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Purpose Tobacco cigarette smoking and decreased concentrations of testosterone are major risk factors of erectile dysfunction (ED) and independent predictors of cardiovascular disease (CVD). We investigated, whether testosterone deficiency has a complementary predictive value for CVD events in smokers with ED. Methods A cohort of 398 men with ED and without known atherosclerotic CVD (mean age: 55±10 years) were followed for the occurrence of major adverse cardiovascular events (MACE), (CVD death, coronary artery disease, stroke). Total testosterone (TT) levels were measured in all patients. Results Among the study population, 205 (52%) were smokers. During a mean follow-up of 6 years (range: 1–11 years), 30 (7.5%) patients demonstrated a MACE. Baseline TT levels were significantly lower and prevalence of smoking was higher in the CV-event group than the event-free survival group (P&amp;lt;0.01 and P&amp;lt;0.05, respectively). Kaplan–Meier analysis showed that patients with low TT (≤4.0 ng/mL) had a worse prognosis than patients with TT &amp;gt;4.0 ng/mL (log rank: 6.52, P=0.011), and that smokers had a greater risk of adverse events than never smokers (log rank: 4.42, P=0.04). We then stratified all patients into four groups, on the basis of smoking status (current/never smokers) and low or high TT (≤ or &amp;gt;4.0 ng/mL) and cardiac event-free survival curves were constructed by Kaplan–Meier analysis (figure). The event-free rate in smokers with low TT is significantly lower than that of smokers with low TT or never smokers with normal TT (log rank: 11.3, P=0.02). Smokers with low TT had an almost 4-fold higher risk of MACEs compared to never smokers with normal TT (adjusted hazard ratio: 3.91; P=0.030). Conclusion Cigarette smoking combined with low TT concentration is associated with a shorter event-free period compared with either smoking or testosterone deficiency alone. The measurement of testosterone concentration may be useful to further stratify the risk of ED smokers without known CVD. Funding Acknowledgement Type of funding sources: None. Smoking testosterone deficiency and MACE

Low testosterone is associated with increased risk of major adverse cardiovascular events in smokers with erectile dysfunction