Effect of hormone therapy and calcitriol on serum lipid profile in postmenopausal older women: association with estrogen receptor-α genotypes.

The aim of this study was to examine the effect of conjugated equine estrogens alone (ET), conjugated equine estrogens + medroxyprogesterone (EPT), calcitriol alone, calcitriol + EPT/ET, or placebo on serum lipid profile and analyze the interaction with estrogen receptor-α gene single nucleotide polymorphisms (ESR-α SNPs) on the response to therapy. A total of 489 postmenopausal women older than 65 years were enrolled into a 3-year double-blind, placebo-controlled clinical trial. In both intent-to-treat and complier (>80% adherent) analysis, there was a significant increase in serum high-density lipoproteins and a significant decrease in serum low-density lipoproteins (LDLs) and the LDL/high-density lipoprotein ratio in all hormone treatment groups compared with placebo (P < 0.05). However, serum triglycerides and very low-density lipoproteins increased in the EPT and ET + calcitriol groups versus placebo (P < 0.05). ESR-α SNPs PvuII and XbaI seemed to have a significant effect on the response to treatment. Genotypes containing the p allele showed a significantly greater decrease in serum cholesterol and very low-density lipoprotein than those having the P allele in the ET + calcitriol group (P < 0.05), and those with the x allele had a significantly greater decrease in serum cholesterol in the hormone therapy + calcitriol group at the end of 3 years versus the X allele, and a greater decrease in serum LDL in alleles x versus the X in the ET + calcitriol group (P < 0.05). ET with or without progesterone had a favorable effect on lipid profile in postmenopausal older women, and this was dependent on estrogen receptor SNPs--PvuII and XbaI. However, this interaction with ESR-α SNPs needs to be confirmed in larger studies.