Testosterone replacement in young male cancer survivors: A 6-month double-blind randomised placebo-controlled trial

Background Young male cancer survivors have lower testosterone levels, higher fat mass, and worse quality of life (QoL) than age-matched healthy controls. Low testosterone in cancer survivors can be due to orchidectomy or effects of chemotherapy and radiotherapy. We have undertaken a double-blind, placebo-controlled, 6-month trial of testosterone replacement in young male cancer survivors with borderline low testosterone (7-12 nmol/l). Methods and findings This was a multicentre United Kingdom study conducted in secondary care hospital outpatients. Male survivors of testicular cancer, lymphoma, and leukaemia aged 25-50 years with morning total serum testosterone 7-12 nmol/l were recruited. A total of 136 men were randomised between July 2012 and February 2015 (42.6% aged 25-37 years, 57.4% 38-50 years, 88% testicular cancer, 10% lymphoma, matched for body mass index [BMI]). Participants were randomised 1:1 to receive testosterone (Tostran 2% gel) or placebo for 26 weeks. A dose titration was performed after 2 weeks. The coprimary end points were trunk fat mass and SF36 Physical Functioning score (SF36-PF) at 26 weeks by intention to treat. At 26 weeks, testosterone treatment compared with placebo was associated with decreased trunk fat mass (-0.9 kg, 95% CI -1.6 to -0.3, p = 0.0073), decreased whole-body fat mass (-1.8 kg, 95% CI -2.9 to -0.7, p = 0.0016), and increased lean body mass (1.5 kg, 95% CI 0.9-2.1, p < 0.001). Decrease in fat mass was greatest in those with a high truncal fat mass at baseline. There was no treatment effect on SF36-PF or any other QoL scores. Testosterone treatment was well tolerated. The limitations of our study were as follows: a relatively short duration of treatment, only three cancer groups included, and no hard end point data such as cardiovascular events. Conclusions In young male cancer survivors with low-normal morning total serum testosterone, replacement with testosterone is associated with an improvement in body composition. Author summaryWhy was this study done? Young male cancer survivors have lower testosterone levels than the healthy population and frequently close to or just below the lower limit of the reference range. A common question of young male cancer survivors to their physician is, would I benefit from testosterone treatment? What did the researchers do and find? We invited young male cancer survivors aged 25-50 years with borderline low testosterone levels to participate in a placebo-controlled double-blind trial of testosterone replacement therapy. Young male cancer survivors who participated in the trial received either a placebo (inactive) gel or active testosterone gel, which they applied each day to their skin for 6 months. Neither the participant nor the physician conducting the study knew whether they were receiving placebo or active testosterone. At the beginning and end of the trial, we measured the participant's body composition and quality of life using questionnaires. At 6 months, the young male cancer survivors treated with testosterone had a decrease in their fat mass, on average, of 1.8 kg and an increase in lean mass of 1.5 kg; however, the quality-of-life questionnaires did not show any difference between those treated with placebo or testosterone. What do these findings mean? A young male cancer survivor with a borderline low morning testosterone level may benefit from testosterone replacement, with an improvement in body composition with loss of fat mass and increase in muscle mass.