Hormone Therapy for Prostate Cancer Linked to Depression

Men who receive pharmacologic androgen deprivation therapy (ADT) as part of their treatment for prostate cancer may be at higher risk for depression, according to the results of a study published in the Journal of Clinical Oncology.

Compared with prostate cancer patients who did not receive ADT, patients treated with ADT had a 23% increased risk of depression and a 29% increased risk of inpatient psychiatric treatment. The ADT-treated patients also had a 7% non-significant increase in outpatient psychiatric treatment compared with men not treated with ADT.

“We know that patients on hormone therapy often experience decreased sexual function, weight gain, and have less energy-many factors that could lead to depression,” said study author Paul L. Nguyen, MD, associate professor of radiation oncology at Harvard Medical School and director of prostate brachytherapy at the Brigham and Women’s Hospital in Boston, in a statement. “After taking a deeper look, we discovered a significant association between men being treated with ADT for prostate cancer and depression. This is a completely underrecognized phenomenon.”

Longer exposure to ADT resulted in an increased risk of depression, from 12% with less than 6 months of therapy to 26% with 7 to 11 months of therapy, and up to 37% among patients treated for 12 months or longer (P < .001).

A similar duration effect was seen for both inpatient and outpatient psychiatric treatment (P < .001 for both).

Nguyen and study coauthors analyzed a cohort of men over the age of 65 with stage I–III prostate cancer from 1992 to 2006 records within the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database. Among the 78,552 men included, the authors analyzed the association between ADT and diagnosis of depression or records of psychiatric treatment. 

ADT combined with radiation therapy has been shown to increase survival for men with high-risk, localized disease. Yet ADT can also be accompanied by metabolic, cardiovascular, bone, and cognitive adverse events. Several prior studies have found a significant association between depression and ADT, yet smaller studies have also shown no link. There is no current consensus on whether ADT is associated with depression, noted the authors.

Forty-three percent of the men included in the cohort received ADT within 6 months of their prostate cancer diagnosis. Median age of patients was 72.6 in the no-ADT cohort and 75.2 in the ADT cohort. Cumulative incidence of newly diagnosed depression from 6 to 36 months after a prostate cancer diagnosis was higher among the men who were treated with ADT compared with the no-ADT cohort (7.1% compared with 5.2%, respectively; P < .001).          

Older age, unmarried status, and greater comorbidity was associated with an increased risk of depression (P < .001 for all three factors). There was no effect on ADT treatment and depression based on the year of diagnosis.

“Patients and physicians must weigh the risks and benefits of ADT, and this additional risk of depression may make some men even more hesitant to use this treatment, especially in clinical scenarios where the benefits are less clear, such as intermediate-risk disease,” noted Nguyen.