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Does Testosterone Mediate the Relationship Between Vitamin D and Prostate Cancer? A Systematic Review and Meta-Analysis Protocol

Research output: Contribution to journalArticle

Original languageEnglish
Number of pages6
JournalSystematic Reviews
Issue number52
DateAccepted/In press - 6 Dec 2018
DatePublished (current) - 12 Feb 2019


Evidence from studies on prostate cancer progression have identified vitamin D to be a potentially important nutrient. However, the World Cancer Research Fund and American Institute for Cancer Research have reported the quality of this evidence to be limited and warrants further investigation. We plan to use the recently developed WCRF International/University of Bristol mechanistic systematic review framework to determine whether the observed association between vitamin D and prostate cancer exists through a plausible biological pathway.

This protocol sets out how we will perform a systematic review of the literature in human and animal studies. We will search the electronic databases MEDLINE, EMBASE, PubMed, and BIOSIS Citation Index without restrictions on year of publication or language. We will extract data from observational and experimental studies examining two inter-linked pathways in the relationship between vitamin D and prostate cancer progression: 1) vitamin D and testosterone, and 2) testosterone and prostate cancer progression. We focus on testosterone as its actions form a potentially novel intermediate mechanism that was identified via our online literature mining tools. The outcomes of interest include incidence or prevalence of prostate cancer, measures of prostate cancer progression (including biochemical recurrence, local or distal metastases) and prostate cancer-specific mortality. We will assess study quality and the level of certainty of the evidence. We will analyse data where possible, using meta-analysis with forest plots or albatross plots; otherwise a narrative synthesis will be performed.

To our knowledge, this will be the first systematic synthesis of the evidence underpinning the vitamin D-testosterone-prostate cancer mechanistic pathway. The results of the review may inform future research, intervention trials and public health messages.

    Research areas

  • Vitamin D, systematic review, mechanistic pathway, prostate cancer, testosterone

    Structured keywords

  • ICEP

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  • s13643-018-0908-1

    Rights statement: This is the final published version of the article (version of record). It first appeared online via Springer Nature at Please refer to any applicable terms of use of the publisher.

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    Licence: CC BY


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