FDA Initiates Removal of Warnings on Hormone Replacement Therapy

This article was exclusively distributed to subscribers on November 17, 2025. Click to receive additional information about how to subscribe and to activate a complimentary trial subscription.

On November 10, the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA) the initiation of a process to remove broad black box warnings from hormone replacement therapy (HRT) products indicated for menopause. The box warnings were included on the drug labels in 2003 to address concerns that arose from a large Women’s Health Initiative study published in the early 2000s that found an increase in the risk of breast cancer. The average age of women in the Women’s Health Initiative study was 63, and the study participants were administered a hormone formulation that is no longer commonly used.

The decision follows the FDA’s review of scientific literature, an informal expert panel discussion, and public comment. The FDA, however, did not hold an advisory committee meeting, which, until this year, had been the primary method FDA relied upon to consult with experts on debated medical issues. The agencies supporting the use of HRT for the relief of menopausal symptoms and noted that initiating therapy within ten years of menopause onset or before age 60 may reduce risks of mortality, cardiovascular disease, Alzheimer’s disease, and bone fractures. Notably, none of the studies that were cited in support of removing the warnings were large, randomized, placebo-controlled trials.

The FDA will work with product manufacturers to update labeling, specifically removing references to cardiovascular disease, breast cancer, and probable dementia risks, while retaining a boxed warning for endometrial cancer in systemic estrogen-alone products.

The FDA also approved a generic version of Premarin to improve treatment accessibility and a non-hormonal therapy for moderate to severe vasomotor symptoms, such as hot flashes, to expand options for women who cannot or choose not to use hormone therapy.

Click to receive additional information about how to subscribe to and to activate a complimentary trial subscription.