Androgen-deprivation therapy in treatment of prostate cancer and risk of myocardial infarction and stroke: a nationwide Danish population-based cohort study

Abstract

Background: Androgen-deprivation therapy (ADT) has been suggested to increase the risk for cardiovascular diseases, including myocardial infarction (MI) and stroke, but data are inconsistent.

Objectives: To investigate the association between ADT and risk for MI and stroke in Danish men with prostate cancer.

Design, setting, and participants: A national cohort study of all patients with incident prostate cancer registered in the Danish Cancer Registry from January 1, 2002, through 2010 was conducted.

Outcome measurements and statistical analysis: We used Cox regression analysis to estimate hazard ratios (HR) of MI and stroke for ADT users versus nonusers, adjusting for age, prostate cancer stage, comorbidity, and calendar period. Additionally, we stratified the analysis on preexisting MI/stroke status.

Results and limitations: Of 31,571 prostate cancer patients, 9204 (29%) received medical endocrine therapy and 2060 (7%) were orchidectomized. Patients treated with medical endocrine therapy had an increased risk for MI and stroke with adjusted HRs of 1.31 (95% confidence interval [CI], 1.16-1.49) and 1.19 (95% CI, 1.06-1.35), respectively, compared with nonusers of ADT. We found no increased risk for MI (HR: 0.90; 95% CI, 0.83-1.29) or stroke (HR: 1.11; 95% CI, 0.90-1.36) after orchiectomy. One limitation of the study is that information on prognostic lifestyle factors was not included and might have further informed our estimates.

Conclusions: In this nationwide cohort study of >30 000 prostate cancer patients, we found that endocrine hormonal therapy was associated with increased risk for MI and stroke. In contrast, we did not find this association after orchiectomy.

Keywords: Castration; Gonadotropin-releasing hormone; Myocardial infarction; Orchiectomy; Prostatic neoplasms; Stroke.