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Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis
  1. Jesse Elliott1,
  2. Shannon E Kelly1,
  3. Adam C Millar2,
  4. Joan Peterson3,
  5. Li Chen1,
  6. Amy Johnston1,
  7. Ahmed Kotb4,
  8. Becky Skidmore5,
  9. Zemin Bai1,
  10. Muhammad Mamdani6,
  11. George A Wells1
  1. 1 Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
  2. 2 Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  3. 3 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  4. 4 School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
  5. 5 Independent Information Specialist, Ottawa, Ontario, Canada
  6. 6 Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
  1. Correspondence to Professor George A Wells; gawells{at}


Objective To assess the relative effects of individual testosterone products among hypogonadal men.

Design Systematic review and network meta-analysis.

Methods We searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (25 May 2017) for randomised-controlled trials (RCTs) and non-randomised studies (NRS) that involved hypogonadal men given testosterone replacement therapy (TRT) for ≥3 months. Comparators were placebo, another TRT, or the same product at a different dose. Outcomes were quality of life, depression, libido, erectile function, activities of daily living and testosterone levels, as well as cardiovascular death, myocardial infarction, stroke, prostate cancer, heart disease, diabetes, serious adverse events, withdrawals due to adverse events and erythrocytosis. RCT data were pooled via meta-analysis and network meta-analysis. Risk of bias was assessed using Cochrane’s risk of bias tool (RCTs) andScottish Intercollegiate Guidelines Network (SIGN)50 (NRS).

Results Eighty-seven RCTs and 51 NRS were included. Most were at high or unclear risk of bias, with short treatment duration and follow-up. When compared as a class against placebo, TRT improved quality of life (standardised mean difference (SMD) −0.26, 95% CI −0.41 to –0.11), libido (SMD 0.33, 95% CI 0.16 to 0.50), depression (SMD −0.23, 95% CI −0.44 to –0.01) and erectile function (SMD 0.25, 95% CI 0.10 to 0.41). Most individual TRTs were significantly better than placebo at improving libido (6/10). Only one TRT was better than placebo at improving quality of life, and no individual TRTs improved depression or erectile function. There was no increased risk of adverse events, with the exception of withdrawals due to adverse events with the use of some TRTs.

Conclusion Despite a class effect of improving quality of life, depression, erectile function and libido, major improvements were not observed with the use of any individual product. We observed no statistically significant increase in the risk of adverse events; however, longer-term high-quality trials are needed to fully assess the risk of harm.

PROSPERO registration number CRD42014009963.

  • testosterone
  • benefits
  • depression
  • quality of life
  • erectile function
  • libido
  • harms
  • cardiovascular-related adverse events
  • systematic review
  • network meta-analysis

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  • Contributors JE, SEK, MM and GAW designed the study. BS developed and executed the search strategy. JE, SEK, JP, AJ, AK and ZB selected studies for inclusion and extracted data. JE, AK and LC analysed the data. JE, SEK, LC, ACM and GAW interpreted the data. JE wrote the first draft of the manuscript, which was critically revised for intellectual content by all authors. All authors approved the final version submitted for publication and agree to be accountable for all aspects of the study.

  • Funding This study was supported in part by the Ontario Drug Policy Research Network, which is funded by a grant from the Ontario Ministry of Health and Long-Term Care Health System Research Fund.

  • Competing interests MM has received honoraria for serving on Advisory Boards for Astra Zeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Hoffman La Roche, Novartis, Novo Nordisk and Pfizer, outside the submitted work. BS is a paid information consultant/contractor to the Ottawa Hospital Heart Institute. All other authors have declared no conflicts of interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Additional data are presented in supplemental files.

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