The effects of transdermal estradiol in combination with oral norethisterone on lipoproteins, coagulation, and endothelial markers in postmenopausal women with type 2 diabetes: A randomized, placebo-controlled study

People with type 2 diabetes have a substantially increased risk of coronary heart disease (CHD). Short-term studies with unopposed oral estradiol in w omen with diabetes have suggested potentially beneficial effects on lipids, thrombotic factors, and insulin sensitivity. However, most (nonhysterectom ized) postmenopausal women require combined estrogen-progesterone preparati ons. We randomized 43 women with type 2 diabetes either to continuous trans dermal estradiol (80-mug patches) in combination with oral norethisterone ( 1 mg daily) or to identical placebos. Blood samples were taken before and a fter 6 months for measurement of lipoproteins, coagulation factors, and end othelial markers. Total cholesterol and triglyceride concentrations decreas ed by 8% and 22%, respectively, in those receiving hormone replacement ther apy (P < 0.05 relative to change in placebo group after adjustment for base line concentrations). There was a trend toward a reduction in high density lipoprotein cholesterol concentration (P = 0.06). Factor VII activity decre ased by 16% (P < 0.001), and von Willebrand factor antigen decreased by 7% (P = 0.014) with active treatment. Levels of fibrinogen, tissue plasminogen activator, fibrin D dimer, very low density lipoprotein cholesterol, low d ensity lipoprotein cholesterol, lipoprotein(a), and leptin were not signifi cantly altered. No change in glycemic control was detected. Overall, lipid changes may be considered slightly beneficial with respect to CHD risk. The significant decrease in factor VII activity in this study is notable, beca use elevated factor VII activity has been associated with an increased risk of coronary thrombosis and normally increases with administration of oral estrogen-containing preparations. In addition, a reduction in von Willebran d factor antigen is consistent with an improvement in endothelial function. We suggest that the regimen used in this study may have the potential to r educe CHD risk in women with type 2 diabetes.