The Food and Drug Administration boxed warning on menopausal hormone therapy: history, impact, and a regulatory inflection point in women’s health

The removal of the Food and Drug Administration boxed warning from menopausal hormone therapy (MHT) products in November 2025 marks a historic regulatory inflection point in women's health. This manuscript reviews the history and purpose of boxed warnings, examines the Women's Health Initiative-era rationale that led to the class-wide application of boxed warnings across all MHT formulations and routes of administration, and analyzes the long-term clinical, educational, and public health consequences of MHT avoidance driven largely by this regulatory action. We synthesize decades of post Women's Health Initiative evidence demonstrating substantial heterogeneity in MHT risk and benefit by age, timing of initiation, formulation, and route of administration. To contextualize the lifecycle of the MHT boxed warning, we compare it with three instructive regulatory parallels: canagliflozin, illustrating regulatory agility when benefit- risk balance evolves; varenicline, showing how a boxed warning led to a sharp decline in prescribing that was later not supported by randomized trial evidence; and topical calcineurin inhibitors, highlighting the pitfalls of route-agnostic class-effect labeling. We further examine the persistent impact of the boxed warning on prescribing patterns, menopause education, and primary care training, and propose a framework for regulatory reform and necessary clinician education.