ORIGINAL ARTICLE Diabetes and male sexual function Khaleeq Rehman MBBS MS, Evette Beshay MD PhD, Serge Carrier MD FRCSC K Rehman, E Beshay, S Carrier. Diabetes and male sexual Diabète et fonctionnement sexuel chez les function. J Sex Reprod Med 2001;1(1):29-33. hommes Diabetes mellitus (DM) is the most common cause of erectile RÉSUMÉ : Le diabète sucré (DS) est la cause la plus fréquente de dysfunction (ED). Up to 28% of men complaining of ED have dysérection; il en est le principal facteur étiologique jusque dans 28 % des cas. Le DS devrait être envisagé chez tous les patients DM as the primary causative factor. DM should be considered qui consultent pour de la dysérection. Il faudrait inciter les in all patients presenting with ED. Known diabetic men hommes diabétiques à maîtriser parfaitement leur glycémie should be encouraged to have excellent control of their DM to pour éviter non seulement les complications chroniques du DS avoid not only the chronic complications of DM but also its mais aussi ses effets immédiats, notamment l'effet de l'hypergly- acute effects, especially the effect of hyperglycemia on erectile cémie sur le fonctionnement érectile. Il sera question, dans le function. The physiological impact of diabetes on sexual présent article, des répercussions physiologiques du diabète sur function in men is reviewed. le fonctionnement sexuel chez les hommes. Key Words: Diabetes mellitus; Ejaculation; Erectile dysfunction; Sexual function; Sexuality exuality is an important aspect in the lives of most indi- ED is usually progressive in these patients, with more than Sviduals and couples. Normal sexual function involves, 50% of diabetic men affected after 10 years of DM (3). however, the interaction and coordination of multiple com- However, ED can occasionally be the first presenting ponents, including psychological, physiological, social, reli- symptom of a new onset of DM. The appropriate treatment gious and emotional factors. Chronic medical conditions, of DM often produces a return of erectile function. such as diabetes, may have an impact on many of these com- Treatment with an oral hypoglycemic medication or ponents, not only physiologically, but also psychologically. insulin does not influence the subsequent development of Over two million Canadians are afflicted with diabetes, the ED. majority (90%) with type 2 diabetes, which is the most com- ED is often associated with microangiopathy; thus, the mon form of adult diabetes. The prevalence of diabetes presence of retinopathy is usually a good predictor of ED (4-6). increases with age. The number of people with diabetes is Age, duration of DM and the presence of other diabetic com- expected to grow substantially as the population ages. plications correlates more with its future development. Diabetes has a detrimental effect on sexual function. The Between the ages of 40 to 70 years, the prevalence of ED is present article briefly reviews the physiological impact of 52% for the general population, whereas in age-matched dia- diabetes on sexual function in men. betics, it is as high as 75% (7). For men younger than 40 years of age, the prevalence of ED is 7.8%, but for men older than Diabetic erectile dysfunction 40 years of age, it increases to 63% for type 1 diabetics and Diabetes mellitus (DM) is the most common cause of 71.1% for type 2 diabetics (8). The use of alcohol or antihy- erectile dysfunction (ED) (1). Up to 28% of men who com- pertensive medication appears to increase the risk of ED in plain of ED have DM as the primary causative factor (2). this population. Department of Surgery, Division of Urology, McGill University, Montreal, Quebec Correspondence: Dr S Carrier, Department of Urology, McGill University Health Center, 687 Pine Avenue West S6-92, Montreal, Quebec H3A 1A1. Telephone 514-842-1231 ext 4302, fax 514-843-1552, e-mail [email protected] Sex Reprod Med Vol 1 No 1 Summer 2001 29 Rehman et al The pathophysiology of ED in diabetes is not well under- Although autonomic nerve testing is found to be abnormal stood (9). Associated neuropathy or vasculopathy (microan- in up to 63% of patients with diabetic ED, some studies have giopathy and generalized vascular disease) is considered to shown no difference from control values. be the most important factors in the pathophysiology of NO has been identified as the principal neurotransmitter DM-induced ED (10). causing the relaxation of penile cavernous smooth muscle. Recently, attention has been increasingly directed toward This smooth muscle relaxation increases arterial blood flow understanding the role of vascular endothelium and its con- and produces an erection. It has been shown in diabetic rats trol of penile cavernous smooth muscle tone (11). The two that NO synthase, the