Haemostasis Evaluation Related to Sexual Hormones: Gender Perspective

Atherothrombotic disorders account for 25% of all deaths among women and for substantial morbidity and resource use in health care. Nonetheless, gender-related differences in the epidemiology of cardiovascular disease (CVD) remain largely unexplained. Thus, the application of sex-gender medicine is strongly recommended by WHO and other international organization. In fact, it is emerging that although men and women are subject to the same cardiovascular diseases (CVD), however, they have different risk factors, disease progression and response to drug treatment.

In the last decades emerging scientific knowledge about platelet role in the atherothrombotic diseases physiopathology provides clues and asks questions about the possibility that a different platelet function modulation could influence the women population cardiovascular disease clinical course, especially considering that, compared to men population, the women one recognizes a worst cardiovascular outcome.

It is widely acknowledged that platelet reactivity plays a pivotal role in thrombus formation and atherosclerosis. Differences in platelet reactivity between women and men have been described using several methods and in response to varying stimuli. In particular, platelets from women without vascular diseases are more reactive than those of men in response to standard concentrations of agonists such as adenosine diphosphate (ADP) and thrombin receptor agonist protein. Mechanisms that could account for such differences are on investigation. Indeed, sex steroid hormones could be involved as they exert multiple direct and indirect effects on cardiovascular physiology. The pleiotropic effects of estradiol-17 (E2) and estrogen receptors (ERs), a part of thei pivotal role in sexual development and reproduction,are a consequence of both the widespread expression of ER in many cell populations within the body as well as possibly reflecting the ancestral status of ER in the steroid receptor family.

Epidemiologic and experimental studies now support an atheroprotective effect of both endogenous and exogenous estrogens. The Women's Health Initiative study did not show a coronary protective effect of estrogen in postmenopausal women, but subsequent studies have shown that this was because of both inappropriate timing (ie, administering the hormone therapy too late) and the identity of the associated progestin.

Physiologic differences between men and women affect also drug activity, including pharmacokinetics and pharmacodynamics. Women are underrepresented in cardiovascular studies, even as their preponderance in the aging population steadily increases. A better understanding of the factors contributing to the observed sex-related differences in platelet biology is warranted. In particular concerns have been raised about the role of specific hormones in mediating platelet activation and function and the differential benefit of antiplatelet medications for women.