An important update about the safety of vaginal estrogen therapies—a topic that affects the millions of women navigating perimenopause & menopause.
On July 17th, a panel of top medical experts, including gynecologists, urologists, menopause specialists, and researchers, met with the FDA to review the science behind hormone therapy and to advocate for the removal of the black box warning on vaginal estrogen.
What is the Black Box Warning on Vaginal Estrogen & How Has it Negatively Impacted Women for Decades?
The Black Box Warning on Vaginal Estrogen indicates that estrogens increase the risk of:
– Endometrial cancer
– Cardiovascular disorders (such as stroke and deep vein thrombosis)
– Breast cancer
– Probable dementia
The Problem
This warning was derived from the 2002 Women’s Health Initiative (WHI) study, which studied oral estrogen (conjugated equine estrogen) and synthetic progestin in women with an average age of 63.
Because most participants were well past the menopause transition, they likely had existing health issues that may have influenced the observed risks associated with hormone therapy. Additionally, starting hormone therapy later in life, beyond the “window of opportunity” within 10 years of menopause, is linked to higher risks and fewer benefits compared to starting treatment earlier.
Furthermore, the WHI study evaluated oral hormone formulations at higher systemic doses than today’s low-dose vaginal estrogen, along with a synthetic progestin now associated with greater health risks. The oral route itself carries higher risks compared to alternatives like vaginal or transdermal therapies, which generally offer improved safety profiles.
Why Low-Dose Localized Vaginal Estrogen is Different
Low-dose vaginal estrogen:
-It is minimally absorbed into the bloodstream.
-Does not increase systemic estrogen levels significantly.
-Has not been shown to increase the risk of breast cancer, stroke, blood clots, heart disease, or dementia.
What You Should Know
The Menopause Society, ACOG, and other experts have called the warning inappropriate and misleading for vaginal estrogen. A 2024 meta-analysis found no increased risk of cancer recurrence or mortality in breast cancer survivors using vaginal estrogen. Endometrial safety has also been demonstrated in trials lasting up to 52 weeks.
Vaginal estrogen is safe: Low-dose vaginal estrogen, used to treat genitourinary syndrome of menopause (GSM)—which includes vaginal dryness, pain with intimacy, and recurrent urinary tract infections—does not significantly raise estrogen levels in the bloodstream.
Vaginal estrogen is highly effective in relieving vaginal, urinary, and vulvar symptoms related to perimenopause and menopause:
– Relieves vaginal symptoms like dryness, itching, burning, and pain during sex
– Improves vaginal health by increasing elasticity and restoring natural balance
– Reduces urinary issues, such as urgency, frequency, and recurrent urinary tract infections (UTIs)
– Safe for long-term use and well tolerated by most women
– May be an option for most breast cancer survivors, with approval from their oncologist
There is no evidence linking vaginal estrogen to increased risk of breast cancer, heart disease, stroke, dementia, or blood clots. Yet, it still carries a black box warning based on outdated studies of systemic (oral) hormone therapy in older women.
Experts agree: Leading menopause specialists called the warning “misleading and harmful.” It prevents many women, including cancer survivors and those with early menopause, from accessing treatment that could greatly improve quality of life.
Vaginal estrogen provides more than symptom relief: it’s preventative care that helps reduce recurrent urinary tract infections and supports long-term health.
Misinformation has caused harm: Since the release of the Women’s Health Initiative (WHI) study in 2002, prescriptions for hormone therapy dropped sharply. New analyses show the study misrepresented risks and left millions of women without safe, effective treatment.
What This Means For You
You deserve accurate information and access to safe therapies. Local vaginal estrogen is a low-dose, targeted treatment that helps restore tissue health, improve comfort, and reduce infections—and it’s time the label reflects what the science shows.
The FDA is currently reviewing expert recommendations, and we’re hopeful that changes will be made soon.
If you’re experiencing symptoms of GSM or menopause and have questions about hormone therapy, we’re here to help. Please don’t hesitate to reach out or schedule a visit with one of our menopause-trained providers.