enzyme that catalyses the production corpus cavernosum, which are the erectile bodies of the of NO in cavernosal tissue, decreased even with insulin penis, consist of multiple lacunar spaces surrounded by cav- treatment (41). The ED in these diabetic rats did not ernous smooth muscle. These lacunar spaces are lined by the improve, suggesting that permanent nerve injury to the endothelium. During sexual activity, neurotransmitters nonadrenergic, noncholinergic nerves may contribute to (nitric oxide [NO] being the most important) are released abnormal response. from either the penile nerve ending or the endothelium that Oxidative stress has recently been implicated in the triggers a relaxation of both cavernosal arteries and smooth pathogenesis of diabetic complications. The deleterious muscle. This increases penile blood flow, causes dilation of effects of high glucose concentrations on cultured Schwann the lacunar space and, eventually, an erection. In DM, it has or endothelial cells appear to be related, in part, to rates of been shown that endothelium-dependent smooth muscle glucose auto-oxidation to advanced glycosylation end prod- relaxation is impaired, although the exact mechanism is not ucts (42). In the course of glucose auto-oxidation, hydrogen known (12,13). Endothelial dysfunction (the small ed) then peroxide is generated from molecular oxygen via the dismu- leads to erectile dysfunction (the big ED) through smooth tation of superoxide anion, thus exerting an additional muscle dysfunction in the microvascular tree of the penis. oxidative stress. The interaction of advanced glycosylation Acute hyperglycemia alone may induce endothelial dys- end products with sulfhydryl-containing proteins, altered function and also decrease the velocity of nerve conduction prostanoid production, and ischemia/reperfusion are fur- in rodents (14,15). Chronic hyperglycemia is associated with ther important sources of reactive oxygen species (ROS) in the loss of myelinated and unmyelinated fibres and attenu- diabetic tissues (43). Interestingly, insulin itself may, under ated nerve fibre regeneration. Diffuse abnormalities of the certain circumstances, activate a membrane-bound hydro- peripheral nerve vasculature (vasa nervosum) are well doc- gen peroxide generating system that could theoretically umented in diabetics (16-20). In the late stages of diabetes, exacerbate oxidative stress in susceptible tissues (44). This there may be complete vascular occlusion with atherosclero- oxidative stress, in turn, may conceivably exhaust local sis, thickening of capillary basement membrane, dilation antioxidant defenses and thereby promote lipid peroxida- and microaneurysms of capillaries as well as endothelial tion of cellular membranes, cytoskeletal damage and ulti- hyperplasia, and desquamation and degeneration of peri- mately cellular degeneration. Furthermore, mitochondrial cytes (21-25). These lesions induce a microangiopathy that DNA mutations have been reported in diabetic tissues (45), leads to endoneurial hypoxia and demyelination. The suggesting oxidative stress-related mitochondrial damage. lesions decrease the blood flow to the vaso nervosum and, Attention has also been recently focused on the role of thus, lead to nerve ischemia (26). A peripheral neuropathy ROS in vascular dysfunction in diabetes, particularly then develops, which initially affects small unmyelinated regarding the reaction of NO with superoxide anion to fibres. Around 61.2% of diabetics who present with impo- form peroxynitrate, a very potent ROS (46). tence show evidence of neuropathy (27). The clinical affect of DM on penile blood flow has been In erectile tissue, there is atrophy of the smooth muscle well documented. Patients with insulin-dependent diabetes cells and lipid deposition in the corpus cavernosum (24). and associated coronary artery disease have significantly Urogenital nerves also show morphological alterations, more severe disease related to the cavernosal artery than nerve conduction is impaired and neurotransmitter levels noninsulin-dependent diabetic patients (47). Benvenuti et al are altered (28-32). Vasoactive intestinal polypeptide (48) proposed that, in diabetic ED, vascular obstruction is a immunoreactivity, and acetylcholine synthesis and release more important factor than nerve damage. The main com- have been shown to be reduced in nerves from diabetic plication of diabetes is atherosclerosis. Increased activation patients (33,34). In the penis, smooth muscle shows of protein kinase C, overexpression of endothelin and impaired neurogenic and endothelium–dependent relax- angiotensin II, increased synthesis of diacylglycerol, oxida- ation (35,36). The dorsal nerve of the penis is involved in tive stress and increased