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Cumulative Androgen Deprivation Therapy Exposure for Prostate Cancer is Associated with an Increased Risk of Dementia

  • Peter E. Lonergan,
  • Samuel L. Washington,
  • Shoujun Zhao,
  • Janet E. Cowan,
  • Jeanette M. Broering,
  • Matthew R. Cooperberg,
  • Peter R. Carroll

Publication: Journal of Urology, September 2021

Introduction and objective

The association between androgen deprivation therapy (ADT) and dementia in men with prostate cancer remains controversial and the strength of this association remains unclear. This study assessed the association between cumulative ADT exposure and the onset of dementia after treatment in a nationwide registry of men with prostate cancer.


A retrospective analysis of men aged ≥ 50 years from the UCSF Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry from 43 primarily community-based US urology practices was performed. The primary outcome was onset of dementia after prostate cancer treatment including radical prostatectomy, external beam radiation therapy (EBRT), brachytherapy with or without EBRT, or active surveillance/watchful waiting. ADT exposure was expressed as a time-varying independent variable of total ADT exposure throughout follow up. The probability of receiving ADT was estimated using a propensity score to reduce selection bias by equating groups based on baseline characteristics. Cox proportional hazards regression was performed to determine the association between ADT exposure and dementia with competing risk of death, adjusted for propensity score and clinical covariates among men receiving various treatments.


Of 13,570 participants, 317 (2.0%) were diagnosed with dementia with a median follow up of 7.0 years (interquartile range [IQR] 3.0-12.0). Cumulative ADT use was significantly associated with dementia (HR 2.02; 95% CI, 1.40-2.91; p=0.0002) after adjustment. In a subset of 8,506 men, propensity score matched by whether or not they received ADT, the association between ADT use and dementia (HR 1.59; 95% CI, 1.03-2.45; p=0.04) remained significant. Primary treatment type was not associated with onset of dementia in the 8,489 men in the cohort who did not receive ADT.


Cumulative ADT exposure was associated with the onset of dementia. This increased risk should be accompanied by a careful and complete discussion of the needs and benefits of ADT in those being considered for such treatment.

Tags: AUA21