The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes

Estrogens protect healthy women from cardiovascular disease. However, epide miological data suggest that women with diabetes are denied the cardioprote ction associated with estrogens. Whether or not hormonal replacement therap y(HRT) confers cardiovascular benefits in postmenopausal women with diabete s is not known. The aim of this study was to examine the effects of HRT on the microvascular reactivity and endothelial function of individuals with a nd without diabetes. We studied the following groups of individuals: premen opausal healthy women [n = 28, age 41 +/- 8 yr (mean =/- SD)], premenopausa l women with type 2 diabetes (n = 16, age 43 +/- 6 yr); postmenopausal heal thy women (n = 12, age 57 +/- 4 yr), postmenopausal women with diabetes (n = 17, age 62 +/- 5 yr); postmenopausal healthy women on HRT (n = 13, age 51 +/- 5 yr), postmenopausal women with diabetes on HRT (n = 11, age 57 +/- 7 yr). We used laser Doppler flowmetry to measure forearm cutaneous vasodila tation in response to iontophoresis of 1% acetylcholine (endothelium depend ent) and 1% sodium nitroprusside (endothelium independent). the endothelium -dependent vasodilation was significantly higher in premenopausal healthy w omen (180 +/-: 67%; increase over baseline) compared to premenopausal diabe tic women (87 +/-: 41%; P < 0.001). endothelium-dependent vasodilation was also higher in postmenopausal healthy women on HRT (143 +/- 52) compared wi th postmenopausal diabetic women on HRT (86 +/- 61), postmenopausal healthy women without HRT (104 +/- 43), and postmenopausal diabetic women without HRT (74 +/- 28; P < 0.001). A similar pattern of responses was observed in the endothelium-independent vasodilation (premenopausal healthy women, 126 +/- 56; premenopausal diabetic women, 88 +/- 26; postmenopausal healthy wom en on HRT, 121 +/- 37; postmenopausal diabetic women on HRT, 88 +/- 41; pos tmenopausal healthy women without HRT, 84 +/- 36; and postmenopausal diabet ic women without HRT, 73 +/- 36; P < 0.001). Soluble intercellular adhesion molecule (sICAM) was also measured among all the women with diabetes. Prem enopausal women with diabetes (248.9 +/- 56 ng/ml) and post menopausal wome n with diabetes on HRT (257.7 +/- 49 ng/ml) had lower sICAM levels compared with the postmenopausal diabetic women without HRT (346.4 +/- 149 ng/ml; P < 0.05). We conclude that menopausal status and type 2 diabetes are associ ated with impaired microvascular reactivity. HRT substantially improves mic rovascular reactivity in postmenopausal healthy women. In contrast, the eff ect of HRT on the microvascular reactivity of postmenopausal diabetic women is less apparent. However, the use of HRT among women with diabetes is ass ociated with lower sICAM levels, suggesting an attenuation in endothelial a ctivation.