Effects of estrogen-progestin and raloxifene therapy on nitric oxide, prostacyclin and endothelin-1 synthesis

This randomized double-blind study was conducted to investigate the effects of 17beta-estradiol plus norethisterone acetate, and raloxifene, on nitric oxide (NO), prostacyclin (PGI(2)) and endothelin-1 (ET-1) serum levels in postmenopausal women. Treatment was initiated after a 28-50 day placebo period. Fourteen women were treated daily with 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E-2 + NETA), and 14 with raloxifene HCl 60 mg for a period of 6 months. Serum NO, PGI(2) and ET-1 levels were estimated at baseline, after placebo, and at months 3 and 6. E-2 + NETA decreased NO levels significantly, while raloxifene did not cause any appreciable change. Both regimens decreased PGI(2) levels and ET-1 levels significantly. Finally, E-2 + NETA and raloxifene increased the NO/ET-1 ratio by 61.4% and 81.1 %, respectively. In conclusion, both regimens may exert a cardio-protective effect by decreasing ET-1 levels and increasing the NO/ET-1 ratio. In contrast, both regimens had a negative influence on PGI(2) levels.