The effect of hormone replacement therapy on the oxidation of low density lipoprotein in postmenopausal women

Abstract

The oxidative modification of low density lipoprotein (LDL) is important in the pathogenesis of atherosclerosis, and oestrogen has been shown to inhibit copper and cell mediated oxidation of LDL in vitro. We have investigated the effect of oral and transdermal oestrogens (oestradiol valerate 1 mg, conjugated equine oestrogens 0.625 mg and patches releasing 50 microg oestradiol daily), oestrogen implants (oestradiol 50 mg) and oral combined oestrogen and progestogen (oestradiol valerate 2 mg with medroxyprogesterone acetate 5 mg and oestradiol valerate 2 mg with norethisterone acetate 1 mg), on the susceptibility of LDL to oxidation in postmenopausal women (total n = 56). Oxidation of LDL was initiated by the addition of copper ions, and monitored by measurement of conjugated dienes. Changes in fasting serum levels of total cholesterol, LDL, HDL and triglycerides were also evaluated, as were changes in LDL composition. Total cholesterol decreased by 5.5% (P < 0.05) with CEE, 6.8% with oestradiol implants (P < 0.05), 9.3% with oestradiol + MPA (P < 0.01) and 10% with oestradiol + norethisterone (P < 0.05). There were reductions in LDL with oral oestradiol valerate (7.8%) (P < 0.05), CEE (13.8%) (P < 0.01) and oestradiol combined with MPA (12.7%) (P < 0.05). HDL increased by 7.1% (P < 0.01) and 6.3% (P < 0.05), with oestradiol valerate and CEE respectively, and decreased by 9% (P < 0.05) with implants and by 14.7% with oestradiol combined with norethisterone (P < 0.01). Triglycerides were significantly increased with CEE (14.9%) and reduced with oestradiol implants (15.2%) (both P < 0.05). While there was no change in the ratio of 'cholesterol ester' to 'free cholesterol' within LDL with any of the HRT preparations, a reduction in total cholesterol and cholesterol ester content of LDL occurred with transdermal oestradiol and a reduction in free cholesterol occurred with oestradiol plus MPA. Although we found a small but significant decrease in plasma hydroperoxide concentration four weeks after insertion of the oestradiol implant from 1.17 +/- 0.06 to 1.03 +/- 0.04 micromol/l (P < 0.05), we found no significant change in the lag time to oxidation, or in the maximum rate of propagation of the reaction, after treatment with any of the above forms of hormone replacement therapy. This study does not therefore support the role of oestrogens as antioxidants in vivo.