edited_VendeiraQ8_Layout 1 27/08/2009 17:09 Page 75
Diabetes-associated Erectile Dysfunction
and Ronald Virag
1. Department of Urology, S. João Central Hospital, Porto; 2. Association for the Advanced Study of Human Sexuality (iSEX);
3. Department of Biochemistry, Faculty of Medicine, University of Porto; 4. Laboratory for Molecular Cell Biology,
Faculty of Medicine, University of Porto; 5. Centre d’Explorations et Traitements de l’Impuissance, Paris
Erectile dysfunction (ED) is a common complication of diabetes, with a prevalence ranging from 15 to 55%. The basis underlying diabetes-
associated ED is multifactorial, involving changes in peripheral nerve activity and alterations in endothelial cell function. Due to the
complexity of this pathology, the development of experimental models has been crucial in evaluating and translating fundamental results
into clinical diabetes-associated ED. The concept of hard-to-treat patients, such as men with diabetes, is now fully accepted due to the
complex mechanisms involved. In these men, the response to common oral treatments with phosphodiesterase type 5 inhibitors (PDE5Is)
is far from desired, and maximal doses of the drugs are often needed. In addition, diabetes is commonly associated with other
co-morbidities, such as hypertension, hypercholesterolaemia and obesity, clusters of the metabolic syndrome (MetS). ED is considered an
early warning sentinel for coronary artery disease, just as endothelial dysfunction is seen as a major risk factor for ED. Testosterone
deficiency syndrome, a very common syndrome in diabetes and MetS, has been shown to be an independent determinant of endothelial
dysfunction, thus contributing to vascular pathology, including ED. This syndrome should be identified among patients, and therapeutic
intervention may be required. PDE5Is may improve erectile function with or without the help of other second- or third-line treatments.
Other strategies to maximise the response to PDE5Is include risk factor modification and daily dosing of the drugs, instead of on-demand
treatment. However, better understanding of the fundamental molecular mechanisms underlying diabetes-associated ED is essential to
improving and developing more effective therapies.
Diabetes, erectile dysfunction, endothelial dysfunction, phosphodiesterase type 5 inhibitors, penile nitric oxide release test (PNORT)
Disclosure: The authors have no conflicts of interest to declare.
Received: 5 May 2009 Accepted: 13 July 2009
Correspondence: Pedro Vendeira, Department of Urology, S João Central Hospital, EPE, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. E: firstname.lastname@example.org
Background and Animal Studies structural and functional properties of ECs and SM, leading to
Diabetes is an increasing disease worldwide, and it is estimated vascular dysfunctions.
that the number of cases will rise to 300 million globally by 2025.
Erectile dysfunction (ED) is a common complication of diabetes and Due to its complex pathophysiology, diabetes-associated ED is less
is responsible for a decreased quality of life in diabetic men,
who responsive to common oral treatments with phosphodiesterase type 5
have a three-fold higher risk of ED development compared with inhibitors (PDE5Is).
Therefore, a better understanding of the
healthy individuals. ED may also be the initial presentation of fundamental molecular mechanisms involved in diabetes-associated
diabetes in 12% of patients subsequently diagnosed with this ED is essential to the development of more effective targeted therapies.
In individuals with diabetes, ED occurs at an earlier age, In addition, diabetes is commonly associated with other co-morbidities,
is more severe and increases with disease duration, being such as hypertension, hypercholesterolaemia and obesity, clusters of
approximately 15% at 30 years of age and rising to 55% at 60 years the metabolic syndrome (MetS), which are considered independent
In individuals with diabetes, ED has been associated with vascular risk factors (VRFs) of endothelial dysfunction and ED.
the underlying neuropathic condition. However, it seems that as a VRFs may contribute to loss of endothelium actions in a synergistic
result of their location, cavernosal vascular endothelial cells (ECs) fashion and to the exacerbation of penile vasculopathy and severity of
are the primordial organ affected by this disease. In fact, metabolic ED. More importantly, it was suggested that ED may be not only a
derangements induced by hyperglycaemia and increased oxidative clinical manifestation of a pathology affecting the penile circulation but
stress disable penile EC functional response in order to maintain also an early warning sign of a more generalised vascular systemic
homeostasis, impairing the endothelium regulatory role on the disorder. In fact, all of the aforementioned VRFs are highly prevalent and
modulation of vascular- and smooth-muscle (SM) contractile tone, frequently co-exist in patients with coronary artery disease (CAD) and
which is crucial for normal erectile functionality. This loss of ED, with a common denominator of the presence of generalised
endothelial ability to vasodilate in response to local and systemic endothelial dysfunction.
Considering ED as a silent indicator of a more
changes is referred to as endothelial dysfunction and recognised as general vascular disorder is crucial for the prevention of cardiovascular
a key feature of diabetes-associated ED.
Ageing may also affect the events in patients with ED and asymptomatic CAD.
© TOUCH BRIEFINGS 2009 75