Black Box Warnings on HRT for Menopause
No black box warnings have been removed from hormone replacement therapy (HRT) for menopause by the FDA. The black box warning remains in place, requiring that estrogen with or without progestin be prescribed at the lowest effective dose and for the shortest duration consistent with treatment goals and individual patient risks 1.
Current FDA Black Box Warning Status
The FDA-mandated black box warning for menopausal hormone therapy has been continuously maintained since its implementation, with no documented removals 1. This warning applies to:
- Combined estrogen-progestin therapy - Must be used at minimum effective doses for shortest duration 1
- Estrogen-only therapy - Same dosing restrictions apply regardless of formulation 1
FDA-Approved Indications (Unchanged)
The FDA has maintained only two approved indications for HRT in postmenopausal women 1:
- Treatment of menopausal symptoms (vasomotor symptoms, hot flashes)
- Prevention of osteoporosis
Notably, HRT is explicitly NOT approved for cardiovascular disease prevention, and guidelines from the American Heart Association and American College of Cardiology state it should not be used for primary or secondary prevention of coronary events 1.
Key Risks That Maintain the Black Box Warning
The black box warning persists because of documented serious adverse events from the Women's Health Initiative trials 1:
Combined Estrogen-Progestin Risks:
- Increased stroke risk (HR 1.23,95% CI 1.08-1.41) 1
- Increased invasive breast cancer (HR 1.25,95% CI 1.07-1.46) after 3-5 years 1, 2
- Increased venous thromboembolism (approximately doubled risk) 1
- Increased dementia risk in women ≥65 years (HR 2.05,95% CI 1.21-3.48) 1
- Trend toward increased cardiac events (HR 1.22,95% CI 0.99-1.51) 1
Estrogen-Only Risks:
- Increased stroke risk (HR 1.36,95% CI 1.08-1.71) - trial stopped early for this reason 1
- Increased venous thromboembolism 1
- No reduction in coronary heart disease (HR 0.95% CI 0.78-1.15) 1
Critical Clinical Context
The FDA has strengthened rather than removed restrictions on HRT. The American Heart Association and American College of Cardiology have issued Class III (Harm) recommendations stating that HRT should not be initiated for cardiovascular disease prevention and should generally be discontinued in women with prior cardiovascular events 1.
Absolute Contraindications (Per Guidelines):
- History of stroke or TIA - HRT is contraindicated regardless of indication 3, 4
- History of myocardial infarction - Should be discontinued immediately 3, 4
- Active cardiovascular disease - Not a candidate for HRT initiation 1
The only scenario where recent evidence suggests potential cardiovascular safety is in women within 10 years of menopause onset or younger than 60 years who are in good cardiovascular health, though this does not constitute an FDA indication change 5, 6, 7.