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 modifies the ability of plasma or serum to regulate the synthesis of prostacyclin and that of endothelin-1 by cultured human umbilical vein endothelial cells.

Design: Prospective, randomized study.

Setting: Department of Obstetrics and Gynecology, Helsinki University Central Hospital.

Patient(s): Thirteen postmenopausal women with climacteric symptoms.

Interventions: Transdermal 17beta-E2 (50 microg/d) continuously combined with norethisterone acetate, (250 microg/d) on days 15-28 of the treatment cycles for 6 months.

Main Outcome Measure(s): Levels of prostacyclin's metabolite 6-keto-prostaglandin F1alpha and of endothelin-1 released by cultured human umbilical vein endothelial cells.

Result(s): Plasma and serum during the E2-only phase of hormone replacement therapy enhanced prostacyclin production by 20% +/- 8% (mean +/- SEM) and 23% +/- 11%, respectively. Plasma or serum taken during the E2 + norethisterone acetate phase failed to affect prostacyclin production. Hormone replacement therapy induced no change in the capacity of plasma or serum to release endothelin-1.

Conclusion(s): Transdermal hormone replacement therapy during the E2-only phase increased the capacity of plasma and serum to enhance production of vasoprotective prostacyclin in human vascular endothelial cells, without affecting production of endothelin-1. Addition of norethisterone acetate prevented this stimulation.