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.