We have previously shown that chronic administration of 17beta-estradiol or vitamin E to humans significantly inhibits oxidation of their low density lipoprotein (LDL). Estrogen has been reported to regenerate alpha-tocopherol (vitamin E) following its oxidation to the alpha- tocopheryl radical, thus restoring its antioxidant potential. In order to assess whether coadministration of estradiol and vitamin E might have greater protective effect on LDL oxidation than either alone, we measured oxidizability of LDL from 14 postmenopausal women, assayed by spectrophotometric measurement of conjugated diene generation following peroxidation with CuCl2. The studies were performed at baseline, after monotherapy with 6 weeks of vitamin E (800 IU/day) or 3 weeks of transdermal estradiol (0.1 mg/day), and after combined administration of vitamin E and estradiol (combined therapy). We found the total cholesterol and LDL concentrations were not changed by monotherapy or combined therapy compared to baseline. Monotherapy with vitamin E or with estradiol similarly prolonged the lag time of LDL oxidation. Combined therapy with vitamin E and estradiol prolonged lag time of LDL oxidation to a similar extent as either agent given alone. Thus, there was no difference between monotherapy and combined therapy with regard to the effect on LDL oxidation. In conclusion, the reduction in oxidizability of LDL is similar between estradiol and vitamin E, with no synergism noted following combined administration. Thus, coadministration of estrogen and vitamin E to postmenopausal women may have no greater effect on atherosclerosis and its sequelae than either alone.
