into prescribing decisions going forward.
The Bigger Picture
This labeling change is the most significant regulatory shift in menopausal hormone therapy since the original boxed warnings were added more than two decades ago. The decision arrives amid growing public and clinical interest in menopause care, fueled in part by social media, direct-to-consumer health platforms, and increasing advocacy from medical societies. How the revised safety messaging translates into prescribing behavior and patient outcomes will be closely watched by clinicians and researchers in the months ahead.
Bottom Line
- The FDA removed menopausal hormone therapy boxed warning language on cardiovascular disease, breast cancer, and dementia from six products across all four HRT categories.
- Updated labels now recommend starting systemic HRT within 10 years of menopause onset or before age 60, reflecting evidence of reduced all-cause mortality and fractures in this population.
- The endometrial cancer warning remains for estrogen-alone products, and residual risks including VTE and stroke remain in labeling.
- How these labeling changes will affect prescribing rates and long-term outcomes remains to be determined.
Sources
- FDA. FDA Approves Labeling Changes to Menopausal Hormone Therapy Products. FDA Press Release. February 12, 2026. Link
- FDA. Menopausal Hormone Therapies with Updated Prescribing Information. FDA Drug Safety and Availability. Updated February 12, 2026. Link
- HHS. HHS Advances Women’s Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy. FDA Press Release. November 10, 2025. Link
- HHS. Fact Sheet: FDA Initiates Removal of “Black Box” Warnings from Menopausal Hormone Replacement Therapy Products. HHS.gov. November 10, 2025. Link
- Makary MA, Nguyen CP, Høeg TB, Tidmarsh GF. Updated Labeling for Menopausal Hormone Therapy. JAMA. 2026;335(2):117-118. doi:10.1001/jama.2025.22259
- The Menopause Society. The Menopause Society Comments on the FDA Announcement on Hormone Therapy. The Menopause Society. November 14, 2025. Link
- Society of Gynecologic Oncology. FDA Removes Black-Box Warnings on Hormone Replacement Therapy. SGO News. November 20, 2025. Link