We Have Arrived: Hormone Replacement and the FDA

Well, ladies, the time has come. The FDA has given the green light and removed most of the warning labels, which I knew were not accurate in the first place!

As of this past November, the FDA has decided to remove some black box warnings on menopausal hormone therapies (MHT), including vaginal estrogen, reflecting new evidence that supports its safety and effectiveness for treating menopause-related conditions. This is big news.

What does it mean for you? Let’s discuss!

What Were the Warnings?

The original black box warnings can be traced back to large-scale studies from 2002 (referred to as the WHI trials) that were stopped early because researchers reported higher rates of breast cancer, heart attacks, and strokes among participants using a specific form of hormone therapy.

Because the findings were dramatic and widely publicized, the FDA applied broad warnings to many hormone products, including local vaginal estrogen. As a result, prescriptions for hormone therapy plummeted, and many women avoided treatment altogether out of fear of serious health complications.

The FDA’s recent action came after a scientific review that determined the original black box warning, based on older studies of systemic hormone therapy in women, didn’t actually apply to low-dose vaginal estrogen. The studies also didn’t include a significant population of hormone therapy candidates: women at the start of menopause, which typically occurs between the ages of 45 and 55. Most women begin hormone therapy in their 40s or early 50s, when their cardiovascular and cancer risk profiles look very different.

Because of this mismatch, the original warning overstated the potential risks of systemic MHT and vaginal estrogen therapy.

Why Did the Labels Change?

To help put your mind at ease and understand the new labeling, it might help to revisit the history. As we mentioned, two studies were conducted in the 1990s and widely published in 2002. These were the Women’s Health Initiative (WHI) trials – large studies that evaluated systemic estrogen therapies that focused on chronic disease prevention in an older population and used formulations not commonly prescribed today.

Over the years, clinicians and women’s health experts expressed concern that the WHI findings were being over-applied to younger women seeking hormone therapy for symptom relief, not disease prevention. Many also pointed out that the WHI population did not resemble the typical patient starting hormone therapy – study participants were mostly in their 60s and 70s.

After reviewing decades of follow-up data, updated scientific literature, and public feedback (including input from an Expert Panel convened in July 2025), the FDA concluded that the risks originally highlighted in the WHI studies do not reflect the risk profile of today’s systemic hormone therapies, and especially low-dose vaginal products.¹

The American Urological Association (AUA); the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU); and the American Urogynecologic Society (AUGS) have all supported the removal of the warning, endorsing low-dose vaginal estrogen as a first-line treatment for genitourinary syndrome of menopause (GSM).^2-3

Current scientific evidence shows that low-dose vaginal estrogen is safe and effective for treating symptoms like those from GSM,^4-6 and the removal of the warning is a significant step for women’s health, allowing for a more open discussion of benefits and risks between patients and doctors.

The FDA itself notes that menopause hormone therapies (MHTs) are designed to relieve vasomotor symptoms such as hot flashes, as well as changes in the vagina, vulva, and urinary tract that occur when estrogen levels decline. Some systemic therapies are also approved to help prevent bone loss.⁷ (MHT comes in different forms, including pills, patches, gels, vaginal creams, tablets, rings, and more. Systemic forms, like pills or patches, circulate throughout the body, while local forms, like vaginal estrogen, act in the tissues where they’re applied.)

Because modern studies have failed to replicate the alarming rates of adverse events seen in 2002, alongside growing bodies of evidence for the efficacy of MHTs, major changes to prescribing information are underway. That includes removing warning language about cardiovascular disease, breast cancer, dementia, and, except with systemic estrogen-only products, endometrial cancer. The previous recommendation to “use the lowest effective dose for the shortest duration” has also been removed. For local vaginal estrogen products specifically, the FDA is condensing the safety information to focus only on what is relevant to low-dose local therapy, acknowledging that it differs greatly from systemic hormone therapy in its effects, absorption, and risk profile.⁷

What Does This Mean for YOU?

