Comments to the FDA on the Expert Panel on Menopause and Hormone Replacement Therapy for Women
Comments Regarding the Food and Drug Administration’s Expert Panel on Menopause and Hormone Replacement Therapy for Women
(FDA-2025-N-2589-0001)
Submitted electronically
Public Citizen, a national nonprofit consumer advocacy organization with over one million members and supporters nationwide, submits the below comments on the Food and Drug Administration’s (FDA’s) Expert Panel on Menopause and Hormone Replacement Therapy for Women.
On July 17, 2025, the FDA convened this expert panel for a meeting,[1] during which FDA Commissioner Dr. Martin Makary and the panelists stated that the boxed warning in the prescribing information of all menopause hormone treatments containing estrogen overstates the risks of these products, thereby potentially harming women who are reluctant to use menopause hormone therapy as a result. The panelists subsequently suggested that updating or removing the boxed warning was appropriate.[2] Makary and several panelists also asserted that hormone therapy may be beneficial for some conditions for which these treatments are currently not approved, such as the prevention of cardiovascular disease or cognitive decline.
Public Citizen is concerned that the FDA may be considering updates to the labeling of menopause hormone therapy without undertaking an impartial rigorous assessment of all available evidence and without adequately addressing gaps in our understanding of these treatments.
We urge the FDA to require additional studies before making any changes to the current boxed warning, to ensure that accurate information about the risks and benefits of menopause hormone therapy is available to clinicians and patients in the prescribing information. We also urge the FDA to convene an advisory committee such as the Obstetrics, Reproductive and Urologic Drugs Advisory Committee or the Drug Safety and Risk Management Advisory Committee, which follow the procedures of the Federal Advisory Committee Act, to advise on the agency’s decision-making on this issue. Moreover, to ensure transparency and accountability going forward, the FDA must ensure that any public meeting convened by the agency to inform regulatory decisions complies with the Federal Advisory Committee Act.[3],[4]
Evidence against unsubstantiated changes to the boxed warning for menopause hormone therapy
Menopause and medications to treat menopausal symptoms safely and effectively are of great importance. Public Citizen calls for a robust discussion about the risks and benefits of menopause hormone therapy, especially the long-term use of such treatments.
Standard hormone therapy for postmenopausal women has only been approved for the treatment of moderate to severe vasomotor symptoms and vulvar and vaginal atrophy.[5] The agency also has approved some of these medications for the prevention, but not treatment, of postmenopausal osteoporosis. Although menopause hormone therapy has been shown to be effective for vasomotor symptoms and vaginal dryness, there are documented risks, especially with long-term use.[6] Accordingly, the prescribing information for all menopause medications that contain estrogen carry a boxed warning, regardless of the formulation (such as oral, transdermal, or vaginal) of the drug.
The boxed warning is largely based on the findings of the Women’s Health Initiative (WHI), a long-term large randomized controlled trial with several sub studies.[7] The boxed warning states that menopause hormone therapy may increase the risk of cardiovascular disorders, probable dementia, invasive breast cancer, and endometrial cancer. Although many panelists at the July 17, 2025, meeting criticized the findings of the WHI,[8] the boxed warning is supported by other high-quality evidence as well.
For instance, other studies have found that systemic menopause hormone therapy increases the risk of breast cancer. A large 2019 meta-analysis published in the Lancet showed that the long-term use of all types of hormone therapy (except vaginal estrogen), especially combination (both estrogen and progestin) hormone therapy, is associated with a higher risk of invasive breast cancer.[9] Although this risk was low after less than one year of hormone therapy, there was a definite increased risk after one to four years of using hormone therapy and progressively greater risks with longer use.
A 2023 systematic review and meta-analysis noted that several observational studies found that menopause hormone therapy reduced the risk of Alzheimer’s disease and all-cause dementia.[10] However, in randomized controlled trials (which are considered to provide higher-quality evidence than observational studies) of postmenopausal women aged 65 and older, the risk of dementia appeared to be higher with combination hormone therapy than with placebo.[11]
During the July 17, 2025, meeting, several panelists mentioned that low-dose vaginal estrogen is safe to use (partially based on data from observational studies) and that the boxed warning should be removed for at least these formulations.[12] However, there are currently no adequate long-term data from randomized controlled trials on the safety of vaginal estrogen.[13] Prior trials investigating such preparations were too short to provide robust evidence on their long-term benefits and risks, for example regarding an increased risk of endometrial cancer.
