Issues In Cardiovascular NursingSex differences and the effects of sex hormones on hemostasis and vascular reactivity*,**
Section snippets
Limitations associated with studies examining the influence of sex hormones on gender differences in hemostasis and vascular reactivity
Because physiological systems that regulate hemostasis and vascular reactivity are extremely complex and have multiple components, and because this is a relatively new area of investigation, the results of mechanistic studies can be variable or even contradictory. Therefore, researchers have taken a reductionistic approach by examining underlying mechanisms of sex differences and the role of sex hormones in vascular function in in vitro systems. Such models include isolated heart or vascular
Sex steroid hormone signal transduction
Signal transduction refers to the cascade of biochemical and biophysical events by which a chemical signal, such as a hormone, transfers information into a cell to elicit a response. Sex hormones can acutely alter cell function, promote cellular differentiation, and in some cases, stimulate cell proliferation. Sex hormones elicit a cellular response by way of 2 general signaling pathways. The better known traditional, or genomic, pathway involves binding of a sex hormone to an intra cellular
The function of the endothelium in regulation of hemostasis and vascular reactivity
Vascular endothelial cells play an extremely important role in regulating hemostasis and vascular reactivity (Fig 2).
Hemostasis
Hemostasis, the cessation of blood flow, occurs by several processes including vasoconstriction, platelet activation, and stimulation of the coagulation cascade. Activation of these processes results in thrombus formation. As thrombogenesis occurs, the fibrinolytic system is simultaneously activated to localize the clot and prevent its extension throughout the vessel. Under physiologic conditions, the endothelial cell surface is positively charged and nonthrombogenic and hemostatic and
Sex differences in platelet activity
Studies in humans have revealed differences between men and women in numbers of platelets, extent of platelet adherence to the vessel wall, and platelet activation and aggregation. Bain50 found that women of several ethnic backgrounds have higher platelet counts than their male counterparts. In contrast, Lawrence et al51 found that premenopausal women tended to have lower platelet counts than age-matched men. The difference however, was not significant. Faraday et al52 found that the number of
Sex differences in coagulation and fibrinolysis
Overall hemostasis is dependent on the balance between platelet activation, coagulation, and fibrinolysis. Differences in platelet activation, as well as sex differences between premenopausal women and men of similar age, have been found in coagulation and fibrinolysis. It has also been demonstrated that estrogen and testosterone exert modulating effects on these systems. For example, premenopausal women have been found to have higher fibrinogen levels than men,51, 75 women aged 25 to 44 years
Effects of sex hormone treatment on hemostatic parameters in transsexuals
Studies of sex hormone supplementation in male-to-female or female-to-male transsexuals provide insight into the effects of estrogens and androgens on hemostasis. In one study,91 13 male-to-female transsexuals received cyproterone acetate (an androgen antagonist) and oral ethinyl estradiol. Ten female-to-male transsexuals received testosterone ester injections every 2 weeks. After 4 months of treatment, hemostatic factors and other parameters were compared with baseline values. Before hormonal
Molecular mechanisms
A rational approach to seeking molecular mechanisms for sex differences in hemostasis would be to determine whether genes coding for proteins involved in hemostasis are regulated by sex hormones. Several genes for proteins involved in coagulation, fibrinolysis, and platelet activity have been shown to be regulated by sex hormones or are candidates for regulation by sex hormones. Protein products of estrogen-regulated genes that are associated with platelet activity include: prostacyclin
Endothelium-dependent and independent vascular reactivity
Vascular reactivity refers to the responsiveness of blood vessels to vasodilator and vasoconstrictor signals. Vascular tone is determined by the sum influence of these signals. Basal blood pressure is primarily regulated by vascular tone and thereby vascular reactivity.109 Vessel wall cells that contribute to regulation of vascular tone are VSMCs and endothelial cells. As alluded to previously, signal molecules can mediate vascular tone by direct effects on VSMCs (endothelium-independent) or by
Summary
The risk of coronary artery disease is significantly lower in premenopausal women compared with men of similar age.189, 190 The pathophysiologic basis of coronary artery disease involves the accumulation of cholesterol-rich low-density lipoproteins in the vascular wall, immune responses, and eventual formation of atherosclerotic plaque. The effect of sex hormones (especially the beneficial effect of estrogen) on lipoprotein metabolism and subsequent effect on development of coronary
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Supported by a grant from the Ralph and Marian Falk Medical Research Trust.
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Reprint requests: Dorie W. Schwertz, PhD, RN, FAAN, Associate Professor, Medical Surgical Nursing and Pharmacology, University of Illinois m/c 802, College of Nursing and College of Medicine, 845 S Damen Ave, Chicago, IL 60612.