Androgen deprivation therapy in prostate cancer may increase dementia risk
Use of androgen deprivation therapy (ADT) in the management of prostate cancer may increase the risk of dementia, a study has found.
Researchers searched multiple electronic databases for relevant articles reporting the outcome of dementia among prostate cancer patients exposed to ADT vs a lesser-exposed comparison group (eg, ADT vs no-ADT; continuous vs intermittent ADT). A total of nine studies were identified, of which seven reported an adjusted effect estimate for dementia risk.
Pooled data from studies reporting any dementia outcome (n=50,541) showed a heightened risk of dementia among ADT users (hazard ratio [HR], 1.47; 95 percent CI, 1.08 to 2.00; p=0.02).
Likewise, results of a separate meta-analysis of studies reporting all-cause dementia and Alzheimer’s disease showed an increase in the risk of the said outcomes following ADT for prostate cancer (HR for all-cause dementia, 1.46; 1.05 to 2.02; p<0.001; HR for Alzheimer’s disease, 1.25; 0.99 to 1.57; p=0.06).
On Egger and Begg’s tests, no evidence of bias from small study effects was detected (Egger, p=0.19; Begg, p=1.00).
According to researchers, the findings may be potentially explained by a causal association between ADT in the treatment of prostate cancer and an increased risk of dementia, which is supported by several factors. First, neuron death is the overarching cause of dementia in general, with androgens having been shown to play a key role in neuron growth and axonal regeneration. Second, previously published laboratory data demonstrated that low testosterone levels predict future dementia and, in addition to ADT, result in increased β-amyloid protein levels. [Hormones Behav 2013;63:301–307; Alzheimers Dement 2014;10:S306–S314; JAMA 2004;292:1431–1432]
ADT may also increase dementia risk through adverse effects on vascular health, with both low testosterone levels and ADT having been linked to cardiometabolic diseases such as diabetes, coronary artery disease, stroke and peripheral arterial disease—conditions that are in turn associated with the risk of dementia. [J Am Geriatr Soc 2005;53:1101–1107; Diabetes Care 2011;34:1669–1675; Eur Urol 2012;61:1119–1128]
“The chronic health implications of cancer therapies are of increasing importance as survival rates following cancer diagnoses continue to improve,” researchers said, adding that the present data contribute to the growing body of evidence linking ADT with neurocognitive dysfunction.
“Further prospective studies are needed to validate [the current] finding and to explore ways of reducing th[e] possible cognitive harm [of ADT],” they said.