hort-term and long-term estrogen administration to postmenopausal women has been shown to improve endothelium-dependent vasodilator responsiveness of the coronary and systemic circula- tion by increasing vascular nitric oxide bioactivity with smooth muscle relaxation. 1,2 Because nitric oxide also has inhibitory effects on thrombosis and inflammation, 3 increased nitric oxide bioactivity may be an important biologic effect of estrogen that accounts in part for the reduction in cardiovascular risk associated with current estrogen usage in postmenopausal women, as suggested ORIGINAL ARTICLES Endocrine and lipid effects of oral L-arginine treatment in healthy postmenopausal women ARNON BLUM,* RICHARD O. CANNON III, RENE COSTELLO, WILLIAM H. SCHENKE, and GYORGY CSAKO BETHESDA, MARYLAND As a substrate for nitric oxide synthesis, L-arginine may give the same protection as estrogen, but its other biologic effects may adversely affect atherogenesis. Therefore, possible endocrine and lipid effects of L-arginine were investigated in a double-blind, placebo-controlled, single crossover study. After randomization, oral L-arginine (9 g) or placebo was given daily for 1 month, with crossover to the alter- nate therapy after a 1-month washout period, to 10 postmenopausal women receiving no estrogen. Compared with placebo, L-arginine increased growth hor- mone (1.5 ± 1.8 mg/L vs 0.6 ± 0.6 mg/L, P = .04) but had no effect on insulin and catecholamines. Total cholesterol, triglyceride, apolipoprotein E, and low-, very- low-, and high-density lipoprotein cholesterol levels were also unaffected. Lipopro- tein(a) measured by an immunoturbidimetric method was increased by L-arginine in 9 of 10 women relative to placebo (0.46 ± 0.35 g/L vs 0.38 ± 0.30 g/L, P = .053), and the changes in lipoprotein(a) levels significantly correlated with the relative increase in growth hormone (r = 0.85, P = .03). However, lipoprotein(a) measured by an enzyme-linked immunosorbent assay failed to demonstrate significant changes. Lack of an increase by L-arginine in lipoprotein(a) with a verifiable apolipoprotein(a) isoform-independent method, despite an increase in growth hor- mone, questions the validity of previous observations for growth hormone-induced increases in lipoprotein(a). The observed lack of effect on major endocrine hor- mones and lipid profile support the safety of oral L-arginine administration. (J Lab Clin Med 2000;135:231-7) Abbreviations: apo = apolipoprotein; CV = coefficient of variation; ELISA = enzyme-linked immunosorbent assay; HDL-C = high-density lipoprotein-cholesterol; LDL-C= low-density lipoprotein-cholesterol; Lp(a) = lipoprotein(a); PAI-1 = plasminogen activator inhibitor type 1; VLDL-C = very-low-density lipoprotein-cholesterol 231 From the Cardiology Branch, National Heart, Lung, and Blood Insti- tute; and the Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health. Submitted for publication May 11, 1999; revision submitted August 25, 1999; accepted September 1, 1999. *Present address: Department of Internal Medicine, Poriya Govern- ment Hospital, Lower Galilee, Israel. Reprint requests: Gyorgy Csako, MD, Clinical Pathology Depart- ment, Clinical Center, National Institutes of Health, Building 10, Room 2C-407, Bethesda, MD 20892-1508. 5/1/104909 doi:10.1067/mlc.2000.104909 S