Androgen-deprivation therapy and the risk of stroke in patients with prostate cancer

Background: Some evidence indicates that androgen-deprivation therapy (ADT) increases the risk of diabetes and cardiovascular disease. To date, few studies have investigated whether this therapy also increases the risk of cerebrovascular events.

Objective: To determine whether different types of ADT increase the risk of stroke/transient ischaemic attacks (TIAs) in patients with prostate cancer.

Design, setting, and participants: We conducted a population-based cohort study using a nested case-control analysis within the United Kingdom's General Practice Research Database population. The cohort included all patients at least 40 yr of age newly diagnosed with prostate cancer between January 1, 1988, and December 31, 2008, and followed until December 31, 2009. Cases consisted of those who experienced a first-ever stroke/TIA during follow-up. Up to 10 controls were matched to each case on age, year of cohort entry, and duration of follow-up.

Measurements: Adjusted rate ratios (RRs) of stroke/TIA associated with the use of different ADTs (gonadotropin-releasing hormone [GnRH] agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, and others) were estimated using conditional logistic regression.

Results and limitations: The cohort included 22 310 patients with prostate cancer, followed for a mean of 3.9 yr, where 938 patients experienced a first-ever stroke/TIA (rate: 10.7 per 1000/yr). Compared with nonusers of ADT, current users of GnRH agonists (adjusted RR: 1.18; 95% confidence interval [CI], 1.00-1.39), oral antiandrogens (adjusted RR: 1.47; 95% CI, 1.08-2.01), and those who underwent bilateral orchiectomy (adjusted RR: 1.77; 95% CI, 1.25-2.39) were at an increased risk of stroke/TIA. No statistically significant increased risks were observed for patients on combined androgen blockade and other ADTs, but the small numbers do not rule out a possible association.

Conclusions: The results of this large population-based study provide additional evidence that different forms of ADT may increase the risk of stroke/TIA.