FDA Removes Hormone Therapy Warnings—What Changed and Why It Matters for Menopause

The U.S. Food and Drug Administration (FDA) has approved labeling changes to six menopausal hormone therapy products, removing cardiovascular disease, breast cancer, and dementia warnings from the most prominent safety alert. This shift reflects a comprehensive review of scientific literature and marks a significant change in how doctors and patients should think about hormone replacement therapy (HRT) for menopause symptoms.

What Exactly Changed in the FDA's Warnings?

In November 2025, the FDA initiated the removal of specific risk statements from the "boxed warning"—the agency's most prominent safety-related alert—for menopausal hormone therapy products. The first batch of approved labeling changes covers six products representing all major categories of HRT: 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.

At the FDA's request, 29 drug companies have submitted proposed labeling changes, though only six have been approved so far. This action is expected to allow women and their healthcare providers to make better-informed decisions about treatment options for menopause symptoms.

Why Is Timing So Critical for Hormone Therapy Safety?

Recent research reveals that when women start hormone therapy matters enormously. 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. This timing window has become central to understanding the risk-benefit profile of these treatments.

A comprehensive review of the scientific literature found that hormone replacement therapy could function as a "geroprotective" strategy, meaning it may help slow or reverse biological aging processes in healthy, mid-life women. The molecular roles of estrogen and progesterone affect multiple aging pathways, with estrogen shown to enhance genomic stability, support telomere maintenance, modulate epigenetic patterns, and promote mitochondrial efficiency.

However, initiating hormone therapy more than 10 years after menopause can increase the risk of stroke and coronary events, which is why timing is considered a crucial factor in personalizing treatment decisions.

What Are the Documented Benefits Beyond Symptom Relief?

While hormone therapy is approved for moderate-to-severe hot flashes, vaginal dryness and discomfort, and bone loss prevention, research suggests broader health benefits when started at the right time. These benefits include:

• Cardiovascular Health: Reducing progression of atherosclerosis and coronary events when initiated early in the menopausal transition.
• Bone Strength: Reducing postmenopausal osteoporosis by decreasing vertebral and hip fractures by around 34%.
• Cognitive Function: Improving different metrics of memory and visuospatial skills in women receiving hormone therapy.
• Metabolic Health: Counteracting aging-related metabolic changes, such as increased body fat and insulin resistance.
• Sleep Quality: Improving sleep quality, which often deteriorates during menopause.
• Sexual Function and Quality of Life: Enhancing sexual function and overall quality of life during and after menopause.

How Should Women and Doctors Personalize Hormone Therapy Decisions?

Experts propose dividing women into three risk categories to guide treatment decisions. The approach recognizes that hormone therapy is not one-size-fits-all and requires individual evaluation.

Low-Risk Group: Women below age 60, less than 10 years since menopause, with a body mass index (BMI) lower than 30 (roughly 210 pounds for someone 5'10"), no cardiovascular diseases, and who do not smoke are considered good candidates for early hormone therapy.

Intermediate-Risk Group: Women with mild metabolic syndrome, a family history of cardiovascular diseases, or a history of smoking may be considered for a personalized approach and should be monitored during use.

High-Risk Group: Women with prior blood clots (venous thromboembolism), stroke, active malignancies, or uncontrolled cardiovascular diseases should avoid hormone replacement therapy.

Beyond these broad categories, experts recommend evaluating aging-related biomarkers to further personalize treatment. These include epigenetic clocks, inflammatory biomarkers (since chronic low-grade inflammation frequently increases during menopause), metabolic markers, cardiovascular aging metrics, bone turnover biomarkers, neurocognitive and sleep biomarkers, and ovarian aging markers. However, experts caution against relying on a single biomarker and recommend integrating information from multiple sources.

Does the Route of Administration Matter?

Yes—how women take hormone therapy significantly affects safety. Transdermal estrogen formulations (applied through the skin) and micronized progesterone are safer when it comes to blood clots, stroke, breast cancer, and metabolic effects compared to oral preparations. Additionally, whether a woman has had a hysterectomy influences the recommendation: women without a uterus can use estrogen-only therapy, while women with a uterus should use combined estrogen and progesterone therapy, with micronized progesterone appearing to be the safer option.

Why Aren't More Women Using Hormone Therapy?

Despite the documented benefits, hormone therapy remains underutilized. In 2020, approximately 41 million U.S. women were aged 45 to 64 years, yet only about 2 million women aged 46 to 65 received a hormone therapy prescription. This gap suggests that many women who could benefit from treatment are not receiving it, possibly due to lingering concerns about safety or lack of awareness about the updated evidence.

The FDA's labeling changes are intended to address this gap by providing clearer, more accurate information about the actual risks and benefits of hormone therapy. Women are encouraged to consult the updated drug labels and discuss treatment options with their healthcare providers to make informed decisions about managing menopause symptoms and supporting long-term health.