ERECTILE DYSFUNCTION

By Dr Alalade B.AEDM Division

LUTH

outline

• Introduction• Definition• Aetiology• Pathophysiology• Investigation• Treatment• Conclusion• References

ANATOMY

• The penis is composed of 3 spongy cylinders. The three cylinders consist of paired corpora cavernosa and a single corpus spongiosum.The tunica albuginea consists of layers of collagen. The substance of the corpora cavernosa consists of numerous sinusoids among trabeculae of smooth muscles and supporting connective tissue

• The dorsal artery provides for engorgement of the glans during erection, whereas the bulbourethral artery supplies the bulb and the corpus spongiosum. The cavernous artery effects tumescence of the corpus cavernosum and thus is principally responsible for erection. The cavernous artery gives off many helicine arteries, which supply the trabecular erectile tissue and the sinusoids. These helicine arteries are contracted and tortuous in the flaccid state and become dilated and straight during erection.

• Venous drainage of the corpora originates in tiny venules that lead from the peripheral sinusoids immediately beneath the tunica albuginea. These venules travel in the trabeculae between the tunica and the peripheral sinusoids to form the subtunical venous plexus before exiting as the emissary veins .

• Nerve supply• Autonomic nerves consist of sympathetics that

arise from lumbar segments L1 and L2 and parasympathetics from S2-4 (nervi erigentes or pelvic nerve).

• Somatic innervation arises from sacral spinal segments S2-4 via the pudendal nerve.

• Sexual behavior involves the participation of autonomic and somatic nerves and the integration of numerous spinal and supraspinal sites in the central nervous system . The penile portion of the process that leads to erections represents only a single component

• The hypothalamic and limbic pathways play an important role in the integration and control of reproductive and sexual functions. The medial preoptic center, paraventricular nucleus, and anterior hypothalamic regions modulate erections and coordinate autonomic events associated with sexual responses.

neurotransmitters and receptors

• Adrenergic nerve fibres and receptors present in the cavernous trabeculae and sorround the deep penile artery

• Noradrenaline• Acetylcholine• Nitric oxide.• Others are VIP,.Prostanoids,calcitonin gene-

related peptide

• Normal erectile process• Erections occur in response to tactile, olfactory, and

visual stimuli. The ability to achieve and maintain a full erection depends not only on the penile portion of the process but also on the status of the peripheral nerves, the integrity of the vascular supply, and biochemical events within the corpora. The autonomic nervous system is involved in erection, orgasm, and tumescence. The parasympathetic nervous system is primarily involved in sustaining and maintaining an erection, which is derived from S2-S4 nerve roots.

ERECTION

• Penile erections are produced by an integration of physiologic processes involving the central nervous, peripheral nervous, hormonal, and vascular systems.Erection involves sinusoidal relaxation, arterial dilatation, and venous compression.

• It could be• Psychogenic:audiovisual• Reflexogenic ;tactile stimulation• Nocturnal -during sleep

• Sexual stimulation triggers release of neurotransmitters from the cavernous nerve terminals. This results in relaxation of these smooth muscles and the following events:

• Dilatation of the arterioles and arteries by increased blood flow in both the diastolic and the systolic phases

• Trapping of the incoming blood by the expanding sinusoids• Compression of the subtunical venular plexuses between the tunica

albuginea and the peripheral sinusoids, reducing the venous outflow

• Stretching of the tunica to its capacity, which occludes the emissary veins between the inner circular and the outer longitudinal layers and further decreases the venous outflow to a minimum

Erectile dysfunction

• Definitions• The National Institutes of Health (NIH)

Consensus Development Conference on Impotence defined erectile dysfunction as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance.

• Approximately 50% of diabetic men will suffer from ED within 10 years of the diagnosis. ED is widely regarded as a manifestation of more systemic vascular disease and is likely to precede a coronary event by 5 years

• Other forms of male sexual dysfunction include poor libido and problems with ejaculation

DSM 5 criteria

• In75-100% sexual activity, the experience of at least 1 of the following 3 symptoms:

• (1) marked difficulty in obtaining an erection during sexual activity, (2) marked difficulty in maintaining an erection until the completion of sexual activity,

• (3) marked decrease in erectile rigidity

• The symptoms above have persisted for approximately 6 months

• The symptoms above cause significant distress to the individual

• The dysfunction cannot be better explained by nonsexual mental disorder, a medical condition, the effects of a drug or medication, or severe relationship distress or other significant stressors

aetiology

• ED usually has a multifactorial etiology. Organic, physiologic, endocrine, and psychogenic factors are involved in the ability to obtain and maintain erections. In general, ED is divided into 2 broad categories, organic and psychogenic.

• Conditions that may be associated with ED include diabetes, hypertension,CAD, neurologic disorders, endocrinopathies, benign prostatic hyperplasia, and depression.Any disease may affect erectile function by altering the nervous, vascular, or hormonal systems..

• Vascular causes• Atherosclerosis, Peripheral vascular disease,

Myocardial infarction, Arterial hypertension, Vascular injury from radiation therapy

• Endocrine conditions. Hyperthyroidism,Hypothyroidism,Hypogonadism,Diabetes

Systemic diseases

• Diabetes mellitus, Scleroderma ,Renal failure, Liver cirrhosis,Idiopathic hemochromatosis, Cancer and cancer treatment,Dyslipidemia, Hypertension

• Neurologic causes.Epilepsy,Stroke,Multiple sclerosis,Guillain-Barré syndrome ,Alzheimer disease,Trauma

• Respiratory disease. Chronic obstructive pulmonary disease,Sleep apnea,

• Penile conditions. Peyronie disease, Epispadias, Priapism• Psychiatric conditions.Depression,Widower

syndrome,Performance anxiety ,Posttraumatic stress disorder• Medications .