Moreover, as pointed out by the Menopause Society (then the North American Menopause Society) in their 2022 hormone therapy position statement, the “risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.”[14] Unfortunately, high-quality data from randomized controlled trials to provide clarity on these interdependent risks, especially for newer hormone therapy formulations, are limited.
The boxed warning specifically indicates that hormone therapy should not be prescribed for the prevention of cardiovascular disease or dementia. Because this statement is supported by several randomized controlled trials, it should not be updated or removed from the boxed warning. Furthermore, the U.S. Preventive Services Task Force consistently recommends against hormone therapy for the prevention of chronic conditions in postmenopausal women because the possible benefits do not outweigh the serious harms.[15],[16] For example, although some evidence shows that estrogen-only therapy lowers the risks of diabetes and fractures, it also increases the risks of gallbladder disease, stroke, blood clots, and urinary incontinence. Likewise, combined estrogen and progestin therapy lowered risks of colorectal cancer, diabetes, and fractures but increased risks of invasive breast cancer, gallbladder disease, stroke, and blood clots in postmenopausal women. It also probably increased the risks of dementia and urinary incontinence.
Of note is that four leading medical societies, the American College of Obstetricians and Gynecologists, the Menopause Society, the American Association of Clinical Endocrinology and American College of Endocrinology, and the Endocrine Society — do not recommend hormone therapy for the prevention of coronary heart disease.[17]
The boxed warning also states that menopause hormone therapy should be prescribed “at the lowest effective doses and for the shortest duration” to minimize the risks.[18] This commonsense statement is largely supported by medical societies. The statement should not be updated or removed from the boxed warning without high-quality evidence to support such a change.
Regulatory considerations
The July 17, 2025, expert panel meeting and the possible “updates to the labeling”[19] come at a time of renewed interest and media attention on menopause and a growing global multibillion-dollar “femtech” market.[20] Pharmaceutical manufacturers that market menopausal hormone therapies have long lobbied for the removal of the boxed warning for menopause hormone therapy. If the boxed warning is removed, these companies are likely to financially benefit. It is of the utmost importance that the FDA decision-making process is both fully transparent and guided by unbiased, high-quality, long-term data on the benefits and risks of menopause hormone therapy.
Before the FDA proposes any changes to the boxed warning for menopause hormone therapy, it should hold a public advisory committee meeting, in accordance with the Federal Advisory Committee Act. The rigorous process of FDA advisory committee meetings protects the agency from interest-driven or one-sided views, and allows clinicians and the public to scrutinize the FDA’s decision-making process.[21] The July 17, 2025, expert panel was not an adequate replacement for such an advisory committee meeting for the following reasons:
- The criteria according to which panelists were selected were not made public. We believe that at least some panelists had conflicts of interest that were not adequately disclosed and that should have disqualified them from participation. For example, several were members of the medical advisory board of the Let’s Talk Menopause group, which is financially supported by pharmaceutical companies.[22]
- The FDA expert panel meeting did not include presentations from FDA scientists, as would have been the case at an advisory committee meeting. As a result, the meeting was less likely to have been objective and representative of scientific consensus on the issues discussed.
Public Citizen urges the FDA not to update or remove the boxed warning in the prescribing information of menopause hormone therapy containing estrogen without proper vetting of available evidence or additional high-quality evidence. Furthermore, we urge the FDA to convene a public advisory committee meeting to inform the agency’s decision-making on this issue and to ensure that the regulatory process is transparent and accountable.
Thank you for your consideration of our comments regarding this important issue.
Sincerely,
Nina Zeldes, Ph.D.
Health Researcher, Health Research Group
Public Citizen
1600 20th St. NW
Washington, D.C. 20009
—
[1] The Food and Drug Administration. FDA expert panel on menopause and hormone replacement therapy for women. July 17, 2025. https://www.fda.gov/patients/fda-expert-panels/fda-expert-panel-menopause-and-hormone-replacement-therapy-women-07172025. Accessed September 24, 2025.
