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 17 beta-estradiol plus norethisterone acetate, and raloxifene, on nitric oxide (NO), prostacyclin (PGI2) 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 17 beta-estradiol 2 mg plus norethisterone acetate 1 mg (E2 + NETA), and 14 with raloxifene HCl 60 mg for a period of 6 months. Serum NO, PGI2 and ET-1 levels were estimated at baseline, after placebo, and at months 3 and 6. E2 + NETA decreased NO levels significantly, while raloxifene did not cause any appreciable change. Both regimens decreased PGI2 levels and ET-1 levels significantly. Finally, E2 + 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 PGI2 levels.
Christodoulakos
G
G
Second Department of Obstetrics and Gynecology, University of Athens-Aretaeion Hospital, Athens, Greece.
Panoulis
C
C
Kouskouni
E
E
Chondros
C
C
Dendrinos
S
S
Creatsas
G
G
D002318:Cardiovascular Diseases / Q000517:prevention & control; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood*; D011464:Epoprostenol / Q000097:blood*; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077563:Norethindrone Acetate; D010919:Placebos; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000627:therapeutic use
D019332:Endothelin-1; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; D009569:Nitric Oxide; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D000077563:Norethindrone Acetate; D011464:Epoprostenol; D009640:Norethindrone