Defined as the consistent inability to attain and maintain an erection adequate for sexual intercourse Usually qualified by being present for several months and occurring at least half the time. Vinik AI, et al. Diabetes Care. 26(5):1553-79, 2003
Marwick C. JAMA. 281(23):2173-4, 1999
Erectile dysfunction (ED) is the most neglected complications of diabetes mellitus A detailed review of 428 charts of male diabetic patients from 10 general practices in UK 53% prevalence Documented in only 8% Only 1%: told about possible treatment options Hackett GI. Diabetes Res 28:75-83, 1995
Incidence: 35-75% (20-52% of T1DM, 36-54% of T2DM) Prevalence differences according to types of DM The majority of prevalence studies have not distinguished between type 1 and type 2 diabetes Malavige LS, Levy JC. J Sex Med. 6(5):1232-47, 2009
Fig. Prevalence of ED in the past 5 years among men with type 2 diabetes versus men with no diabetes. Malavige LS, Levy JC. J Sex Med. 6(5):1232-47, 2009
Erectile dysfunction in diabetic subjects in Italy. Men aged 20-69 years with a diagnosis of IDDM or NIDDM who were observed on randomly selected days in 178 diabetes centers in Italy. Of the 9,868 diabetic men interviewed, 3,534 (35.8%) reported ED. Fedele D, et al. Diabetes Care. 21(11):1973-7, 1998
Duration of diabetes Glycemic control Chronic complications Smoking ORs: 1.5 (95% CI 1.3 1.6) for current smokers and 1.4 (95% CI 1.3 1.6) for ex-smokers. increased with number of cigarettes smoked per day Fedele D, et al. Diabetes Care. 21(11):1973-7, 1998
Neuropathy Fig. Mechanisms contributing to diabetic ED. Moore CR, Wang R. Asian J Androl. 8(6):675-84, 2006
Multifactorial Neurogenic Diabetic neuropathy Vasculogenic(arterial or cavernosal) Diabetes mellitus Lue TF. N Engl J Med. 342(24):1802-13, 2000 Caused by other systemic diseases and aging Diabetes mellitus
D/D with psychogenic ED Jackson G. Int J Clin Pract. 58(4):358-62, 2004
Penis (H&E, x3) Corpus spongiosum(h&e, x6) Penile erectile tissue (H&E, x30)
Lue TF. N Engl J Med. 342(24):1802-13, 2000
Adapted from Krane RJ, et al. N Engl J Med. 321(24):1648-59, 1989
Simonsen U, et al. J Vasc Res. 39(4):283-303, 2002
Phase 0 Sympathetic nerve stimulation keeps penis flaccid (arterioles and cavernosal smooth muscle contracted) Phase 1 (Filling) Parasympathetic nerve stimulation, arteriolar dilatation and trabecular relaxation. Sinusoids fill, no increase in pressure Phase 2 (Tumescence) Pressure rises, fall in inflow, flow becomes systolic only, venous plexi compressed, penis elongates Phase 3 (Full erection) Pressure rises to 90% systolic. Compression of emissary veins
Phase 4 (Rigid erection) Pudendal nerve, ischiocavernosus contracts Pressure exceeds systolic Inflow ceases. Penis is closed space Phase 5 (Initial detumescence) Skeletal muscle fatigues Sympathetic nerves activated Phase 6 (Slow detumescence) Trabecular smooth muscle contracts Helicines constrict Pressure begins to fall Phase 7 (Fast detumescence) Sympathetic nerve stimulation Fall in inflow and in pressure, with rapid increase in venous outflow
Sympathetic pathways responsible for detumescence regulate arterial blood flow Parasympathetic pathways excitatory input to penis vasodilatation of penile vasculature relaxation of corporal smooth muscle Somatic NS Afferent Aδand C via dorsal nerve of penis and pudendal Pudendalefferentssupply ischio-and bulbocavernosus muscles Giuliano F, et al. Am J Physiol. 273(6 Pt 2):R1990-7, 1997
Nerves in Corpora Cavernosa Adrenergic and Cholinergic α 1 receptors in erectile tissue Noradrenaline is the main adrenergic transmitter α 2 in vessels NO the main cholinergic transmitter Non-Adrenergic Non-Cholinergic (NANC) NO VIP large amounts of neuropeptide Y
