FDA Requests Removal of Hormone Therapy Boxed-Warning Risks (2025)

Table of Contents

1. 1. What the FDA Did on 10 November 2025
2. 2. The Terms Used in the FDA’s Documents
3. 3. Before the Request: the 17 July 2025 Expert Panel and Public Input
4. 4. What the FDA Asked to Be Removed
5. 5. What the FDA Asked to Be Added or Kept
6. 6. The Reasons the FDA Statement Gives
7. 7. How the HHS Press Release Presented the Request
8. 8. The Two Drug Approvals Announced the Same Day
9. 9. What the Request Did Not Do
10. 10. Dates and Status as of 11 October 2026
11. 11. How the Request Fits the FDA’s Earlier Handling of Hormone Therapy
12. 12. Primary Documents
13. Key Research Papers
14. Connections

1. What the FDA Did on 10 November 2025

Two FDA documents carry the action, both dated 10 November 2025.

• The FDA statement, “FDA Requests Labeling Changes Related to Safety Information to Clarify the Benefit/Risk Considerations for Menopausal Hormone Therapies,” published under the agency’s Drug Alerts and Statements. It records that “Today, the U.S. Food and Drug Administration (FDA) informed application holders of menopausal hormone therapies (MHT) … about requested labeling changes aimed to better clarify the benefit/risk considerations for these medications.” Its subtitle describes the content as the “proposed removal of risk statements about cardiovascular diseases, breast cancer, and probable dementia from the Boxed Warnings, as well as other proposed safety-related labeling changes.”
• The HHS and FDA news release, “HHS Advances Women’s Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy.” It states that the FDA “is initiating the removal of broad ‘black box’ warnings from HRT products for menopause,” and that the agency “is working with companies to update language in product labeling.”

According to the release, the announcement was made by the Secretary of Health and Human Services, Robert F. Kennedy, Jr., and the FDA Commissioner, Marty Makary, M.D., M.P.H., at a press conference at HHS with more than 200 people in attendance.

The action took the form of a request to companies, not a rule. Neither document cites a Federal Register notice or a public docket number for it; the earlier public-input step is described in section 3.

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2. The Terms Used in the FDA’s Documents

• Label (prescribing information): the FDA-approved document that sets out what a prescription drug is approved to treat, how it is used and its known risks.
• Application holder: the company that holds the FDA approval for a drug. The label belongs to that company’s approval, so the FDA’s November step was a request to those companies to submit revised wording, which the agency would then review and approve.
• Boxed Warning: a warning printed inside a border at the top of the label, which the FDA statement calls “the agency’s most prominent safety-related warning.” The press release uses the everyday name “black box” warning.
• Menopausal hormone therapy (MHT): estrogen, alone or with a progestogen (progesterone or a progesterone-like drug), used for menopause symptoms; the FDA notes it is also commonly called HRT.
• Systemic and local vaginal products: systemic products act throughout the body; local vaginal estrogen products are applied in the vagina for symptoms there.
• Vasomotor symptoms (VMS): the FDA’s term for hot flashes and night sweats.
• Genitourinary syndrome of menopause (GSM): changes to the vagina, vulva and urinary tract caused by lower estrogen, formerly called vulvovaginal atrophy (VVA).
• Women’s Health Initiative (WHI): the large U.S. trials of hormone therapy whose results in 2002–2004 led to the original warnings (section 11).

The FDA statement lists the approved uses as relief of moderate to severe hot flashes and of VVA, and, for some products, prevention of osteoporosis (bone weakening).

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3. Before the Request: the 17 July 2025 Expert Panel and Public Input

The FDA statement places the November request at the end of a sequence of steps. After describing years of questions about the warnings (section 6), it says: “Most recently, FDA held an Expert Panel on July 17, 2025, and the panel focused on the risks and benefits of MHT. After the Expert Panel meeting, FDA requested broad public input on the risks and benefits related to menopause hormone therapy.”

The press release gives the same sequence in one sentence: the FDA is initiating removal of the boxed warnings “following a comprehensive review of the scientific literature, an expert panel in July, and a public comment period.”

The statement names three inputs to the decision:

1. a “comprehensive assessment of relevant literature” published since the two large WHI studies;
2. an “updated drug utilization review” (the FDA’s analysis of how many women receive prescriptions, described in section 6);
3. “public input about MHTs.”

