Addition of metformin to sildenafil treatment for erectile dysfunction in eugonadal nondiabetic men with insulin resistance. A prospective, randomized, double-blind pilot study.

Erection depends largely on the release of nitric oxide (NO) by vascular endothelial cells. Insulin resistance (IR) is a metabolic abnormality that produces endothelial dysfunction characterized by decreased synthesis and release of NO. The aim of this paper is to evaluate the effect of treatment with metformin on the response to sildenafil in patients with erectile dysfunction (ED) and IR enrolled in a prospective, randomized, controlled, double-blind placebo study. We included 30 male patients with ED, IR, and poor response to sildenafil. Exclusion criteria included pharmacologic, anatomic, or endocrine ED; diabetes; prostatic surgery; or chronic illnesses. Erectile function was rated according to the International Index of Erectile Function 5 (IIEF-5); IR was measured by homeostasis model assessment (HOMA; IR = HOMA ≥ 3). Patients were randomized to receive metformin (n = 17) or placebo (n = 13). After treatment with metformin, patients with ED showed a significant increase in IIEF-5 score and a significant decrease in HOMA, both occurring at month 2 (IIEF-5: 17.0 ± 6.0 vs 14.3 ± 3.9, P = .01; HOMA: 3.9 ± 1.6 vs 5.5 ± 2.4, P = .01) to 4 of treatment (IIEF-5: 19.8 ± 3.8 vs 14.3 ± 3.9, P = .005; HOMA: 4.5 ± 1.9 vs 5.5 ± 2.4, P = .04), with no changes in these parameters in patients with ED receiving placebo. Patients treated with metformin had more adverse events than those who received placebo: 61.5% compared with 7.7%, P = .03, respectively. Adverse events were mild, mainly gastrointestinal, and did not cause discontinuation of treatment. Treatment with metformin in patients with ED and poor response to sildenafil reduced the IR and improved erectile function.

Erectile dysfunction, obesity, insulin resistance, and their relationship with testosterone levels in eugonadal patients in an andrology clinic setting.

Erectile dysfunction (ED) is associated with metabolic and endocrine diseases including obesity, metabolic syndrome (MS), and type 2 diabetes mellitus (DM2). Insulin resistance (IR), present in patients with obesity, MS, and DM2, causes disturbances in the signaling pathways required for nitric oxide production, with subsequent endothelial dysfunction. In addition, IR appears to alter testosterone production. We evaluated in eugonadal patients with ED: 1) the presence of obesity and IR, 2) testosterone levels and their association with obesity and IR, and 3) the degree of ED according to the presence of IR. In a prospective study, 78 eugonadal patients with ED (group P) were recruited and compared with 17 men without ED as a control group (group C). Erectile function was evaluated according to the International Index of Erectile Function 5 (IIEF-5). IR was measured by homeostasis model assessment (HOMA). IR was defined as HOMA of 3 or greater. Patients with ED had significantly higher body mass index (BMI), waist circumference (WC), HOMA values, and prevalence of IR when compared with group C. Total (TT) and bioavailable testosterone (BT) levels were lower in group P compared with group C. There was a significant negative correlation between HOMA and IIEF-5, HOMA and TT, WC and IIEF-5, WC and TT, and WC and BT. Group P patients with IR had higher WCs and lower IIEF-5 scores when compared with patients in group P without IR. In conclusion, patients with ED showed a higher BMI, WC, and HOMA and lower levels of TT and BT. There is a negative correlation between erectile function and IR and abdominal obesity. The TT levels are lower in patients with increased BMI, WC, and IR. However, a negative correlation was shown only between BT (biologically active fraction) and abdominal obesity.