Androgen Deprivation Therapy Linked to Alzheimer Disease

Summary and Comment |
February 12, 2016

Androgen Deprivation Therapy Linked to Alzheimer Disease

  1. Robert Dreicer, MD, MS, FACP, FASCO

The risk for developing Alzheimer disease increased with the duration of therapy.

  1. Robert Dreicer, MD, MS, FACP, FASCO

Androgen deprivation therapy (ADT) has been the standard of care for management of metastatic prostate cancer for more than 70 years. Its use in locally advanced disease is defined by prospective evidence in a number of clinical settings. However, during the past 25 years, the greatest growth in use has been in the prostate-specific antigen (PSA)-only disease state, for which prospective evidence is lacking. Whereas the metabolic and bone issues related to ADT are well described, the impact on neurocognitive function remains poorly defined.

Using a novel, text-processing pipeline method to interrogate data from electronic medical records, investigators analyzed data from two large academic medical centers to explore a potential association between ADT and the development of Alzheimer disease (AD). During a 19-year period, data from approximately 40 million patient encounters led to identification of 16,888 men with prostate cancer who met the study criteria, which excluded men subsequently treated with chemotherapy or who had a history of dementia or stroke. Of this group, 14% received ADT with a median time from prostate cancer diagnosis to therapy of 36 days.

During a median follow-up of 2.7 years, 125 new diagnoses of AD occurred (median time to diagnosis, 4.0 years). Propensity-score–matched analysis and multivariable cox analysis showed that AD was associated with ADT and that risk for developing AD increased with duration of ADT use.


As noted by an editorialist, the analysis had notable limitations, including a lack of information on possible confounding variables that may affect both prostate cancer and AD risk. However, these results, in combination with a recent prospective study that provided provocative data regarding the potential negative impact of ADT on cognitive function (NEJM JW Oncol Hematol Jul 2015 and J Clin Oncol 2015 33:2021) provide fertile ground for future research.

Editor Disclosures at Time of Publication

  • Disclosures for Robert Dreicer, MD, MS, FACP, FASCO at time of publication Consultant / Advisory board Medivation; Genentech/Roche; Bind Pharmaceuticals; Astellas Editorial boards Urology; Clinical Genitourinary Cancer; Current Urology Reports Leadership positions in professional societies National Cancer Institute (Co-Chair, GU Oncology Steering Committee); American Board of Internal Medicine (member, Medical Oncology Test Writing Committee); Bladder Cancer Advocacy Network (member, scientific advisory board)


Reader Comments (3)


The comments by Victor Kantariya, MD above are accurate and there is some evidence that ADT is associated with more severe problems than orchiectomy. Unfortunately ADT therapy has been very profitable and thus has been pushed without carefully evaluating the problems associated with using it.

victor kantariya Physician, Family Medicine/General Practice

Low testosterone(T) in men is not good for your brain. Low blood levels of T or dihydrotestosterone appear to be independent predictors of stroke among aging men( J Clin Endocrinol Metab.2014). Free T inversly related to carotid atherosclerosis in men with T2D (Diabetes Care 2003). Too Low T maybe Bad for Head. Victor Kantariya,MD

victor kantariya Physician, Family Medicine/General Practice

ADT linked to cognitive impairment (JCO 2014), primary ADT increased metabolic syndrome risk, raised diabetes risk by 60% ( J Urol.2015). More patients who received ADT experienced increased risk for high-grade hypertension (Eur J Cancer.2015) and other serious CV outcomes. Victor Kantariya, MD

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