“We are going to stop the fear machine steering women away from this life-changing, even lifesaving, treatment… The FDA is taking action to remove the black box warnings from estrogen-related products. This is based on a robust review of the latest scientific evidence.” – FDA Commissioner Marty Makary⁸

This change in regulatory action is amazing! It allows for more accurate conversations about the benefits and risks of treatment. It also addresses a hurdle that prevented many doctors from prescribing the therapy.

The revised labeling provides a more accurate and evidence-based picture of the risks versus benefits of hormone replacement therapies for appropriate patients. You can now have a more nuanced conversation with your doctor about which therapy may be a good option for you.

A word of caution: We cannot stress enough the importance of discussing your symptoms and treatment options with your healthcare provider. We have to be on the same page as far as specific symptoms, risk factors, and treatment goals are concerned. Just because medications may become more readily available doesn’t mean the therapy is appropriate for everyone. As with any prescription drug, side effects and contraindications still exist. An individualized conversation about vaginal estrogen therapy, and especially systemic hormone therapy, with a knowledgeable healthcare provider is essential to keeping you healthy and safe.

If you’ve been struggling with the symptoms of GSM, menopausal hormone therapy just might be your solution. Contact our team at Aayla – we can have that discussion now!

1. U.S. Food and Drug Administration. (2025, November 10). FDA Requests Labeling Changes Related to HRT. FDA. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-labeling-changes-related-safety-information-clarify-benefitrisk-considerations. 
2. Kaufman, M. R., Ackerman, A. L., Amin, K. A., Coffey, M., Danan, E., Faubion, S. S., Hardart, A., Goldstein, I., Ippolito, G. M., Northington, G. M., Powell, C. R., Rubin, R. S., Westney, O. L., Wilson, T. S., & Lee, U. J. (2025). Executive Summary: The AUA/SUFU/AUGS Guideline on Genitourinary Syndrome of Menopause. Urogynecology (Philadelphia, Pa.), 31(11), 1005–1014. https://doi.org/10.1097/SPV.0000000000001753. 
3. American Urogynecologic Society. (2025, August). August-2025-FDA-Estrogen-Labeling. Www.augs.org. https://www.augs.org/wp-content/uploads/2025/11/August-2025-FDA-Estrogen-Labeling.pdf. 
4. Ali, A., Iftikhar, A., Tabassum, M., Imran, R., Shaid, M. U., Hashmi, M. R., Saad, M., Humayun, M., Imtiaz, S., & Baig, E. (2024). Efficacy and Safety of Intravaginal Estrogen in the Treatment of Atrophic Vaginitis: A Systematic Review and Meta-Analysis. Journal of menopausal medicine, 30(2), 88–103. https://doi.org/10.6118/jmm.23037. 
5. Agrawal, P., Singh, S. M., Able, C., Dumas, K., Kohn, J., Kohn, T. P., & Clifton, M. (2023). Safety of Vaginal Estrogen Therapy for Genitourinary Syndrome of Menopause in Women With a History of Breast Cancer. Obstetrics and gynecology, 142(3), 660–668. https://doi.org/10.1097/AOG.0000000000005294. 
6. McVicker, L., Labeit, A. M., Coupland, C. A. C., Hicks, B., Hughes, C., McMenamin, Ú., McIntosh, S. A., Murchie, P., & Cardwell, C. R. (2024). Vaginal Estrogen Therapy Use and Survival in Females With Breast Cancer. JAMA oncology, 10(1), 103–108. https://doi.org/10.1001/jamaoncol.2023.4508. 
7. U.S. Food and Drug Administration. (2025, November 10). FDA Requests Labeling Changes Related to HRT. FDA. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-labeling-changes-related-safety-information-clarify-benefitrisk-considerations. 
8. Bendix, A., & Edwards, E. (2025, November 10). Hormone replacement therapy will no longer carry a warning label, FDA says. NBC News. https://www.nbcnews.com/health/womens-health/hormone-replacement-therapy-no-warning-label-fda-rcna243008.