Neither of the two November documents lists the panel’s members, summarizes what individual panelists said, or gives the length of the public-input period or the number of comments received, so this page does not either.

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4. What the FDA Asked to Be Removed

The FDA statement says that, having “re-considered the benefit/risk balance of these drugs,” the agency was requesting the following key changes. For all menopausal hormone therapies, systemic and local vaginal alike:

In the Boxed Warning:

• remove the language related to cardiovascular diseases, breast cancer and probable dementia;
• remove the language related to endometrial cancer (cancer of the lining of the uterus), except in the systemic estrogen-alone drugs;
• remove the recommendation to use the lowest effective dose for the shortest amount of time.

In the labeling as a whole:

• remove the probable dementia warning.

The difference between the two levels matters. Taking a risk out of the boxed warning moves it out of the bordered box at the top; taking it out of “the labeling as a whole” deletes it from the label. Of the risks named in the box, the statement asks for the probable-dementia warning to go from the whole label.

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5. What the FDA Asked to Be Added or Kept

The rest of the request differs by product type.

Systemic products, in the labeling as a whole:

• add consideration of starting hormone therapy for moderate to severe vasomotor symptoms in women younger than 60 or less than 10 years since menopause;
• add WHI data in women aged 50 to 59;
• retain the Boxed Warning about endometrial cancer in the systemic estrogen-alone products;
• retain the information about cardiovascular diseases and breast cancer warnings.

Local vaginal estrogen products, in the labeling as a whole:

• condense safety information and prioritize the information most relevant to the local vaginal formulation.

Read with section 4, the request moves the cardiovascular and breast-cancer information for systemic products out of the box but keeps it in the body of the label, and leaves one boxed warning in place, on endometrial cancer, for systemic estrogen taken without a progestogen. The site’s background on local products is on the Genitourinary Syndrome of Menopause and Vaginal Estrogen page.

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6. The Reasons the FDA Statement Gives

Questions over the years. The statement says the agency “received questions about whether the Boxed Warnings resulting from the WHI findings were warranted, particularly for local vaginal estrogen-only products,” that certain groups raised concerns about how the WHI studies’ methods and interpretations applied to menopausal women for whom MHT is warranted, and that the women’s health community raised concerns that many symptomatic women for whom MHT is indicated “are not prescribed MHT or decline treatment with MHT because of these Boxed Warnings.”

Age of the trial participants. The statement says the WHI trials’ primary aim was to evaluate hormone therapy’s effect on cardiovascular disease and other chronic conditions in postmenopausal women of all ages, with an average participant age of 63. Bothersome vasomotor symptoms typically occur earlier (average age ranging between 45 and 55), and the average age of menopause in the U.S. is 51, so “the age-related health conditions in the WHI population did not match the typically younger and healthier women who may start MHT for bothersome VMS.” The FDA says it considered “multiple additional analyses and long-term follow-up of the WHI participants” to describe risks in the younger group. On dementia, it notes the WHI dementia studies enrolled women aged 65 to 79, “a population much older than women starting MHT.”

How many women use it. The statement cites U.S. Census Bureau data that about 41 million U.S. women were aged 45 to 64 in 2020, a 2021 study (Nappi and colleagues, listed below) that put the prevalence of moderate to severe vasomotor symptoms in women aged 45 to 65 at about 34%, and the FDA’s review of U.S. outpatient prescriptions showing that about 2 million women aged 46 to 65 received a prescription for systemic estrogen-alone or estrogen plus progestogen in 2020. It concludes that “such drug use data suggest MHT may be under-utilized among women likely to benefit from MHT.”

The follow-up page discusses these reasons alongside the 2026 approvals; the published WHI reports by age and years since menopause are listed under Key Research Papers below.

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7. How the HHS Press Release Presented the Request

The press release describes the same action in stronger language than the statement. These are the release’s own words and figures, reported as such.

