Differential effects of subcutaneous estrogen and progesterone on low- density lipoprotein size and susceptibility to oxidation in postmenopausal rhesus monkeys

Objective: To study the differential effects of subcutaneous E₂ alone or in combination with P on the susceptibility of low-density lipoprotein (LDL) cholesterol to oxidation in naturally postmenopausal diet-controlled rhesus monkeys. Design: Prospective, longitudinal controlled study. Setting: Oregon Health Sciences University, Portland, Oregon, and Oregon Regional Primate Research Center, Beaverton, Oregon. Patient(s): Five naturally postmenopausal rhesus monkeys. Intervention(s): Estradiol was administered subcutaneously for the first 4 weeks, followed by E₂ plus P for 4 weeks, followed by a third 4-week washout period. Main Outcome Measure(s): Changes in plasma lipoprotein levels and oxidation of LDL and serum concentrations of E₂ and P. Result(s): Levels of LDL cholesterol fell after 4 weeks of treatment with E₂, compared with baseline. The lag time to half maximal light absorbency after 4 weeks of E₂ treatment was significantly increased compared with baseline. The maximal absorbance values and the slope of the propagation phase after 4 weeks of treatment with E₂ were decreased compared with baseline. After 4 weeks of combined E₂ and P treatment, all values were comparable to baseline. Conclusion(s): These results suggest that subcutaneous E₂ therapy appears to enhance LDL resistance to oxidation and that this effect is attenuated by the addition of the P.