Objective: To evaluate the relationship between erectile dysfunction (ED), based on the five-item International Index of Erectile Function questionnaire (IIEF-5), and presence of metabolic syndrome (MetS) or its components based on Adult Treatment Panel III guidelines. We also explored the impact of increasing insulin resistance (IR), as calculated using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) equation, on severity of ED. Pathophysiological links between ED and testosterone were re-evaluated. Patients and methods: In all, 357 patients with ED were evaluated; 53 patients with primary, psychogenic, surgical, post-traumatic or drug-induced ED were excluded. The remaining 304 patients were evaluated after obtaining written informed consent. The Institutional Review Board approved the study. We assessed comorbidities, IIEF-5 scores, lower urinary tract symptoms (LUTS) based on International Prostate Symptom Score (IPSS), blood sugars, lipid and hormonal profiles, and vitamin D3 levels. Further evaluation was done when indicated. Results: In all, 171 patients had MetS and 134 had pre-existing comorbidities (diabetes mellitus, 58; hypertension, 73; coronary artery disease, 13). The mean (SD) age was 44.6 (9.21) years and IIEF-5 score was 13.81 (3.17). ED severity was significantly correlated with presence of MetS. On multivariate analysis, there were significant correlations between ED and waist circumference, serum triglycerides, and fasting blood sugar. There was a statistically significant positive correlation between serum testosterone and IIEF-5 score (r = +0.292). The mean (SD) IR value (using the HOMA-IR formula) was 2.64 (2.87), which was statistically and negatively correlated with IIEF-5 scores (r = - 0.398). Receiver operating characteristic analysis showed that an IIEF-5 score of <14 predicted MetS and a HOMA-IR value of >2.1778 predicted MetS. Conclusion: MetS or its components were present in 56.25% of the patients. Therefore presence of ED merits further evaluation for presence of MetS. This may help to prevent catastrophic and life-threatening consequences of MetS. Abbreviations: BMI: body mass index; CRP: C-reactive protein; CVD: cardiovascular disease; DBP: diastolic blood pressure; DM: diabetes mellitus; ED: erectile dysfunction; FBS: fasting blood sugar; HDL: high-density lipoprotein; HOMA-IR- Homeostatic Model Assessment for Insulin Resistance; HTN: hypertension; IIEF-5: five-item version of the International Index of Erectile Function; IR: insulin resistance; LDL: low-density lipoprotein; LUTS: lower Urinary Tract Symptoms; MetS: metabolic syndrome; NO: nitric oxide; OR: odds ratio; PPBS: post-prandial blood sugar; ROC: receiver operating characteristic; SBP: systolic blood pressure; TG: triglyceride; WC: waist circumference.

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