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.


METHODS
Prospective, randomized study.


METHODS
Department of Obstetrics and Gynecology, Helsinki University Central Hospital.


METHODS
Thirteen postmenopausal women with climacteric symptoms.


METHODS
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.


METHODS
Levels of prostacyclin's metabolite 6-keto-prostaglandin F1alpha and of endothelin-1 released by cultured human umbilical vein endothelial cells.


RESULTS
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.


CONCLUSIONS
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.
Mikkola
T
T
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland. tomi_mikkola@hotmail.com
Viinikka
L
L
Ylikorkala
O
O
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000279:Administration, Cutaneous; D001769:Blood; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077563:Norethindrone Acetate; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage*; D011446:Prospective Studies; D014471:Umbilical Veins
D019332:Endothelin-1; D011372:Progestins; D004958:Estradiol; D015121:6-Ketoprostaglandin F1 alpha; D005640:Follicle Stimulating Hormone; D000077563:Norethindrone Acetate; D011464:Epoprostenol; D009640:Norethindrone