雄激素剥夺治疗期间的糖尿病和心血管疾病：前列腺癌退伍军人的观察性研究。
Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer.
机构信息
Division of General Internal Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
出版信息
J Natl Cancer Inst. 2010 Jan 6;102(1):39-46. doi: 10.1093/jnci/djp404. Epub 2009 Dec 7.
BACKGROUND
Previous studies indicate that androgen deprivation therapy for prostate cancer is associated with diabetes and cardiovascular disease among older men. We evaluated the relationship between androgen deprivation therapy and incident diabetes and cardiovascular disease in men of all ages with prostate cancer.
METHODS
We conducted an observational study of 37,443 population-based men who were diagnosed with local or regional prostate cancer in the Veterans Healthcare Administration from January 1, 2001, through December 31, 2004, with follow-up through December 31, 2005. Cox proportional hazards models were used to assess whether androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) agonists, oral antiandrogens, the combination of the two (ie, combined androgen blockade), or orchiectomy was associated with diabetes, coronary heart disease, myocardial infarction, sudden cardiac death, or stroke, after adjustment for patient and tumor characteristics. All statistical tests were two-sided.
RESULTS
Overall, 14,597 (39%) of the 37,443 patients were treated with androgen deprivation therapy. Treatment with GnRH agonists was associated with statistically significantly increased risks of incident diabetes (for GnRH agonist therapy, 159.4 events per 1000 person-years vs 87.5 events for no androgen deprivation therapy, difference = 71.9, 95% confidence interval [CI] = 71.6 to 72.2; adjusted hazard ratio [aHR] = 1.28, 95% CI = 1.19 to 1.38), incident coronary heart disease (aHR = 1.19, 95% CI = 1.10 to 1.28), myocardial infarction (12.8 events per 1000 person-years for GnRH agonist therapy vs 7.3 for no androgen deprivation therapy, difference = 5.5, 95% CI = 5.4 to 5.6; aHR = 1.28, 95% CI = 1.08 to 1.52), sudden cardiac death (aHR = 1.35, 95% CI = 1.18 to 1.54), and stroke (aHR = 1.22, 95% CI = 1.10 to 1.36). Combined androgen blockade was statistically significantly associated with an increased risk of incident coronary heart disease (aHR = 1.27, 95% CI = 1.05 to 1.53), and orchiectomy was associated with coronary heart disease (aHR = 1.40, 95% CI = 1.04 to 1.87) and myocardial infarction (aHR = 2.11, 95% CI = 1.27 to 3.50). Oral antiandrogen monotherapy was not associated with any outcome studied.
CONCLUSION
Androgen deprivation therapy with GnRH agonists was associated with an increased risk of diabetes and cardiovascular disease.
背景
之前的研究表明，前列腺癌的雄激素剥夺疗法与老年男性的糖尿病和心血管疾病有关。我们评估了雄激素剥夺疗法与所有年龄段患有前列腺癌男性的糖尿病和心血管疾病发病风险之间的关系。
方法
我们对 2001 年 1 月 1 日至 2004 年 12 月 31 日期间在退伍军人医疗保健管理局接受局部或区域性前列腺癌诊断的 37443 名基于人群的男性进行了一项观察性研究，随访至 2005 年 12 月 31 日。使用 Cox 比例风险模型评估使用促性腺激素释放激素（GnRH）激动剂、口服抗雄激素、两者的组合（即联合雄激素阻断）或睾丸切除术进行雄激素剥夺治疗是否与糖尿病、冠心病、心肌梗死、心源性猝死或中风相关，同时调整了患者和肿瘤特征。所有统计检验均为双侧检验。
结果
总体而言，37443 名患者中有 14597 名（39%）接受了雄激素剥夺治疗。使用 GnRH 激动剂治疗与糖尿病发病风险显著增加相关（对于 GnRH 激动剂治疗，每 1000 人年发生 159.4 例事件，而无雄激素剥夺治疗为 87.5 例，差异=71.9，95%置信区间[CI] = 71.6 至 72.2；调整后的危险比[aHR] = 1.28，95%CI = 1.19 至 1.38）、冠心病（aHR = 1.19，95%CI = 1.10 至 1.28）、心肌梗死（每 1000 人年发生 12.8 例事件 GnRH 激动剂治疗与无雄激素剥夺治疗的 7.3 例，差异=5.5，95%CI = 5.4 至 5.6；aHR = 1.28，95%CI = 1.08 至 1.52）、心源性猝死（aHR = 1.35，95%CI = 1.18 至 1.54）和中风（aHR = 1.22，95%CI = 1.10 至 1.36）。联合雄激素阻断与冠心病发病风险增加显著相关（aHR = 1.27，95%CI = 1.05 至 1.53），而睾丸切除术与冠心病（aHR = 1.40，95%CI = 1.04 至 1.87）和心肌梗死（aHR = 2.11，95%CI = 1.27 至 3.50）相关。单独使用口服抗雄激素治疗与任何研究结果均无关。
结论
使用 GnRH 激动剂的雄激素剥夺疗法与糖尿病和心血管疾病风险增加相关。
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