title: Effects of estrogen replacement therapy on plasma levels of nitric oxide in postmenopausal women.
abstract: OBJECTIVE
  Our purpose was to assess the effects of estrogen replacement therapy on plasma levels of nitric oxide in postmenopausal women.
  
  
  METHODS
  The study, designed as a randomized, double-blind placebo-controlled crossover trial, involved 28 healthy postmenopausal women who had previously undergone hysterectomy. Women received either transdermal estradiol (50 g/day) (estradiol group) or placebo (placebo group) for 6 months continuously. At the end of month 6 the treatment allocations were opened, and then the treatments were exchanged for 1 month. The serum concentration of estradiol was measured at baseline before treatment and at the end of months 6 and 7. The plasma concentration of the stable oxidation products of nitric oxide was assessed before treatment and monthly until month 7.
  
  
  RESULTS
  The mean baseline concentrations of nitric oxide metabolites in the estradiol and placebo groups were similar (mean and SD: 19+/-4.3 vs 21+/-5.6 micromol/L, respectively). At subsequent measurements from months 1 to 6, the mean concentration of nitric oxide metabolites increased significantly in the estradiol group alone, in which the concentration ranged between 33 6.4 and 36 8.5 micromol/L. At the end of month 7 the mean level of nitric oxide metabolites in women previously treated with estradiol fell to baseline value (19 2.6 micromol/L), whereas in the placebo group the level increased significantly (34 4.4 micromol/L).
  
  
  CONCLUSIONS
  Estrogen replacement therapy induces a sustained increase in plasma levels of nitric oxide in postmenopausal women; the suspension of estrogen replacement therapy is followed by a significant reduction in nitric oxide levels. The results of this study suggest that a nitric oxide-related mechanism may help to explain the cardioprotective effect of estrogen replacement therapy in the postmenopausal period.
authors.affiliation: Department of Obstetrics and Gynecology, University of Bari Medical School, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cicinelli
authors.forename: L J
authors.initials: LJ
authors.lastname: Ignarro
authors.forename: M G
authors.initials: MG
authors.lastname: Matteo
authors.forename: P
authors.initials: P
authors.lastname: Galantino
authors.forename: L M
authors.initials: LM
authors.lastname: Schonauer
authors.forename: N
authors.initials: N
authors.lastname: Falco
mesh_terms: D000279:Administration, Cutaneous; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D010919:Placebos; D017698:Postmenopause / Q000097:blood*