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

Department of Obstetrics and Gynecology (M.S., M.T., I.K., K.O.) and First Department of Internal Medicine (Y.H., K.N., M.K., K.C.), Faculty of Medicine, Hiroshima University, Hiroshima 734-8551, Japan

Address all correspondence and requests for reprints to: Mitsuhiro Sanada, M.D., Ph.D., Department of Obstetrics and Gynecology, Faculty of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail: msanada64{at}hotmail.com.

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.

This study was supported in part by the Tsuchiya Memorial Foundation.

Abbreviations: ACE, Angiotensin-converting enzyme; CEE, conjugated equine estrogen; CHD, coronary heart disease; FBF, forearm blood flow; HDL, high-density lipoprotein; HERS, Heart and Estrogen/Progestin Replacement Study; HRT, hormone replacement therapy; LDL, low-density lipoprotein; MDA, malondialdehyde; MPA, medroxyprogesterone acetate; NO, nitric oxide; NTG, nitroglycerin; PRA, plasma renin activity; TG, triglycerides; WHI, Women’s Health Initiative.

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