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Study Finds Inflammation Due to Androgen-Deprivation Therapy May Contribute to Fatigue, Other Side Effects in Men With Prostate Cancer


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Many patients with prostate cancer are treated with androgen-deprivation therapy. However, patients receiving androgen-deprivation therapy often experience higher levels of fatigue, depression, and cognitive impairment. In a new study published by Hoogland et al in the journal Cancer, researchers investigated whether inflammation in the body, a side effect of androgen-deprivation therapy, contributes to these symptoms, and they pinpointed a specific inflammation marker that is associated with increased fatigue in this group of patients.

“This is the first study that we know of that examines the association between inflammation and symptoms of fatigue, depression, or cognitive impairment in prostate cancer patients receiving androgen-deprivation therapy,” said Heather Jim, PhD, the study’s corresponding author and co-leader of the Health Outcomes & Behavior Program at Moffitt Cancer Center. “Because the blocking of testosterone can increase inflammation in the body, we believe that inflammation may also be contributing to these symptoms.” 

Increased Fatigue and Discovery of a Marker

For the study, the research team evaluated two groups of men: patients with prostate cancer beginning androgen-deprivation therapy, and a control group of healthy men of the same age. The men were assessed at baseline and again at 6 and 12 months. Assessments included fatigue, depression, and other neuropsychological tests, as well as a blood draw. The bloodwork was performed to check for circulating markers of inflammation, specifically interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), soluble tumor necrosis factor receptor-2 (sTNF-R2), and C-reactive protein (CRP).

Although the groups did not differ at baseline, researchers noticed a significant increase in fatigue and depressive symptoms in the patients treated with androgen-deprivation therapy over the 12-month period. They also saw an increase in one inflammation marker—IL-6—in this group of patients. Treatment‐related increases in IL‐6 were associated with worsening fatigue, but not depressive symptomatology or cognitive impairment.

“Interleukin-6 is a proinflammatory cytokine that is often associated with disruption of sleep, and therefore, fatigue,” said Aasha Hoogland, PhD, lead study author and an applied research scientist in the Health Outcomes & Behavior Program at Moffitt. “Studies have shown testosterone can suppress the effects of IL-6, but androgen-deprivation therapy limits testosterone production in the body, which is why we may be seeing increased levels in this patient group.”  

The researchers said additional studies are needed to see if interventions, such as anti-inflammatory medications and exercise, can help alleviate fatigue and depressive symptoms in patients undergoing treatment with androgen-deprivation therapy.

Disclosure: This study was supported by the National Institutes of Health and a Miles for Moffitt Milestone Award. For full disclosures of the study authors, visit acsjournals.onlinelibrary.wiley.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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