Abstract
Previous studies have shown a consistent association between hormone therapy (HT), such as androgen deprivation therapy, to treat prostate cancer and depression risk. However, the association between second-generation antiandrogens (AAs) and depression is unknown. To test the a priori hypothesis that second-generation AAs are associated with an increased risk of depression, including compared with traditional forms of HT. This retrospective cohort study analyzed patients aged 66 years and older who were diagnosed with prostate cancer without a second cancer in 12 months from January 2011 to December 2015. Patients with continuous Medicare Parts A, B, and D coverage were included. Individuals who received any form of HT prior to prostate cancer diagnosis and those previously diagnosed with depression were excluded. Data were collected from the Surveillance, Epidemiology, and End Results-Medicare and Texas Cancer Registry-Medicare linked databases. Data were analyzed from February to May 2021. The following treatment groups were compared: (1) no HT group, (2) traditional HT group (HT without second-generation AA exposure), and (3) second-generation AA group. Risk of depression in the second-generation AA group compared with the no HT and traditional HT groups, determined prior to data collection, stratified by diagnosis stage. Of 210 804 patients diagnosed with prostate cancer during the study window, 30 069 men (11 484 [38%] aged 66-70 years; 22 594 [75%] White) who met inclusion criteria were identified. Overall, 17 710 (59%) received no HT, 11 311 (38%) received traditional HT only, and 1048 (3%) received a second-generation AA. Those receiving a second-generation AA were more likely to be older (aged ≥81 years: second-generation AA group, 246 [24%]; traditional HT group, 1997 [18%]; no HT group, 1173 [7%]) and present with advanced disease (eg, distant disease: second-generation AA group, 562 [24%]; traditional HT group, 876 [8%]; no HT group, 129 [0.7%]). Multivariable Cox proportional hazards analysis showed that the second-generation AA group had an increased risk of depression compared with the no HT group (hazard ratio [HR], 2.15; 95% CI, 1.79-2.59; P < .001) and the traditional HT group (HR, 2.26; 95% CI, 1.88-2.73; P < .001), including specifically among those with metastatic disease at diagnosis (HR, 2.40; 95% CI, 1.38-4.15; P = .002). In this cohort study, patients with prostate cancer who received a second-generation AA had a large and clinically significant increased risk of depression compared with patients who received traditional HT alone or no HT, including when limiting our analysis to individuals with metastatic disease at diagnosis.
Highlights
Prostate cancer accounts for more than 1 in 5 of all new cancers diagnosed in the United States.[1]
Multivariable Cox proportional hazards analysis showed that the second-generation AA group had an increased risk of depression compared with the no hormone therapy (HT) group and the traditional HT group (HR, 2.26; 95% CI, 1.88-2.73; P < .001), including among those with metastatic disease at diagnosis (HR, 2.40; 95% CI, 1.38-4.15; P = .002)
In this cohort study, patients with prostate cancer who received a second-generation AA had a large and clinically significant increased risk of depression compared with patients who received traditional HT alone or no HT, including when limiting our analysis to individuals with metastatic disease at diagnosis
Summary
Prostate cancer accounts for more than 1 in 5 of all new cancers diagnosed in the United States.[1] Hormone therapy (HT), including androgen deprivation therapy (ADT), is frequently used in localized prostate cancer along with radiation and is a mainstay of treatment for metastatic, locoregional, and recurrent disease.[2,3]. HT deprives prostate cancer cells of the androgen stimulation that promotes prostate cancer growth and progression, resulting in improvements in overall survival.[4] HT is typically achieved through medical castration, or androgen deprivation, with luteinizing hormone-releasing hormone (LHRH) agonists with or without antiandrogen (AA) therapy. Despite high initial response rates, most men with advanced prostate cancer progress to castration-resistant disease, which can be treated with second-generation AAs.[5,6] Second-generation AAs are used in combination with traditional forms of HT as first-line therapy in patients with hormone-naive metastatic prostate cancer. This increased potency may carry a greater risk of adverse effects related to blocking and suppressing testosterone.[7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
