A Comparison of Low-Dose and Standard-Dose Oral Estrogen on Forearm Endothelial Function in Early Postmenopausal Women

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Abstract
We investigated the effects of low-dose estrogen plus progestin on endothelial function. Postmenopausal women received daily doses of conjugated equine estrogen (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg) (standard-dose group, n = 18), CEE (0.3 mg) plus MPA (2.5 mg) (low-dose group, n = 18), or no treatment (control group, n = 15) for 3 months. Serum concentrations of lipids and malondialdehyde (MDA)-modified low-density lipoprotein (LDL) were measured. Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin administration was measured by strain-gauge plethysmography. Decreases in serum concentrations of LDL cholesterol and MDA-modified LDL and increases in high-density lipoprotein cholesterol and nitrite/nitrate were observed in both treatment groups. After 3 months of treatment, similar increases in the maximal FBF response during reactive hyperemia were observed in both treatment groups (standard-dose group, from 35.8 ± 3.0 to 47.5 ± 2.8 ml/min per 100 ml tissue; and low-dose group, from 35.2 ± 2.2 to 46.8 ± 3.4 ml/min per 100 ml tissue, P < 0.01). FBF levels in the control group were unchanged. Treatment did not affect nitroglycerin-induced dilation. The incidences of vaginal bleeding and breast tenderness were lower with the low-dose group than with the standard-dose group. Low-dose CEE plus MPA augments endothelial function in forearm resistance arteries and decreased MDA-modified LDL levels similarly to standard doses of CEE plus MPA, with fewer side effects.

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