Mikkola T, Ranta V, Orpana A, Viinikka L, Ylikorkala O
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Fertil Steril. 1996 Sep;66(3):389-93. doi: 10.1016/s0015-0282(16)58506-9.
To determine if hormone replacement therapy (HRT) modifies the ability of plasma or serum to regulate the synthesis of vasodilatory prostacyclin and that of vasoconstrictive endothelin-1 by cultured human umbilical vein endothelial cells.
Plasma and serum collected before and during the sixth treatment cycle of HRT from 13 healthy postmenopausal women were added to cultured endothelial cells.
Helsinki University Central Hospital, Department of Obstetrics and Gynecology, Helsinki, Finland.
Thirteen postmenopausal women (> or = 1 year since their last menstruation, FSH level > 40 mIU/mL [conversion factor to SI unit, 1.00], clear vasomotor symptoms) that suffered from incapacitating menopausal symptoms necessitating the initiation of HRT were studied.
A combined regimen consisting of 2 mg oral E2 for 12 days followed by 2.0 mg oral E2 + 1.0 mg norethisterone acetate for 10 days and 1.0 mg E2 for 6 days.
The releases of prostacyclin, as assessed by its metabolite 6-keto-prostaglandin F1 alpha, and that of endothelin-1 by cultured human umbilical vein endothelial cells in the presence of 10% plasma or 10% serum collected from the study subjects.
Hormone replacement therapy enhanced the ability of plasma to stimulate prostacyclin production by 21% +/- 6% (mean +/- SEM) during the E2 + norethisterone acetate phase and tended to do so also during the E2-only phase (11% +/- 10%) but caused no change in endothelin-1 release. In contrast, HRT decreased the ability of serum to stimulate prostacyclin production by 12% +/- 5% during the E2-only phase and increased that of endothelin-1 by 8% +/- 4% during the E2 + norethisterone acetate phase.
Because plasma flushes endothelial cells in vivo, our data on the HRT-induced stimulation of the capacity of plasma to enhance the production of vasoprotective prostacyclin without a concomitant change in endothelin-1 release in cultured human umbilical vein endothelial cells may provide one new explanation for the cardiovascular protection of HRT.
