Effects of estrogen replacement therapy on plasma levels of nitric oxide in postmenopausal women

OBJECTIVE: Our purpose was to assess the effects of estrogen replacement therapy on plasma levels of nitric oxide in postmenopausal women. STUDY DESIGN: 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 mu mol/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 mu mol/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 mu mol/L), whereas in the placebo group the level increased significantly (34 +/- 4.4 mu mol/L). CONCLUSION: 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.