If you haven’t yet read our blog on Menopause Hormone Therapy: A Primer, be sure to check it out.
For many years, menopause hormone therapy carried a “black box warning” from the United States Food and Drug Administration (FDA). A black box warning is the strongest safety warning the FDA places on prescription medications.1 Its purpose is to inform users of the potential of severe adverse reactions, such as death, severe injury, or disability. Black box warnings are placed prominently on the medication’s packaging. A box warning is a bold, black bordered notice at the top of a drug’s label or informational package inserts. These warnings are required when reasonable evidence links a medication to a serious hazard, even if a direct causal relationship has not been fully proven.
Black box warnings are added when substantial clinical data shows the drug can cause severe harm, hospitalization, or death. A black box warning is also considered in situations where benefits might not outweigh risks. These warnings are common on certain types of medications, including antidepressants (for risks of worsening depression and suicidal thoughts in young adults), opioid painkillers (for risks related to addiction, abuse, overdose, and death), and ACE inhibitors (for risks of harm or death to an unborn baby during pregnancy).1 More than 400 drugs carry black box warnings.1
Yet, these labels can be modified or removed if new scientific evidence shows that the risks are overstated or don’t apply to current patient populations.
Hormone replacement drugs, which are used to treat menopause symptoms, have had a black box warning since 2003.1 This warning was based on results from the 2002 Women’s Health Initiative study.2 The study linked combination hormone replacement (estrogen and progestin) to increased risks of breast and endometrial cancer, stroke, blood clots, heart attacks, and dementia.2 After the warning was implemented, the use of HRT fell from nearly 30% to 5% between 1999 to 2020.3 The presence of the black box warning on menopause hormone therapy products shaped how clinicians prescribed hormone therapy as well as how patients felt about taking it.
The findings from the study were broadly applied to all women, yet the study participants were older, postmenopausal, and using older oral hormones. Re-analysis of the data found that for women under age 60, within 10 years of menopause, the risks of HRT are lower, and the benefits are greater.4,5
The original study evaluated one specific formulation of oral hormones. Today, different types of hormone therapy exist, including different delivery methods (such as transdermal patches) and lower doses of hormones. The different formulations have different risk profiles than the formulations used in the Women’s Health Initiative study. Therefore, a single box warning may not accurately represent the safety profile of today’s hormone therapy options.
Overall, the data indicates the risks and benefits depend significantly on age and timing of initiation of hormone replacement, with benefits often outweighing risks for candidates who are deemed appropriate.
Thus, in November 2025, the FDA initiated the removal of these warnings.1
Remember that even without a black box warning, there is a spectrum of risk that needs to be considered when menopause hormone therapy is being discussed and prescribed. Certain individuals, such as those with a history of breast cancer, blood clotting disorders, and certain cardiovascular conditions, may still be at heightened risks for adverse effects from hormone therapy.4,5 The risks and benefits should always be carefully considered and discussed with a healthcare provider. Organizations such as the North American Menopause Society and the American College of Obstetricians and Gynecologists support individualized decision-making rather than broad avoidance.4,5
All in all, menopause care should be individualized and include a combination of modalities and strategies, including nutrition, movement, sleep hygiene, stress management, and possibly hormone replacement. An individual’s symptoms, health history, and treatment goals should be considered in hormonal decision making.
Stay tuned for our conversation on menopause hormone therapy with Dr. Anna Barbieri coming soon to the Eat Kale and Cupcakes podcast.
References
1.Coulson M. What Is a Black Box Warning? John Hopkins Bloomberg School of Public Health. December 19, 2025. https://publichealth.jhu.edu/2025/what-is-a-black-box-warning
- Writing Group For The Women’s Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women’s Health Initiative Randomized Controlled Trial. JAMA: The Journal of the American Medical Association. 2002;288(3):321-333. doi:10.1001/jama.288.3.321
- Anderer S. Only About 5% of US Women Now Use Menopausal Hormone Therapy. JAMA. 2024;332(21):1779. doi:10.1001/jama.2024.22564
- Faubion SS, Crandall CJ, Davis L, et al. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767-794. doi:10.1097/GME.0000000000002028.
- Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013;310(13):1353-1368. doi:10.1001/jama.2013.278040
