Clinical and Experimental Evidence for the Pathological Mechanisms Underlying Aspects of Sexual Dysfunction: Impact of Adiposity and Chronic Kidney Disease
Maio Twofoot, Maria Tina
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Cardiovascular disease (CVD) and erectile dysfunction (ED) have common etiologies, such as increased adiposity and chronic diseases. Incident ED is known to be a sentinel of CVD, providing a unique opportunity for early lifestyle interventions to attenuate the progression of disease. The internal pudendal artery (IPA) plays an important role in controlling resistance to penile blood flow and thereby erections. Although morphological and functional disturbances in the IPA have been associated with ED, few studies have characterized changes in the IPA as it relates to increased adiposity and chronic diseases (e.g., chronic kidney disease [CKD]). Finally, although both vascular calcification and ED have been shown to be prevalent in patients with CKD, there has yet to be an assessment of associated mechanisms. The effect of lifestyle modifications on erectile function was evaluated in both experimental and clinical settings. Specifically, the studies assessed the effect of caloric restriction (CR) in rats and of chronic exercise in sedentary, overweight or obese male and female subjects. In rats, structural and functional changes of the IPA and erectile responses were characterized in relation to increasing adiposity and to CKD. Experimentally, the susceptibility of various vascular beds to calcification in CKD was determined. Clinically, erectile and female sexual function was assessed in patients with Stage 3 to 5 CKD, who had no history of CVD. In rats, CR blunted the accumulation of abdominal adiposity, and attenuated progression of both endothelial dysfunction and ED, independently of morphological changes in the IPA. Rats with CKD had an increased frequency of ED, greater endothelial dysfunction, and altered vascular morphology, yet vascular calcification per se did not account for ED. In the clinical study, sedentary and overweight or obese males with ED, but not females, had a significantly higher body mass index (BMI) and waist circumference. Chronic exercise significantly improved ED and female sexual dysfunction (FSD). Clinically, CKD was associated with ED and FSD as well as increased coronary artery calcification and endothelial dysfunction. These findings support the concept that early detection of cardiovascular abnormalities, using incident ED as a sentinel, should facilitate early interventions in otherwise asymptomatic populations.