On July 17, 2025, an advisory panel convened by the U.S. Food and Drug Administration made a significant recommendation: remove the boxed warning on vaginal estrogen products used for menopause treatment. The warning has long cautioned about elevated risks of breast cancer, blood clots, and stroke, but panel members argued that current evidence does not support those claims, at least not in the context of localized hormone therapy.
The boxed warning originates from a 2002 National Institutes of Health (NIH) study, which linked systemic hormone therapy to potential cardiovascular and cancer risks. That study set off widespread concern and led many physicians to halt prescriptions for hormone replacement therapy (HRT). Millions of women discontinued use, often abruptly, due to fears of long-term harm.
FDA Commissioner Dr. Marty Makary, who called for the meeting, stated the goal was to “separate medical dogma from evidence.” He cited several modern clinical findings that challenge the conclusions drawn from the 2002 research. Notably, he emphasized that no clinical trials have shown an increase in breast cancer mortality from these therapies. He also highlighted data showing a potential cardioprotective effect of estrogen, particularly when therapy begins within ten years of menopause onset.
According to Makary, initiating estrogen therapy during this window may reduce the risk of fatal heart attacks and cardiovascular disease by 25 to 50 percent. These statistics echo findings published over the last decade, as researchers have reexamined the risk-benefit profile of menopausal hormone therapy, especially when used at the right time and in the right form.
Physicians and advocacy organizations are increasingly vocal about the need to revisit the FDA’s position. Both the North American Menopause Society and the American College of Obstetricians and Gynecologists have called for the warning to be removed. They argue that the label discourages both physicians and patients from considering therapies that could significantly improve quality of life for menopausal women.
Dr. Heather Hirsch of the Cleveland Clinic echoed this sentiment, stating, “History got it wrong when it comes to menopausal women.” She explained that vaginal estrogen is a low-risk therapy with important long-term benefits, and the boxed warning does not reflect the evidence available today. She also pointed out that medical education still lacks adequate training on menopause management, leaving providers without the tools to confidently prescribe these treatments.
Dr. Barbara Levy added a personal note, describing the fallout from the 2002 study as “devastating.” She and others on the panel urged the FDA to reconsider the warnings and acknowledge the unintended harm that resulted from decades of cautionary messaging.
For life sciences companies and regulatory professionals, this development is worth watching. While the panel’s recommendation does not carry the weight of a regulatory decision, it does increase the likelihood that the FDA could revise its labeling guidance in the near future. Companies developing HRT products may soon face an updated regulatory landscape, with fewer barriers to approval or prescribing.
At EMMA International, we monitor safety communications and advisory committee developments closely to help our clients plan ahead. Label changes, especially boxed warnings, are among the most significant regulatory hurdles a product can face. Knowing when those requirements may shift allows companies to stay proactive rather than reactive.
For more information on how EMMA International can assist, visit www.emmainternational.com. Contact EMMA International at (248) 987-4497 or by email at info@emmainternational.com to learn more.
Resources:
Eglovitch, J.S. (2025, July 17). Panel urges FDA to remove boxed warning on women’s hormone therapy. Regulatory News.
