DIFFERENTIAL-EFFECTS OF ESTROGEN ON LOW-DENSITY-LIPOPROTEIN SUBCLASSES IN HEALTHY POSTMENOPAUSAL WOMEN

The use of estrogen by postmenopausal women decreases plasma low-density lipoprotein (LDL) cholesterol levels. To determine whether LDL subclass profiles influence this response, we studied 31 healthy postmenopausal women who were administered two doses (0.625 and 1.25 mg/d) of conjugated equine estrogen in a placebo-controlled double-blind crossover study. Lipid-stained gradient gels were used to categorize LDL subclass patterns. All women were classified as LDL subclass pattern A (predominant LDL peak ≥260 Å). Within the pattern A classification, there were 12 women during placebo treatment with LDL subclass I pattern (predominant LDL peak >271 Å) and 19 women with LDL subclass II pattern (predominant LDL peak ≤ 271 and ≥ 260 Å). Postmenopausal women with LDL subclass I on placebo treatment had significantly lower LDL cholesterol levels compared with women having LDL subclass II (126 ± 28 v 147 ± 23 mg/dL, P < .03). Postmenopausal women with LDL subclass I also had significantly (P < .05) lower very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, and VLDL apo B levels and significantly higher (P < .05) high-density lipoprotein 2 (HDL2) cholesterol, HDL3 cholesterol, and HDL2 apo A-I levels. Estrogen replacement significantly (P < .05) decreased LDL cholesterol levels and increased VLDL and LDL triglyceride, HDL2 and HDL3 cholesterol and apo A-I, and HDL2 apo A-II levels to a similar extent in postmenopausal women with LDL I or II subclass patterns. Estrogen replacement at either dose in postmenopausal women with the LDL I subclass pattern decreased LDL I relative peak area and LDL II peak particle diameter from 55% ± 1.7% to 39% ± 2.3% (mean ± SEM, P < .001) and from 269 ± 0.5 to 267 ± 0.7 Å (mean ± SEM, P < .001), respectively. In postmenopausal women with the LDL II subclass pattern, no significant change in LDL subclass distribution or peak diameter was noted. The prevalence of pattern B (predominant LDL peak <260 Å) and the mean proportion of LDL subclass III particles (<260 Å, 12%) were unaffected by estrogen treatment. In summary, estrogen replacement therapy decreased the proportion of large LDL I particles and increased the proportion of intermediate-size LDL II particles in healthy postmenopausal women with a predominance of large LDL particles at baseline. However, estrogen treatment did not increase the proportion of small, dense LDL III particles or result in conversion to LDL pattern B, attributes of LDL that have been associated with increased coronary artery disease risk in men. © 1993.