madman
Super Moderator
The review discusses the growing concern about cardiovascular complications arising from androgen deprivation therapy (ADT) for prostate cancer patients. These complications are not solely due to androgen suppression, as specific types of ADT lead to distinct cardiovascular issues. The purpose of the review is to comprehensively grasp the biological and clinical effects of ADT on the cardiovascular system. Recent findings reveal that GnRH agonists are linked to more cardiovascular events compared to GnRH antagonists. Androgen receptor antagonists elevate the risk of conditions like long QT syndrome, torsades de pointes, and sudden cardiac death. Androgen synthesis inhibitors increase the likelihood of hypertension, atrial tachyarrhythmia, and in rare cases, heart failure. Overall, ADT heightens the risk of cardiovascular diseases, but the risk varies among different ADT drugs. Therefore, a careful evaluation is crucial to devise an optimal treatment plan for prostate cancer patients.
Key Takeaways:
*Historically, testosterone was thought to increase cardiovascular disease (CVD) risk, with men being more susceptible to CVD than women. However, this sex difference diminishes after menopause due to estrogen's cardioprotective role.
*The impact of testosterone on cardiovascular health is still debated. Some retrospective studies suggest supplemental testosterone could elevate CV event risk, while low endogenous testosterone might also increase CVD risk with negative metabolic effects.
Recent literature suggests protective effects of testosterone on the cardiovascular system:
*Vascular Impact: Testosterone plays roles linked to reduced CV risk and cardioprotection. It affects endothelial progenitor cells (EPCs) critical for vascular healing and maintains vascular integrity. Testosterone enhances nitric oxide synthesis, promoting vasorelaxation, and other androgens stimulate endothelial cell proliferation and angiogenesis.
*Myocardial Impact: Testosterone enhances the beneficial effects of alpha1-adrenergic receptor stimulation, providing cardioprotection in ischemic heart disease. This includes reduced myocardial injury, arrhythmias, and improved contractile recovery. Androgen receptor blockade diminishes these effects, suggesting an androgen receptor-mediated mechanism. Testosterone also positively influences cardiomyocyte AMP-activated protein kinase (AMPK), mitochondrial function, insulin sensitivity, and glucose uptake, improving myocardial energetics.
*Cardiac Action Potential and Ca2+ Regulation: Testosterone regulates cardiac action potentials and Ca2+ homeostasis. It affects L-type Ca2+ channels, influencing cardiac contractility and action potential duration.
*Physiological levels of androgens seem to have protective effects on the cardiovascular system. Low endogenous testosterone might increase the risk of adverse CV events.
*Male hypogonadism, characterized by testosterone deficiency (TD), is associated with various cardiovascular risk factors like hyperlipidemia, adiposity, insulin resistance, type 2 diabetes, hypertension, atherosclerosis, CVD, and mortality.
*The benefits of testosterone replacement therapy (TRT) for hypogonadism are debated, with some studies suggesting benefits and others indicating no significant benefit or potential increased risk.
*Discrepancies in TRT studies could result from varying doses and resultant serum testosterone concentrations.
*While total endogenous testosterone levels appear inversely associated with CV risk, the optimal strategy for replacing serum testosterone needs further clarification.
In summary, Androgen Deprivation Therapy (ADT) has played a crucial role in reducing mortality rates among prostate cancer (PCa) patients by disrupting the endocrine system's feedback loop that regulates hormone production. However, the substantial cardiovascular risks associated with long-term ADT use must be addressed. The potential cardioprotective effects of androgens on heart health are only partially understood, necessitating further research to comprehend how ADTs contribute to cardiovascular disease (CVD). Future studies could employ gene expression and bioinformatic analysis to uncover how different ADTs modulate genes in the cardiovascular system. This insight would enable personalized medicine approaches, tailoring treatment to individual patients and paving the way for the future of cancer therapy and managing CV complications.
Key Takeaways:
*Historically, testosterone was thought to increase cardiovascular disease (CVD) risk, with men being more susceptible to CVD than women. However, this sex difference diminishes after menopause due to estrogen's cardioprotective role.
*The impact of testosterone on cardiovascular health is still debated. Some retrospective studies suggest supplemental testosterone could elevate CV event risk, while low endogenous testosterone might also increase CVD risk with negative metabolic effects.
Recent literature suggests protective effects of testosterone on the cardiovascular system:
*Vascular Impact: Testosterone plays roles linked to reduced CV risk and cardioprotection. It affects endothelial progenitor cells (EPCs) critical for vascular healing and maintains vascular integrity. Testosterone enhances nitric oxide synthesis, promoting vasorelaxation, and other androgens stimulate endothelial cell proliferation and angiogenesis.
*Myocardial Impact: Testosterone enhances the beneficial effects of alpha1-adrenergic receptor stimulation, providing cardioprotection in ischemic heart disease. This includes reduced myocardial injury, arrhythmias, and improved contractile recovery. Androgen receptor blockade diminishes these effects, suggesting an androgen receptor-mediated mechanism. Testosterone also positively influences cardiomyocyte AMP-activated protein kinase (AMPK), mitochondrial function, insulin sensitivity, and glucose uptake, improving myocardial energetics.
*Cardiac Action Potential and Ca2+ Regulation: Testosterone regulates cardiac action potentials and Ca2+ homeostasis. It affects L-type Ca2+ channels, influencing cardiac contractility and action potential duration.
*Physiological levels of androgens seem to have protective effects on the cardiovascular system. Low endogenous testosterone might increase the risk of adverse CV events.
*Male hypogonadism, characterized by testosterone deficiency (TD), is associated with various cardiovascular risk factors like hyperlipidemia, adiposity, insulin resistance, type 2 diabetes, hypertension, atherosclerosis, CVD, and mortality.
*The benefits of testosterone replacement therapy (TRT) for hypogonadism are debated, with some studies suggesting benefits and others indicating no significant benefit or potential increased risk.
*Discrepancies in TRT studies could result from varying doses and resultant serum testosterone concentrations.
*While total endogenous testosterone levels appear inversely associated with CV risk, the optimal strategy for replacing serum testosterone needs further clarification.
In summary, Androgen Deprivation Therapy (ADT) has played a crucial role in reducing mortality rates among prostate cancer (PCa) patients by disrupting the endocrine system's feedback loop that regulates hormone production. However, the substantial cardiovascular risks associated with long-term ADT use must be addressed. The potential cardioprotective effects of androgens on heart health are only partially understood, necessitating further research to comprehend how ADTs contribute to cardiovascular disease (CVD). Future studies could employ gene expression and bioinformatic analysis to uncover how different ADTs modulate genes in the cardiovascular system. This insight would enable personalized medicine approaches, tailoring treatment to individual patients and paving the way for the future of cancer therapy and managing CV complications.
