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Oral, more than transdermal, oestrogen therapy lowers asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebo‐controlled study
Author(s) -
VERHOEVEN M. O.,
HEMELAAR M.,
MOOREN M. J. VAN DER,
KENEMANS P.,
TEERLINK T.
Publication year - 2006
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.2005.01602.x
Subject(s) - medicine , asymmetric dimethylarginine , placebo , transdermal , endocrinology , oral administration , arginine , pharmacology , chemistry , biochemistry , alternative medicine , amino acid , pathology
. Objective. To compare the effects of oral and transdermal hormone therapy (HT) on asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in postmenopausal women. Design. In a multicentre, placebo‐controlled, double‐blind study, 152 hysterectomized healthy women were randomized to receive daily transdermal 17 β ‐oestradiol (tE 2 , n = 33), or oral micronized 17 β ‐oestradiol either unopposed (oE 2 , n = 37), or continuous combined with gestodene (oE 2 + G, n = 33), or placebo ( n = 49) for 13, 28‐day treatment cycles. Plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured at baseline and in treatment cycles 4 and 13 with a high‐performance liquid chromatography method. Results. After 13 cycles all active treatment groups showed a significant reduction in ADMA compared with placebo: tE 2 , −4.0% (95% CI: −7.5 to −0.6%); oE 2 , −7.7% (95% CI: −10.9 to −4.4%) and oE 2 + G, −7.5% (95% CI: −10.8 to −4.3%). ancova showed a significantly larger reduction in the oral groups compared with the transdermal group (tE 2 vs. oE 2 and tE 2 vs. oE 2 + G, both P < 0.01). Oral, but not transdermal treatment, significantly reduced arginine compared with placebo. All active treatments reduced SDMA; however, this was only statistically significant in the oE 2 group. Conclusion. Reduction of ADMA was more pronounced after oral than after tE 2 administration. Adding gestodene to oral 17 β ‐oestradiol did not alter the reduction of ADMA. The clinical implications of these findings remain uncertain; however, the decrease of ADMA by 17 β ‐oestradiol could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal HT.