madman
Super Moderator
Abstract
Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Testosterone (T) is an important sex hormone that triggers several genomic and non-genomic pathways, leading to improvements of several cardiovascular risk factors and quality of life in men. At the vascular level, the key effect of T is the vasorelaxation. This review discusses the molecular pathways and clinical implications of T in the vascular system. Firstly, the mechanisms involved in the T vasodilator effect will be presented. Then, it will be discussed the association of T with the main risks for CVD, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia and hypertension. Several studies have shown a correlation between low T levels and an increased prevalence of several CVD. These observations suggest that T has beneficial effects on the cardiovascular system and that testosterone replacement therapy may become a therapeutic reality for some of these disorders
Conclusions and Future Directions
Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. The knowledge about the vascular effects of testosterone (T) is crucial to understand its clinical implications and may lead to new therapeutic targets in the future. Studies performed over the years agree that T is an important sex hormone that triggers several genomic and non-genomic pathways, leading to improvements of several cardiovascular risk factors and quality of life in men, contrary to what had been suggested at first instance. T presents genomic and nongenomic actions at the vascular level, and both effects may overlap, which makes it difficult to define the broad vascular effects of androgens. However, the key T effect at the vascular level is the vasorelaxation, a non-genomic action (rapid effect).
Several studies have established a relationship between the low levels of T and an increase in the CVD prevalence, which seems to be mainly linked to the nongenomic actions of T, namely vasorelaxation. This effect involves several mechanisms including the nuclear receptor activation, the influence of vascular endothelium and the activation or blocking of ion channels. So, the vasodilator mechanisms of T are crucial to understanding the relationship between the risk factors for CVD and this sex hormone.
Several clinical and epidemiological studies observed that men with type 2 diabetes mellitus, obesity, metabolic syndrome, atherosclerosis, dyslipidaemia, and higher blood pressure had lower levels of T, suggesting a beneficial role of T on the cardiovascular system. Therefore, testosterone replacement therapy (TRT) could be a solution to improve these CVD risk factors. However, this issue has been the subject of controversy, as recent studies suggest that TRT is associated with an increase of CVD. Concerning type 2 diabetes mellitus and metabolic syndrome, most of the studies showed an association with low levels of T and that TRT improves these risk factors in men with hypogonadism. Regarding atherosclerosis and dyslipidaemia, low levels of T were also associated with an improvement of some parameters of these risk factors. Moreover, TRT seems to induce a more favourable lipid profile, contributing to increased protection for the development or progression of atherosclerosis. Regarding the association between T and blood pressure, few studies have been performed, but it seems that T is beneficial to diastolic and systolic blood pressure as well as the resting heart rate. Furthermore, excess or insufficient androgen production during pregnancy may trigger the development of preeclampsia or gestational hypertension. These studies also indicate that the administration of androgens in hypertensive pregnant women is a near possibility. Nevertheless, further clinical studies are needed.
In sum, the vascular effects of testosterone have clinical implications. However, a consensus on the T effects or the risks associated with TRT on the cardiovascular system needs to be established. Considering the overlap between both genomic and non-genomic effects, and even a possible divergence in the effects of both actions, it is evidenced that a better understanding of the vascular mechanisms of testosterone is crucial. Only then their clinical implications will be correctly established and the development of new therapeutic targets for cardiovascular diseases can be discovered.
Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Testosterone (T) is an important sex hormone that triggers several genomic and non-genomic pathways, leading to improvements of several cardiovascular risk factors and quality of life in men. At the vascular level, the key effect of T is the vasorelaxation. This review discusses the molecular pathways and clinical implications of T in the vascular system. Firstly, the mechanisms involved in the T vasodilator effect will be presented. Then, it will be discussed the association of T with the main risks for CVD, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia and hypertension. Several studies have shown a correlation between low T levels and an increased prevalence of several CVD. These observations suggest that T has beneficial effects on the cardiovascular system and that testosterone replacement therapy may become a therapeutic reality for some of these disorders
Conclusions and Future Directions
Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. The knowledge about the vascular effects of testosterone (T) is crucial to understand its clinical implications and may lead to new therapeutic targets in the future. Studies performed over the years agree that T is an important sex hormone that triggers several genomic and non-genomic pathways, leading to improvements of several cardiovascular risk factors and quality of life in men, contrary to what had been suggested at first instance. T presents genomic and nongenomic actions at the vascular level, and both effects may overlap, which makes it difficult to define the broad vascular effects of androgens. However, the key T effect at the vascular level is the vasorelaxation, a non-genomic action (rapid effect).
Several studies have established a relationship between the low levels of T and an increase in the CVD prevalence, which seems to be mainly linked to the nongenomic actions of T, namely vasorelaxation. This effect involves several mechanisms including the nuclear receptor activation, the influence of vascular endothelium and the activation or blocking of ion channels. So, the vasodilator mechanisms of T are crucial to understanding the relationship between the risk factors for CVD and this sex hormone.
Several clinical and epidemiological studies observed that men with type 2 diabetes mellitus, obesity, metabolic syndrome, atherosclerosis, dyslipidaemia, and higher blood pressure had lower levels of T, suggesting a beneficial role of T on the cardiovascular system. Therefore, testosterone replacement therapy (TRT) could be a solution to improve these CVD risk factors. However, this issue has been the subject of controversy, as recent studies suggest that TRT is associated with an increase of CVD. Concerning type 2 diabetes mellitus and metabolic syndrome, most of the studies showed an association with low levels of T and that TRT improves these risk factors in men with hypogonadism. Regarding atherosclerosis and dyslipidaemia, low levels of T were also associated with an improvement of some parameters of these risk factors. Moreover, TRT seems to induce a more favourable lipid profile, contributing to increased protection for the development or progression of atherosclerosis. Regarding the association between T and blood pressure, few studies have been performed, but it seems that T is beneficial to diastolic and systolic blood pressure as well as the resting heart rate. Furthermore, excess or insufficient androgen production during pregnancy may trigger the development of preeclampsia or gestational hypertension. These studies also indicate that the administration of androgens in hypertensive pregnant women is a near possibility. Nevertheless, further clinical studies are needed.
In sum, the vascular effects of testosterone have clinical implications. However, a consensus on the T effects or the risks associated with TRT on the cardiovascular system needs to be established. Considering the overlap between both genomic and non-genomic effects, and even a possible divergence in the effects of both actions, it is evidenced that a better understanding of the vascular mechanisms of testosterone is crucial. Only then their clinical implications will be correctly established and the development of new therapeutic targets for cardiovascular diseases can be discovered.
Last edited:
