News from the WHI Study

On November 10, 2025, the FDA announced changes to the FDA labeling for Menopausal Hormone Therapy¹

WHI does not have a position on the black box warning for menopausal hormone therapy

We note that in the years since the results of the WHI were published there has been no new information from similarly large randomized trials that would change the balance of known overall risks versus benefits for oral menopausal hormone therapy. WHI did not test other forms (transdermal or vaginal) of hormone therapy.

The gold standard WHI trials showed that oral hormone therapy increased risks of stroke and blood clots and did not prevent heart attacks in women aged 50-79. In fact, during the first few years the risk of heart attacks was increased. In addition, combination estrogen plus progestin increased the risk of breast cancer irrespective of age and this risk became more significant over time in the trial and with longer duration of follow-up. Oral hormone therapy reduced diabetes and fracture risk, but increased risks of gallbladder disease, urinary incontinence and dementia in women over 65 years of age.

For younger women, the benefit of vasomotor symptom reduction may outweigh the small cardiovascular risks, but it is uncertain whether any cardiovascular benefit seen in younger ages with estrogen alone will carry over into older ages as women and their arteries age.

Our original conclusions still stands: oral menopausal hormone therapy should not be used for chronic disease prevention. Using menopausal hormone therapy for relief of moderate to severe vasomotor symptoms is reasonable but it should be limited to the lowest dose for the shortest time needed for this indication.

Irrespective of whether the black box warning for oral hormone therapy remains or is removed, it is essential that that women be fully informed about the overall risks versus benefits. This information should be based on the most rigorous science rather than anecdotes. There are no large, randomized trials to inform decision-making about non-oral (transdermal or intra-vaginal) menopausal hormone therapies and this too should be made transparent.

¹ Makary MA, Nguyen CP, Høeg TB, Tidmarsh GF. Updated Labeling for Menopausal Hormone Therapy. JAMA. Published online November 10, 2025. doi:10.1001/jama.2025.22259

See WHI response to the FDA Expert Panet on MHT use in July of 2025 here: https://www.whi.org/doc/banner/WHI_response_to_FDA_Expert_Panel_on_MHT_use_09.19.2025.pdf