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Keywords:

  • arginine;
  • asymmetric dimethylarginine;
  • gestodene;
  • oestradiol;
  • postmenopausal;
  • symmetric dimethylarginine

Abstract.

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 17β-oestradiol (tE2, n = 33), or oral micronized 17β-oestradiol either unopposed (oE2, n = 37), or continuous combined with gestodene (oE2 + 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: tE2, −4.0% (95% CI: −7.5 to −0.6%); oE2, −7.7% (95% CI: −10.9 to −4.4%) and oE2 + 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 (tE2 vs. oE2 and tE2 vs. oE2 + 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 oE2 group.

Conclusion.  Reduction of ADMA was more pronounced after oral than after tE2 administration. Adding gestodene to oral 17β-oestradiol did not alter the reduction of ADMA. The clinical implications of these findings remain uncertain; however, the decrease of ADMA by 17β-oestradiol could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal HT.