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 mec hanism by which estrogen replacement therapy protects postmenopausal w omen against coronary artery disease. However, combined hormone replac ement therapy is more frequently used owing to the risk of uterine can cer with estrogen-only therapy. Concurrent progesterone treatment may attenuate the beneficial effects of estrogens not only on the lipid pr ofile but also on the endothelium. Methods and Results-We studied endo thelial vasomotor function in 100 healthy postmenopausal women aged 53 .3+/-2.9 years randomized to either combined hormone replacement thera py (n=46) or no substitution (n=54) 2.9+/-0.5 years earlier. In additi on, 30 healthy premenopausal women aged 30.3+/-4.2 years were studied. With external ultrasound, brachial artery diameter was measured at re st, during reactive hyperemia (with increased flow causing endothelium -dependent dilation), and after sublingual nitroglycerin (causing endo thelium-independent dilation). Compared with premenopausal women, flow -mediated dilation was significantly reduced in both postmenopausal gr oups. 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 pos tmenopausal 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 endo thelial vasomotor function in healthy postmenopausal women. This suppo rts the view that progesterone may attenuate the beneficial effects of unopposed estrogen replacement.