Short-term hormone therapy improves sCD40L and endothelial function in early menopausal women: potential role of estrogen receptor polymorphisms

Maturitas. 2012 Apr;71(4):389-95. doi: 10.1016/j.maturitas.2012.01.001. Epub 2012 Jan 23.

Abstract

Objective: Hormone therapy (HT) has been suggested to improve vascular function and inflammation in menopausal women, although not consistently. We aimed to investigate the effects of HT on endothelial function and inflammation, especially sCD40L, in early menopausal women, and the effect of common estrogen receptor (ER) polymorphisms on vascular responses to HT.

Study design: Eighty-four early menopausal women (<3 years in menopause) with menopausal complaints eligible for HT. Forty women received transdermal 17β-estradiol plus cyclical micronized progesterone for 3 months while 44 did not (controls).

Main outcome measures: Brachial artery flow-mediated dilation (FMD) and vascular inflammation markers (sICAM, sP-Selectin and sCD40L). Genetic polymorphisms of ERα (PvuII 454-397T>C and XbaI 454-351A>G) and ERβ (AluI 1730A>G) were also assessed.

Results: The two groups did not differ at baseline. Following HT, vasomotor complaints' severity, blood pressure, LDL, sCD40L, sICAM and sP-Selectin decreased and FMD increased compared to controls (P<0.05 for all). ERβ AluI A allele presence was the most important independent predictor of HT-induced increase in FMD while ERα XbaI A allele was the only independent predictor of decrease in sCD40L.

Conclusions: Short-term HT in early menopausal women improved endothelial function and inflammation. Specific ER polymorphisms that were found to be main determinants of HT-induced effects on endothelium could identify subgroups of women who may benefit the most from HT.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Alleles
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Brachial Artery / drug effects
  • CD40 Ligand / blood*
  • Cell Adhesion Molecules / blood
  • Cholesterol, LDL / blood
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Estradiol / therapeutic use*
  • Estrogen Receptor alpha / genetics*
  • Estrogen Replacement Therapy*
  • Estrogens / therapeutic use
  • Female
  • Genotype
  • Hot Flashes / drug therapy
  • Hot Flashes / genetics
  • Humans
  • Inflammation / drug therapy
  • Inflammation Mediators / metabolism
  • Menopause / blood
  • Menopause / genetics*
  • Middle Aged
  • P-Selectin / blood
  • Polymorphism, Genetic*
  • Progesterone / therapeutic use
  • Progestins / therapeutic use
  • Severity of Illness Index
  • Vasodilation / drug effects
  • Vasodilation / genetics

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • Cholesterol, LDL
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Estrogens
  • Inflammation Mediators
  • P-Selectin
  • Progestins
  • CD40 Ligand
  • Progesterone
  • Estradiol