Estrogens and cardiovascular disease risk revisited: the Women's Health Initiative

In 2002 and 2004, the Women's Health Initiative found no evidence that hormone therapy with estrogen or estrogen with progestin (E + P) protected against cardiovascular disease (CVD). Since then, further analyses have been performed. This review summarizes current analyses on the effects of hormone therapy on CVD and CVD risk factors.

The negative effects of hormone therapy vary by the type of CVD event. Estrogen alone and E + P show consistent effects on CVD, but E + P has more impact on coronary heart disease (CHD) and venous thromboembolism. Women of all ethnicities, including those who are obese, have diabetes, or are taking daily aspirin or statins remain at risk for adverse effects from hormone therapy. Although younger women or more recently menopausal women taking hormone therapy may be at relatively lower risk for CHD and myocardial infarction, they remain at risk for stroke, venous thromboembolism and peripheral artery disease. Adverse effects are enhanced in older women with menopausal symptoms. Although hormone therapy lowers LDL cholesterol and lipoprotein (a) and raises high-density lipoprotein cholesterol, it has adverse effects on triglyceride, lipoprotein composition, and inflammatory and hemostatic markers. Baseline metabolic syndrome and high LDL cholesterol increase the CHD risk with hormone therapy. Analyses of discontinuation data in the estrogen-alone and E + P trials suggest that the adverse effects of hormone therapy on CVD are reversible.

Recent analyses do not justify postmenopausal hormone therapy for CVD prevention. Further research on the role of hormone therapy-induced changes in CVD risk factors along with genetic studies may increase understanding and aid in developing safer therapies for menopausal symptoms.