Low Testosterone Levels and Increased Inflammatory Markers in Patients with Cancer and Relationship with Cachexia

Context: Male cancer patients suffer from fatigue, sexual dysfunction, and decreased functional performance and muscle mass. These symptoms are seen in men with hypogonadism and/or inflammatory conditions. However, the relative contribution of testosterone and inflammation to symptom burden in cancer has not been well-established. Objective: The aim of this study was to measure testosterone levels in male cancer patients and determine the relationship between testosterone, inflammation, and symptom burden. Design/Setting: This cross-sectional study enrolled patients from a tertiary-care center. Subjects/Outcome Measures: Subjects included males with cancer-cachexia (CC; n = 45) and cancer without cachexia (CNC; n = 50), as well as noncancer controls (CO; n = 45). Total testosterone (TT), bioavailable testosterone, C-reactive protein (CRP), and IL-6 were measured in plasma. Functional performance was assessed by the ECOG (Eastern Cooperative Oncology Group) and KPS (Karnofsky Performance Scales), and sexual function was assessed by the IIEF (International Index of Erectile Function). Results: Low testosterone levels were seen in more than 70% of CC cases. TT was lower in CC compared to CNC(P < 0.05). Also, CC had lower bioavailable testosterone, grip strength, IIEF scores, appendicular lean body mass, and fat mass and higher IL-6 and CRP compared to controls (P <= 0.05). ECOG and KPS were lower in CC and CNC compared to controls (P <= 0.05). On multiple regression analysis, TT, albumin, and CRP predicted symptoms differentially in cancer patients. Conclusions: CC patients have higher inflammation and lower testosterone, grip strength, functional status, erectile function, fat mass, and appendicular lean body mass. Inflammation, TT, and albumin are associated with heavier symptom burden in this population. Interventional trials are needed to determine whether testosterone replacement and/or antiinflammatory agents benefit cancer patients. (J Clin Endocrinol Metab 97: E700-E709, 2012)