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Diabetes-associated Erectile Dysfunction
penile circulation and ultrastructural changes in the SM and tunica Figure 1: Apoptosis Assay in Control Individual without
albuginea lead to inadequate filling of the cavernous bodies and an
Diabetes or Erectile Dysfunction (A) and Human
Cavernosal Tissue from a Patient with Diabetes and
inability to achieve penile rigidity. This condition is frequent in
Erectile Dysfunction (B)
diabetes patients and is called caverno-venous leakage.
AB
Diabetes-associated Erectile Dysfunction
Recent studies are unanimous concerning the role of risk factors for ED.
In fact, age, hypertension and duration of diabetes are significantly
associated with the presence and severity of ED. Glycated haemoglobin
(HbA
1c
) levels and waist circumference are additional predictors of ED.
27
Increased insulin resistance has also been associated with endothelial
dysfunction and impaired NO signalling in corporeal SM.
28,29
Men with
the characteristics of MetS, including obesity and physical inactivity, are
Labelled in green: cavernosal endothelial cells in apoptosis detected by TUNEL assay (24);
at an increased risk of ED.
30
In addition, of particular severity for ED is
Labelled in blue: all cavernosal nuclei stained with DAPI (4',6-diamidino-2-phenylindole) (24).
Magnification: x200.
the association of diabetes and smoking.
Table 1: Basic Evaluation of Erectile Dysfunction in
A considerable body of evidence exists suggesting a link between
Individuals with Diabetes
reduced testosterone plasma levels, type 2 diabetes and insulin
resistance. In fact, low testosterone precedes elevated fasting insulin,
1. IIEF-5
glucose and HbA
1c
values and may even predict the onset of diabetes.
2. Check for other vascular risk factors
Traish et al.
31
suggest that androgen deficiency is associated with type
Smoking habits
2 diabetes, MetS and increased deposition of visceral fat, which serves Hypertension
as an endocrine organ, producing inflammatory cytokines and thus Hypercholesterolaemia
promoting endothelial dysfunction and vascular disease. Although
Obesity (waist circumference)
endothelial dysfunction and oxidative stress are common factors in 3. Biological evaluation
both type 1 and type 2 diabetes, androgen deprivation and veno-
HbA
1c
occlusive disorders may play a larger part in ED associated with type 2
Creatinine
diabetes. In fact, type 2 diabetes is associated with components of
Cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides
MetS and provides a unique environment in which ED develops.
32
Testosterone (total, free and/or bioavailable)
Testosterone deficiency syndrome (TDS) was shown to be an
4-Echo-doppler of penile arteries
PNORT
independent determinant of endothelial dysfunction, thus contributing
If abnormal PNORT:
to vascular pathology, including ED.
33
As TDS contributes to MetS
pharmaco-Doppler after intracavernous injection of PGE1;
pathologies that adversely affect the endothelium, resulting in multiple
or electromyography
vascular injuries, it can also be regarded as a common denominator of
HbA = glycated haemoglobin; IIEF = International Index of Erectile Function; 1c
the various pathologies affecting endothelium and a central factor in PNORT = penile nitric oxide release test.
the development of MetS.
34
Many studies have confirmed that
testosterone is important in modulating the regulation of erectile attention of their specialist concerning ED, which is an important
function.
35,36
Animal studies have shown that testosterone deprivation complication of the disease. In fact, ED is one of the most frequent
reduces intracavernosal pressure. In addition, testosterone deprivation concerns of men with diabetes. Questionnaires, such as the
affects erectile function and induces structural alterations in the International Index of Erectile Function (IIEF), particularly the shorter
corpus cavernosum, with veno-occlusive dysfunction.
37,38
Therefore, version, IIEF-5, are recommended for easy self-evaluation of the patients
testosterone treatment may be a valuable option in the management regarding the quantification of the decrease or lack of erections (see
of hypogonadal men with ED. Table 1). In these men, loss of sexual appetite and/or ejaculation
problems are frequent. Loss of sexual appetite is commonly linked to
TDS may also be associated with other components of MetS, such as decreased testosterone levels, and ejaculation problems occur due to
increased triglyceride levels. ED patients with MetS and diabetes also retrograde or absent ejaculations linked to peripheral neuropathy.
have a higher prevalence of TDS.
39
Interestingly, TDS may play two
different roles in type 1 diabetes and type 2 diabetes patients. In type In addition to the IIEF, systemic endothelial dysfunction, a key feature
1 diabetes there is a microcirculation defect in the testes that causes of diabetic-associated ED, should also be assessed. The most
alterations in their vascularisation and a decrease in testosterone common non-invasive techniques are Doppler flow-mediated dilation
production. In type 2 diabetes, and particularly in cases of MetS (FMD) of the brachial artery
40
and digital plethysmography.
41
Regarding
and/or obesity, there is a switch in the metabolism with the ED, a more specific non-invasive local test for endothelial function
transformation of testosterone in estradiol. Because TDS plays an evaluation is the PNORT, which assesses the FMD of the cavernous
important role in diabetes, the use of testosterone supplementation arteries.
25,26
As stated previously,
24
the severity of diabetic penile
has been suggested as part of the treatment regimen, alone or in endothelial alterations is directly related to a lower PNORT response.
association with PDE5I. In addition, below a certain PNORT index these patients are
unresponsive to PDE5Is. PNORT is able to determine patients with low
Evaluation in Diabetes-associated Erectile Dysfunction response who will need further evaluation by duplex scan echography
Questionnaires and evaluation of ED should be part of any diabetic care after intracavernous injections (ICIs) of vasoactive medications,
facility unit. Many patients with diabetes complain of the lack of especially prostaglandin E1 (PGE1), and exploring arterial lesions and
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