A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women

Abstract

Background: Cancer cachexia negatively impacts cancer-related treatment options, quality of life, morbidity, and mortality, yet no established therapies exist. We investigated the anabolic properties of testosterone to limit the loss of body mass in late stage cancer patients undergoing standard of care cancer treatment.

Methods: A randomized, double-blind, placebo-controlled phase II clinical trial was undertaken to assess the potential therapeutic role of adjunct testosterone to limit loss of body mass in patients with squamous cell carcinoma of the cervix or head and neck undergoing standard of care treatment including chemotherapy and chemoradiation. Patients were randomly assigned in blocks to receive weekly injections of either 100 mg testosterone enanthate or placebo for 7 weeks. The primary outcome was per cent change in lean body mass, and secondary outcomes included assessment of quality of life, tests of physical performance, muscle strength, daily activity levels, resting energy expenditure, nutritional intake, and overall survival.

Results: A total of 28 patients were enrolled, 22 patients were studied to completion, and 21 patients were included in the final analysis (12 placebo, nine testosterone). Adjunct testosterone increased lean body mass by 3.2% (95% confidence interval [CI], 0-7%) whereas those receiving placebo lost 3.3% (95% CI, -7% to 1%, P = 0.015). Although testosterone patients maintained more favourable body condition, sustained daily activity levels, and showed meaningful improvements in quality of life and physical performance, overall survival was similar in both treatment groups.

Conclusions: In patients with advanced cancer undergoing the early phase of standard of care therapy, adjunct testosterone improved lean body mass and was also associated with increased quality of life, and physical activity compared with placebo.

Keywords: Cachexia; Cancer; Female; Muscle; Quality of life; Testosterone.

© 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Figures

Figure 1

History of study participation from screening through analysis for patients with cervical (C) or head and neck (H/N) cancer. In this double‐blind study, cancer patients were randomly assigned to receive weekly doses of testosterone (T) or placebo (P) for 7 weeks. Blood chemistry was monitored for safety, and hormone levels tested regularly. Nutritional intake and activity was monitored throughout. Patients with pre and post‐treatment measurements were analysed for body composition (dual‐energy X‐ray absorptiometry), resting energy expenditure (REE), physical performance (Biodex and Short Physical Performance Battery), and quality of life questionnaires (General Functional Assessment of Cancer Therapy).

Figure 2

Overall survival of cervical or head and neck cancer patients for one year following 7 weeks of testosterone or placebo treatment (no patient data was censored before 12 months).

Figure 3

Baseline blood testosterone levels (A) for cervical and head and neck cancer patients. Horizontal line depicts a threshold of 300 ng/dL for men36 and 30 ng/dL for women.37 Average blood levels (±SD) of testosterone (B), free testosterone (C), and sex hormone‐binding globulin (D) for patients with head and neck or cervical cancer before and during 7 weeks of testosterone or placebo. Pre‐treatment levels were measured before beginning injections and treatment levels were the average of mid‐treatment and final measures.

Figure 4

Per cent change (±SD) in (A) total body mass, (B) bone mineral content, (C) lean body mass, (D) fat mass, and (E) body mass index at pre‐treatment, mid‐treatment, and post‐treatment intervals over 7 weeks for patients with cervical or head and neck cancer receiving testosterone or placebo. Significant difference in pairwise comparison with pre‐treatment values is denoted with ‘*’. Significant difference in per cent change between testosterone and placebo groups at mid‐treatment and post‐treatment time points are denoted with ‘‡’.

Figure 5

Peak torque (A) and peak power (B) generated by leg extension for head and neck or cervical cancer patients before during and after 7 weeks of testosterone or placebo treatment.

Figure 6

Average weekly activity budget over a 7 week study period for head and neck or cervical cancer patients receiving weekly placebo (A) or testosterone (B) injections. Activity was monitored by patient worn accelerometers and categorized by the per cent of total time spent in activity categories of sedentary, light activity, moderate activity, and vigorous activity. The number and per cent of total placebo (n = 12) and testosterone (n = 9) patients that met the minimum threshold of wearing the activity monitor at least 40% of the time for each week are listed below the axis. Vigorous activity averaged <0.5% of weekly activity at all time points and is therefore not discernable in these figures.