Drug Safety

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Androgen Deprivation Therapy for Prostate Cancer and the Risk of Rheumatoid Arthritis: A Population-Based Cohort Study

  • Adi J. Klil-Drori
  • Christina Santella
  • Koray Tascilar
  • Hui Yin
  • Armen Aprikian
  • Laurent AzoulayEmail author
Original Research Article



Two recent observational studies have investigated the association between androgen deprivation therapy (ADT) and rheumatoid arthritis (RA), but generated discrepant findings and had important methodological limitations. Thus, the objective of this study was to determine whether the use of ADT is associated with an increased risk of RA in men with prostate cancer.

Patients and Methods

We conducted a population-based cohort study using the United Kingdom Clinical Practice Research Datalink. The cohort included all men, at least 40 years of age, newly diagnosed with prostate cancer between 1 January 1988 and 31 March 2014, with follow-up until 30 September 2014. Exposure to ADT was treated as a time-varying variable and lagged by 1 year to account for diagnostic delays and latency. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of RA, comparing use of ADT with non-use. Secondary analyses were conducted to assess whether the association varied according to ADT type and cumulative duration of use. Finally, we conducted several sensitivity analyses to assess the robustness of our findings.


The cohort included 32,302 men followed for a median of 3.3 years. During follow-up, 63 patients were newly diagnosed with RA, generating an incidence rate of 46.5/100,000 person-years. Compared with non-use, the use of ADT was not associated with an increased risk of RA (HR 0.84, 95% CI 0.49–1.45). In secondary analyses, the association did not vary according to ADT type or with cumulative duration of use (p trend = 0.53). The results remained consistent in sensitivity analyses.


In this population-based study, the use of ADT was not associated with an increased risk of RA in men with prostate cancer.


Compliance with Ethical Standards


This study was funded by a Foundation Scheme Grant from the Canadian Institutes of Health Research. Dr Laurent Azoulay holds a Chercheur-Boursier Senior Award from the Fonds de la Recherche du Québec – Santé and is the recipient of a William Dawson Scholar Award from McGill University.

Conflict of interest

The funding source had no role in the design, analysis, or interpretation of the results. Adi Klil-Drori, Christina Santella, Koray Tascilar, Hui Yin, Armen Aprikian, and Laurent Azoulay have no conflicts of interest that are directly relevant to the content of this study.

Ethical approval

The study protocol was approved by the Independent Scientific Advisory Committee of the CPRD [protocol number 14_228A] and the Research Ethics Committee of the Jewish General Hospital, Montreal, Canada.

Supplementary material

40264_2019_847_MOESM1_ESM.pdf (87 kb)
Supplementary material 1 (PDF 87 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Adi J. Klil-Drori
    • 1
  • Christina Santella
    • 1
    • 3
  • Koray Tascilar
    • 1
    • 4
  • Hui Yin
    • 1
  • Armen Aprikian
    • 5
  • Laurent Azoulay
    • 1
    • 2
    • 3
    Email author
  1. 1.Center for Clinical Epidemiology, Jewish General HospitalLady Davis InstituteMontrealCanada
  2. 2.Gerald Bronfman Department of OncologyMcGill UniversityMontrealCanada
  3. 3.Department of Epidemiology, Biostatistics, and Occupational HealthMcGill UniversityMontrealCanada
  4. 4.Department of Internal MedicineUniversitätsklinikum ErlangenErlangenGermany
  5. 5.McGill University Health CentreMcGill UniversityMontrealCanada

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