Primary Prevention of Cardiovascular Disease With HRT

Kate Maclaran; John C Stevenson


Women's Health. 2012;8(1):63-74. 

In This Article

Biological Mechanisms Why Estrogen May be Beneficial

Many biological mechanisms have been identified as to why estrogen may be cardioprotective in postmenopausal women.[11] These can be divided into effects on classical risk factors for CHD, such as dyslipidemia and insulin resistance, or actions directly on the vessel wall and endothelial function.

Systemic Effects

Dyslipidemia is a well-recognized cardiovascular risk factor and the menopausal transition is associated with adverse changes to women's lipid profiles, with increases in total and low-density lipoprotein (LDL) cholesterol and reductions in high-density lipoprotein (HDL) cholesterol.[12] Menopause is also associated with changes in other cardiovascular risk markers, including android fat deposition and deterioration of insulin sensitivity.[13]

Oral estrogen therapy results in decreased LDL cholesterol and increased HDL cholesterol; however, this is at the expense of an increase in triglycerides.[14] Other beneficial effects include reductions in lipoprotein (a),[15] changes in LDL particle size and clearance, and inhibition of LDL oxidation.[16] Estrogen also has a positive effect on insulin metabolism and glucose,[17] and a beneficial effect on body fat distribution.[18]

Vascular Effects

The short- and long-term effects of estrogen directly on the vascular wall are thought to play an even greater role than the metabolic effects. Estrogen has been shown in several animal models to prevent early atheroma[19,20] and this effect is mediated largely by effects on the endothelium via the ER-α.[21] Translational studies in nonhuman primates demonstrated that treatment of postmenopausal cynomolgus monkeys with 17β-estradiol was associated with a 50% reduction in atherosclerosis.[22]

Animal models have demonstrated that estrogen has a beneficial effect on the vascular wall via a variety of different mechanisms, including improved vasodilation, accelerated endothelial healing and decreased proinflammatory mediators (Box 1). In healthy postmenopausal women, conjugated equine estrogens (CEEs) have been shown to improve endothelial function.[23] In addition, estrogen may have anti-ischemic action, as 17β-estradiol therapy has been associated with a reduction in coronary endothelial and myocardial ischemia-induced damage in mouse models.[24]


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