FDA Alert

HHS, FDA Initiate Removal of Black Box Warning on Hormone Therapy Products for Menopause

Kate Young

Key Highlights

  • HHS announced that the FDA would be removing the black box warning from hormone therapy products for menopause.
  • The FDA is not initiating the removal of black box warnings for systemic estrogen products for endometrial cancer.
  • The decision was made citing research that indicates improved health outcomes with hormone therapy use in patients with menopause.
  • While this decision is widely celebrated, some health organizations urge caution when assessing benefits and risks of hormone therapy.  

On November 10, the U.S. Department of Health and Human Services (HHS) announced that the FDA would be initiating the removal of black box warning labels from certain hormone replacement therapy (HRT) products for menopause.1

“A male-dominated medical profession – let’s be honest – has minimized the symptoms of menopause, and as a result, women’s health issues have not received the attention that they deserve,” Marty Makary, MD, MPH, commissioner of food and drugs at the FDA, said at the HHS press conference. “Women deserve the same rigorous science as is used for men.”

In an article published in JAMA, Makary and colleagues outline several updates to the hormone therapy label, including:

  • Removal of warnings for cardiovascular disease, stroke, breast cancer, and probable dementia, but keeping the warning in systemic estrogen products for endometrial cancer.
  • Removal of recommendations to prescribe the lowest effective dose for the shortest duration.
  • Revised safety data reflecting the risks relevant to specific formulation of hormone therapy products.
  • Emphasis on safety findings relevant to topical vaginal use for topical products rather than broad warnings relevant to systemic exposure.
  • Updated guidance on timing for initiating treatment.

In the article, Makary and colleagues also discuss evidence of long-term health benefits associated with hormone therapy initiated within a decade of perimenopause onset.2 They cite a 2008 study of 343 women, which found that short-term hormone therapy administered 2 to 3 years in the postmenopausal years may have protective effects against cognitive impairment,3 as well as a 1980 study of 327 women aged 50 to 74 years, which found that the risk of hip or lower forearm fracture was 50-60% lower in women who had used estrogen for 6 years or longer compared with women who had not used hormone therapy.4 Furthermore, a 1991 study supported unopposed oral estrogen as protective against coronary events in postmenopausal women.5

“There may be no other medication in the modern era that can improve the health outcomes of women on a population level than hormone replacement therapy,” Dr Makary said at the press event.

Headshots of speakers at the HHS press conference

 

At the HHS press conference, Alicia Jackson, PhD, Director, Advanced Research Projects Agency for Health at the HHS, and Rachel Rubin, MD, urologist and sexual medicine specialist, both spoke about the harm fear of hormone therapy has done to patients experiencing complications related to menopause. Dr Jackson noted that cardiovascular disease is the leading cause of death in postmenopausal women. Dr Rubin outlined urinary tract infection (UTI) risks in patients with menopause and emphasized the importance of understanding that different formulations and modalities are associated with different risks.

In April, the American Urological Association released new guidelines to provide clinicians with information about identifying, diagnosing, and counseling patients with genitourinary syndrome of menopause, which included a strong recommendation to offer local, low-dose vaginal estrogen for vulvovaginal discomfort, dryness, and dyspareunia as well as recurrent UTI.6  

Kelly Casperson, MD, urologist and author of The Menopause Moment, spoke at the HHS conference about the many patients who are prescribed HRT but avoid filling their prescription out of fear created by the warning label, leading to underutilization.

While organizations like the American Society of Clinical Oncology (ASCO) and the Society for Women’s Health Research have expressed support for the decision to remove the black box warning, they also urge caution and call for more research to understand how hormone therapy may impact long-term health.7,8

“Systemic hormone replacement therapy remains contraindicated for people who previously had breast cancer, particularly those with hormone receptor-positive disease, or other estrogen-responsive cancers (for example, certain gynecologic cancers), due to an increased risk of cancer recurrence,” ASCO warned in a recent press release responding to the HHS decision.

Resources

  1. HHS advances women’s health, removes misleading FDA warnings on hormone replacement therapy. https://www.fda.gov/news-events/press-announcements/hhs-advances-womens-health-removes-misleading-fda-warnings-hormone-replacement-therapy. Published Nov. 10, 2025. Accessed Nov. 19, 2025.
  2. Makary MA, Nguyen CP, Høeg TB, Tidmarsh GF, et al. Updated Labeling for Menopausal Hormone Therapy. JAMA. 2025;66(6):329-337. doi:10.1111/ajd.14560
  3. Bagger YZ, Tankó LB, Alexandersen P, Qin G, Christiansen C; PERF Study Group. Early postmenopausal hormone therapy may prevent cognitive impairment later in life. Menopause. 2005;12(1):12-17. doi:10.1097/00042192-200512010-00005
  4. Weiss NS, Ure CL, Ballard JH, Williams AR, Daling JR. Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N Engl J Med. 1980;303(21):1195-1198. doi:10.1056/NEJM198011203032102
  5. Rossouw  JE, Aragaki  AK, Manson  JE,  et al.  Menopausal hormone therapy and cardiovascular diseases in women with vasomotor symptoms: a secondary analysis of the Women’s Health Initiative randomized clinical trials. JAMA Intern Med. Published online September 15, 2025. doi:10.1001/jamainternmed.2025.4510
  6. American Urological Association Releases New Guideline on Genitourinary Syndrome of Menopause. https://www.auanet.org/about-us/media-center/press-center/american-urological-association-releases-new-guideline-on-genitourinary-syndrome-of-menopause. Published April 28, 2025. Accessed Nov. 19, 2025.
  7. ASCO Statement: HHS Revision of Black Box Warning for Hormone Replacement Therapy and its Implications for Cancer Care. https://www.asco.org/news-initiatives/policy-news-analysis/statement-HHS-revision-black-box-warning. Published Nov. 13, 2025. Accessed Nov. 19, 2025.
  8. Celebrating the removal but cautioning the removal of all warnings on HRT. https://swhr.org/celebrating-the-removal-but-cautioning-the-removal-of-all-warnings-on-hrt/. Published Nov. 10, 2025. Accessed Nov. 19, 2025.