Department of Urology, Medical University of Vienna, Vienna, Austria.
King Fahad Specialist Hospital, Dammam, Saudi Arabia.
J Urol. 2021 Jan;205(1):60-67. doi: 10.1097/JU.0000000000001341. Epub 2020 Aug 28.
Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies.
We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months).
A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months).
Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.
雄激素剥夺疗法是某些局限性前列腺癌和几乎所有转移性前列腺癌患者的标准疗法。尽管一些临床队列研究已经确定了雄激素剥夺疗法对认知功能的影响，但之前的综述无法进行精心设计的定量综合分析，以总结痴呆症和/或阿尔茨海默病的风险。因此，关于这种风险的系统评价和荟萃分析仍然缺乏，包括最近的研究。
我们对评估接受与未接受雄激素剥夺疗法的前列腺癌患者的痴呆症和/或阿尔茨海默病发生率差异的文献进行了系统评价和荟萃分析。我们查询了 2020 年 1 月 1 日至 3 日的 PubMed®和 Web of Science™数据库。根据 I 统计量，我们使用随机或固定效应荟萃分析模型，存在或不存在异质性。我们根据雄激素剥夺治疗的持续时间（12 个月或更长时间）进行了 6 项荟萃分析，以评估所有原因的痴呆症、阿尔茨海默病和所有原因的痴呆症或阿尔茨海默病。
在考虑纳入和排除标准后，共选择了 14 项研究。其中 9 项报告了所有原因的痴呆症（即包括阿尔茨海默病在内的所有类型的痴呆症），其中 8 项报告了阿尔茨海默病。5 项研究根据雄激素剥夺治疗的持续时间评估了这些结果。与未接受雄激素剥夺治疗的患者相比，接受雄激素剥夺治疗的前列腺癌患者新发痴呆（所有原因）和阿尔茨海默病的风险更高（HR 1.21，95%CI 1.11-1.33和 HR 1.16，95%CI 1.09-1.24）。接受雄激素剥夺治疗超过 12 个月的前列腺癌患者的痴呆（所有原因）风险更高（HR 1.36，95%CI 1.07-1.72）；然而，对于接受雄激素剥夺治疗不到 12 个月的患者，差异无统计学意义（HR 1.06，95%CI 0.77-1.28）。雄激素剥夺治疗持续时间与阿尔茨海默病风险之间没有关联（暴露时间为 12 个月以下的 HR 为 1.21，95%CI 为 0.97-1.51，暴露时间大于 12 个月的 HR 为 1.39，95%CI 为 0.69-2.79）。
与未接受雄激素剥夺治疗的男性相比，接受雄激素剥夺治疗的前列腺癌患者发生痴呆症和/或阿尔茨海默病的风险增加；当雄激素剥夺治疗持续时间超过 12 个月时，这种风险更为明显。
