The U.S. Food and Drug Administration has proposed labeling revisions for menopausal hormone therapies, also known as hormone replacement therapy, to better clarify benefit–risk considerations for patients. These therapies are approved for the treatment of vasomotor symptoms, genitourinary syndrome of menopause, and, in some cases, the prevention of postmenopausal osteoporosis. The proposed updates follow a comprehensive U.S. Food and Drug Administration (FDA) review of relevant literature, postmarket utilization data, and public input, including recommendations from an Expert Panel convened on July 17, 2025.
The FDA’s reassessment was informed by data from the Women’s Health Initiative (WHI) studies, which evaluated estrogen plus progestin and estrogen-alone regimens in postmenopausal women aged 50 to 79 years. Both trials were discontinued early after reports of increased risks for breast cancer, stroke, and probable dementia, leading to class-wide Boxed Warnings in 2003. The agency noted that the WHI cohort, with a mean age of 63 years, did not reflect the population most likely to initiate menopausal hormone therapies (MHT)—women aged 45 to 55 years experiencing moderate to severe menopausal symptoms.
Based on long-term WHI follow-up and more recent analyses, the FDA is requesting several key labeling modifications. For all MHT products, the agency proposes removing Boxed Warning statements referencing cardiovascular disease, breast cancer, and probable dementia, as well as the recommendation to use the lowest effective dose for the shortest duration. The dementia warning would also be removed from labeling entirely.
For systemic products, new language would highlight initiating therapy in women younger than 60 years or within 10 years of menopause onset, include WHI data specific to women aged 50 to 59 years, and retain the Boxed Warning for endometrial cancer in estrogen-alone formulations. For local vaginal estrogen products, safety information would be condensed and limited to data most relevant to the local formulation.
Dr. Marty Makary, FDA Commissioner, stated on X, “With the exception of vaccines or antibiotics, there's no medication that can improve the health of women on a population level more than hormone replacement therapy.”
The FDA stated that the proposed labeling revisions are intended to reflect current evidence on the benefits and risks of menopausal hormone therapy.
Source: FDA