Lue TF. N Engl J Med. 342(24):1802-13, 2000
McVary KT. N Engl J Med.357(24):2472-81, 2007
Toda N, et al. Pharmacol Ther. 106(2):233-66, 2005
Integration is in hypothalamus (MPOA, PVN) integrate tactile, olfactory, auditory and mental stimuli
Koppiker N, et al. Endocr Pract. 9(1):52-63, 2003
Reduced or absent parasympathetic activity needed for relaxation of the smooth muscle of the corpus cavernosum Malavige LS, Levy JC. J Sex Med. 6(5):1232-47, 2009
Apoptotic pathways are present in the cavernous nerves Selective nitrergic degeneration result in decreased nnosactivity and diminished NO production resulting in impaired nitrergicrelaxations in the corpus cavernosumof diabetics oxidative damage through the formation of oxygen free radicals contribute to the neurodegeneration Impairment in vasodilatoryneurons versus the unaltered sympathetic neurons
The role of endothelial dysfunction in the pathophysiology of erectile dysfunction in diabetes and in determining response to treatment 33 men, aged 35 65 years, with ED (20 diabetic, 13 non-diabetic) IIEF questionnaire, endothelial function and autonomic function *Endothelial function: assessed by changes in brachio-radial and femoro-tibialarterial pulse-wave velocity (pulse-wave velocity) during reactive hyperemia, expressed as percentage endothelium-dependent dilatation. Pegge NC, et al. Diabet Med. 23(8):873-8, 2006
The role of endothelial dysfunction in the pathophysiology of erectile dysfunction in diabetes and in determining response to treatment 33 men, aged 35 65 years, with ED (20 diabetic, 13 non-diabetic) IIEF questionnaire, endothelial function and autonomic function *Autonomic function: assessed by heart rate variation during expiration and inspiration (E/I ratio) and during the valsalva maneuver. Pegge NC, et al. Diabet Med. 23(8):873-8, 2006
Sáenz de Tejada I, et al. J Sex Med. 2(1):26-39, 2005
International index of erectile function (IIEF) Jackson G. Int J Clin Pract. 58(4):358-62, 2004
Designed to distinguish psychogenic from organic, and vascular from neuropathic impotence Doppler ultrasound measurement of brachial and penile systolic blood pressure Nocturnal penile tumescence and rigidity measurement by strain gauge Penile response to intracavernosalinjection of vasodilators Bulbocavernousreflex response latency and sensory tests
ED as a predictor of CV events and death in diabetic patients with angiographically proven asymptomatic CAD Case-control studies Type 2 diabetic men (n=291) with silent CAD angiographically, F/U period of 47.2±21.8 months ED was associated with a higher rate of MACE (log-rank test: 41.847; p < 0.001). Fig. Kaplan-Meier analysis in diabetic patients with silent coronary artery disease Gazzaruso C, et al. J Am Coll Cardiol. 51(21):2040-4, 2008
Erectile dysfunction predicts coronary heart disease in type 2 diabetes A consecutive cohort of men with no clinical evidence of CVD (2,306 subjects) Ma RC, et al. J Am Coll Cardiol. 51(21):2045-50, 2008
Erectile dysfunction predicts coronary heart disease in type 2 diabetes Fig. Kaplan-Meier analysis in diabetic patients with silent coronary artery disease Ma RC, et al. J Am Coll Cardiol. 51(21):2045-50, 2008
Clinical impacts marker for the development of generalized vascular disease and for premature demise from a myocardial infarct Penile failure may be a portent of upcoming, and possibly preventable, cardiovascular events. in diabetics, alert the physician to perform cardiovascular evaluation. Vinik AI, et al. Diabetes Care. 26(5):1553-79, 2003
Prevalence of erectile dysfunction (ED) Mechanisms of normal physiology Pathogenesis of ED ED assessment Clinical significance of ED