In a significant development for women’s health, a growing coalition of physicians, scientists, and public health advocates is urging the U.S. Food and Drug Administration (FDA) to lift the black box warning currently required on low-dose vaginal estrogen products. This longstanding warning, which suggests an increased risk of serious health issues such as cancer, stroke, and blood clots, is now under intense scrutiny for being outdated and overly broad—particularly when applied to localized, low-dose treatments that have been shown to have minimal systemic effects.
The Origins of the Warning
The black box warning traces its origins to findings from the early 2000s, particularly the large-scale Women’s Health Initiative (WHI) study. This study linked hormone replacement therapy (HRT)—specifically systemic estrogen combined with progestin—to elevated risks of breast cancer and cardiovascular events. As a result, the FDA implemented its most serious label warning across all estrogen-containing therapies, including low-dose vaginal estrogen.
However, over the past two decades, medical understanding of hormone therapy has evolved. Multiple studies and expert reviews have concluded that topically applied, low-dose vaginal estrogen behaves very differently in the body than systemic hormone therapy. Localized estrogen is absorbed minimally into the bloodstream and is intended to treat symptoms such as vaginal dryness, atrophy, and recurrent urinary tract infections—issues that affect over 50% of postmenopausal women.
Despite these findings, the same stark black box warning appears on both systemic and local estrogen therapies, leading to what many experts believe is widespread confusion and unnecessary fear among patients and providers alike.
Minimal Absorption, Minimal Risk
Unlike oral or transdermal systemic hormone therapies, low-dose vaginal estrogen products—such as creams, rings, and tablets—deliver estrogen directly to the vaginal tissue. According to data published in Contemporary OB/GYN, low-dose vaginal estrogen has been shown to increase serum estrogen levels only slightly, often remaining within the postmenopausal range. This means that the risk of serious systemic side effects is significantly reduced.
A 2022 position statement by The North American Menopause Society (NAMS) explicitly supported the safety of vaginal estrogen, stating that “the data do not support the application of a black box warning on these products” (NAMS PDF).
In fact, the European Medicines Agency (EMA) and regulatory bodies in countries like Canada and the UK have not required black box warnings for similar vaginal estrogen therapies, illustrating a sharp contrast in regulatory approaches and sparking calls for the FDA to reconsider its position.
The Real-World Impact on Patients
The existing warning has had a measurable impact on care. Many women report avoiding vaginal estrogen due to fear of cancer or stroke, while some healthcare providers hesitate to prescribe it, worried about legal or reputational risk. The result is that women experiencing painful intercourse, chronic vaginal dryness, or urinary tract infections—conditions often caused by genitourinary syndrome of menopause (GSM)—are left untreated.
Dr. Ashley Winter, a urologist and vocal advocate for updating FDA guidance, recently wrote in Urology Times that “Vaginal estrogen is one of the safest and most effective medications in medicine. It is being withheld due to misinformation.” Her perspective is echoed by gynecologists, endocrinologists, and patient advocacy groups who argue that fear-based messaging is leading to widespread undertreatment and suffering.
A national survey conducted by AARP found that fewer than 25% of women over 50 had ever used vaginal estrogen, despite nearly half reporting moderate to severe symptoms of GSM. When asked why, the most common responses were fear of side effects and confusing labeling.
A New FDA Review Panel and Its Recommendations
In response to mounting pressure, the FDA established a new advisory panel in 2024, led by FDA Commissioner Marty Makary, to re-evaluate hormone therapies for menopause. This initiative aims to modernize regulatory guidelines in light of improved research tools, more targeted therapies, and better understanding of menopause-related conditions.
The panel’s recommendation to remove the black box warning for low-dose vaginal estrogen was announced during a recent open session and is currently under review. Although advisory panel opinions are not binding, they carry considerable weight and often signal a shift in agency policy.
In a recent BioPharma Dive article, experts emphasized that failure to remove the warning could continue to cause harm by disincentivizing use of an otherwise safe treatment. “We now have decades of data supporting its safety,” said one panel member. “The warning no longer reflects current science.”
Opposition and Remaining Concerns
Not all voices agree with the proposed change. Some patient advocacy groups worry that removing the warning entirely might lead to misunderstandings or casual overuse. They advocate for more balanced labeling—perhaps in the form of a cautionary note rather than a black box—to ensure that patients are still informed about any potential risks, however small.
Others urge the FDA to launch a public education campaign alongside any label changes, to counter misinformation and improve provider knowledge. This could help restore confidence in hormone therapy options and reduce the stigma surrounding menopause-related treatments.
Moving Toward a New Era in Women’s Health
If the FDA follows through on the recommendation, it could pave the way for broader reforms in menopausal care—an area that has historically received less research and public attention than other health issues. Women may finally have access to low-risk, effective treatment options without the looming fear of misleading warnings.
This could also lead to new innovations in hormone therapy and help reframe menopause as a natural life phase that deserves the same evidence-based care and medical resources as any other.
