Effects of metformin on endothelial health and erectile dysfunction

Erectile dysfunction (ED) affects approximately 18 million American men. ED may be attributed to several etiologies, including arteriogenic, psychogenic, neurogenic, hormonal, drug-induced, and systemic disease or aging related factors. Specific to arteriogenic ED, three major mechanisms have been identified: (I) endothelium-dependent vasodilatory impairment; (II) sympathetic nerve activity elevation; (III) atherosclerotic luminal narrowing. Additionally, these insults have been linked to the insulin resistant state, which in turn is comorbid with obesity, dyslipidemia, diabetes, and hypertension. In this review, we summarize the evidence regarding the impact of metformin-an insulin sensitizer-on the three mechanisms of arteriogenic ED. We report that metformin treatment positively affects two of three pathways, specifically through enhanced endothelium-dependent vasodilation and sympathetic nerve activity attenuation, but does not seem to have a significant impact on hypertension regulation. Given the encouraging data found in both animal and clinical studies, we advocate for further studies on metformin use in ED.