Why is estrogen hormone replacement therapy (HRT) contraindicated in coronary artery disease (CAD)?

From the Guidelines

Estrogen hormone replacement therapy (HRT) is contraindicated in patients with coronary artery disease (CAD) because it increases the risk of cardiovascular events rather than providing protection. The most recent and highest quality study, the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1, recommends that hormone therapy with estrogen plus progestin, or estrogen alone, should not be given as new drugs for secondary prevention of coronary events to post-menopausal women after non-ST-elevation acute coronary syndromes (NSTE-ACS) and should not be continued in previous users unless the benefits outweigh the estimated risks.

Key Points

• The Women's Health Initiative and other large randomized controlled trials have demonstrated that estrogen therapy, particularly when combined with progestin, increases the risk of heart attacks, strokes, and blood clots in women with established coronary disease 1.
• The mechanism involves estrogen's prothrombotic effects, which promote blood clot formation, and its inflammatory actions on already damaged blood vessels.
• Estrogen can also worsen lipid profiles in some patients and increase triglycerides.
• For women with CAD requiring management of menopausal symptoms, non-hormonal alternatives such as selective serotonin reuptake inhibitors (SSRIs), gabapentin (300-900 mg daily), or clonidine (0.1-0.2 mg daily) should be considered instead.
• If vasomotor symptoms are severe and other treatments ineffective, the lowest effective dose of HRT may be considered only after thorough cardiovascular risk assessment and with close monitoring.

Recommendations

• Hormone therapy should not be initiated for secondary prevention of coronary events in post-menopausal women with CAD 1.
• Non-hormonal alternatives should be considered for management of menopausal symptoms in women with CAD.
• The benefits and risks of HRT should be carefully weighed in women with CAD who are already taking HRT, and it should be discontinued unless the benefits outweigh the estimated risks 1.

From the Research

Estrogen Hormone Replacement Therapy and Coronary Artery Disease

• Estrogen hormone replacement therapy (HRT) is contraindicated in coronary artery disease (CAD) due to potential adverse effects on cardiovascular health 2, 3, 4.
• Studies have shown that HRT may increase the risk of cardiovascular events, such as myocardial infarction and stroke, in postmenopausal women with pre-existing CAD 2, 3.
• The Heart and Estrogen/Progestin Replacement Study (HERS) found that HRT should not be given to women with existing heart disease without careful monitoring 2.
• The use of HRT for cardiovascular risk prevention is not recommended, and prescription of HRT should be based on symptom-related and other indications, rather than solely for cardiovascular risk reduction 4.

Mechanisms and Effects of Estrogen on CAD

• Estrogen has been shown to have both beneficial and adverse effects on cardiac risk factors, such as hyperlipidemia and vasomotor tone 5, 2.
• The degree to which estrogen affects the lipid profile and other risk factors is relatively modest and does not seem to account for all of the benefits of estrogen 5.
• Activation of the G protein-coupled estrogen receptor (GPER) may afford therapeutic benefit for primary and secondary prevention in patients with or at risk for CAD 3.

Current Recommendations for HRT Use

• HRT should not be prescribed for cardiovascular risk prevention, but may be appropriate for symptom-related and other indications in the early years after menopause with onset at a normal age 4, 6.
• The benefits and potential risks associated with HRT use in menopausal women should be carefully considered, and evidence-based recommendations should guide clinical decision-making 6.