Fluvastatin combined with 17 beta-estradiol and norethisterone: effect on the proliferation of smooth muscle cells from human coronary artery

Treatment of lipid disturbance in postmenopausal women with menopausal symp toms may require administration of a potent lipid-lowering drug, e.g. the s tatins, to estrogen replacement which is usually combined with a gestagen. Since both statins and 17 beta-estradiol may have antiatherosclerotic prope rties via direct effects on the vasculature, the interaction of these subst ances in this respect is of interest. Gestagens can counteract beneficial e strogenic effects. We have investigated the effect of fluvastatin (one of t he statins), 17 beta-estradiol and the gestagen norethisterone on the proli feration of smooth muscle cells from human coronary artery. Fluvastatin alo ne significantly inhibited cell proliferation by 22% and by 70% at 0.1 and 1 mu M, respectively. 17 beta-estradiol reduced cell numbers only at 1 mu M by 17%, whereas norethisterone elicited no significant changes in cell num bers compared to controls. The combination of fluvastatin with 17 beta-estr adiol and with 17 beta-estradiol and norethisterone was not significantly d ifferent in its inhibitory action on cell proliferation compared to the eff ect of fluvastatin alone. Fluvastatin and 17 beta-estradiol elicit an antia therogenic effect by inhibiting smooth muscle cell proliferation from human coronary artery which is not negatively influenced when these substances a re combined or when norethisterone is given in addition. Therefore, the com bination of these drugs may be useful for the prevention of coronary heart disease in postmenopausal women. Med Sci Res 27:705-706 (C) 1999 Lippincott Williams & Wilkins.