Cardiac Sciences Program, Winnipeg Regional Heath Authority, Winnipeg, Canada.
Division of Radiation Oncology, University of Manitoba, Winnipeg, Canada.
Br J Clin Pharmacol. 2021 Apr;87(4):1801-1813. doi: 10.1111/bcp.14568. Epub 2020 Nov 20.
Aldosterone has been found to influence cancer cell growth, cell cycle regulation and cell migration, including in prostate cancer cells. Spironolactone is an aldosterone antagonist used for managing chronic heart failure (HF) with known antiandrogenic effects. We examined the effect of spironolactone exposure amongst men with HF on the incidence of prostate cancer.
This retrospective cohort study utilized provincial clinical and administrative databases from the Manitoba Centre for Health Policy. Incident cases of prostate cancer were identified from the provincial cancer registry, and spironolactone exposure was quantified from pharmacare databases. A multivariable proportional hazards model was used to assess the time-dependent impact of spironolactone exposure on prostate cancer incidence.
A total of 18 562 men with newly diagnosed HF from 2007 to 2015 with a median age of 72 years (interquartile range: 61-81) and a median follow-up from HF diagnosis to prostate cancer incidence of 2.7 years (interquartile range: 1.1-4.9) were included. A time-dependent multivariable analysis of spironolactone exposure following HF diagnosis found a reduced the risk of prostate cancer hazard ratio 0.55 (95% confidence interval 0.31-0.98, P = .043).
Spironolactone exposure significantly reduced the incidence of prostate cancer amongst men with HF. These findings support the plausibility of aldosterone as a promoter of prostate cancer growth and development. Prospective clinical trials are warranted to further assess the role of spironolactone or other mineralocorticoid receptor antagonists as a means to prevent prostate cancer development or as an adjunctive measure to prostate cancer treatments.
醛固酮已被发现影响癌细胞的生长、细胞周期调控和细胞迁移,包括前列腺癌细胞。螺内酯是一种用于治疗慢性心力衰竭(HF)的醛固酮拮抗剂,具有已知的抗雄激素作用。我们研究了 HF 男性患者螺内酯暴露对前列腺癌发病率的影响。
本回顾性队列研究利用了马尼托巴省卫生政策中心的省级临床和行政数据库。前列腺癌的发病病例是从省级癌症登记处确定的,螺内酯的暴露情况是从药物保险数据库中量化的。使用多变量比例风险模型评估螺内酯暴露对前列腺癌发病率的时间依赖性影响。
共纳入了 18562 名 2007 年至 2015 年新诊断为 HF 的男性患者,中位年龄为 72 岁(四分位距:61-81),从 HF 诊断到前列腺癌发病的中位随访时间为 2.7 年(四分位距:1.1-4.9)。HF 诊断后螺内酯暴露的时间依赖性多变量分析发现,前列腺癌的风险比降低了 0.55(95%置信区间 0.31-0.98,P =.043)。
HF 男性患者螺内酯暴露显著降低了前列腺癌的发病率。这些发现支持了醛固酮作为促进前列腺癌生长和发展的可能性。需要进行前瞻性临床试验,以进一步评估螺内酯或其他盐皮质激素受体拮抗剂作为预防前列腺癌发展的手段,或作为前列腺癌治疗的辅助措施。