Lower doses of estrogen replacement therapy and the risk of cardiovascular disease.

Therapy and the Risk of Cardiovascular Disease To the Editor: In their interesting study, Koh et al demonstrated that lower dosage of oral conjugated equine estrogen (CEE) eliminated the adverse effects of conventional dosage of CEE on markers of vascular inflammation and coagulation, in addition to preserving the favorable effects of estrogen on endothelial function.1 Similar to their report, our previous findings demonstrated that CEE at a dosage of 0.625 mg increased inflammatory markers such as C-reactive protein, serum amyloid protein A, and interleukin-6, whereas CEE at a dosage of 0.3125 mg did not elevate these markers. Additionally, low-dose CEE has an effect comparable to high-dose CEE on endothelium,2 and low-dose CEE has benefits of plasma triglyceride and the size of low-density lipoprotein (LDL). High-dose CEE increases plasma concentrations of triglyceride, and this estrogeninduced increase in plasma triglyceride reduces the size of LDL particles that are more susceptible to oxidation. In contrast, plasma triglyceride concentrations and the size of LDL particles are unaffected and the oxidative susceptibility of LDL is inhibited by low-dose CEE administration.3 The Heart and Estrogen/Progestin Replacement Study and the Women’s Health Initiative reported that hormone therapy increased the risk of coronary heart disease (CHD) in postmenopausal women. In contrast, Grodstein et al demonstrated that CEE at a daily dosage of 0.625 mg increases the risk for stroke, whereas 0.3 mg of CEE daily is associated with a reduction in the risk for stroke.4 In addition, Ferrara et al also demonstrated that low dosage but not medium or high dosage estrogen decreased the risk of myocardial infarction (MI) in diabetic women without a recent MI.5 Thus, low dosage estrogen administration can ameliorate the adverse effects of conventional dosage of estrogen and could have a different effect on clinical outcome. Studies are needed to investigate whether low dosage estrogen therapy is protective against the risk of CHD in postmenopausal women.