Administration of transdermal estrogen without progestin increases the capacity of plasma and serum to stimulate prostacyclin production in human vascular endothelial cells

Objective: To determine whether transdermal hormone replacement therapy mod ifies the ability of plasma or serum to regulate the synthesis of prostacyc lin and that of endothelin-1 by cultured human umbilical vein endothelial c ells. Design: Prospective, randomized study. Setting: Department of Obstetrics and Gynecology, Helsinki University Centr al Hospital. Patient(s): Thirteen postmenopausal women with climacteric symptoms. Interventions: Transdermal 17 beta-E-2 (50 mu g/d) continuously combined wi th norethisterone acetate, (250 mu g/d) on days 15-28 of the treatment cycl es for 6 months. Main Outcome Measure(s): Levels of prostacyclin's metabolite 6w-keto-prosta glandin F-1 alpha and of endothelin-1 released by cultured human umbilical vein endothelial cells. Result(s): Plasma and serum during the E-2-only phase of hormone replacemen t therapy enhanced prostacyclin production by 20% +/- 8% (mean +/- SEM) and 23% +/- 11%, respectively. Plasma or serum taken during the E-2 + norethis terone acetate phase failed to affect prostacyclin production. Hormone repl acement therapy induced no change in the capacity of plasma or serum to rel ease endothelin-1. Conclusion(s): Transdermal hormone replacement therapy during the E-2-only phase increased the capacity of plasma and serum to enhance production of v asoprotective prostacyclin in human vascular endothelial cells, without aff ecting production of endothelin-1. Addition of norethisterone acetate preve nted this stimulation. (Fertil Steril(R) 2000;73:72-4. (C) 1999 by American Society for Reproductive Medicine.)