Can hormone replacement therapy (HRT) help prevent heart attacks in postmenopausal women?

HRT Should Not Be Used to Prevent Heart Attacks

Hormone replacement therapy (HRT) should not be initiated or continued for the purpose of preventing heart attacks in postmenopausal women, as it does not reduce cardiovascular events and actually increases the risk of coronary heart disease, stroke, and venous thromboembolism. 1, 2

Evidence Against HRT for Cardiovascular Prevention

Primary Prevention

• The American Heart Association explicitly recommends against initiating HRT for cardiovascular disease prevention (Class III, Level A recommendation). 1, 2
• Combined estrogen-progestin therapy increases coronary heart disease events by 29% (RH 1.29; 95% CI 1.02-1.63), with the highest risk occurring in the first year of therapy—a 52% increase in cardiovascular events compared to placebo. 2
• Randomized controlled trials, including the landmark Women's Health Initiative (WHI), consistently fail to show cardiovascular benefit from HRT, contradicting earlier observational studies that were biased by selection effects (healthier women were more likely to receive HRT). 1, 3

Secondary Prevention

• The American College of Cardiology states that HRT does not prevent recurrent cardiovascular events in women with established coronary disease. 1
• The Heart and Estrogen/progestin Replacement Study (HERS) demonstrated no reduction in cardiovascular events with HRT in women with coronary artery disease and found an increased risk of cardiac events in the first 1-2 years of therapy. 4
• Women who develop acute coronary events while on HRT should consider discontinuation. 1, 4

Additional Cardiovascular Risks

Beyond failing to prevent heart attacks, HRT significantly increases other serious cardiovascular risks:

• Stroke risk increases by 41% (RH 1.41; 95% CI 1.10 to 1.89), with oral estrogen-containing HRT carrying excess stroke risk and should be avoided. 1, 2, 5
• Venous thromboembolism risk increases nearly 3-fold (RR 2.15; 95% CI 1.61-2.86), with pulmonary embolus risk similarly elevated (RR 2.15; 95% CI 1.41-3.28). 1, 2, 5

The Critical Timing Hypothesis

While HRT should not be used for cardiovascular prevention, understanding the timing hypothesis is important for context:

• Women under 60 years old and within 10 years of menopause onset have the most favorable benefit-risk profile if HRT is used for severe menopausal symptoms (not cardiovascular prevention). 1
• Women over 60 years old or more than 10 years past menopause face excess cardiovascular and stroke risk from HRT. 1
• The WHI tested HRT initiation a decade or more after menopause (mean age 63 years), which is when cardiovascular risks are most pronounced. 2, 6

Appropriate Use of Cholesterol-Lowering Therapy Instead

For cardiovascular prevention in postmenopausal women, statins are strongly preferred over HRT. 7

• The 4S, CARE, and AFCAPS/TexCAPS trials demonstrated that statins decrease cardiovascular morbidity and mortality by at least 29% in women, including those over 65 years old (Evidence level A, RCTs/meta-analyses). 7
• The ATP III guidelines prefer the initial use of cholesterol-lowering agents over HRT for cardiovascular risk reduction. 7

Absolute Contraindications to HRT

HRT should not be prescribed in women with: 1

• Coronary heart disease or prior myocardial infarction
• Active or history of venous thromboembolism or stroke
• History of spontaneous coronary artery dissection (SCAD)
• Antiphospholipid syndrome or positive antiphospholipid antibodies

Clinical Decision Algorithm

If seeking HRT solely for cardiovascular or osteoporosis prevention: Do not prescribe HRT. 1

If treating severe vasomotor symptoms: 1, 4

• Screen for absolute contraindications first
• Consider non-hormonal pharmacological options as first-line therapy
• Use the lowest effective dose for the shortest possible time if HRT is necessary
• Regularly reassess the risk-benefit ratio

Common Pitfalls to Avoid

• Do not rely on outdated observational studies suggesting cardiovascular benefit from HRT—these were confounded by selection bias. 1
• Do not assume all routes of administration are equivalent—transdermal estradiol may have lower thrombotic risk than oral preparations, though definitive data are limited. 1
• Do not continue HRT in women with established cardiovascular disease based on the mistaken belief it provides secondary prevention. 4