Impact on SGO Members: While many of the black-box warnings for menopausal hormone replacement therapy (HRT) are being removed, the Food and Drug Administration (FDA) is not seeking to remove the warning for endometrial cancer for systemic estrogen-alone products.
On November 10, the leadership of the FDA, together with that of the Department of Health and Human Services, announced that they will initiate the removal of broad black-box warnings on HRT products to provide relief from menopausal symptoms. Following a comprehensive review of the scientific literature, an expert panel, and public comment period, the FDA will remove the warnings related to the risk of cardiovascular disease, breast cancer, and probable dementia.
For the gynecologic oncology community, it is important to note that the warning for endometrial cancer on systemic estrogen-alone therapy in women with a uterus will remain. This unchanged warning underscores that oncologic considerations around risk remain valid. Therefore, decisions around HRT must remain individualized and providers must continue to counsel patients about potential risks, particularly in the context of hormone-sensitive cancers.
This policy change signals a major shift in safety messaging for HRT and may increase its use in appropriate candidates. The agency’s updated labeling will emphasize the timing of therapy – initiating before age 60 or within 10 years of the onset of menopause – to optimize the benefit-risk balance. As highlighted by the FDA, the potential benefits include a reduced risk of all-cause mortality and fractures. Additionally, HRT has been associated with reductions in heart attack risk, cognitive decline, and a lower risk of Alzheimer’s disease.