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

Background: 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. Patients and methods: 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. Results: 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). Conclusions: 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.

Androgen deprivation therapy for prostate cancer and dementia risk: a systematic review and meta-analysis.

BACKGROUND: Androgen deprivation therapy (ADT) to treat prostate cancer may be associated with an increased risk of dementia, but existing studies have shown conflicting results. Here we synthesize the literature on the association of ADT for the treatment of prostate cancer with dementia risk. METHODS: We conducted a systematic review of articles reporting the outcome of dementia among individuals with prostate cancer in those exposed to ADT versus a lesser-exposed comparison group (for example, ADT versus no-ADT; continuous versus intermittent ADT) using PubMed (1966-present), Web of Science (1945-present), Embase (1966-present) and PsycINFO (1806-present). The search was undertaken on 4 December 2016 by two authors. We meta-analyzed studies reporting an effect estimate and controlling for confounding. Random- or fixed-effects meta-analytic models were used in the presence or absence of heterogeneity per the I2 statistic, respectively. Small study effects were evaluated using Egger and Begg's tests. RESULTS: Nine studies were included in the systematic review. Seven studies reported an adjusted effect estimate for dementia risk. A random-effects meta-analysis of studies reporting any dementia outcome, which included 50 541 individuals, showed an increased risk of dementia among ADT users (hazard ratio (HR), 1.47; 95% confidence interval (CI), 1.08-2.00; P=0.02). We separately meta-analyzed studies reporting all-cause dementia (HR, 1.46; 95% CI, 1.05-2.02; P<0.001) and Alzheimer's disease (HR, 1.25; 95% CI, 0.99-1.57; P=0.06). There was no evidence of bias from small study effects (Egger, P=0.19; Begg, P=1.00). CONCLUSION: The currently available combined evidence suggests that ADT in the treatment of prostate cancer may be associated with an increased dementia risk. The potential for neurocognitive deficits secondary to ADT should be discussed with patients and evaluated prospectively.