• Its framing. It calls the action “historic action to restore gold-standard science to women’s health” after “more than two decades of fear and misinformation surrounding hormone replacement therapy.”
• Its account of the WHI. It says HRT use “plummeted in the early 2000s” when the FDA applied boxed warnings “following a Women’s Health Initiative study that found a statistically non-significant increase in the risk of breast cancer diagnosis,” that the average participant age of 63 was “over a decade past the average age of a woman experiencing menopause,” and that participants “were given a hormone formulation no longer in common use.” The published 2002 WHI results are listed under Key Research Papers for readers who want the trial’s own figures.
• Its benefit figures. The release states that randomized studies show that women who start HRT within 10 years of the onset of menopause (generally before age 60) have a reduction in all-cause mortality and fractures, and that women “may also reduce their risk of cardiovascular diseases by as much as 50%, Alzheimer’s disease by 35%, and bone fractures by 50 to 60%.” The release cites no study for any of these percentages; they are the release’s statements, not findings drawn by this site, and the FDA statement of the same day does not repeat them.
• Its description of the label wording. The release says that starting time and duration “are decisions made between the prescriber and the individual patient,” but that “the FDA’s labeled recommendation will be to start HRT within 10 years of menopause onset or before 60 years of age for systemic HRT.” The FDA statement words the same element as adding “consideration of starting hormone therapy” in that group (section 5).

The release quotes four officials:

• The Secretary of Health and Human Services: “For more than two decades, bad science and bureaucratic inertia have resulted in women and physicians having an incomplete view of HRT. We are returning to evidence-based medicine and giving women control over their health again.”
• The FDA Commissioner: “Tragically, tens of millions of women have been denied the life-changing and long-term health benefits of hormone replacement therapy because of a medical dogma rooted in a distortion of risk.”
• The Director of the Advanced Research Projects Agency for Health (ARPA-H), Alicia Jackson, Ph.D.: “Estrogen is a key hormone for women’s health,” calling the removal of the boxed warning “an incredible step forward.”
• The HHS Deputy Secretary, Jim O’Neill, who said the Secretary and Commissioner were “removing a barrier on this treatment.”

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8. The Two Drug Approvals Announced the Same Day

The press release adds that, “in addition to the removal of boxed warnings,” the FDA was approving two drugs for menopausal symptoms:

1. A generic conjugated-estrogens product. The release describes it as the first generic approval in more than 30 years for a widely used conjugated-estrogens hormone therapy, expected “to improve affordability and access” while maintaining the same quality, safety and effectiveness as the brand-name drug. (A generic is a copy of an approved drug that the FDA approves as equivalent to it.)
2. A non-hormonal treatment for moderate to severe vasomotor symptoms associated with menopause, which the release says “provides relief for women who cannot or choose not to use hormone therapy.” The release does not name it or its drug class.

Both are separate approvals, not part of the labeling request. The site’s overview of non-hormonal approaches is on the Non-Hormonal Options for Menopause page.

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9. What the Request Did Not Do

• It did not change any label on 10 November 2025. It was a request to application holders. A label changes only when the FDA approves a company’s revised labeling; the first approvals came on 12 February 2026 (section 10).
• It did not remove every boxed warning. Both documents state that the endometrial-cancer boxed warning stays on systemic estrogen-alone products.
• It did not remove cardiovascular and breast-cancer information from systemic product labels. The request asks that it be retained in the body of the label.
• It did not approve a new use. The request concerns the wording of labels for drugs already approved for the uses listed in section 2. The two approvals in section 8 were separate actions.
• It was not a regulation. No rule was proposed or finalized, and no Federal Register notice is cited in the documents.

Decisions about starting, continuing or stopping any hormone therapy belong with a clinician; the label is one of the documents such decisions draw on.

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10. Dates and Status as of 11 October 2026

• 17 July 2025: FDA Expert Panel on the risks and benefits of menopausal hormone therapy, followed by a request for broad public input.
• 10 November 2025: FDA informs application holders of the requested labeling changes; HHS and the FDA announce the action at a press conference, together with the two drug approvals in section 8.
• 12 February 2026: the FDA announces approval of revised labels for the first six products; 29 companies had submitted proposed changes. The FDA statement, updated that day, adds that “the prescribing information has been updated on these MHT products.”

Status. The 10 November 2025 request was carried out in 2026 through product-by-product label approvals, which are final FDA actions on each approved label. The approvals, the four product categories the first six labels cover, and the September 2026 FDA workshop on testosterone in menopausal women are covered on FDA Approves New Menopausal Hormone Therapy Labels (2026).

