Estrogen replacement therapy in postmenopausal women must be combined with progestin to avoid endometrial cancer. However, progestin addition could antagonize cardioprotective effects of estradiol. Therefore we investigated the effect of the two most commonly used progestins--medroxyprogesterone acetate (progesterone-derivative) and norethisterone acetate (nortestosterone-derivate)--alone and in combination with 17 beta-estradiol on copper-mediated oxidation of low density lipoprotein (LDL). Whereas 17 beta-estradiol alone inhibited the onset of LDL oxidation at the concentrations 0.5, 1.0, 5 and 10 microM, the progestins alone did not demonstrate any significant effect. In the estrogen-progestin combinations of 0.5 microM 17 beta-estradiol with 0.5, 1.0, 5 and 10 microM progestin, respectively, the estradiol effect was not changed. These results suggest that medroxyprogesterone acetate as well as norethisterone acetate do not counteract the beneficial effect of 17 beta-estradiol on LDL oxidation when used in hormone replacement therapy.