Improvement of endothelial function following initiation of testosterone replacement therapy

BACKGROUND: Isolated recent studies have suggested an increased risk of heart attack as early as 3 months following testosterone replacement therapy (TRT). Such a rapid risk increase would likely require rapid deterioration of arterial endothelial function. Our goal was to assess arterial endothelial function in hypogonadal men prior to and at least 3 months after initiation of TRT. METHODS: Adult men were consented if they had symptoms of hypogonadism, a total testosterone <350 ng/dL, and planned to begin TRT. Endothelial function was non-invasively assessed using the EndoPAT-2000 machine. We measured the augmentation index (AI) (normal <3%), a measure of arterial stiffness and reactive hyperemia index (RHI), a measure of endothelial vasodilation (normal >1.69). Prior studies suggest that a 10% level of day-to-day test variability is expected. Endothelial function was reassessed at the next clinic visit, between 3 and 6 months if the patients were compliant with therapy. Changes in continuous variables were assessed with the paired t test. RESULTS: Twenty-three patients were consented with a mean age of 52.7 years (range, 34–68 years) and starting testosterone 196.9 ng/dL (range, 35–339 ng/dL). There was a history of diabetes in four, hypertension in ten and coronary artery disease in five. Mean RHI was 1.67±0.37 (70% were abnormal) and mean AI was 2.57%±14.0% (39% were abnormal). There were no cardiac events. At follow-up 20 patients were compliant with therapy and retested. Mean testosterone increased from 203 to 511 (P<0.0001). Mean RHI improved from 1.70 to 2.14 (P=0.01). Mean AI improved from 2.9% to −1.75% (P=0.01). In four men RHI worsened but in each case less than the 10% error of the test. No man had worsened AI. CONCLUSIONS: Men with symptomatic hypogonadism often have abnormal arterial endothelial function. Following TRT, endothelial function either remains unchanged or improves.