1999 WHRG Grant Program

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Diabetes, Arterial Vasoactivity and Estrogen (DAVE) Trial
Maura Whiteman
School of Medicine, University of Maryland, Baltimore

Coronary heart disease (CHD) is the most common cause of death among postmenopausal women. For most postmenopausal women, estrogen replacement therapy (ERT) is recommended for the prevention of CHD as well as to prolong and improve the quality of life. Such recommendations are based on substantial observational evidence that ERT reduces cardiovascular morbidity and mortality in postmenopausal women. Additionally, clinical trials have shown that ERT improves the levels of CHD risk factors, namely lipids. It has become evident that in addition to its effects on lipids, estrogen exerts cardioprotection through direct effects on the vasculature. Postmenopausal women given ERT in several clinical trials have experienced improved endothelial function, an intermediate biological measure of CHD whose association with cardiovascular disease is well established.

Diabetic women are at a risk of CHD that is three- to five times the risk of non-diabetic women. However, few women with diabetes have been included in studies of ERT and as a result very little is known about the effects of ERT in diabetic postmenopausal women. Theoretically, postmenopausal women with non-insulin dependent diabetes mellitus (NIDDM), who typically have less favorable levels of CHD risk factors than healthy women, stand to benefit even more from ERT than non-diabetics. Impaired endothelial function is also common among individuals with diabetes. Although there are few studies of ERT in postmenopausal women with NIDDM, they suggest that diabetic women will derive the same benefits from ERT as non-diabetics, including its effects on endothelial function, blood sugar control, and lipids.

We propose a pilot study to test the hypothesis that short-term ERT in postmenopausal women with NIDDM will improve endothelial function, as measured non-invasively in the brachial artery. We will also test the hypothesis that short-term ERT improves lipid levels and blood sugar control in postmenopausal women with NIDDM.

To test our hypotheses, we will recruit postmenopausal women between the ages of 45 and 64 with a confirmed diagnosis of NIDDM. Endothelial function will be assessed using a brachial artery vasoactivity test before and after 8 weeks of treatment with 0.625 mg/day of conjugated equine estrogen (Premarin). In addition, lipids (HDL-cholesterol, LDL-cholesterol, and triglycerides) and measures of blood sugar control (glucose, insulin, and glycosylated hemoglobin) will be measured before and after treatment. Changes in endothelial function, lipid levels, and blood sugar control associated with ERT will be assessed.

The proposed clinical trials will be the first to our knowledge that will examine the effects of ERT on an intermediate biological measure of CHD in diabetic postmenopausal women. Using a non-invasive technique we will be able to measure endothelial function and its response to short- term ERT. Furthermore, the present literature indicates a lack of knowledge regarding the effects of hormone replacement on carbohydrate metabolism in diabetics. The current study intends to examine diabetes control measures as well. This study will provide the foundation for a larger placebo-controlled clinical trial of ERT in postmenopausal women with NIDDM. Such a trial will provide valuable information that may lead to marked improvements in the health of postmenopausal diabetic women through reducing their risk of CHD and its associated morbidity and mortality.