Background
Despite the obvious benefits of this treatment, there is controversy regarding its application. Clinical trials indicate that the risk of venous thromboembolism (clotting of the veins) is about two to three times higher among current users of oral hormone replacement therapy containing estradiol, conjugated equine estrogen, and selective estrogen receptor modulators (SERMs) than among women who are not using hormone replacement therapy. (Conjugated equine estrogen (Premarin) contains 50-65 percent estrone sodium sulfate and 20-35 percent sodium equilin sulfate. Raloxifene is a synthetic estrogenic compound approved for clinical use in humans for prevention of osteoporosis.)
Many factors contribute to venous thrombosis including changes in the veins themselves, decreases in blood flow and increases in coagulation of the blood. Estrogen replacement drugs are known to alter coagulation, but little is known about affects on veins.
Veins are composed on a cell lining called endothelium and smooth muscle which contracts and relaxes resulting in changes in diameter of the veins. These changes in diameter are regulated by chemicals released from the endothelium and the direct action of other chemicals on the smooth muscle. Platelets are fragments of cells in the blood, which participate in formation blood clots. When activated, platelets release chemicals, which also stimulate the endothelium and smooth muscle. Platelets, endothelium and smooth muscle contain receptors that are stimulated by different estrogen-related compounds. But it is not known how stimulation of these receptors by different compounds changes the functions of veins. Experiments were designed to answer this question.
Study
Adult female pigs had their ovaries removed and then were either untreated or treated with either Premarin or raloxifene for four weeks. At this time the femoral veins were removed for study. “Hormone Replacement and Function of Veins" is the subject of a study recently conducted by Murat Avsar, Ph.D., and Virginia Miller, Ph.D., both from the Mayo Clinic, Rochester, Mn. Their findings, are being presented at the American Physiological Society (APS) conference, Genomes and Hormones: An Integrative Approach to Gender Differences in Physiology, sponsored by October 17-20, 2001, at the Westin Convention Center, Pittsburgh, Pa.
Results
Both types of hormone replacement modified responses of veins. However, the way the responses of veins were modified was different for the Premarin and raloxifene treated animals. For example, veins from raloxifene-treated pigs contracted more than veins from pigs treated with Premarin. In addition, relaxations to substances released from platelets had a greater affect on the smooth muscle from veins of raloxifene treated pigs. Production of contractile factors from the endothelium were also modified differently by the treatments with more endothelium-derived contractile factors being produced in endothelium of veins from untreated-ovariectomized pigs and from raloxifen treated pigs.
Conclusions
Therefore, although both raloxifene and Premarin treatments increase risk of venous thrombosis, it is likely that they do so by altering different cellular processes in veins.
The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.
Contact: Donna Krupa
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