Androgen deprivation therapy reversibly increases endothelium-dependent vasodilation in men with prostate cancer

Androgen deprivation therapy (ADT) is a standard treatment for patients with aggressive prostate cancer. Although ADT improves survival, it increases the risk of diabetes. Emerging evidence suggests that ADT increases adverse cardiovascular events as early as 3 months after initiation in patients with cardiovascular disease, but the mechanism is unknown. We hypothesized that ADT may impair endothelium-dependent vasodilation due to increases in lipids and insulin resistance and may provide a link for heightened cardiovascular risk in this population.

We prospectively evaluated conduit artery endothelium-dependent and -independent vasodilation, lipids, and insulin resistance in 16 consecutively treated men (mean age 66 ± 7 years; 25% with diabetes) with prostate cancer before and after 3 months of ADT. High-resolution B-mode ultrasound was used to assess flow-mediated (endothelium-dependent) and nitroglycerine-mediated (endothelium-independent) brachial artery vasodilation. ADT significantly increased insulin resistance, total cholesterol, HDL, and LDL. Endothelium-dependent vasodilation was greater at 3 months than at baseline (10.8% [interquartile range: 7.7% to 14.6%] versus 8.9% [interquartile range: 4.0% to 12.6%], respectively; P=0.046, allometric P=0.037). Nitroglycerine-mediated vasodilation did not change from baseline (P>0.2). The subset of participants on ADT for 6 months returned for reevaluation at 1 year. In this group, endothelium-dependent vasodilation increased from baseline to 3 months and returned to baseline 6 months after ADT withdrawal (9.4% [interquartile range: 6.9% to 10.9%], 11.6% [interquartile range: 7.9% to 15.2%], and 9.0% [interquartile range: 5.1% to 12.5%], respectively; P=0.05).

In contrast to our expectation, ADT improved endothelium-dependent vasodilation and its cessation returned endothelium-dependent vasodilation to baseline. Determining the mechanism of this change requires further investigation.