Testosterone Replacement May Improve Body Composition in Male Cancer Survivors

Testosterone replacement therapy may improve body composition in young male cancer survivors with borderline-low testosterone levels.

Testosterone replacement therapy may be associated with loss of fat mass and increase in muscle mass in young male cancer survivors with borderline-low morning testosterone levels, according to study results published in PLOS Medicine.

While the diagnosis of testosterone deficiency is usually based on clinical signs of clearly low serum testosterone, the diagnosis is more complex in cancer survivors, as there are multiple other causes for the signs and symptoms typical of testosterone deficiency. Furthermore, there are no data on the management of male cancer survivors with borderline-low testosterone levels.

The goal of the current study was to assess the effect of testosterone replacement therapy on body composition and physical function in this population. The primary end points were changes in trunk fat mass and quality of life measured by Short Form 36 (SF-36) physical functioning score at 26 weeks in the intention-to-treat population. Secondary end points included whole-body fat mass and lean mass among several anthropometric measurements, as well as other quality of life measures, including self-esteem and fatigue.

The Testosterone Replacement in Young Male Cancer Survivors study was a prospective multicenter randomized double-blind placebo-controlled parallel-group superiority trial that included individuals from 10 secondary care centers in the United Kingdom. Young male cancer survivors aged 25 to 50 years with borderline-low testosterone (201.73-345.82 ng/dL) were randomly assigned 1:1 to placebo gel or active testosterone 2% gel, applied daily to the skin for 6 months. The patients’ body composition and questionnaires to assess quality of life were measured at baseline, 13 weeks, and 26 weeks.

The cohort included 136 men (42.6% aged 25-37 years; 57.4% aged 38-50 years) randomly assigned to testosterone gel (68 patients; mean body mass index, 27.6 kg/m2) or placebo (68 patients; mean body mass index, 28.1 kg/m2). The most common cancer diagnoses were testicular cancer (88.2% in both groups) and lymphoma (8.8% in the active group and 10.3% in the placebo group).

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At 26 weeks, testosterone treatment was associated with decreased trunk fat mass (-0.9 kg; 95% CI, -1.6 to -0.3 kg; P =.0073) and whole-body fat mass (-1.8 kg; 95% CI, -2.9 to -0.7 kg; P =.0016). There was also an increase in whole-body lean mass of 1.5 kg (95% CI, 0.9-2.1 kg; P <.001). A greater decrease in trunk fat mass with testosterone treatment was associated with older age (P =.031), and the greatest decrease in trunk fat mass was observed in men in the highest tertile of baseline trunk fat mass. There was no observed effect of testosterone therapy on metabolic profile.

With regard to quality-of-life end points, there was no associated change in fatigue or self-esteem scores. There was also no treatment effect on SF-36 score, although the researchers noted that these data were heavily skewed and that they could not definitively confirm a null effect of testosterone therapy.

There were no serious adverse events in testosterone treatment group.

The researchers acknowledged several study limitations, including the relatively short duration of treatment, limited number of cancer groups included, and lack of hard end point data such as cardiovascular events.

“In young adult male cancer survivors with low and low-normal fasting morning total testosterone…testosterone treatment is associated with improvement in adverse body composition, and the reduction in trunk fat mass with testosterone treatment is potentially more beneficial in those with an increased trunk fat mass. We suggest that in these patients, testosterone replacement be considered in the context of other interventions to improve body composition,” concluded the researchers.

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Walsh JS, Marshall H, Smith IL, et al. Testosterone replacement in young male cancer survivors: a 6-month double-blind randomised placebo-controlled trial [published November 12, 2019]. PLoS Med. doi:10.1371/journal.pmed.1002960