Coronary Heart Disease Risk Reduction in Postmenopausal Women: The Role of Statin Therapy and Hormone Replacement Therapy

Michael Clearfield, DO


Prev Cardiol. 2004;7(3) 

In This Article

Abstract and Introduction

The incidence of coronary heart disease in women rises sharply in the years following menopause, and prescribing of hormone replacement therapy in the belief that it might compensate for the loss of estrogen-mediated cardioprotection is widespread. However, controlled trials have failed to show a beneficial effect of hormone replacement therapy on the incidence of coronary events, and recent evidence suggests that hormone replacement therapy may even have a deleterious effect on primary coronary heart disease prevention. Statins are recommended as first-line treatment for lowering low-density lipoprotein cholesterol levels in women and are extremely valuable in reducing coronary heart disease risk in this group. An awareness of the benefits of appropriate statin treatment, and evidence showing that they can be safely added to hormone replacement therapy prescribed for the relief of menopausal symptoms and osteoporosis, provides the opportunity to optimize clinical outcomes for coronary heart disease among the large and expanding population of postmenopausal women.

Cardiovascular disease (CVD) is the leading cause of death among women worldwide; in 2001, it accounted for 32% of all estimated mortality among women compared with 26.9% among men.[1] Although morbidity from coronary heart disease (CHD) is more than six times higher in men than women between the ages of 35-44 years, it increases more rapidly in women than men after age 45 years, resulting in similar rates in both sexes by the age of 75 years (Figure 1).[2]

Incidence of coronary heart disease morbidity and mortality in men and women during a 26-year follow-up of the Framingham Study. Reproduced with permission from Elsevier from Am Heart J. 1986.111:383-390.[2]

Gradual changes in hormone levels related to menopause have been implicated in the rapid rise in CHD risk in women with increasing age.[2,3,4] The percentage of women aged >50 years has tripled in the past century in the developed world, and more than one third of women's lives will be lived beyond menopause.[5] This has important consequences for the current and future management of CHD in older women.

The view that women receiving hormone replacement therapy (HRT) for the relief of menopausal symptoms might also benefit from the cardioprotective effects of restored estrogen levels has been challenged recently by the results of the first randomized trial of HRT for primary CHD prevention.[6] In this study, the overall health risk of HRT exceeded its benefits in healthy postmenopausal women compared with the untreated group. Although these results may not be applicable to other HRT regimens (different preparations, dosages, and routes of administration), there are concerns that HRT use may further contribute to the increased risk of CHD in postmenopausal women.

This review examines the consequences of estrogen deficiency following menopause in contributing to the increased CHD risk in women and discusses key clinical trials of HRT and statins for both the prevention and treatment of CHD.


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