Defined as the consistent inability to attain and maintain an erection adequate for sexual intercourse Usually qualified by being present for several

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2 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): , 2003

3 Marwick C. JAMA. 281(23):2173-4, 1999

4 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

5 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): , 2009

6 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): , 2009

7 Erectile dysfunction in diabetic subjects in Italy. Men aged 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.

8 Duration of diabetes Glycemic control Chronic complications Smoking ORs: 1.5 (95% CI ) for current smokers and 1.4 (95% CI ) for ex-smokers. increased with number of cigarettes smoked per day Fedele D, et al. Diabetes Care. 21(11):1973-7, 1998

9 Neuropathy Fig. Mechanisms contributing to diabetic ED. Moore CR, Wang R. Asian J Androl. 8(6):675-84, 2006

10 Multifactorial Neurogenic Diabetic neuropathy Vasculogenic(arterial or cavernosal) Diabetes mellitus Lue TF. N Engl J Med. 342(24): , 2000 Caused by other systemic diseases and aging Diabetes mellitus

11 D/D with psychogenic ED Jackson G. Int J Clin Pract. 58(4):358-62, 2004

12 Penis (H&E, x3) Corpus spongiosum(h&e, x6) Penile erectile tissue (H&E, x30)

13 Lue TF. N Engl J Med. 342(24): , 2000

14 Adapted from Krane RJ, et al. N Engl J Med. 321(24): , 1989

15 Simonsen U, et al. J Vasc Res. 39(4): , 2002

16 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

17 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

19 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

20 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

21 Lue TF. N Engl J Med. 342(24): , 2000

22 McVary KT. N Engl J Med.357(24): , 2007

23 Toda N, et al. Pharmacol Ther. 106(2):233-66, 2005

24 Integration is in hypothalamus (MPOA, PVN) integrate tactile, olfactory, auditory and mental stimuli

25 Koppiker N, et al. Endocr Pract. 9(1):52-63, 2003

26 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): , 2009

28 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

29 The role of endothelial dysfunction in the pathophysiology of erectile dysfunction in diabetes and in determining response to treatment 33 men, aged 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

30 The role of endothelial dysfunction in the pathophysiology of erectile dysfunction in diabetes and in determining response to treatment 33 men, aged 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

31 Sáenz de Tejada I, et al. J Sex Med. 2(1):26-39, 2005

32 International index of erectile function (IIEF) Jackson G. Int J Clin Pract. 58(4):358-62, 2004

33 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

34 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: ; 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

35 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): , 2008

36 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): , 2008

37 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): , 2003

38 Prevalence of erectile dysfunction (ED) Mechanisms of normal physiology Pathogenesis of ED ED assessment Clinical significance of ED

MALE SEXUAL DYSFUNCTION. Urology Division, Surgery Department Medical Faculty, University of Sumatera Utara

MALE SEXUAL DYSFUNCTION. Urology Division, Surgery Department Medical Faculty, University of Sumatera Utara MALE SEXUAL DYSFUNCTION Urology Division, Surgery Department Medical Faculty, University of Sumatera Utara DEFINITION The inability to achieve a satisfactory sexual relationship May involve : - inadequacy