Androgen deprivation therapy and risk of rheumatoid arthritis in patients with localized prostate cancer.

Androgens are generally immunosuppressive, and men with untreated hypogonadism are at increased risk for autoimmune conditions. To date, there has been no evidence linking androgen deprivation therapy (ADT) to autoimmune diseases, including rheumatoid arthritis (RA). We investigated the association between ADT and RA in patients with prostate cancer.

We identified 105 303 men age 66 years or older who were diagnosed with stages I-III prostate cancer from 1992 through 2006 using the Surveillance, Epidemiology, and End Results-Medicare linked database, excluding patients with a history of RA. χ2 test was used to compare 5-year Kaplan-Meier rates of RA diagnoses. Competing risk Cox regression using inverse probability of treatment weighting was utilized to examine the association between pharmacologic ADT and diagnosis of RA.

The 43% of patients (N = 44 785) who received ADT experienced a higher 5-year rate of RA diagnoses compared with men who did not (5.4% versus 4.4%, P < 0.001). Receipt of any ADT was associated with a 23% increased risk of being diagnosed with RA (hazard ratio 1.23, 95% confidence interval 1.09-1.40, P = 0.001). The risk of being diagnosed with RA increased with a longer duration of ADT, from 19% with 1-6 months and 29% with 7-12 months to 33% with ≥13 months (Ptrend < 0.001).

Consistent with the immunosuppressive properties of androgens, we demonstrated for the first time that ADT was associated with an elevated risk of being diagnosed with RA in this large cohort of elderly men with prostate cancer. The risk was higher with a longer duration of ADT. Linking ADT to an increased risk of being diagnosed with an autoimmune condition adds to mounting evidence of the adverse effects of ADT that should prompt physicians to thoughtfully weigh its risks and benefits.

Annals of oncology : official journal of the European Society for Medical Oncology. 2018 Feb 01 [Epub]

D D Yang, A Krasnova, K T Nead, T K Choueiri, J C Hu, K E Hoffman, J B Yu, D E Spratt, F Y Feng, Q-D Trinh, P L Nguyen

Harvard Medical School, Boston., Center for Surgery and Public Health, Brigham and Women's Hospital, Boston., Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia., Department of Urology, Weill Cornell Medicine, New York., Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston., Department of Therapeutic Radiology, Yale University School of Medicine, New Haven., Department of Radiation Oncology, University of Michigan, Ann Arbor., Department of Radiation Oncology, University of California at San Francisco, San Francisco.