FDA removes black box warnings on HRT drugs after two decades

The US Food and Drugs Administration has initiated the removal of the black box warning from menopausal hormone replacement therapy (HRT) products, marking a dramatic reversal of policy that has shaped women’s healthcare for over two decades.

This regulatory shift follows mounting evidence that the therapy’s risks were dramatically overstated, while its benefits for appropriately selected patients have been systematically underutilized.

The rise and fall of HRT

Hormone replacement therapy gained widespread acceptance in the 1960s and 1970s as a solution for menopausal symptoms and chronic disease prevention. By the 1990s, prescriptions peaked at 90 million annually, with physicians believing HRT protected against heart disease and osteoporosis.

This confidence shattered in 2002 when the Women’s Health Initiative (WHI) released preliminary findings linking combined estrogen-progestin therapy to increased risks of breast cancer, heart disease, stroke, and blood clots. The study halted prematurely, and in 2003, the FDA imposed black box warnings, triggering an 80% plunge in prescriptions and leaving a generation of clinicians untrained in menopause care.

Re-examining the evidence

Medical consensus began shifting as researchers identified critical flaws in the WHI study design. The trial’s participants had an average age of 63—over a decade beyond typical menopause onset—using hormone formulations (conjugated equine estrogen and medroxyprogesterone acetate) and oral delivery methods now considered outdated.

“The older women may have already had cardiovascular issues, like years of plaque build-up, that worsened when exposed to HRT,” explains Steven J. Fleischman, president of the American College of Obstetricians and Gynecologists .Younger women, however, showed no increased cardiovascular or breast cancer risk.

The turning point arrived with the WHI’s 20-year follow-up data, published in May 2024, demonstrating no increase in deaths from breast cancer or cardiovascular disease among HRT users. Strikingly, women initiating therapy before age 60 showed decreased all-cause mortality. Additional research revealed that estrogen-only therapy actually reduced breast cancer risk, while transdermal patches eliminated the blood clot risks associated with oral hormones.

The FDA’s decision rested on several pivot al studies. An analysis of 30 trials involving 26,708 women found HRT was not associated with increased cancer mortality, with early initiators showing decreased mortality risk.

For women starting treatment within 10 years of menopause onset or before age 60, data showed a 50% reduction in heart attack risk, 64% reduction in cognitive decline, and 35% lower Alzheimer’s risk

The 2025 TRAVERSE trial further validated hormone therapy safety, demonstrating that testosterone replacement in men did not increase cardiovascular events (7.0% vs 7.3% placebo). This prompted removal of cardiovascular warnings from testosterone products earlier in 2025, setting precedent for the menopausal HRT decision

Medical consensus

Today, major medical organizations support HRT as safe and effective for appropriately selected patients. The FDA now recommends initiating systemic HRT within 10 years of menopause onset or before age 60. Bioidentical hormones—chemically identical to endogenous hormones—show particular promise, with micronized progesterone demonstrating lower breast cancer risk markers than synthetic progestins.

Despite this progress, only 1.7% of women over 40 currently use systemic hormone therapy, down from 25% before 2002.