SUN-055 Reduction of Mortality and Major Adverse Cardiovascular Events (MACE) in Men with Hypogonadism Treated with Long-Term Testosterone Therapy (TTh) with Testosterone Undecanoate Injections (TU): 10-Year Data from a Registry Study in a Urological Setting

Abstract

Background: 3 studies reported an increased cardiovascular risk with TTh while hundreds of studies have demonstrated cardiovascular benefits of TTh in men with hypogonadism. Material and Methods: A prospective, cumulative registry study to investigate long-term effectiveness and safety of depot TU to treat hypogonadism was established in 2004 in a urological setting. Of 805 hypogonadal men, 412 received parenteral TU 1000 mg/12 weeks following an initial 6-week interval (T-group) for up to 12 years. 393 men opted against TTh and served as controls (CTRL). Mean changes over time between groups were compared by mixed effects model for repeated measures with random effect for intercept and fixed effects for time, group and their interaction and adjusted for age, weight, waist circumference, fasting glucose, blood pressure and lipids to account for baseline differences between groups. Results: Baseline age: 57.7±7.4 (T-group), 63.7±4.8 years (CTRL) (p<0.001). Total follow-up time comprised approximately 6.500 patient-years. Testosterone levels at baseline were 9.7 nmol/L in both groups (p=0.841). Anthropometry: 66.3% (T-group) and 48% (CTRL) were obese. Waist circumference decreased by 9.9 cm (T-group) and increased by 4.4 cm (CTRL). Weight decreased by 16.6% (T-group) and increased by 4.6% (CTRL). Glycemic control: 34.2% (T-group) and 43.3% (CTRL) had type 2 diabetes. HbA1c decreased by 2.1% (T-group) and increased by 2.1% (CTRL). Lipids: HDL increased by 1.5 mmol/L (T-group) and by 0.9 mmol/L (CTRL). LDL decreased by 1.6 mmol/L (T-group) and increased by 0.9 mmol/L (CTRL). Non-HDL decreased by 4.1 mmol/L (T-group) and increased by 3.3 mmol/L (CTRL). Blood pressure (BP): systolic BP decreased by 21.2 mmHg (T-group) and increased by 9 mmHg (CTRL), diastolic BP decreased by 11.3 mmHg (T-group) and increased by 5.2 mmHg (CTRL). In the T-group, 45 patients (10.9%) had had a previous myocardial infarction (MI), in CTRL, 43 patients (10.9%) (p=0.993). 162 men (39.3%) had been smokers at baseline, 145 (36.9%) in CTRL (p=0.359). The mean baseline Framingham risk score was 15.5 in the T-group and 15.8 in CTRL (p<0.05). The mean 10-year risk was 22.7% in the T-group and 23.5% in CTRL (p=0.11). The risk declined in the T-group to 17% after 1 year and 13% after 2 years and remained stable thereafter. In CTRL, risk remained unchanged during the first 4 years and then increased to 29% for the remaining observation period. During the entire observation, there were 16 deaths (3.9%) in the T-group. In CTRL, there were 74 deaths (18.8%), 70 MIs (17.8%) and 59 strokes (15%). The reduction of cardiovascular events by TTh after applying a linear mixed effect model was 24.7% and 15.5% after applying a random effect longitudinal model. Medication adherence in the T-group was 100 per cent as all TU-injections were performed in the office and documented. Conclusions: In hypogonadal men, long-term TTh reduces MACE and mortality.