Potential Link Between Androgen-Deprivation Therapy for Prostate Cancer and Risk for Dementia


Key Points

  • Use of androgen-deprivation therapy for prostate cancer was associated with an increased risk for dementia.
  • At 5 years, the risk was 7.9% in users of androgen-deprivation therapy vs 3.5% for nonusers.

In a single-center analysis reported in JAMA Oncology, Nead et al found that the use of androgen-deprivation therapy for prostate cancer was associated with an increased risk for dementia.

The study involved electronic medical record data from the Stanford University Health System from 1994 to 2013. A total of 9,272 men with prostate cancer without a history of dementia were identified. Of them, 1,826 (19.7%) had received androgen-deprivation therapy. Patients had a mean age of 66.9 years, and 59% were white. Median follow-up was 3.4 years (interquartile range = 1.0–7.2 years).

The effect of androgen-deprivation therapy on the risk of dementia was assessed using propensity score–matched Cox proportional hazards regression. Analysis was adjusted for age at prostate cancer diagnosis; race/ethnicity; smoking status; use of antiplatelet, anticoagulant, antihypertensive, and statin medications; and a history of cardiovascular disease, diabetes, stroke, or malignant neoplasms.

Increased Risk of Dementia

Use of androgen-deprivation therapy was associated with a significantly increased risk for dementia (hazard ratio [HR] = 2.17, P < .001). In a sensitivity analysis, the risk was similar when patients with Alzheimer’s disease were excluded (HR = 2.32, P < .001). The absolute increased risk of developing dementia among those who received androgen-deprivation therapy was 4.4% at 5 years (7.9% vs 3.5% in those not receiving androgen-deprivation therapy).

Analyses stratified by the duration of therapy found that use of androgen-deprivation therapy for ≥ 12 months was associated with the highest absolute increased risk of dementia (HR = 2.36, P < .001). Kaplan-Meier analysis showed that users of androgen-deprivation therapy aged ≥ 70 years had the lowest cumulative probability of remaining free of dementia (P < .001).

The investigators concluded: “Androgen deprivation therapy in the treatment of prostate cancer may be associated with an increased risk of dementia. This finding should be further evaluated in prospective studies.”

The study was supported by grants from the National Library of Medicine and the National Institute of General Medical Sciences.

Kevin T. Nead, MD, MPhil, of the University of Pennsylvania Perelman School of Medicine, is the corresponding author of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.