Erectile Dysfunction Epidemiology & Pathophysiology by Dr. Anmar Nassir

1. Erectile DysfuntionEPIDEMIOLOGY AND PATHOPHYSIOLOGY Dr. Anmar Nassir, FRCS(C) Canadian board in General Urology Fellowship in Andrology(U of Ottawa) Fellowship in EndoUrology and Laparoscopy (McMaster Univ) Assisstent Prof Umm Al-Qura Consultant Urology King Faisal Specialist Hospital

2. Before age 40  1- 9% • from 40 to 59  5-30% • from 60 to 69  20- 40% • men in their 70s and 80s50-75% 24 international studies between 1993 and 2003

3. Males : 40 and 70 years • 52% reported some degree of ED. • 40  70 the probability of: • complete impotence tripled from 5.1%  15% • moderate impotence doubled from 17%  34% • minimal impotence remained constant at 17%. • By the age of 70 years 68 % have ED. 1709 noninstitutionalized men The Massachusetts Male Aging Study 1994

4. ED in SA • 680 patients: AI El-sakka, 2004 International Journal of Impotence Research

5. ED = consistent or recurrent inability to attain and/or maintain penile erection sufficient for sexual performance.

6. Anatomy

8. Physiology

10. PENILE SMOOTH MUSCLE RELAXATION CAUSES ERECTION Sexual stimulation Sympathetic + parasymp Smooth muscle relaxation Arterial dilation + venous occlusion • Relaxation of the cavernous smooth muscle is the key to penile erection.

11. CNS psych imagination auditory Hypothalamus tactile memory Testosterone Sexual Ctre olfactory visual Estradiol Sympathetic + parasympathetic

12. Nitric oxide • Synthesis of NO is catalyzed by NOS, • converts l-arginine and oxygen  l-citrulline and NO. • NOS exists as three isoforms in mammals: • nNOS - in neurons cells • eNOS - in endothelial cells, • iNOS in virtually all cell types. • In the corpus cavernosum: • nNOS initiating erection • eNOS  sustaining erection. • Future: • Gene transfer of nNOS or eNOS to the penis has been shown to augment erectile responses in animal studies.

13. Nitric oxide • Upon entering the smooth muscle cells, stimulates the production of cGMP. • Cyclic GMP • activates protein kinase G, • opens potassium channels and closes calcium channels. • Low cytosolic calcium favors smooth muscle relaxation. • The smooth muscle regains its tone when cGMP is degraded by phosphodiesterase.

14. Phosphodiesterase • All PDEs have been identified in the corpus cavernosum • With the exception of PDE6, which is specifically expressed in photoreceptor cells. • PDE5 is the principal PDE for the termination of cavernous cGMP signaling. • Inhibition of the cGMP-catalytic activity of PDE5 by specific inhibitors has been shown to be highly effective in treating ED .

16. Nitric Oxide-cGMP Mechanism of Corpus Cavernosal Smooth Muscle Relaxationand Penile Erection 3 1 2

17. !!! • Other substrates relevant to vascular or cavernous smooth muscle functions are as follows: • Inositol 1,4,5-trisphosphate (IP3) receptor • IP3 receptor-associated PKG substrate (IRAG) • Phospholamban (PLB) • Heat shock-related protein (HSP20) • Myosin phosphatase (MP) • Phosphatase inhibitor-1 (PPI-1) • GTPase RhoA

18. Etiology Etiology of Erectile Dysfunction • For simplicity, erectile dysfunction can be classified as • Organic - due to vasculogenic, neurologic, hormonal, or cavernosal abnormalities or lesions • Psychogenic - due to central inhibition of the erectile mechanism without a physical insult However, in most patients with erectile dysfunction, a combination of organic and psychogenic components is involved.

19. A functional classification of impotence. • Note that it is unlikely for an individual patient’s impotence to derive solely from one source

20. Causes of ED

22. Major organic causes of ED

23. ED in SA • 680 patients: • Significant association to severity of ED: • diabetes, • hypertension, • dyslipidemia, • smoking, • increased BMI, AI El-sakka, 2004 International Journal of Impotence Research

24. Organic vs. psychogenic causes for ED

25. Psychogenic dysfunction • Two possible mechanisms to explain the inhibition of erection: • Direct inhibition of the spinal erection center by the brain • exaggeration of the normal suprasacral inhibition • Excessive sympathetic outflow or elevated peripheral catecholamine levels, • increase penile smooth muscle tone to prevent its necessary relaxation.

26. Organic dysfunction Diabetes Mellitus • Diabetes mellitus is a common chronic disease • Affecting 0.5% to 2% worldwide. • The overall prevalence of DM in KSA is 23.7%. • males  26.2% • females  21.5%. Saudi Med J. 2004 Al-Nozha et al

27. Organic dysfunction Diabetes Mellitus • The prevalence of ED is three times higher in diabetic men (28% versus 9.6%) • occurs at an earlier age, • increases with disease duration, being approximately 15% at age 30 and rising to 55% at 60 years

28. Chronic Renal Failure • Sexual dysfunction has been reported in 20% to 50% of men with chronic renal failure

29. Cavernous (Venogenic) • Failure of adequate venous occlusion is the most common causes of vasculogenic impotence. • It may result from: • degenerative tunical changes: Peyronie's disease, old age, and diabetes • fibroelastic structural alterations, • traumatic injury to the tunica albuginea: penile fracture • insufficient trabecular smooth muscle relaxation: anxious individuals with excessive adrenergic tone patients with inadequate neurotransmitter release • venous shunts

30. Anti HTN and ED • The underlying disorder may be more relevant for ED than the medication. • Thiazide diuretic • Associated with higher rates of ED, • This may be reduced by combination therapy and weight loss. • The α1 blockers and Angiotensin II receptor blocker • Tend to improve sexual functioning • Calcium Channel Blockers • No adverse effect on erection

31. Effect of Antihypertensive

32. Antipsychotics • The prevalence of sexual dysfunction ranged from 40% to 70%. • Newer agents such as clozapine showed a lower reduction in sexual desire. • The group taking risperidone had the greatest decrease in erectile frequency.

33. Antidepressants • Tricyclics • Antagonize 5-HT receptors. • Controlled clinical studies suggest that orgasmic disorders in both sexes are frequent, explaining the use of these drugs as inhibitors of ejaculation

34. Antidepressants • Monoamine oxidase inhibitors • associated with higher rates of orgasmic dysfunction in controlled trials

35. Antidepressants • Selective serotonin reuptake inhibitors(SSRIs) • Commonly used to treat depression. • They inhibit the reuptake of 5-HT into CNS neurons produce stimulatory effects on 5-HT receptors. • 50% of patients experience a change in sexual function • mainly anorgasmia, • adverse effects can be modified by co-treatment with sildenafil

36. Antidepressants • SSRIs differ in their ability to cause ED. • A high incidence has been observed in patients treated with paroxetine • A lesser impact has been reported with citalopram. • Thus, the ability to produce ED and the mechanism by which SSRIs cause ED may differ with the specific SSRI compound.

37. Antidepressants • Recently developed antidepressants such as mirtazapine and nefazodone tend to have beneficial effects on sexual function, • Possibly by activating the 5-HT1 C receptor, • augments sexual response, • But still antagonize the 5-HT2 C receptor.

38. Tobacco • Tobacco induce vasoconstriction and penile venous leakage. • Smokers reported an inverse correlation between nocturnal erection (both rigidity and duration) and the number of cigarettes smoked per day: • men who smoked more than 40 had the weakest and shortest nocturnal erections.