Androgen deprivation therapy and risk of cognitive dysfunction in men with prostate cancer: is there a possible link?

Abstract

The expansion of the indication to use androgen deprivation therapy (ADT) to treat patients with advanced or metastatic prostate cancer has dramatically increased over the recent decades, resulting in the progress of patients' survival. However, chronic health implications can become more apparent as the number of long-term cancer survivors is expected to be increased along with the adverse effect of ADT. In particular, interest in investigating ADT, especially luteinizing hormone-releasing hormone (LHRH) agonist association with cognitive dysfunction has been growing. Previous studies in animals and humans suggest that the level of androgen decreases with age and that cognitive decline occurs with decreases in androgen. Correspondingly, some of the extensive studies using common neurocognitive tests have shown that LHRH agonists may affect specific domains of cognitive function (e.g., visuospatial abilities and executive function). However, the results from these studies have not consistently demonstrated the association because of its intrinsic limitations. Large-scale studies based on electronic databases have also failed to show consistent results to make decisive conclusions because of its heterogeneity, complexity of covariates, and possible risk of biases. Thus, this review article summarizes key findings and discusses the results of several studies investigating the ADT association with cognitive dysfunction and risk of dementia from various perspectives.

Keywords: AD, Alzheimer's disease; ADT, androgen deprivation therapy; Adverse effects; Androgen deprivation; Cognitive dysfunction; DHEA, dehydroepiandrosterone; DHEAS, dehydroepiandrosterone sulfate; DHT, dihydrotestosterone; Dementia; HR, hazard ratio; LHRH, luteinizing hormone-releasing hormone; NHIS, National Health Insurance Service; PCa, Prostate cancer; Prostate cancer; SHBG, sex hormone-binding globulin.

Fig. 1

The potential mechanism of testosterone affecting cognition.