Insulinorresistencia y disfunción eréctil: Efecto del tratamiento con metformina / Insulin resistance and erectile dysfunction: Effect of treatment with metformin

La erección depende de la liberación de óxido nítrico (ON) endotelial. La insulinorresistencia (IR) produce disfunción endotelial por menor síntesis y liberación de ON. El tratamiento con metformina mejora la función eréctil en ratones con IR y disfunción eréctil (DE). Objetivos: Evaluar en pacientes con DE: 1) la presencia de IR; 2) el grado de severidad de la DE según la presencia de IR y 3) el efecto del tratamiento con metformina sobre la función eréctil en pacientes con DE e IR. Material y métodos: Estudio prospectivo, randomizado, doble ciego con placebo. Se incluyeron 81 pacientes con DE y 20 hombres sin DE (grupo control). Se evaluó función eréctil con el cuestionario IIEF-5. Se evaluó IR con el índice HOMA. Se consideró IR si HOMA ≥3. Treinta pacientes con DE, IR y pobre respuesta al sildenafil fueron randomizados para recibir tratamiento con metformina o placebo. Resultados: Se encontró una diferencia significativa entre pacientes con DE y el grupo control en HOMA: 4.9±2.8 versus 3.6±2.6 (p=0.03). La prevalencia de IR fue mayor en los pacientes con DE que en el grupo control: 77.7% versus 45.0% (p=0.008). Se halló una correlación negativa entre HOMA e IIEF-5: r:-0.21 (p=0.04). Los pacientes con DE e IR tuvieron menor score IIEF-5 que los pacientes con DE sin IR. Luego del tratamiento con metformina, los pacientes con DE tuvieron un incremento significativo en el score IIEF-5 y una disminución significativa del HOMA a los 2 y 4 meses de tratamiento, no se observaron cambios en IIEF-5 ni HOMA en los pacientes que recibieron placebo. Conclusión: nuestros hallazgos hacen suponer que la disfunción endotelial causada por IR podría ser uno de los mecanismos fisiopatológicos de la DE. El tratamiento con metformina en pacientes con DE reduce la IR y podría mejorar la respuesta al tratamiento con sildenafil. Rev Argent Endocrinol Metab 47: 13-20, 2010. Los autores declaran no tener conflictos de interés.

Erection depends largely on the release of nitric oxide (NO) by vascular endothelium. Insulin resistance (IR), present in most subjects who have obesity, metabolic syndrome (MS) or type 2 diabetes mellitus (DM2) is a metabolic abnormality that produces endothelial dysfunction determined by minor synthesis and release of NO. Treatment with metformin improves erectile function in mice with erectile dysfunction (ED) and IR. Aims: To evaluate in ED patients: 1) the presence of IR; 2) the degree of severity of ED according to the presence of IR; 3) the effect of treatment with metformin on erectile function in patients with ED and IR. Methods: Prospective, randomized, controlled, double-blind placebo study. We included 81 patients with ED and 20 men without ED (control group). Exclusion criteria: pharmacologic, anatomic or endocrine ED (hypogonadism or hyperprolactinemia), DM2, prior prostatic surgery or chronic illnesses. The erectile function was rated according the International Index of Erectile Function 5. IR was measerud by HOMA index. Thirty patients with ED, IR and poor response to sildenafil were randomized to receive metformin or placebo. Results: Patients with ED had higher HOMA index versus control group: 4.9 ± 2.8 versus 3.6 ± 2.6, p=0.03. The prevalence of IR was higher in ED group versus control group: 77.7% versus 45.0%, p=0.008. We found a negative correlation between HOMA and IIEF-5: r:-0.21, p=0.04. Patients with ED and IR (n=62) had lower IIEF-5 score when compared with those without IR (n=19): 13.6 ± 4.3 versus 16.0 ± 3.1, p=0.04. After treatment with metformin patients with ED showed a significant increase in IIEF-5 score and a significant decrease in HOMA index both at 2 and 4 months of treatment. Changes in the IIEF-5 score and HOMA index were not observed in patients with ED receiving placebo. Conclusion: Our findings suggest that endothelial dysfunction caused by IR could be one of the pathophysiologial mechanisms of ED. Treatment with metformin in patients with ED reduces IR and could improve response to treatment with sildenafil. Rev Argent Endocrinol Metab 47: 13-20, 2010 No competing finantial interests exist.

Altered testicular hormone production in infertile patients with idiopathic oligoasthenospermia.

We studied the kinetics of testicular response to human chorionic gonadotropin (hCG) in oligoasthenospermic and asthenospermic patients (OAZ-AZ). The responses of testosterone (T), androstenedione (A), 17 OH-progesterone (17OHP), and estradiol (E2) were evaluated in 60 OAZ-AZ patients and compared to those of 10 normal men. The responses of T, A, and 17OHP to hCG in the control group displayed a biphasic pattern with an initial peak at 4 hours and a second peak after 24 hours. The E2 response showed a single peak between 24 and 48 hours after hCG administration. OAZ-AZ patients had two types of T responses: group 1 (n = 40) had no first peak and group 2 (n = 20) had a normal response pattern. The response of A was similar to that of T, and the E2 response was normal in both groups. There were three types of 17OHP responses in group 1 (low, high, or normal); however, the 17OHP response was normal in group 2. Treatment of group 1 with aromatase inhibitors (aminoglutethimide or testolactone) induced an improvement of the acute T response only in patients with high or normal 17OHP response to hCG, whereas no effects were observed in patients with low 17OHP response. In group 2, the aromatase inhibitors induced no changes in the T response. These results demonstrate that in some OAZ-AZ patients (group 1, blunted T response) testicular hormone production is altered. They also suggest the presence of two enzyme blocks: one at the 17,20 desmolase level, mediated by E2, and another at early biosynthetic steps, not mediated by E2.