Prostate cancer patients treated with androgen deprivation therapy are more than twice as likely as those who were not to develop dementia, according to a review of 9,272 prostate cancer cases at Stanford (Calif.) University.
Almost 8% of the 1,826 men treated with androgen deprivation therapy (ADT), a mainstay against prostate cancer, were diagnosed with dementia at 5 years, versus 3.5% of the 7,446 men not treated with ADT (JAMA Oncol. 2016 Oct 13. doi: 10.1001/jamaoncol.2016.3662).
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“Our study extends previous work supporting an association between use of ADT and Alzheimer disease and suggests that ADT may more broadly affect neurocognitive function,” said the investigators, led by Kevin Nead, MD, formerly at Stanford but now a radiation oncology resident at the University of Pennsylvania, Philadelphia.
New-onset senile dementia, vascular dementia, frontotemporal dementia, and Alzheimer dementia were linked to ADT in both a propensity score-matched analysis (HR, 2.17; 95% CI, 1.58-2.99; P < .001) and multivariate analysis (adjusted HR, 2.21; 95% CI, 1.72-2.83; P < .001). The results held up when Alzheimer disease, just 30% of the 314 dementia cases, was excluded.
Men with at least 12 months of ADT had the greatest increased risk of dementia (HR, 2.36; 95% CI, 1.64-3.38; P < .001), suggesting a dose-response relationship; men on ADT who were at least 70 years old had the lowest cumulative probability of not developing dementia.
The link, the team said, is biologically plausible. Androgens have a role in neuron health and growth, and testosterone analogues have neuroprotective effects. Testosterone may be converted to estrogen, which is also neuroprotective. Low testosterone levels and ADT, meanwhile, have been shown to increase the risk of cardiometabolic diseases, which increase the risk of dementia.
The analyses controlled for age at prostate cancer diagnosis; race; smoking status; use of antiplatelet, anticoagulant, antihypertensive, and statin medications; and histories of cardiovascular disease, type 1 or 2 diabetes, stroke, and malignant neoplasms.
The men were treated at Stanford from 1994-2013. ADT patients tended to be older than their peers (70 versus 66 years), less likely to white (54% versus 60%), more likely to have smoked (44% versus 38%), and more likely to have other health problems.
More than 20 medications in the study were used for ADT, including leuprolide, goserelin, and triptorelin. Data were collectedd from electronic health records, and included diagnostic codes, medication lists, and clinical notes.
The work was funded by the National Institutes of Health. The senior author, Nigam Shah, PhD, has patents pending on the data-mining methods used in the study.