Oxidized low-density lipoproteins (oxLDL) are involved in initiation of atherosclerosis. Paraoxonase 1 (PON1), the isoenzyme of PON, is located on high-density lipoprotein (HDL) and protects against the oxidative modification of both HDL and LDL by hydrolysing lipid peroxides. Postmenopausal women have a higher risk of cardiovascular events compared with premenopausal women. The aim of this clinical study was to evaluate the effects of hormone replacement therapy (HRT) on oxLDL and PON1 activity in menopausal status. The subjects included 45 healthy postmenopausal women, aged 43 to 57 years, and 30 premenopausal women with regular cycles, aged 31 to 40 years. None of the participating women had a history of hypertension, diabetes mellitus or medications known to affect the cardiovascular system. Twenty five of the postmenopausal women received conjugated estrogens at dose of 0.625 mg/day per oral (P.O.) and medroxyprogesterone acetate (MPA) (1 mg/d P.O.) for 10 days. Twenty of the postmenopausal women received 17-beta estradiol (2 mg/day) and norethysterone acetate (NETA) (5 mg/day P.O.) for 10 days. Fasting blood samples were taken from premenopausal women (baseline) and postmenopausal women after HRT of 6 months to determine serum malondialdehyde (MDA), oxLDL, and PON1 activity. After 6-month therapy, MDA and oxLDL levels showed a statistically significant reduction in the treated groups versus baseline (P < 0.05), whereas PON1 activities were increased (p < 0.05). Increase in oxidative status may be one of the factors leading to reduction in PON1 activity and increased oxLDL in menapouse. HRT may be effective on oxidative stress and lipoprotein metabolism in apparrently healthy postmenopausal women. - hormone replacement therapy; paraoxonase; oxidized low-density lipoprotein (oxLDL); malondialdehyde (MDA); oxidative stress (C) 2005 Tohoku University Medical Press.