Mechanisms regulating LDL metabolism in subjects on peroral and transdermal estrogen replacement therapy

To study the mechanisms of low density lipoprotein (LDL) cholesterol loweri ng by peroral and transdermal estrogen replacement therapy (ERT), 79 hyster ectomized postmenopausal women aged 48 to 62 years were randomized in a dou ble-blind double-dummy trial to receive either peroral estradiol valerate ( 2 mg/d) or transdermal estradiol gel (1 mg/d) for 6 months. Plasma LDL chol esterol decreased from 4.19+/-0.83 (mean+/-SD) to 3.39+/-0.78 mmol/L (P<0.0 01) in the peroral group and from 4.11+/-0.86 to 3.72+/-0.78 mmol/L (P<0.00 1) in the transdermal estrogen group. Peroral estrogen did, but transdermal treatment did not, enhance the fractional catabolic rate (FCR) and product ion of LDL apolipoprotein B (apoB). However, the decrease of LDL cholestero l was related to an increase in FCR for LDL apoB on both peroral and transd ermal ERT (r=-0.645, P<0.001 and r=-0.627, P<0.001, respectively). These ch anges were associated with changes in the serum estrogen level. Both therap ies reduced absorption of dietary cholesterol by 6% to 10% (P<0.05). The ef fects of estrogen were not modified by the polymorphisms of apoE and apoB o r cholesterol 7 alpha-hydroxylase. In conclusion, the ERT-induced LDL chole sterol-lowering effect is related to changes in estrogen level, which presu mably enhance LDL receptor activity, which is manifested as an increase in FCR for LDL apoB. The small decrease in the absorption efficiency of dietar y cholesterol does not seem to contribute largely to the cholesterol loweri ng on either transdermal or peroral ERT.