Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer.
Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer.
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DOI：
10.5534/wjmh.200109
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发表时间：
2021-07
期刊：
影响因子：
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通讯作者：
Maggi M
中科院分区：
文献类型：
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作者：
Corona G;Filippi S;Bianchi N;Dicuio M;Rastrelli G;Concetti S;Sforza A;Maggi M
雄激素剥夺治疗（ADT）是局部晚期或转移性前列腺癌（PC）患者的金标准治疗。新出现的证据已经证明ADT与身体成分之间存在密切联系，沿着代谢特征受损。这些变化可能是观察到的ADT相关心血管（CV）和血栓栓塞（静脉血栓栓塞，VTE）死亡率和发病率增加的基础。然而，这些协会的具体机制尚未完全阐明。在本综述中，我们总结并讨论了ADT与心脏代谢风险增加相关的现有证据，使用临床前和临床数据。如果可能，首选荟萃分析研究。使用促性腺激素释放激素类似物诱导的性腺功能减退症的兔模型的临床前证据表明，诱导的病症与内脏肥胖的急剧增加和乙酰胆碱诱导的血管舒张的受损相关，沿着脂肪肝倾向的增加。这表明ADT在诱导代谢特征恶化方面具有直接作用。相反，现有的临床数据不足以阐明睾酮（T）减少和代谢改变之间的直接致病联系。事实上，尽管T剥夺与代谢改变相关，但ADT与CV或VTE风险之间的相关性可能只是选择偏倚的结果，与晚期PC患者的健康状况较差有关。尽管有上述考虑，所有ADT候选患者应在基线时筛查CV风险因素，并在治疗期间进行监测。强烈鼓励改变生活方式和进行体育锻炼。
Androgen deprivation therapy (ADT) is the gold standard treatment in patients with locally advanced or metastatic prostate cancer (PC). Emerging evidence has documented a tight association between ADT and body composition, along with metabolic profile impairment. These alterations might underpin the observed ADT-related increase in cardiovascular (CV) and thromboembolic (venous thromboembolism, VTE) mortality and morbidity. However, the specific mechanisms underlying these associations have not yet been completely elucidated. In the present review we summarize and discussed the available evidence linking ADT to increased cardio-metabolic risk, using both preclinical and clinical data. When possible, meta-analytic studies were preferred. Preclinical evidence, using a rabbit model of gonadotrophin-releasing hormone analogue-induced hypogonadism, indicates that the induced condition is associated with a dramatic increase in visceral adiposity and with an impairment of acetylcholine induced vascular relaxation, along with an increased propensity towards fatty liver. This suggests a direct role of ADT in inducing a worsened metabolic profile. In contrast, available clinical data are not sufficient to clarify a direct pathogeniclink between reduced testosterone (T) and altered metabolism. In fact, although T deprivation is associated with an altered metabolism, it is possible that the association between ADT and CV or VTE risk could simply be the result of a selection bias, related to the poor health status of patients with advanced PC. Despite the aforementioned considerations, all patients who are candidatesfor ADT should be screened for CV risk factors at baseline and monitored during the therapy. Life-style modifications and physical exercise are strongly encouraged.