title: Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women.
abstract: BACKGROUND
  Epidemiological studies indicate that estrogen replacement therapy decreases the risk of cardiovascular events in postmenopausal women. Estrogen may confer cardiovascular protection by improving endothelial function because it increases endothelium-dependent vasodilation. It is not known whether progesterone attenuates the beneficial effects of estrogen on endothelial function.
  
  
  RESULTS
  Seventeen postmenopausal women with mild hypercholesterolemia were enrolled in a placebo-controlled, crossover trial to evaluate the effect of transdermal estradiol, with and without vaginal micronized progesterone, on endothelium-dependent vasodilation in a peripheral conduit artery. Brachial artery diameter was measured with high-resolution B-mode ultrasonography. To assess endothelium-dependent vasodilation, brachial artery diameter was determined at baseline and after a flow stimulus induced by reactive hyperemia. To assess endothelium-independent vasodilation, brachial artery diameter was measured after administration of sublingual nitroglycerin. During estradiol therapy, reactive hyperemia caused an 11.1+/-1.0% change in brachial artery diameter compared with 4. 7+/-0.6% during placebo therapy (P<0.001). Progesterone did not significantly attenuate this improvement. During combined estrogen and progesterone therapy, flow-mediated vasodilation of the brachial artery was 9.6+/-0.8% (P=NS versus estradiol alone). Endothelium-independent vasodilation was not altered by estradiol therapy, either with or without progesterone, compared with placebo. There was a modest decrease in total and LDL cholesterol during treatment both with estradiol alone and when estradiol was combined with progesterone (all P<0.001 versus placebo). In a multivariate analysis that included serum estradiol, progesterone, total and LDL cholesterol concentrations, blood pressure, and heart rate, only the estradiol level was a significant predictor of endothelium-dependent vasodilation.
  
  
  CONCLUSIONS
  The addition of micronized progesterone does not attenuate the favorable effect of estradiol on endothelium-dependent vasodilation. The vasoprotective effect of hormone replacement therapy may extend beyond its beneficial actions on lipids.
authors.affiliation: Department of Medicine, Obstetrics and Gynecology , Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gerhard
authors.forename: B W
authors.initials: BW
authors.lastname: Walsh
authors.forename: A
authors.initials: A
authors.lastname: Tawakol
authors.forename: E A
authors.initials: EA
authors.lastname: Haley
authors.forename: S J
authors.initials: SJ
authors.lastname: Creager
authors.forename: E W
authors.initials: EW
authors.lastname: Seely
authors.forename: P
authors.initials: P
authors.lastname: Ganz
authors.forename: M A
authors.initials: MA
authors.lastname: Creager
mesh_terms: D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D008078:Cholesterol, LDL; D011374:Progesterone; D004958:Estradiol