On November 10, 2025, the U.S. Food and Drug Administration (FDA) announced a major update to menopausal hormone therapy labeling: the agency is removing the broad black box warning from estrogen-containing products used for menopause, with one important exception—systemic estrogen-alone products will retain the boxed warning for endometrial cancer risk in women with an intact uterus.¹

For pharmacists, this isn’t just a labeling change. It’s a clinical counseling opportunity to help patients understand who hormone replacement therapy (HRT) is appropriate for, when it is most beneficial, and which risks still require screening and monitoring.

How We Got Here: The Women’s Health Initiative (WHI) and the “HRT Fear” Era

The Women’s Health Initiative (WHI), launched in the 1990s and sponsored by the National Heart, Lung, and Blood Institute (NHLBI), enrolled more than 161,000 postmenopausal participants.² One key goal was to evaluate whether hormone therapy could prevent cardiovascular disease, fractures, and cancer.

Key WHI findings (as widely interpreted at the time):

• Estrogen + progestin was associated with increased risk of coronary heart disease, stroke, venous thromboembolism (VTE), breast cancer, and dementia.
• Estrogen alone (in women with prior hysterectomy) showed more favorable outcomes in younger subgroups and was associated with reduced coronary heart disease and all-cause mortality in some analyses. It also showed a statistically significant reduction in invasive breast cancer incidence overall.

The practical takeaway became blunt: HRT was seen as broadly dangerous, HRT prescribing dropped sharply, and many women stopped therapy or avoided it altogether.

What was often lost in translation: the average age in the WHI hormone trial was around 63—well beyond the typical menopause transition—and the regimen studied (oral conjugated equine estrogen plus medroxyprogesterone) does not represent the full range of current hormone therapy options. Risk estimates were frequently generalized to younger, newly menopausal patients, even though their benefit–risk profile can differ meaningfully.

What Exactly Is the FDA Changing in 2025?

In the November 2025 announcement, the FDA and HHS began removing broad boxed warnings that had linked systemic menopausal hormone therapy to cardiovascular disease, breast cancer, and probable dementia. The agencies explicitly described prior warnings as “misleading” when interpreted without clinical context and current evidence.¹

What remains: the FDA will retain the boxed warning for endometrial cancer on systemic estrogen-alone products, reinforcing the importance of appropriate progestogen use (or other uterine protection strategies) for patients with a uterus.

A centerpiece of the updated position is the FDA’s endorsement of the timing hypothesis: the benefit–risk balance of systemic HRT depends heavily on when therapy starts. The FDA cited randomized data suggesting that women who initiate systemic hormone therapy within 10 years of menopause onset or before age 60 may experience benefits such as fewer fractures and reduced all-cause mortality, along with favorable relative risk changes for certain cardiovascular outcomes.¹

What This Means for Pharmacists: Counseling That’s Accurate, Individualized, and Confidence-Building

For years, counseling often defaulted to: “Use the lowest dose for the shortest time—only if absolutely necessary.” The updated labeling supports a more nuanced approach.

1. Age and timing now matter more in patient conversations
   A healthy 52-year-old within a few years of her final menstrual period does not share the same baseline risk profile as a 68-year-old initiating hormone therapy for the first time. Pharmacists can help frame this distinction clearly and consistently.
2. Route, formulation, and regimen matter—and WHI isn’t the full story The WHI primarily studied a specific oral regimen. Today’s practice commonly involves:
• estradiol,
• micronized progesterone,
• lower doses, and
• individualized schedules.

As boxed warnings are removed, pharmacists play an even bigger role in helping patients understand why “estrogen” is not one uniform exposure.

3. Removing a black box warning is not the same as removing risk Pharmacists should still screen for contraindications and red flags—especially in patients with:
• history of estrogen-dependent cancer (including many breast cancers),
• active or high-risk VTE, known thrombophilia, or prior stroke,
• unexplained vaginal bleeding,
• severe liver disease,
• uncontrolled or significant cardiovascular disease (depending on route/regimen).

And the “uterus rule” remains critical: unopposed systemic estrogen in a patient with an intact uterus increases risk of endometrial hyperplasia and endometrial cancer, and the boxed warning for this risk remains.¹

4. Expect fear, confusion, and skepticism—and be ready for it Many patients have internalized the message that “hormones cause cancer and heart attacks.” A helpful counseling approach:
• acknowledge why patients were warned for decades,
• explain what we’ve learned since WHI (especially the role of age, timing, and regimen),
• emphasize shared decision-making with the prescriber.

Bottom Line for Pharmacy Practice

The FDA’s removal of the broad black box warning on estrogen therapy for menopause is a course correction, not a claim that estrogen is risk-free.

For pharmacists, this moment means:

• Updating how we explain HRT risk and benefit in plain language.
• Shifting from “avoid at all costs” to patient-specific risk–benefit counseling.
• Helping patients understand why labeling changed and how that supports informed decision-making.

Many women will spend a large portion of life in the postmenopausal phase, and symptom relief plus long-term health considerations are real quality-of-life issues. Pharmacists are uniquely positioned to translate this regulatory update into balanced, evidence-informed guidance.

References

1. U.S. Food and Drug Administration. HHS advances women’s health, removes misleading FDA warnings on hormone replacement therapy. FDA Newsroom. November 10, 2025. Accessed December 29, 2025. FDA Newsroom
2. National Heart, Lung, and Blood Institute. Women’s Health Initiative (WHI). NHLBI, National Institutes of Health. Accessed December 29, 2025. NHLBI WHI