Abstract
The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no ex vivo studies suggest that circulating androgen levels influence the activation and reactivity of blood platelets – one of the main components of the haemostasis system directly involved in atherosclerosis. The levels of testosterone, dihydrotestosterone and oestradiol in plasma from men and women aged from 60 to 65 years were measured by LC-MS; the aim was to identify any potential relationships between sex steroid levels and the markers of platelet activation (surface membrane expression of GPII/IIIa complex and P-selectin) and platelet reactivity in response to arachidonate, collagen or ADP, monitored with whole blood aggregometry and flow cytometry. The results of the ex vivo part of the study indicate that the concentrations of testosterone and its reduced form, dihydrotestosterone are significantly negatively associated with platelet activation and reactivity. These observations were confirmed in an in vitro model: testosterone and dihydrotestosterone significantly inhibited platelet aggregation triggered by arachidonate or collagen. Our findings indicate that testosterone and dihydrotestosterone are significant haemostatic steroids with inhibitory action on blood platelets in older people.
Highlights
IntroductionThe risk of cardiovascular events increases with age, and this is paralleled by the declined levels of circulating T in aging men
Testosterone (T) has recently been identified as a cardiovascular hormone, in addition to its basic role in the regulation of male reproduction [1, 2].The risk of cardiovascular events increases with age, and this is paralleled by the declined levels of circulating T in aging men
The subpopulation of men suffering from type 2 diabetes mellitus and/or obesity, which are widely recognized as factors perpetuating atherosclerosis, exhibit decreased levels of T, which is associated with the severity of hyperglycaemia and obesity [5]
Summary
The risk of cardiovascular events increases with age, and this is paralleled by the declined levels of circulating T in aging men This decline is observed only in the part of the elderly male population and is not as common as widely believed [3]. Some men undergoing androgen deprivation therapy due to prostate cancer present an increased risk of impaired glucose and/or lipid metabolism, often contributing to cardiovascular ischaemic events [4]. This implies that T may be somehow involved in carbohydrate and lipid metabolism and may indirectly contribute to the ongoing onset of atherogenesis. The subpopulation of men suffering from type 2 diabetes mellitus and/or obesity, which are widely recognized as factors perpetuating atherosclerosis, exhibit decreased levels of T, which is associated with the severity of hyperglycaemia and obesity [5]
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