Indirect evidence that estrogen replacement therapy stimulates nitric oxide synthase in postmenopausal women

The aim of the study was to investigate the effects of estrogen replacement therapy (ERT) on nitric oxide (NO) activity in healthy postmenopausal wome n. The study group consisted of 22 postmenopausal women (last menses at least 12 months prior to study entry) who were randomized to receive treatment fo r 2 months with patches that delivered either 50 mu g/day of 17 beta-estrad iol or placebo in a cross-over design. Blood samples for measurements of se rum citrulline and arginine were collected at the start of the study and at the end of each treatment course. Serum citrulline and arginine were measu red using high-performance liquid chromatography with fluorometric detectio n. Arginine levels were significantly lower in the ERT group compared to the p lacebo group, while citrulline levels did not change. The percentage citrul line/arginine ratio was significantly higher in the ERT group (42.9 +/- 21. 6) compared to the placebo group (33.9 +/- 18.5) (p < 0.01). The citrulline /arginine ratio, both at baseline and during either ERT or placebo administ ration demonstrated a positive linear correlation with body mass index (BMI ). No correlations were found between follicle stimulating hormone, estradi ol and insulin levels and BMI. No correlations were found between age, time since menopause and baseline arginine and citrulline levels or the citrull ine/arginine ratio. These data indirectly demonstrate that transdermal estradiol replacement in postmenopausal women is able to stimulate NO production through the involv ement of endogenous L-arginine. A positive linear correlation was found bet ween BMI and the citrulline/arginine ratio, suggesting an additional protec tive cardiovascular effect in overweight women.