THE EFFECT OF HORMONE REPLACEMENT THERAPY ON THE OXIDATION OF LOW-DENSITY-LIPOPROTEIN IN POSTMENOPAUSAL WOMEN

The oxidative modification of low density lipoprotein (LDL) is importa nt in the pathogenesis of atherosclerosis, and oestrogen has been show n to inhibit copper and cell mediated oxidation of LDL in vitro. We ha ve investigated the effect of oral and transdermal oestrogens (oestrad iol valerate 1 mg, conjugated equine oestrogens 0.625 mg and patches r eleasing 50 mu g 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 ox idation in postmenopausal women (total n = 56). Oxidation of LDL was i nitiated by the addition of copper ions, and monitored by measurement of conjugated dienes. Changes in fasting serum levels of total cholest erol, LDL, HDL and triglycerides were also evaluated, as were changes in LDL composition. Total cholesterol decreased by 5.5% (P < 0.05) wit h GEE, 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), w ith oestradiol valerate and CEE respectively, and decreased by 9% (P < 0.05) with implants and by 14.7% with oestradiol combined with noreth isterone (P < 0.01). Triglycerides were significantly increased with C EE (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 'f ree cholesterol' within LDL with any of the HRT preparations, a reduct ion in total cholesterol and cholesterol ester content of LDL occurred with transdermal oestradiol and a reduction in free cholesterol occur red with oestradiol plus MPA. Although we found a small but significan t decrease in plasma hydroperoxide concentration four weeks after inse rtion of the oestradiol implant from 1.17 +/- 0.06 to 1.03 +/- 0.04 mu mol/l (P < 0.05), we found no significant change in the lag time to o xidation, 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 antio xidants in vivo. (C) 1997 Elsevier Science Ireland Ltd.