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

Abstract

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.

Trial registration: ISRCTN: 70274195, EudraCT: 2011-000677-31.

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: JSW receives speaker's honoraria from Eli Lilly and Sandoz, grant funding from Alexion and Immunodiagnostic Systems, donations of drug from Eli Lilly, Prostrakan (Kyowa Kirin) and Consilient for clinical studies, donations of assay kits from Biomedica, and consulting fees from Shire, Mereo Biopharma, Kyowa Kirin, UCB Pharma and PharmaCosmos. JMB received CRUK research grant funding for this project. JAS is Chair of the NHS England Specialised Commissioning Clinical Reference Group for Blood and Marrow Transplantation. REC has received consulting and speaker fees from Amgen, Astellas, Eisai, Genomic Health, Inbiomotion and Scancell; he is a patent holder for a biomarker developed by Inbiomotion; he is a former employee of prIME Oncology. RH is a member of Partnership in Cancer Centre London, Wimbledon. RJR is a Director of Diurnal Plc and owns stock. No other authors have competing interests.

Figures

Fig 1. CONSORT diagram.

CONSORT, Consolidated Standards of Reporting Trials; DXA, dual-energy X-ray absorptiometry.

Fig 2. Change in trunk fat mass, whole-body fat mass, and whole-body lean mass at 26 weeks in placebo and Tostran groups.

Boxes represent the IQR, circles indicate the mean, lines inside the box indicate the median, whiskers represent the range excluding outliers, and asterisks indicate outliers. IQR, interquartile range.

Fig 3. Change in trunk fat mass at 26 weeks in placebo and testosterone-treated groups by tertile of baseline trunk fat mass.

Boxes represent the IQR, circles indicate the mean, lines inside the box indicate the median, whiskers represent the range excluding outliers, and asterisks indicate outliers. IQR, interquartile range.