ARE THE ANTIOXIDATIVE EFFECTS OF 17-BETA-ESTRADIOL MODIFIED BY CONCOMITANT ADMINISTRATION OF A PROGESTIN

Objective: Estrogens are known to exhibit antioxidative effects. At pr esent little information exists on the influence of co-administered pr ogestins upon this effect. Therefore we investigated the influence of levonorgestrel, a potent antiestrogenic progestin, on the inhibition o f the low-density lipoprotein (LDL) oxidation by 17 beta-estradiol or 17 beta-estradiol valerate in vitro and ex vivo. Methods: After isolat ion from blood, the in vitro oxidation of LDL was induced by copper io ns and measured continuously by monitoring the formation of conjugated dienes. In 21 female ovariectomized White New Zealand rabbits the ant ioxidative action of 17 beta-estradiol alone or in combination with le vonorgestrel after subcutaneous infusion for 3 days was determined usi ng the copper-induced LDL-oxidation as an endpoint. Eleven postmenopau sal women were exposed to sequential estrogen-progestin replacement th erapy (day 1-21: 2 mg estradiol valerate/day, day 10-21: 0.15 mg levon orgestrel/day). Blood samples were collected at three times: on day 1, on day 10, on day 22 (after the combination phase). The lag time of e x vivo oxidation of LDL, the plasma estradiol and estrone levels were estimated. Results: In the chosen cell-free system, 17 beta-estradiol increased the lag time of the LDL-oxidation in a dose-dependent manner . Levonorgestrel showed neither pro-oxidative nor antioxidative effect s when administered alone in different concentrations. Go-administrati on of different doses of levonorgestrel did not modify the antioxidati ve action of estrogen either. The two ex-vivo models confirmed these r esults. In rabbits the co-administered 19-nortestosterone derivative l evonorgestrel did not impair or reverse the estradiol-dependent effect . In postmenopausal women the daily oral administration of levonorgest rel in conjunction with 17 beta-estradiol valerate did not diminish th e antioxidative action of this estrogen given for the first 9 days. Co nclusion: The antioxidative potential of estradiol and estradiol valer ate is maintained in the presence of levonorgestrel.