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11. How the Request Fits the FDA’s Earlier Handling of Hormone Therapy

1990s–2004: the WHI trials. According to the FDA statement, two long-term WHI studies tested estrogen plus progestin (“WHI EP”) in women with a uterus and estrogen alone (“WHI E”) in women without a uterus, in postmenopausal women aged 50 to 79, for the prevention of heart disease, cancer and fractures. Both began in the 1990s and were stopped early: WHI EP in 2002, after investigators reported an increased risk of breast cancer at an average of about five years of follow-up, and WHI E in 2004, after an increased risk of stroke and a lack of evidence of coronary artery disease prevention at about seven years. Two further WHI studies in women aged 65 to 79 reported an increased risk of probable dementia.

From 2003: class-wide warnings. Based on the WHI findings, the FDA began approving class-wide labeling changes in 2003 (the same wording applied across a whole group of products) for estrogen plus progestogen and estrogen-alone products. The statement says these changes “would eventually include a Boxed Warning for increased risk of serious adverse events, including cardiovascular disorders, invasive breast cancer, and probable dementia.” That is the boxed warning the 2025 request addressed.

2025: reassessment. The July expert panel, the public-input request and the November labeling request described on this page.

2026: approvals. The first six revised labels, approved 12 February 2026 (follow-up page).

The request was one of several 2025 label actions on widely used drugs; others on this site include the opioid long-term-use labeling and the acetaminophen-in-pregnancy label change. The longer history of hormone therapy is on the site’s Menopause and HRT: History and Discovery page.

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12. Primary Documents

1. U.S. Food and Drug Administration (2025). FDA Requests Labeling Changes Related to Safety Information to Clarify the Benefit/Risk Considerations for Menopausal Hormone Therapies. Drug Alerts and Statements, 10 November 2025 (page content current as of 12 February 2026). No Federal Register citation or docket — fda.gov drug statement
2. U.S. Department of Health and Human Services and U.S. Food and Drug Administration (2025). HHS Advances Women’s Health, Removes Misleading FDA Warnings on Hormone Replacement Therapy. FDA News Release, 10 November 2025 — fda.gov press announcement

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Key Research Papers

1. Rossouw JE, Anderson GL, Prentice RL, et al. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321-333 — PubMed PMID: 12117397
2. Anderson GL, Limacher M, Assaf AR, et al. (2004). Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 291(14):1701-1712 — PubMed PMID: 15082697
3. Shumaker SA, Legault C, Rapp SR, et al. (2003). Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289(20):2651-2662 — PubMed PMID: 12771112
4. Shumaker SA, Legault C, Kuller L, et al. (2004). Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA 291(24):2947-2958 — PubMed PMID: 15213206
5. Rossouw JE, Prentice RL, Manson JE, et al. (2007). Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 297(13):1465-1477 — PubMed PMID: 17405972
6. Manson JE, Chlebowski RT, Stefanick ML, et al. (2013). Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 310(13):1353-1368 — PubMed PMID: 24084921
7. Nappi RE, Kroll R, Siddiqui E, Stoykova B, Rea C, Gemmen E, Schultz NM (2021). Global cross-sectional survey of women with vasomotor symptoms associated with menopause: prevalence and quality of life burden. Menopause 28(8):875-882 — PubMed PMID: 34033602

Papers 1–2 are the published results of the two WHI trials whose stoppage the FDA describes; papers 3–4 are the two WHI dementia studies in women aged 65 to 79; papers 5–6 are later WHI analyses by age, years since menopause and extended follow-up (the FDA statement says it considered such analyses but does not name them); paper 7 is the 2021 study the FDA statement cites. None of them is the source of the press release’s percentage figures, which cite no study.

PubMed Topic Searches

1. PubMed: menopausal hormone therapy and the timing hypothesis
2. PubMed: Women’s Health Initiative results in women aged 50–59
3. PubMed: boxed warnings and hormone therapy prescribing

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Connections

• FDA Actions of 2025
• FDA and Regulation
• FDA Approves New Menopausal Hormone Therapy Labels (2026)
• Menopause and Hormone Replacement Therapy
• Menopause and HRT: History and Discovery
• Genitourinary Syndrome of Menopause and Vaginal Estrogen
• Non-Hormonal Options for Menopause
• HRT Risks: Breast Cancer, Clots, and Stroke
• Postmenopausal Osteoporosis and Hormone Therapy
• FDA Requires New Opioid Labeling on Long-Term Use (2025)
• FDA Starts an Acetaminophen-in-Pregnancy Label Change (2025)
• FDA Crackdown on Misleading Drug Advertising (2025)

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