Keating Nancy L, O'Malley A James, Smith Matthew R
Division of General Internal Medicine, Department of Medicine, Brigham and Women's Hospital, USA.
J Clin Oncol. 2006 Sep 20;24(27):4448-56. doi: 10.1200/JCO.2006.06.2497.
Androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist is associated with increased fat mass and insulin resistance in men with prostate cancer, but the risk of obesity-related disease during treatment has not been well studied. We assessed whether androgen deprivation therapy is associated with an increased incidence of diabetes and cardiovascular disease.
Observational study of a population-based cohort of 73,196 fee-for-service Medicare enrollees age 66 years or older who were diagnosed with locoregional prostate cancer during 1992 to 1999 and observed through 2001. We used Cox proportional hazards models to assess whether treatment with GnRH agonists or orchiectomy was associated with diabetes, coronary heart disease, myocardial infarction, and sudden cardiac death.
More than one third of men received a GnRH agonist during follow-up. GnRH agonist use was associated with increased risk of incident diabetes (adjusted hazard ratio [HR], 1.44; P < .001), coronary heart disease (adjusted HR, 1.16; P < .001), myocardial infarction (adjusted HR, 1.11; P = .03), and sudden cardiac death (adjusted HR, 1.16; P = .004). Men treated with orchiectomy were more likely to develop diabetes (adjusted HR, 1.34; P < .001) but not coronary heart disease, myocardial infarction, or sudden cardiac death (all P > .20).
GnRH agonist treatment for men with locoregional prostate cancer may be associated with an increased risk of incident diabetes and cardiovascular disease. The benefits of GnRH agonist treatment should be weighed against these potential risks. Additional research is needed to identify populations of men at highest risk of treatment-related complications and to develop strategies to prevent treatment-related diabetes and cardiovascular disease.
使用促性腺激素释放激素（GnRH）激动剂进行雄激素剥夺治疗与前列腺癌男性患者脂肪量增加和胰岛素抵抗有关，但治疗期间肥胖相关疾病的风险尚未得到充分研究。我们评估了雄激素剥夺治疗是否与糖尿病和心血管疾病发病率增加有关。
对一个基于人群的队列进行观察性研究，该队列包括73196名年龄在66岁及以上的按服务收费的医疗保险参保者，他们在1992年至1999年期间被诊断为局限性前列腺癌，并随访至2001年。我们使用Cox比例风险模型评估使用GnRH激动剂或睾丸切除术治疗是否与糖尿病、冠心病、心肌梗死和心源性猝死有关。
超过三分之一的男性在随访期间接受了GnRH激动剂治疗。使用GnRH激动剂与糖尿病发病风险增加相关（调整后的风险比[HR]，1.44；P <.001）、冠心病（调整后的HR，1.16；P <.001）、心肌梗死（调整后的HR，1.11；P =.03）和心源性猝死（调整后的HR，1.16；P =.004）。接受睾丸切除术治疗的男性更易患糖尿病（调整后的HR，1.34；P <.001），但与冠心病、心肌梗死或心源性猝死无关（所有P>.20）。
对局限性前列腺癌男性患者使用GnRH激动剂治疗可能与糖尿病和心血管疾病发病风险增加有关。GnRH激动剂治疗的益处应与这些潜在风险相权衡。需要进一步研究以确定治疗相关并发症风险最高的男性人群，并制定预防治疗相关糖尿病和心血管疾病的策略。
