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Title: Research Highlights Hormonal Control of Cardiovascular Functions

"Research Highlights Hormonal Control of Cardiovascular Functions"

CHEVY CHASE, MD -- August 17, 2004 -- Three new studies published this month in The Journal of Clinical Endocrinology and Metabolism showcase the important role that hormones play in cardiovascular functions. While one study examines the beneficial role of hormones in women who experience early menopause, a second highlights the possible benefits of metformin in treating a pre-diabetes condition. A third study demonstrates that an insulin sensitizer could lessen the risk of diabetes for women with a common endocrine disorder. Women with Premature Ovarian Failure Face Increased Risk of Cardiovascular Disease -- Hormone Therapy Lessens Risk During menopause, women experience endothelial dysfunction, which can lead to atherosclerosis. However, despite numerous studies on normal menopause and cardiovascular disease in women, little is known about the cardiovascular impact of ovarian failure in young women. New research shows that women who experience premature menopause (or premature ovarian failure) are at an increased risk for developing endothelial dysfunction. However, it appears that hormone therapy can lessen the cardiovascular risk for these women. Dr. Sophia Kalantaridou and researchers at the University of Ioannina Medical School in Greece assessed the endothelial function in 18 women before and after 6 months of hormone therapy (oral estrogen/progestogen cyclic treatment) and compared the results to a group of age and body-mass index matched premenopausal women. Endothelial function was assessed using a non- invasive ultrasound technique in the arteries of the arm. The researchers found that 6 months of hormone therapy restored endothelial function in women with premature ovarian failure. Also, as expected, following hormone therapy, lipid levels in the women with premature ovarian failure improved and were the same as in the control group. Also, flow mediated dilatation of the brachial artery, a measure of endothelial function, improved in women with premature ovarian failure. "We are seeing for the first time that endothelial dysfunction, which contributes to the development of atherosclerosis, begins very early in young women who experience premature ovarian failure," notes Dr. Kalantaridou. "Women who suffer from premature ovarian failure should be monitored for cardiovascular risk factors. At the same time, hormone therapy could help decrease the cardiovascular risk for these women. Additional studies are needed to determine the optimal hormone formulations, dosages and duration of treatment. " Metformin May Improve Vascular Function in Patients at High Risk for Diabetes Patients with impaired glucose tolerance (IGT) are at an increased risk for diabetes as well as cardiovascular disease. Endothelial dysfunction in people with IGT may contribute to these risks. Previous research has shown that metformin has a beneficial effect on cardiovascular risk factors in diabetic patients. However, it has been unknown whether these benefits would be seen in patients with IGT and whether the benefits are a result of metformin's impact on vascular function or its associated weight loss and reduction of hyperglycemia. Through a 16-week double-blind, randomized, placebo-controlled study, Dr. Aguilar-Salinas and researchers in Mexico sought to answer these questions. Markers of endothelial activation, inflammation and coagulation were measured in 55 patients with IGT before, during and after treatment with metformin. All subjects participated in a one-month stabilization period for diet and physical activity. Following this period, patients were randomized to receive either metformin (1000 mg twice daily) or a placebo. The Patients who received metformin experienced an improvement in several endothelial function markers, including weight, fasting plasma glucose, soluble intercellular adhesion molecule and soluble vascular cell adhesion molecule. "The results of our study provide new mechanistic insights regarding the vascular protective effect of metformin. Our findings indicate that metformin may have a direct beneficial effect on vascular function in patients with IGT," explains Dr. Aguilar-Salinas. "Additional studies are needed to confirm these findings and to further assess the effects of metformin on atherosclerosis." Insulin Sensitizer Proves Beneficial to Women with Common Endocrine Disorder Women with polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women, which is characterized by hyperandrogenism, infertility, the inability to ovulate and insulin resistance -- a pre-diabetes condition -- improve metabolic and reproductive function following treatment with the insulin sensitizer pioglitazone. The new findings could eventually offer a new therapy to the six to 10% of reproductive aged women who suffer from PCOS. A team of researchers at the University Hospital Basel in Basel, Switzerland, led by Drs. Christian De Geyter and U. Keller, randomly assigned forty patients with PCOS to either pioglitazone, a member of the thiazolidinediones class of drugs, or a placebo for three months to determine whether the pioglitazone diminishes hyperandrogenism and insulin resistance, which can lead to type 2 diabetes. The women treated with pioglitazone experienced a significant decline in their fasting serum insulin levels as well as an increase in insulin sensitivity and a decrease in insulin secretion. Pioglitazone treatment also resulted in a significant decrease in the free androgen index, follicle stimulating and luteinizing hormone levels. Finally, more than 41% of the women who took pioglitazone experienced normal ovulatory cycles compared with only 5.6% of the placebo group. "Our study indicates that pioglitazone may safely and effectively improve insulin resistance and ovulation rates in women with PCOS. These findings support the notion that insulin resistance and hyperinsulinemia play a pathogenic role in PCOS and that treatment with a thiazolidinedione, such as pioglitazone, improves the associated symptoms. Further studies are needed to evaluate the long-term role of thiazolidinediones in preventing the long-term complications of PCOS," says Dr. De Geyter. At present, thiazolidinediones can not be given to infertile women, because the effect of these compounds on the developing embryo has not yet been evaluated. SOURCE: The Endocrine Society

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