title: Oestrogen replacement therapy lowers plasma levels of asymmetrical dimethylarginine in healthy postmenopausal women.
abstract: Oestrogen replacement therapy (ERT) has been shown to lead to favourable changes in the cardiovascular risk profile of postmenopausal women. Part of this effect is ascribed to increased production or bioavailability of nitric oxide (NO). We have tested the hypothesis that ERT lowers plasma levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of NO synthase (NOS). In a randomized double-blind study design, 40 hysterectomized postmenopausal women received conjugated equine oestrogen (CEE; 0.625 mg/day; n =14), the selective oestrogen receptor modulator raloxifene (150 mg/day; n =13) or placebo ( n =13). At baseline and after 6, 12 and 24 months of treatment, plasma was analysed for levels of arginine, ADMA, and symmetrical dimethylarginine (SDMA), a stereoisomer of ADMA that does not inhibit NOS. An overall treatment effect on ADMA levels was observed in the CEE group ( P =0.004 compared with placebo), but not in the raloxifene group ( P =0.50). The decrease of ADMA levels by CEE treatment was consistent over the 2-year study period, without significant differences between the effects at 6, 12 and 24 months. The average post-baseline change in ADMA in the CEE group compared with placebo was -7.8% (95% confidence interval -12.8% to -2.9%; P =0.003). Arginine or SDMA levels did not change during treatment in any of the groups. Thus ERT with oral conjugated oestrogen, but not with raloxifene, significantly reduced plasma concentrations of the cardiovascular risk factor ADMA in healthy postmenopausal women.
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. t.teerlink@vumc.nl
authors.forename: T
authors.initials: T
authors.lastname: Teerlink
authors.forename: S J M
authors.initials: SJ
authors.lastname: Neele
authors.forename: S
authors.initials: S
authors.lastname: de Jong
authors.forename: J C
authors.initials: JC
authors.lastname: Netelenbos
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000704:Analysis of Variance; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D017698:Postmenopause / Q000097:blood; D020033:Protein Isoforms / Q000097:blood; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D012680:Sensitivity and Specificity
chemical_list: D004966:Estrogens, Conjugated (USP); D020033:Protein Isoforms; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase