Combined hormone replacement therapy does not protect women against the age-related decline in endothelium-dependent vasomotor function

Background-Improvement in endothelial function may be an important mechanism by which estrogen replacement therapy protects postmenopausal women against coronary artery disease. However, combined hormone replacement therapy is more frequently used owing to the risk of uterine cancer with estrogen-only therapy. Concurrent progesterone treatment may attenuate the beneficial effects of estrogens not only on the lipid profile but also on the endothelium. Methods and Results-We studied endothelial vasomotor function in 100 healthy postmenopausal women aged 53.3+/-2.9 years randomized to either combined hormone replacement therapy (n=46) or no substitution (n=54) 2.9+/-0.5 years earlier. In addition, 30 healthy premenopausal women aged 30.3+/-4.2 years were studied. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia (with increased flow causing endothelium-dependent dilation), and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with premenopausal women, flow-mediated dilation was significantly reduced in both postmenopausal groups. In the postmenopausal women, total cholesterol was lower in the treated women (5.66+/-0.83 versus 6.13+/-0.92 mmol/L; P=.025), whereas HDL cholesterol was similar (1.91+/-0.53 versus 1.85+/-0.46 mmol/L; P=NS). Dilation to flow and to nitroglycerin was similar in the two postmenopausal groups (flow: 2.5+/-2.9% versus 2.2+/-2.2%, P=NS; nitrate: 18.7+/-5.9% versus 17.2+/-6.2%, P=NS). Conclusion-Long-term combined oral hormone replacement therapy is without beneficial effects on endothelial vasomotor function in healthy postmenopausal women. This supports the view that progesterone may attenuate the beneficial effects of unopposed estrogen replacement.