Context: Endothelial dysfunction in resistance arteries after menopause is important for the development of high blood pressure and cardiovascular disease.

Objective: To study the effects of different hormone replacement therapies (HRT) on the function and morphology of isolated resistance arteries, and to look for their mechanistic basis.

Design and setting: A randomized, placebo-controlled double-blind study in a University hospital, along with laboratory-based studies.

Patients and interventions: We isolated resistance arteries in subcutaneous biopsies from 55 postmenopausal women before and after 3 months of therapy with estradiol (E2), medroxyprogesterone acetate (MPA), E2 + MPA or placebo. In addition, we studied isolated human endothelial cells.

Main Outcome Measures and Results: Artery flow-mediated dilatation was augmented after treatment with E2 or E2+MPA, whereas MPA or placebo had no effect. Pressure-induced myogenic tone was reduced by E2 + MPA, while it was unchanged in the other groups. Scanning microscopy showed that E2 improved endothelial cell morphology and decreased signs of endothelial apoptosis, but the addition of MPA impaired these events. E2, MPA or the combination all increased the expression and phosphorylation of the actin-binding protein, moesin and of the focal adhesion complex controller, focal adhesion kinase and induced the rearrangement of cytoskeletal actin and vinculin fibers. All treatments promoted endothelial cell horizontal migration, with E2 inducing the strongest effect.

Conclusions: This study suggests that HRT with estrogens or in combination with MPA may benefit the function of resistance arteries and may preserve the morphological integrity of endothelial cells by regulatory actions on the cytoskeleton.