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Dr. Daniell correctly points out that opioid-induced androgen deficiency (OPIAD) is a common cause of fatigue in patients with cancer. Although we reported1 that the effects of cancer and its treatment on the hypothalamic-pituitary-gonadal axis contribute to fatigue, we did not fully discuss the specific role of OPIAD or other forms of hypogonadism because of space constraints. In our experience, hypogonadism is detected frequently in patients who receive chronic antineoplastic therapy, irrespective of the use of opioids. These patients develop hypogonadotropic hypogonadism (variably associated with central hypocorticism) and growth hormone deficiency. Although we did not report or analyze specific data in our review, we share Dr. Daniell's conclusion that replacement therapy with testosterone or testosterone analogs results in substantial subjective improvement and plays a relevant role in the management of fatigue. Nevertheless, hypogonadism is rarely the only identifiable cause of fatigue in patients with cancer. We would like to emphasize once again that the pathogenesis of this symptom most often is multifactorial and necessitates thorough patient evaluation. Current efforts to elucidate the pathophysiology of cancer-related fatigue should provide important insights in the future.

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