Introduction
As of 2018, prostate cancer (PCa) was the second leading cause of cancer and the sixth common cause of cancer-related death in men [1]. Almost 20% of patients have locally advanced or metastatic disease at the time of first diagnosis [2]. The primary goal in the treatment of metastatic disease is to keep the serum androgen level below the castration level of 50 ng/dL [3]. Medical castration with antiandrogen- or gonadotropin-releasing hormone (GnRH) agonists and surgical castration with bilateral orchiectomy are cornerstones of metastatic disease management [4]. However, lowering the serum testosterone below castration level may increase the risks of osteoporosis, anemia, gynecomastia, erectile dysfunction, and systemic disorders including diabetes and cardiovascular events [5,6].
Androgen deprivation affects cognitive functions in a majority of men over 65 years of age, whereas atherosclerotic or degenerative changes are more common. Although there are some relevant reports in the current literature [7], further comprehensive, prospective studies are needed to examine the effect of ADT on cognitive function. McGinty et al. conducted one of the largest and the most up-to-date systematic reviews, evaluating 14 studies (417 patients) and 7 cognitive domains and concluded that cognitive functions other than visuomotor ability remain largely unchanged [8]. Furthermore, Sun et al. conducted a meta-analysis of androgen deprivation therapy and concluded that it does not cause cognitive impairment [9]. However, due to the small number of prospective studies, the debate is still open regarding the impact of ADT on cognitive changes. Furthermore, greater age, advanced stage of primary disease, and presence of accompanying comorbidities may worsen underlying cognitive disorders in patients under long-term ADT.
The present study aimed to evaluate changes in cognitive functions and depressive symptoms in men who received ADT for metastatic prostate cancer using GnRH analogues.