Impact of combined hormone replacement therapy on serum lipid metabolism: new aspects

The objective of this study was to evaluate the impact of combined estrogen-progestogen therapy on low density lipoprotein (LDL) particle size (determined by the LDL cholesterol/apolipoprotein B ratio). The prospective study was carried out on 139 healthy Danish early postmenopausal women. The subjects were randomized to placebo or to 2 mg estradiol valerate equivalents, either sequentially combined with 75 micrograms levonorgestrel, 10 mg medroxyprogesterone acetate (MPA), or 150 micrograms desogestrel, or continuously combined with 1 mg cyproterone acetate. LDL particle size was calculated before treatment and at nine-well-defined times during the subsequent 84 days. LDL particle size was reduced by all four treatments. This change was statistically significant for estradiol valerate combined with levonorgestrel and MPA (6.2 +/- 2.7% and 5.6 +/- 2.1% (mean +/- SEM), respectively; p < 0.05 for both, placebo-corrected). Estradiol valerate combined with MPA induced cyclic (progestogen-minus estrogen-related values) decreases (-6.3 +/- 2.6%; p < 0.05), and with levonorgestrel there were cyclic increases (5.1 +/- 2.7%; p = 0.067) in LDL particle size (placebo-corrected). In conclusion, combined estrogen-progestogen therapy causes a decrease in LDL particle size. A cyclic variation in LDL cholesterol/apolipoprotein B ratio was observed during sequential treatment.