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Androgen deprivation therapy and the risk of parkinsonism in men with prostate cancer

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Abstract

Purpose

Case reports and anecdotal experiences suggest that some men develop parkinsonism after initiating androgen deprivation therapy (ADT) for the treatment of prostate cancer, possibly due to neurophysiological effects of changes in testosterone and/or estrogen. We hypothesized that ADT would increase the risk of parkinsonism.

Methods

Using linked administrative databases in Ontario, Canada, men age 40 or older with prostate cancer on continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 38,931) were matched 1:1 with men with prostate cancer who had never received ADT. Treated and untreated groups were range-matched on age at index date and year of diagnosis, and propensity-matched on comorbidities, medications, cardiovascular risk factors, and socio-economic variables. A competing risk analysis was conducted where the primary outcome was time to a new diagnosis of parkinsonism.

Results

The cohort was followed for a mean of 5.76 years. Based on the results from the multivariable cause-specific hazard regression model, the adjusted relative rate of experiencing parkinsonism among ADT users compared to non-users was 0.74 (95% confidence interval (CI) 0.67–0.83, p < 0.0001). The adjusted relative rate of experiencing the competing event of death among ADT users compared to non-users was 1.33 (95% CI 1.30–1.36, p < 0.0001). The 5-year incidence of parkinsonism was 1.03% in ADT users versus 1.56% in non-users.

Conclusion

Contrary to our hypothesis, continuous ADT use for at least 6 months in men with prostate cancer was not associated with an increased risk of parkinsonism after accounting for the substantial competing risk of death.

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Author contributions

JWSY Project development, data analysis, and manuscript writing/editing. RS Project development, data analysis, and manuscript writing/editing. JR Data collection/management, data analysis, and manuscript writing/editing. CM Project development and manuscript writing/editing. NF Project development and manuscript writing/editing. SMHA Project development, data analysis, and manuscript writing/editing.

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Authors and Affiliations

  1. Departments of Medicine, University of Toronto, Toronto, ON, Canada

    James W. S. Young & Shabbir M. H. Alibhai

  2. Department of Neurology, University of Toronto, Toronto, ON, Canada

    Connie Marras

  3. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Neil Fleshner

  4. The Institute for Clinical Evaluative Sciences, Toronto, ON, Canada

    Rinku Sutradhar & Jagadish Rangrej

  5. Brampton Civic Hospital, N4. 760, 2100 Bovaird Drive East, Brampton, ON, L6R 3J7, Canada

    James W. S. Young

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  1. James W. S. Young
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  2. Rinku Sutradhar
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  4. Connie Marras
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  6. Shabbir M. H. Alibhai
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Correspondence to James W. S. Young.

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The authors declare that they have no conflict of interest.

Ethical standards

Ethics approval was obtained from the University Health Network. As all data were anonymized from existing databases and results were presented in aggregate; the requirement for informed consent was waived.

Funding/support

Financial support was provided in part by the Toronto General & Toronto Western Hospital Research Foundation.

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Young, J.W.S., Sutradhar, R., Rangrej, J. et al. Androgen deprivation therapy and the risk of parkinsonism in men with prostate cancer. World J Urol 35, 1417–1423 (2017). https://doi.org/10.1007/s00345-017-2010-z

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  • DOI: https://doi.org/10.1007/s00345-017-2010-z

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