Beitzen-Heineke Antonia, Wise David R, Berger Jeffrey S
Department of Medicine, New York University Grossman School of Medicine, 530 First Avenue, Skirball 9R, New York, NY, 10016, USA.
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Cardiooncology. 2024 Dec 5;10(1):87. doi: 10.1186/s40959-024-00278-2.
Androgen deprivation therapy (ADT), a key element of prostate cancer treatment, is associated with increased risk for cardiovascular morbidity and mortality. The underlying mechanisms include adverse metabolic alterations, but further mechanisms are likely. Animal studies suggest increased progression of atherosclerosis in androgen deprived conditions. Based on in vitro studies, lack of androgens may modulate immune cells including monocytes, macrophages, and T-cells towards a pro-inflammatory phenotype and pro-atherogenic function. As a novel aspect, this review summarizes existing data on the effect of androgens and androgen deprivation on platelet activity, which play a major role in inflammation and in the initiation and progression of atherosclerotic lesions. Testosterone modulates platelet aggregation responses which are affected by dose level, source of androgen, and age. Data on the effects of ADT on platelet activity and aggregation are limited and conflicting, as both increased and decreased aggregation responses during ADT have been reported. Gaps in knowledge about the mechanisms leading to increased cardiovascular risk during ADT remain and further research is warranted. Improved understanding of pathogenic pathways linking ADT to cardiovascular risk may help identify clinically useful diagnostic and prognostic biomarkers, and accelerate finding novel therapeutic targets, and thus optimize prostate cancer treatment outcomes.
雄激素剥夺疗法（ADT）是前列腺癌治疗的关键要素，与心血管疾病发病率和死亡率增加相关。其潜在机制包括不良代谢改变，但可能还存在其他机制。动物研究表明，在雄激素缺乏的情况下动脉粥样硬化进展加快。基于体外研究，雄激素缺乏可能使包括单核细胞、巨噬细胞和T细胞在内的免疫细胞向促炎表型和促动脉粥样硬化功能转变。作为一个新的方面，本综述总结了关于雄激素和雄激素剥夺对血小板活性影响的现有数据，血小板在炎症以及动脉粥样硬化病变的发生和发展中起主要作用。睾酮可调节血小板聚集反应，这受剂量水平、雄激素来源和年龄的影响。关于ADT对血小板活性和聚集影响的数据有限且相互矛盾，因为有报道称ADT期间血小板聚集反应既有增加也有减少。ADT期间导致心血管风险增加的机制方面仍存在知识空白，有必要进一步研究。更好地理解将ADT与心血管风险联系起来的致病途径，可能有助于识别临床上有用的诊断和预后生物标志物，并加速寻找新的治疗靶点，从而优化前列腺癌的治疗效果。
