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Quantifying observational evidence for risk of dementia following androgen deprivation therapy for prostate cancer: an updated systematic review and meta-analysis

Prostate Cancer and Prostatic Diseases volume 24, pages 15–23 (2021)Cite this article

Subjects

Abstract

Background

Androgen deprivation therapy (ADT) administration was recently reported and might be positively associated with dementia. However, the existing studies showed controversial results. The aim of this study was to evaluate the relationship between ADT and the risk of dementia through a meta-analysis.

Methods

Original articles published up to March 2020 were retrieved from Embase, Pubmed, the Cochrane library, and Web of Science for studies focusing on associations between ADT for prostate cancer (PCa) and incidence of dementia. A meta-analysis was conducted using a hazard ratio (HR) and 95% confidence interval (CI) as effect measures. Heterogeneity between the studies was examined using I2 statistics. Subgroup analyses, sensitivity analyses, and meta-regression were conducted, and publication bias was assessed by Egger’s test.

Results

Thirteen studies were included in this systematic review. Eleven cohort studies involving 339,400 cases and 436,851 controls were included in the main meta-analysis. ADT administration was associated with a 21% increase in dementia risk (pooled HR = 1.21, 95% CI: 1.13–1.30, P < 0.001). Subgroup analyses based on ADT types showed that luteinizing hormone-releasing hormone agonists (HR = 1.14, P < 0.001), bilateral orchiectomy (HR = 1.42, P < 0.001), oral antiandrogens (HR = 1.35, P = 0.138), and combined androgen blockade (HR = 1.22, P = 0.097) were positively related to subsequent risk of dementia, although the differences were not statistically significant with oral antiandrogens and combined androgen blockade.

Conclusions

The current study indicated that ADT administration, no matter with types of ADT, is associated with the risk of dementia in patients with PCa. Future studies are needed to determine whether ADT causes dementia or is merely associated with increased risk.

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Fig. 1: Flow diagram of literature search and study selection.
Fig. 2: Forest plot for the association of risk of subsequent dementia with ADT administration for the treatment of PCa.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81972372 to XG), the Department of Science and Technology of Jilin Province (20190901006JC to GW), and the People’s Government of Jilin Province (JJKH20190028KJ to XG).

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  1. Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, China

    Haiying Cui, Fei Li, Guangyu He, Zongmiao Jiang, Xiaokun Gang & Guixia Wang

  2. Department of Orthopedics, The Second Hospital Jilin University, Changchun, 130021, Jilin Province, China

    Yao Wang

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Cui, H., Wang, Y., Li, F. et al. Quantifying observational evidence for risk of dementia following androgen deprivation therapy for prostate cancer: an updated systematic review and meta-analysis. Prostate Cancer Prostatic Dis 24, 15–23 (2021). https://doi.org/10.1038/s41391-020-00267-3

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