J Cachexia Sarcopenia Muscle (2012) 3:149–155 dysfunction in cancer patients come from prostate cancer studies [49, 50], which may not be a representative subgroup to study given that part of the treatment of prostate cancer includes induction of profound hypogonadism. Common fac- tors that affect sexual function in cancer patients other than hypogonadism include pelvic surgery, resulting in damage to nerve/blood supply and radiation/chemotherapy-induced pe- ripheral nerve damage. Greenfield and colleagues reported greater degree of sexual dysfunction in cancer patients with testosterone levels in lower quartiles compared to patients with testosterone in high quartiles [48]. Similar results were published by Fleishman et al. who reported lower scores in FACT-P sexual function questionnaire in hypogonadal cancer patients compared to eugonadal cancer patients [11]. Few other general symptoms have been linked to hypo- gonadism. Del Fabbro et al. [51] recently showed that hypogonadism in cancer patients is associated with insom- nia. This was attributed to the disruption of normal circadian rhythm and sleep. In the same study, the investigators also found that lower testosterone levels were associated with dyspnea. It was postulated that lower levels of testosterone resulted in loss of lean body mass and wasting of respiratory muscles, causing dyspnea. 5 Hypogonadism and cancer survival To date, there has been only one study that looked into survival of hypogonadal patients with cancer. The result of this single center study showed that survival of male patients with total testosterone levels <185 ng/dl was decreased compared to patients with level of testosterone >185 ng/dl (93 vs. 433 days) [51]. In another study, there was a trend towards lower overall survival in patients with baseline low testosterone who were receiving anti-androgen therapy for prostate cancer [52]. Whether hypogonadism contributes to a decrease in survival by a not well-characterized mecha- nism or is simply a marker of severity of disease is not known. 6 Treatment of hypogonadism in cancer patients In non-cancer, hypogonadal men, testosterone replacement has a positive effect on several parameters that are also impaired in the setting of cancer, and treatment of hypogo- nadism is clinically indicated in symptomatic men with low testosterone [53]. Furthermore, testosterone administration has been shown to increase lean body mass and bone mineral density, to improve quality of life, and to decrease fatigue in this setting [54, 55]. Sexual function and mood parameters improve rapidly and are maintained throughout testosterone treatment [56, 57]. Also, testosterone replacement reduces 153 cytokine levels in hypogonadal men [19, 20] and induces a reduction in inflammatory markers and clinical remission in other hypogonadal states such as arthritis [21]. Treatment of hypogonadism in HIV patients with wasting has been beneficial. Previous studies have shown improve- ment in body weight, muscle strength, lean body mass, and improved quality of life in HIV patients on testosterone replacement therapy [58–60]. Whether similar benefits will apply to hypogonadal cancer patients is not known. Chlebowski et al. showed decreased severity of weight loss in cancer patients who were treated with nandrolone [10]. However, Loprinzi and colleagues did not show any benefit of fluoxymesterone, an anabolic corticosteroid which was found to be inferior to dexamethasone and megestrol with respect to appetite enhancement [61]. Certainly, there is paucity of data when it comes to interventional studies looking at the safety and efficacy of testosterone in this patient population, although several studies are ongoing using testosterone or selective androgen receptor modu- lators (SARMs) which would potentially present the advantage of good oral bioavailability and decreased pros- tatic and virilizing side effects. Recently, a phase II study using the SARM ostarine was reported to cause a dose- dependent increase in lean body mass and functional perfor- mance [62]. 7 Conclusion The development of therapies for the prevention or treatment of cancer-related symptoms is desperately needed because they significantly reduce quality of life in these patients. The prevalence of hypogonadism is higher in cancer patients than in non-cancer patients. It is associated with poor quality of life, and it likely contributes to weight loss, sexual dysfunction, fatigue, and weakness. Hypogonadism is also associated with poor survival in cancer patients. Data regarding the effectiveness and safety of testosterone treatment in this population are scant, and more prospective trials are needed to determine if testosterone replacement therapy will improve muscle mass and strength, quality of life, sexual function, and fatigue in this setting. Acknowledgments Dr. Garcia received research support from MERIT grants from the Dept. of Veterans Affairs (I01-BX000507, CX000174) and from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (R21HD060870). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute Of Child Health & Human Development or the National Institutes of Health. The authors of this manuscript certify that they comply with the principles of ethical publishing in the Journal of Cachexia, Sarcopenia, and Muscle [63].