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.