Antihypertensives,antidepressants,Antipsychotics,Antiulcer agents (eg, cimetidine),5-Alpha reductase inhibitors (eg, finasteride and dutasteride),Cholesterol-lowering agents

• Conditions associated with reduced nerve and endothelium function (eg,aging, hypertension, smoking, hypercholesterolemia, and diabetes) alter the balance between contraction and relaxation factors leading to arterial insufficiency.

Pathophysiology

• The balance between contraction and relaxation is controlled by central and peripheral factors that involve many transmitters and transmitter systems.

• The nerves and endothelium of sinusoids and vessels in the penis produce and release transmitters and modulators that control the contractile state of corporal smooth muscles.

• Factors that mediate contraction in the penis include noradrenaline, endothelin-1, neuropeptide Y, prostanoids, angiotensin II, and others not yet identified..

• Factors that mediate relaxation include acetylcholine, nitric oxide (NO), vasoactive intestinal polypeptide, pituitary adenylyl cyclase–activating peptide, calcitonin gene–related peptide, adrenomedullin, adenosine triphosphate, and adenosine prostanoids

• Nitric oxide pathway• The NO pathway is of critical importance in the

physiologic induction of erections. The drugs currently used to treat ED were developed as a result of experimental and clinical work showing that NO released from nerve endings relaxes the vascular and corporal smooth muscle cells of the penile arteries and trabeculae, resulting in an erection.

• In the corpora cavernosa, NO activates guanylate cyclase, with increase in cyclic guanosine monophosphate (cGMP). Relaxation of vascular smooth muscles by cGMP leads to vasodilation and increased blood flow.

• Alteration of NO levels is the focus of several approaches to the treatment of ED. Inhibitors of phosphodiesterase, which primarily hydrolyze cGMP type 5, provided the basis for the development of the PDE5 inhibitors.

• Sexual stimulation causes the release of neurotransmitters from cavernosal nerve endings and relaxation factors from endothelial cells lining the sinusoids. NOS produces NO from L-arginine, and this, in turn, produces other muscle-relaxing chemicals, such as cGMP and cyclic adenosine monophosphate (cAMP), which work via calcium channel and protein kinase mechanisms.

Management

• The first step in the management of ED is a thorough history that includes the following:

• Sexual history• Medical history• Psychosocial history

• A physical examinationof the genitourinary, vascular, and neurologic systems. A focused examination entails evaluation of the following:

• Blood pressure• Peripheral pulses• Sensation• Status of the genitalia and prostate• Size and texture of the testes• Presence of the epididymis and vas deferens• Abnormalities of the penis (eg, hypospadias, Peyronie

plaques

• Laboratory testing • Evaluation of hormonal status (testosterone,

serum hormone–binding globulin, luteinizing hormone [LH], prolactin, thyroid-stimulating hormone [TSH])

• Screening blood studies (hemoglobin A1c, serum chemistry panel, lipid profile)

• Prostate-specific antigen levels,

• Functional tests that may be helpful include the following:

• Direct injection of prostaglandin E1 (PGE1; alprostadil) into the corpora cavernosa

• Biothesiometry • Nocturnal penile tumescence testing

• Imaging studies • Ultrasonography of the penis and testes • Transrectal ultrasonography • Angiography

• Management• Treatment options for ED include the following:• Sexual counseling, if no organic causes can be

found for the dysfunction• Oral medications• Injected, implanted, or topically applied

medications• External vacuum and constriction devices• Surgery

• Many patients with ED also have cardiovascular disease; thus, treatment of ED in these patients must take cardiovascular risks into account.

• According to American Urological Association (AUA) guidelines, oral phosphodiesterase type 5 (PDE5) inhibitors are first-line therapy unless contraindicated. Agents include sildenafil,Vardenafil,Tadalafil,Avanafil

• In patients with ED refractory to oral PDE5 inhibitors, one of these agents can be combined with an injection of PGE1.

• Hormone replacement in severe hypogonadism and as adjunctive therapy when other treatments are unsuccessful. Replacement androgens are available in oral, injectable, gel, and transdermal preparations.

• Intracavernosal injection therapy . effective if the vasculature within the corpora cavernosa is healthy. Agents used include the following Alprostadil, phentolamine,Papaverine

• The Medicated Urethral System for Erections (MUSE) involves the formulation of alprostadil (PGE1) into a small intraurethral suppository that can be inserted into the urethra. This may be useful for men who do not want to use self-injections or those in whom oral medications have failed.

• External devices that may be used include the following:

• Vacuum devices to draw blood into the penis• Constriction devices placed at the base of the

penis to maintain erection

• Selected patients with ED are candidates for surgical treatment.

• Revascularization • Surgical elimination of venous outflow • Placement of penile implant (semirigid or

malleable rod implant, fully inflatable implant, or self-contained inflatable unitary implant)

prevention

• Optimal management of diabetes, heart disease, and hypertension

• Lifestyle modifications to improve vascular function (eg, not smoking, maintaining ideal body weight, and engaging in regular exercise

conclusion

• attaining and maintaining a firm erection requires good vascular function, it is reasonable to assume that lifestyle modifications to improve vascular function (eg, smoking cessation, maintenance of ideal body weight, and regular exercise) may prevent or reverse ED.

• THANK YOU

References

• Robert C.D,Tom.F.L. Physiology of penile erection and pathophysiology of Erectile.Urol. Clin North Am. 2005;32(4)379-391

• Medscape . Erectile dysfunction• Williams textbook of Endocrinology• American Urological Association Guideline on

management of erectile dysfunction