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

PLoS Med. 2019 Nov 12;16(11):e1002960. doi: 10.1371/journal.pmed.1002960. eCollection 2019 Nov.


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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adult
  • Body Composition / drug effects
  • Cancer Survivors
  • Double-Blind Method
  • Humans
  • Leukemia / complications
  • Lymphoma / complications
  • Male
  • Middle Aged
  • Placebo Effect
  • Quality of Life
  • Testicular Neoplasms / complications
  • Testicular Neoplasms / drug therapy*
  • Testosterone / pharmacology*
  • Testosterone / therapeutic use*
  • United Kingdom


  • Testosterone

Associated data

  • ISRCTN/ISRCTN70274195,
  • EudraCT/2011-000677-31