Discussion
According to the American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice, the prevalence of obesity increased sharply. It continues to be a global problem over the past three decades. Not only adults but also children and adolescents are at risk of overweight or obesity [12]. To date, many reports have been published showing the association between MetS and cardiovascular diseases and ED and cardiovascular diseases. Still, only several analyses showed the associations between ED and MeTS. The common feature of the coronary and genital arteries’ destructive process is that these arteries have similar structures and are easily affected by risk factors such as MeTS. Cavernosal arteries tend to be involved at first glance due to their smaller diameters than coronary counterparts, and the presence of MeTS often worsens the ED [1]. The presence of the MeTS has been linked with a two-fold increased risk of ten years of cardiovascular events [13]. Liu et al. sought whether MetS was an independent risk factor for ED or just a silent marker of ED, and they showed in a meta-analytical study that MeTS significantly increased the risk for ED [14]. Smoking causes a decrease in endothelial elasticity over time through a direct toxic effect on the endothelium. [15]. Previous reports have reported that smoking has a dose-dependent impact on ED, and more than 20 years/pack smoking accelerates the ED process. In our study, smoking volumes were less than 20 packs/year for groups [16]. This finding could explain that the ED progressed similarly. However, in particular populations such as in patients with MeTS, it would not be misleading to think that a lower smoking volume could accelerate the ED process where complex risk factors coexistent. Smoking is an independent but preventable risk factor. Creamer et al. reported that three out of five smokers succeed in quitting in 2018 [17].
MeTS may predispose to ED by decreasing the circulating androgen level [18]. High blood lipid profile and high systolic blood pressure are associated with a decrease in endothelial elasticity [19], increased amounts of cytokines, adipokines, and fatty acids and their interactions with the endothelium cause decreased nitric oxide release, and subsequently, ED manifests. Increased cytokines, adipokines, fatty acids and their interactions with the endothelium cause decreased nitric oxide release, and later, ED embodies [6]. Patients with MeTS prone to have moderate to severe ED than those without MeTS [20]. The complexity of pathophysiological changes could be a challenging factor in patients with MeTS. In patients with MeTS, we observed a proportional increase in the severity of ED as the number of MeTS components increased. Indeed, in Group 1, the sum of severe and moderate ED rate was significantly higher than Group 2 (61.5% vs 39.1%). Although the decrease of total testosterone was similar in groups, the conversion of some circulating androgen levels upon the peripheric aromatase activity may accelerate the ED process [21].
Several reports have shown that mean VAI levels tend to rise in ED patients compared to non-ED patients [22,23]. Some authors have also reported an increase of VAI from different disciplines [24]. Our previous study showed that VAI increased in men with moderate and severe ED might be a reliable, independent risk factor for ED, especially at values above 4.33. We also concluded that researchers could use the VAI for monitoring the ED before it manifests or clinically manifested at a very early stage. However, as far as we know, the present study is the first to show that the mean VAI level in the MeTS arm increased by at least twice, reached 9.3 ±4.4. A significant increase of the VAI is suspected to increase ED upon several complex pathways. A decrease of endothelial nitric oxide release, low T / E2 secondary to circulating peripheral aromatase activity, increased circulating leptin, and diminished self-esteem may cause a potential increase in MeTS [10]. Still, any combination of multiple risk factors, including MeTS, could incredibly likely accelerate ED severity. As far as we know, this study is the first to show that the VAI level doubled in patients with MeTS. Our opinion is that researchers should take into account the rapid increase of the VAI in patients with MeTS. Contrary to previous reports, high VAI levels in patients with MeTS may challenge ED management. Therefore, management of such cases should cover a comprehensive metabolic and endocrinological evaluation in addition to andrological work up.
Contrary to current reports, some studies conflicting results that MeTS was not associated with an increased risk of ED. In one of them, the authors stated no difference in the prevalence of ED between men with or without MetS but, age, presence of depressive symptoms and lower education were significant predictors of ED [25]. Plata et al. also reported no relationship between MetS and ED among urological patients, probably due to the low prevalence of MetS [26]. The methodological settings of these studies due to the low number of MeTS patients might have been insufficient to explain the relationship between MeTS and ED.
Strengths & Limitations: This study’s main strength is the first to investigate very high VAI levels in men with ED in a specific risk group such as METS. Lack of assessment of the penile vascular system using penile duplex ultrasonography, lack of measurement of cytotoxic end-products that may interfere with endothelial function and only a single testosterone measurement using the enzyme-linked immunosorbent assay are the limiting factors.