title: Effects of intranasal versus oral hormone therapy on asymmetric dimethylarginine in healthy postmenopausal women: a randomized study.
abstract: OBJECTIVE
  Oral estrogens reduce asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and an independent risk factor for cardiovascular disease. This study was conducted to compare the effect on ADMA between intranasal and oral 17beta-estradiol (E2) combined with norethisterone (acetate) (NET(A)) administration in postmenopausal women.
  
  
  METHODS
  In a two-center, randomized, double-blind, comparative study 90 healthy postmenopausal women (age 56.6+/-4.7 years) received daily continuous combined intranasal E2/NET 175 microg/275 microg (n=47) or oral E2/NETA 1 mg/0.5 mg (n=43) for one year. At baseline, week 12 and 52, plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured by high-performance liquid chromatography.
  
  
  RESULTS
  Oral E2/NETA reduced ADMA concentrations (-7.4%; 95% confidence interval (CI) -10.4 to -4.4%), while intranasal E2/NET had no effect (-0.8%; 95% CI -3.7 to 2.1%) after 52 weeks. In both groups, arginine was transiently decreased compared to baseline at week 12 (intranasal: -6.1%; 95% CI -9.1 to -3.0%; oral: -6.5%; 95% CI -10.9 to -2.1%). Only oral E2/NETA reduced SDMA concentrations.
  
  
  CONCLUSIONS
  Oral administration of E2/NETA reduced ADMA and SDMA concentrations, whereas intranasal administration did not. Both treatments transiently reduced arginine. The decrease in ADMA by oral estrogens could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal hormone therapy.
authors.affiliation: Project Aging Women and the Institute for Cardiovascular Research-Vrije Universiteit, Department of Obstetrics & Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marieke O
authors.initials: MO
authors.lastname: Verhoeven
authors.forename: Majoie
authors.initials: M
authors.lastname: Hemelaar
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Peter
authors.initials: P
authors.lastname: Kenemans
authors.forename: Marius J
authors.initials: MJ
authors.lastname: van der Mooren
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives / Q000737:chemistry; D000077563:Norethindrone Acetate; D017698:Postmenopause; D016896:Treatment Outcome
chemical_list: C487735:dimethylarginine; D004958:Estradiol; D001120:Arginine; D000077563:Norethindrone Acetate; D009640:Norethindrone