Additive antioxidative effect of hormone replacement therapy combined with a statin

In treating postmenopausal women both statins and estrogens have been shown to elicit favourable effects on lipids and lipoproteins. In addition direct beneficial effects of these substances on the vascular wall are discussed. However, progestin addition to estrogen replacement therapy, which is mandatory in women with an intact uterus. is thought to deteriorate at least partly estradiol-induced direct effects on the vasculature. Oxidation of LDL, which mainly takes place in the vessel wall, seems to be a crucial step in the development of atherosclerosis. Therefore, for the first time, the effect of a statin and an estrogen/progestin combination on the in vitro oxidation of human LDL was investigated comparing the monosubstances fluvastatin. 17beta-estradiol and norethisterone acetate (NETA) as well as the effect of the combination. LDL was isolated from human female serum and oxidation was initiated by copper(II)-chloride. The progression of LDL oxidation was monitored spectrometrically at 234 nm for 300 min. Fluvastatin significantly delayed the onset of LDL oxidation (controls = 85 min) by 21 min at 1 microM, by 99 min and by 210 min at 5 and 10 microM. respectively. 17beta-estradiol significantly reduced the onset by 73 min at 1 microM and by more than 300 min at 5 and 10 microM. NETA had no significant effect. The combination of I microM 17beta-estradiol and 1 microM fluvastatin with 1, 5 and 10 microM NETA showed an additive antioxidative effect of estradiol and fluvastatin and no deterioration by the addition of NETA even at high dosages. It can be concluded that treatment of postmenopausal women with fluvastatin and a combination of 17beta-estradiol with NETA may have not only beneficial effects on lipid disorders but may also elicit a direct potent antiatherosclerotic action on the vasculature.