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

Abstract

Objective: 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.

Methods: A total of 489 postmenopausal women older than 65 years were enrolled into a 3-year double-blind, placebo-controlled clinical trial.

Results: 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).

Conclusions: 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.

FIG. 1

Schematic diagram–estrogen receptor-α gene: it consists of eight exons encompassing six domains. PvuII and XbaI restriction fragment length polymorphisms produce C/T and A/G variations, respectively.

FIG. 2

STOP IT randomization. STOP IT, Sites Testing Osteoporosis Prevention or Intervention Treatment; HT, hormone therapy.

FIG. 3

Percent change in serum cholesterol and serum triglycerides in the various treatment groups after adjustment for confounders (intent-to-treat analysis). EPT, estrogen + medroxyprogesterone therapy; ET, estrogen therapy; C, calcitriol. ^aP < 0.05 as compared with placebo. ^bP < 0.01 as compared with placebo. ^cP < 0.05 as compared with EPT.

FIG. 4

Percent change in serum HDL, LDL, LDL/HDL ratio, and VLDL in the various treatment groups after adjustment for confounders (intent-to-treat analysis). EPT, estrogen + medroxyprogesterone therapy; ET, estrogen therapy; C, calcitriol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low density lipoprotein. ^aP < 0.05 as compared with placebo. ^bP < 0.01 as compared with placebo. ^cP < 0.05 as compared with C. ^dP < 0.01 as compared with C. ^eP < 0.01 as compared with EPT + C.

FIG. 5

Percent change in serum cholesterol and serum triglycerides in the various treatment groups after adjustment for confounders (complier analysis). EPT, estrogen + medroxyprogesterone therapy; ET, estrogen therapy; C, calcitriol. ^aP < 0.01 as compared with placebo. ^bP < 0.05 as compared with calcitriol. ^cP < 0.01 as compared with calcitriol.

FIG. 6

Percent change in serum HDL, LDL, LDL/HDL ratio, and VLDL in the various treatment groups after adjustment for confounders (complier analysis). EPT, estrogen + medroxyprogesterone therapy; ET, estrogen therapy; C, calcitriol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low density lipoprotein. ^aP < 0.01 as compared with placebo. ^bP < 0.01 as compared with C. ^cP < 0.05 as compared with EPT.