Risk of Dementia and Depression in Young and Middle-aged Men Presenting with Nonmetastatic Prostate Cancer Treated with Androgen Deprivation Therapy

Karl H Tully; David-Dan Nguyen; Peter Herzog; Ginger Jin; Joachim Noldus; Paul L Nguyen; Adam S Kibel; Maxine Sun; Bradley McGregor; Shehzad Basaria; Quoc-Dien Trinh

doi:10.1016/j.euo.2019.08.003

Risk of Dementia and Depression in Young and Middle-aged Men Presenting with Nonmetastatic Prostate Cancer Treated with Androgen Deprivation Therapy

Eur Urol Oncol. 2021 Feb;4(1):66-72. doi: 10.1016/j.euo.2019.08.003. Epub 2019 Oct 14.

Authors

Affiliations

¹ Division of Urological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Urology and Neurourology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany.
² Division of Urological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Faculty of Medicine, McGill University, Montreal, QC, Canada.
³ Division of Urological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Department of Urology and Neurourology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany.
⁶ Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁷ Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁸ Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Division of Urological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: qtrinh@bwh.harvard.edu.

PMID: 31624049
DOI: 10.1016/j.euo.2019.08.003

Abstract

Background: Previous studies have found an association between androgen deprivation therapy (ADT) and an increased risk of dementia and depression in elderly men. This association remains controversial, and little is known about the effects of ADT in younger men.

Objective: To examine the association between the receipt of ADT and these outcomes in young men aged 40-64 yr presenting with nonmetastatic prostate cancer (PCa).

Design, setting, and participants: For this observational study, we identified 9117 men aged 40-64 yr diagnosed with localized PCa between 2007 and 2014, without a pre-existing neurocognitive diagnosis, using the TRICARE military database.

Outcome measurements and statistical analysis: Kaplan-Meier curves were fitted to compare ADT versus no ADT. We also performed a subgroup analysis in patients undergoing ADT for ≥12 mo. The association between ADT and new-onset dementia or depression was evaluated using inverse-probability-of treatment-weight-adjusted Cox proportional hazards regression analysis.

Results and limitations: Patients receiving ADT had a significantly higher incidence of depression (30.2 vs 15.8 per 1000 person years) and dementia (17.9 vs 7.5 per 1000 person years). The risk of developing either outcome was higher in the ADT cohort (depression: hazard ratio [HR] 2.07, p < 0.001; dementia: HR 1.70, p = 0.052). Additionally, there was a dose-response relationship between the duration of ADT and either outcome.

Conclusions: In our cohort of young men with PCa, the receipt of ADT was associated with an increased risk of developing dementia and depression. Long-term use of ADT was associated with the highest risk of neurocognitive outcomes.

Patient summary: In this study, we looked at the risk of dementia and depression in patients <65 yr of age undergoing androgen deprivation therapy (ADT) for prostate cancer. We found that these patients had a higher risk of dementia and depression than those who did not undergo ADT.

Keywords: Androgen deprivation; Dementia; Depression; Prostate cancer.

Publication types

Observational Study

MeSH terms

Aged
Androgen Antagonists / adverse effects
Androgens
Dementia* / epidemiology
Depression / chemically induced
Depression / epidemiology
Humans
Male
Middle Aged
Prostatic Neoplasms* / drug therapy
Prostatic Neoplasms* / epidemiology

Substances

Androgen Antagonists
Androgens