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Androgen deprivation therapy for prostate cancer and neurocognitive disorders: a systematic review and meta-analysis

Prostate Cancer and Prostatic Diseases (2024)Cite this article

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Abstract

Background

Prostate cancer is a prevalent disease that urgently needs to address its treatment-related complications. By examining existing evidence on the association between Androgen Deprivation Therapy (ADT) and dementia, this study contributes to the understanding of potential risks. We sought to analyze the currently available evidence regarding the risk of dementia, Alzheimer’s disease (AD), vascular dementia, and Parkinson’s disease (PD) in patients undergoing ADT.

Methods

A systematic search of PubMed, EMBASE, Scopus, and Google Scholar was performed to identify studies published from the databases’ inception to April 2023. Studies were identified through systematic review to facilitate comparisons between studies with and without some degree of controls for biases affecting distinctions between ADT receivers and non-ADT receivers. This review identified 305 studies, with 28 meeting the inclusion criteria. Heterogeneity was assessed using Higgins I2%. Variables with an I2 over 50% were considered heterogeneous and analyzed using a Random-Effects model. Otherwise, a Fixed-Effects model was employed.

Results

A total of 28 studies were included for analysis. Out of these, only 1 study did not report the number of patients. From the remaining 27 studies, there were a total of 2,543,483 patients, including 900,994 with prostate cancer who received ADT, 1,262,905 with prostate cancer who did not receive ADT, and 334,682 patients without prostate cancer who did not receive ADT. This analysis revealed significantly increased Hazard Ratios (HR) of 1.20 [1.11, 1.29], p < 0.00001 for dementia, HR 1.26 [1.10, 1.43], p = 0.0007 for Alzheimer’s Disease, HR 1.66 [1.40, 1.97], p < 0.00001 for depression, and HR 1.57 [1.31, 1.88], p < 0.00001 for Parkinson’s Disease. The risk of vascular dementia was HR 1.30 [0.97, 1.73], p < 0.00001.

Conclusion

Based on the analysis of the currently available evidence, it suggests that ADT significantly increases the risk of dementia, AD, PD, and depression.

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Fig. 1
Fig. 2: Displays a summary forest plot with Hazard Ratios for key primary outcomes: Dementia (All-Cause), Alzheimer’s, Vascular Dementia, Depression, and Parkinson’s Disease.
Fig. 3: Displays summary forest plot with Hazard Ratios for subgroup analysis of dementia stratified by androgen deprivation therapy type, duration, and patient age.
Fig. 4: Displays summary forest plot with Hazard Ratios for subgroup analysis of Alzheimer’s Disease stratified by androgen deprivation therapy type, duration, and patient age.
Fig. 5: Displays summary forest plot with Hazard Ratios for subgroup analysis of dementia stratified by geographic region of analyzed population.
Fig. 6: Displays summary forest plot with Hazard Ratios for subgroup analysis of Alzheimer’s Disease stratified by geographic region of analyzed population.

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Data availability

The data that support the findings of this study are available from the corresponding author, DEH, upon reasonable request.

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Authors and Affiliations

  1. Department of Urology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRB 1102, Boston, MA, 02114, USA

    David E. Hinojosa-Gonzalez, Gal Saffati, Shane Kronstedt & Mohit Khera

  2. Scott Department of Urology, Baylor College of Medicine, 7200 Cambridge Street, Houston, TX, 77030, USA

    Affan Zafar & Dimitar V. Zlatev

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  1. David E. Hinojosa-Gonzalez
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Contributions

David E. Hinojosa-Gonzalez: Conceptualization (Lead), Data curation (Equal), Formal analysis (Lead), Investigation (Equal), Methodology (Equal), Project administration (Equal), Supervision (Equal), Validation (Equal), Visualization (Equal), Writing – original draft (Equal), Writing – review & editing (Equal). Affan Zafar: Conceptualization (Supporting), Data curation (Equal), Formal analysis (Supporting), Writing – review & editing (Equal). Gal Saffati: Conceptualization (Supporting), Data curation (Equal), Formal analysis (Supporting), Investigation (Equal), Methodology (Equal), Visualization (Equal), Writing – original draft (Equal), Writing – review & editing (Equal). Shane Kronstedt: Conceptualization (Supporting), Data curation (Equal), Formal analysis (Supporting), Investigation (Equal), Methodology (Equal), Visualization (Equal), Writing – original draft (Equal), Writing – review & editing (Equal). Mohit Khera: Conceptualization (Supporting), Methodology (Equal), Supervision (Equal), Writing – review & editing (Equal)

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Correspondence to David E. Hinojosa-Gonzalez.

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M.K is a consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast, Halozyme and an Investor in Sprout. The rest of the authors have nothing to disclose.

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Hinojosa-Gonzalez, D.E., Zafar, A., Saffati, G. et al. Androgen deprivation therapy for prostate cancer and neurocognitive disorders: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis (2024). https://doi.org/10.1038/s41391-023-00785-w

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