Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: A preliminary double-blind placebo-controlled trial

Background: Uncontrolled studies show fatigue, anorexia, depression, and mortality are associated with low testosterone in men with cancer. Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions. The primary objective was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer, by the Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-Fatigue) at day 29. Methods: This is a randomized, double-blinded placebo-controlled trial. Outpatients with advanced cancer, bioavailable testosterone (BT) <70 ng/dL and fatigue score >3/10 on the Edmonton Symptom Assessment Scale were eligible. Intra-muscular testosterone or sesame seed oil placebo was administered every 14 days to achieve BT levels 70-270 ng/dL. Results: Sixteen placebo and 13 testosterone-treated subjects were evaluable. No statistically significant difference was found for FACIT-fatigue scores between arms (-2 ± 12 for placebo, 4 ± 8 for testosterone, p = 0.11). Sexual Desire Inventory score (p = 0.054) and performance status (p = 0.02) improved in the testosterone group. Fatigue subscale scores were significantly better (p = 0.03) in those treated with testosterone by day 72. Conclusions: Four weeks of intramuscular testosterone replacement in hypogonadal male patients with advanced cancer did not significantly improve quality of life. Larger studies of longer duration are warranted.