Written By: Shreya Bendsure, BPharm and Sheetal Barbade, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has recently announced a landmark decision to remove the “black box” warnings from estrogen-based menopausal hormone therapy (MHT) products. This change marks a significant shift in the regulation and perception of hormone replacement therapy (HRT), which has long been used to alleviate menopausal symptoms such as hot flashes, vaginal dryness, and mood changes. The black box warnings previously cautioned users about increased risks of breast cancer, cardiovascular disease, and dementia. After a comprehensive review of scientific data, the FDA concluded that these risks were overstated, especially for women under 60 or within ten years of menopause onset, opening the door for broader access to this therapy.
FDA’s Review Process: Expert Panel and Public Comments
The decision to initiate the removal of boxed warnings followed a rigorous scientific and regulatory process. In July 2025, the FDA convened an expert panel consisting of leading specialists in women’s health, cardiology, neurology, and gynecology.
This panel thoroughly assessed the risks and benefits of menopausal hormone therapy, focusing on breast cancer, uterine cancer, cardiovascular risks, bone health, genitourinary effects, and cognitive outcomes such as dementia. The experts discussed how these risks and benefits vary by factors including age at hormone initiation, hormone formulation, dosage, and duration of use.
Following the panel’s recommendations, the FDA opened a public comment period inviting broad input from healthcare professionals, researchers, patients, and stakeholders. This inclusive feedback process ensured that diverse perspectives and emerging scientific evidence were considered comprehensively before updating the safety labeling of MHT products.
Background and Historical Context
Since the early 2000s, hormone therapies for menopause carried the FDA’s most serious safety alert a black box warning based largely on the Women’s Health Initiative (WHI) study. That study linked HRT to increased risks of breast cancer, strokes, blood clots, and dementia. However, the study involved an older demographic (average age 63) and hormone formulations no longer commonly used, making its findings less applicable to the typical menopausal population. As a result, many women and clinicians became careful of hormone therapy due to perceived safety risks, leading to a decline in the use of these therapies.
FDA’s Final Decision and Implications for Women’s Health
The FDA’s extensive review concluded that the evidence no longer supported broad black box warnings linking estrogen-based MHT to breast cancer, cardiovascular disease, and probable dementia for most women, particularly those under 60 or within ten years of menopause onset. The agency will remove these warnings from systemic estrogen-alone and combined hormone products, except for the boxed warning regarding endometrial cancer, which remains on systemic estrogen-alone drugs. Additionally, guidance recommending the lowest dose for the shortest duration was removed to reflect current clinical practice.
Randomized studies have demonstrated that women, who start hormone replacement therapy within 10 years of menopause onset, typically before age 60, experience significant health benefits. These include a reduction in all-cause mortality and fractures. Furthermore, HRT may reduce the risk of cardiovascular diseases by as much as 50%, lower Alzheimer’s disease risk by approximately 35%, and decrease bone fractures by 50 to 60%. This evidence underscores the importance of timely hormone therapy initiation to maximize long-term health outcomes for menopausal women.
This regulatory update is expected to positively impact women’s health by making HRT more accessible without the stigma of severe black box warnings. The FDA Commissioner highlighted that hormone replacement therapy may improve health outcomes significantly for menopausal women, encouraging appropriate use while supporting personalized risk assessment and shared decision-making between patients and healthcare providers.
Safety Considerations and Expert Recommendations
Despite removing the black box warnings, the FDA emphasizes individualized care. Women with a personal history of breast cancer, cardiovascular disease, or clotting disorders may still face risks associated with hormone therapy. Thus, it remains crucial for patients and clinicians to discuss benefits and risks based on personal health profiles. Updated labeling will reflect nuanced safety information to guide informed decisions.
Key Opinion
Secretary Robert F. Kennedy emphasized that this move empowers every woman experiencing menopause symptoms to understand her treatment options based on solid evidence rather than fear. For over two decades, women and physicians were hindered by outdated science and regulatory caution that painted an incomplete and often misleading picture of hormone therapy risks. FDA Commissioner Makary highlighted the tragic impact of this medical dogma, which denied millions of women access to potentially life-changing benefits. The FDA’s action restores evidence-based medicine and returns control over health decisions to women and their healthcare providers, allowing treatment choices grounded in current scientific data, not unfounded fears.
References
HHS Advances Women’s Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy, 10 Nov 2025, US FDA, https://www.fda.gov/news-events/press-announcements/hhs-advances-womens-health-removes-misleading-fda-warnings-hormone-replacement-therapy?fbclid=IwY2xjawN_ZVtleHRuA2FlbQIxMQBzcnRjBmFwcF9pZAwzNTA2ODU1MzE3MjgAAR4ZVFnT7LQAWuU2h6WL0_HXO74gnHZehc8vM1-zTdqwXo-pkwcpY5hPDJmYYA_aem_86HfR1MrAhocppCazI5_eQ
FDA Expert Panel on Menopause and Hormone Replacement Therapy for Women,17 July 2025, US FDA, https://www.fda.gov/patients/fda-expert-panels/fda-expert-panel-menopause-and-hormone-replacement-therapy-women-07172025#event-information
FACT SHEET: FDA Initiates Removal of “Black Box” Warnings from Menopausal Hormone Replacement Therapy Products, US Department of Health and Human Services, https://www.hhs.gov/press-room/fact-sheet-fda-initiates-removal-of-black-box-warnings-from-menopausal-hormone-replacement-therapy-products.html
FDA Requests Labeling Changes Related to Safety Information to Clarify the Benefit/Risk Considerations for Menopausal Hormone Therapies, 10 November 2025, US FDA, https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-labeling-changes-related-safety-information-clarify-benefitrisk-considerations
FDA Direct: Removing Black Box Warnings for HRT (Part 1/2) and (2/2), FDA Direct Podcast, 10 November 2025, US FDA, https://www.fda.gov/news-events/fda-direct-podcast/fda-direct-removing-black-box-warnings-hrt-part-12