Association of Androgen Deprivation Therapy and Thromboembolic Events: A Systematic Review and Meta-analysis

Abstract

There is increasing evidence that androgen deprivation therapy (ADT) may be associated with thromboembolic event risk. Here we undertake a systematic review and meta-analysis of the association of ADT for prostate cancer with thromboembolic events. PubMed, Web of Science, and Scopus were queried April 5, 2017. The World Health Organization International Trials Registry Platform was queried June 23rd, 2017. Eligible studies reported thromboembolic events among individuals with prostate cancer exposed to ADT versus a lesser-exposed group. 569 unique studies were identified with 65 undergoing full-text review. We utilized the MOOSE statement guidelines and the Cochrane Review Group’s data extraction template. Study quality was evaluated by Newcastle-Ottawa Scale criteria. We conducted random-effects meta-analyses to calculate summary statistic risk ratios and 95% confidence intervals. Heterogeneity was quantified using the I2 statistic. Small study effects were evaluated using Begg and Egger statistics. In 10 studies “ADT without estrogen” increased the risk of thromboembolic events (RR 1.43, 95% CI 1.15-1.77, p=0.001). In 9 studies estrogen therapy alone was associated with an increased risk of thromboembolic events (RR 3.72, 95% CI 1.78-7.80, p<0.001). We found an increased risk of thromboembolic events from ADT use without estrogen when limited to localized disease (RR 1.10, 95% CI 1.05-1.16, p<0.001). Heterogeneity was resolved in those studies examining localized disease. There was no evidence of small study effects. The currently available evidence suggests that ADT without estrogen is associated with an increased the risk of thromboembolic events.