[2] Rabin RC. F.D.A. panelists call for removal of warnings on menopause treatments. The New York Times. July 17, 2025. https://www.nytimes.com/2025/07/17/health/hormone-therapy-menopause-fda.html. Accessed September 24, 2025.
[3] The Federal Advisory Committee Act (FACA): Overview and considerations for Congress. https://www.congress.gov/crs-product/R47984. Accessed September 24, 2025.
[4] Alexander GC. The FDA’s pivot from ad comms to ‘expert’ panels is bad medicine. STAT. September 5, 2025. https://www.statnews.com/2025/09/05/fda-expert-panels-advisory-committees-talc-ssris-formula/. Accessed September 24, 2025.
[5] Pfizer, Inc. Label: Conjugated estrogens (PREMARIN). April 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/004782s179lbl.pdf. Accessed September 24, 2025.
[6] Fugh-Berman A, Mintzes B. Menopausal hormone therapy: Limited benefits, significant harms. Am Fam Physician. 2025 Jul;112(1):15-16.
[7] Pfizer, Inc. Label: Conjugated estrogens (PREMARIN). April 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/004782s179lbl.pdf. Accessed September 24. 2025.
[8] The Food and Drug Administration. FDA expert panel on Menopause and hormone replacement therapy for women. July 17, 2025. https://www.fda.gov/patients/fda-expert-panels/fda-expert-panel-menopause-and-hormone-replacement-therapy-women-07172025. Accessed September 24, 2025.
[9] Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: Individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019;394(10204):1159-1168.
[10] Nerattini M, Jett S, Andy C, et al. Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer’s disease and dementia. Front Aging Neurosci. 2023;15 (October 23):1260427.
[11] Mintzes B, Fugh-Berman A. Does menopause hormone therapy prevent Alzheimer’s disease and dementia? Drug Ther Bull. 2024;62(12):179-182.
[12] The Food and Drug Administration. FDA expert panel on Menopause and hormone replacement therapy for women. July 17, 2025. https://www.fda.gov/patients/fda-expert-panels/fda-expert-panel-menopause-and-hormone-replacement-therapy-women-07172025. Accessed September 24, 2025.
[13] Pharmed Out. Letter to the FDA re: Potential label change for vaginal estrogen. July 14, 2025. https://georgetown.app.box.com/s/dndom4jy6fk4yneaiw00e6ptatkt903j. Accessed September 24, 2025.
[14] The 2022 Hormone Therapy Position Statement of The North American Menopause Society Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767-794.
[15] US Preventive Services Task Force, Mangione CM, Barry MJ, et al. Hormone therapy for the primary prevention of chronic conditions in postmenopausal persons: US Preventive Services Task Force recommendation statement. JAMA. 2022;328(17):1740-1746.
[16] USPSTF reaffirms recommendations against using menopausal hormone therapy to prevent chronic conditions. Worst Pills, Best Pills News. April 2023. https://www.worstpills.org/newsletters/view/1526. Accessed September 24, 2025.
[17] Cho L, Kaunitz AM, Faubion SS, et al. Rethinking menopausal hormone therapy: For whom, what, when, and how long? Circulation. 2023;147(7):597-610.
[18] Pfizer, Inc. Label: Conjugated estrogens (PREMARIN). April 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/004782s179lbl.pdf. Accessed September 24. 2025.
[19] The Food and Drug Administration. FDA expert panel on menopause and hormone replacement therapy for women. July 17, 2025. https://www.fda.gov/patients/fda-expert-panels/fda-expert-panel-menopause-and-hormone-replacement-therapy-women-07172025. Accessed September 24, 2025.
[20] Christakis MK, Roebotham T, Sterry S, et al. Menopause misinformation is harming care. BMJ. 2025;390(August 20):r1695.
[21] Alexander GC. The FDA’s pivot from ad comms to ‘expert’ panels is bad medicine. STAT. September 5, 2025. https://www.statnews.com/2025/09/05/fda-expert-panels-advisory-committees-talc-ssris-formula/. Accessed September 24, 2025.
[22] Let’s Talk Menopause. Our team. https://www.letstalkmenopause.org/our-team. Accessed September 24, 2025.