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Erectile Dysfunction Dr. S. Ram Gopal MBBS (Osm), M.Ch (Russia) EPOR Model Historical Aspects The first description of erectile dysfunction dates from about 2000 B.C. and was set down on Egyptian papyrus Hippocrates described many cases of male impotence among the rich inhibitions of Scythia and concluded that too much horseback riding was the cause. (The poor were not affected because they travelled on foot) Various theories : arterial polsters (Receptors) (Von Ebner, 1900; Kiss, 1921), arterial and venous polsters (Conti, 1952), the sluice theory (Deysach, 1939), an arteriovenous shunt (Newman et al, 1964; Newman and Northrup, 1981; Wagner et al 1982), and contraction of the cavernous smooth muscles (Goldsterin et al, 1982) Among these, Conti’s hypothesis that arterial and venous polsters regulate penile blood flow is the most frequently quoted. Nitric oxide (NO) as the major neurotransmitter involved in erection. Incidence and Epidemiology In older men, alterations in the vascular supply, hormonal changes, neurologic dysfunction, medication, and associated systemic diseases are the main causes The prevalence of complete impotence tripled from 5% to 15% Autonomic Pathways Eleventh thoracic to the second lumbar Cavernous nerves 4 to 7 mm lateral to the sphincter Stimulation of the pelvic plexus and the cavernous nerves induces erection, whereas stimulation of the hypogastric nerve or the sympathetic trunk causes detumescence When parasympathetic centers are injured. In man, many patients with sacral spinal cord injury retain psychogenic erectile ability even though relexogenic erection is abolished No psychogenic erection occurs in patients with lesions above T9 Contraction of the ischiocavernosus muscles produces the rigid erection phase. Rhythmic contraction of the bulbocavernosus muscle is necessary for ejaculation Pathophysiology of Erectile Dysfunction Psychogenic Neurogenic Arteriogenic Endocrines Drug induced Psychogenic Increased central sympathetic tone may be one of the causes of psychogenic erectile dysfunction and may explain why some patients respond poorly to injection therapy with no evidence of vascular or neurogenic disorders A subclassification of psychogenic erectile dysfunction has been proposed recently (Lue, 1994a): Type 1 anxiety, fear of failure (widower’s syndrome, sexual phobia, performance anxiety, and so on) Type 2 depression (including drug or disease induced depression) Type 3 marital conflict, strained relationship Type 4 ignorance & misinformation (e.g, about normal anatomy, sexual function, or aging), religious scruples Type 5 obsessive compulsive personality (anhedonia, sexual deviation, psychotic disorders) Neurogenic Sensory input from the genitalia is essential in achieving and maintaining reflexogenic erection, and the input becomes even more important when older people gradually lose the capability of psychogenic erection : circumcision decrease performance. Endocrinologic Hyperprolactinemia, symptoms may include loss of libido, erectile dysfunction, galactorrhea, gynecomastia, and infertility. Erectile dysfunction may also be associated with both hyperthyroidism and hypothyroidism. Hyperthyroidism is commonly associated with diminished libido, which may be due to the increased circulating estrogen levels and less often with erectile dysfunction. In hypothyroidism, low testosterone secretion and elevated prolactin levels contribute to erectile dysfunction. Arteriogenic In the majority of patients with arteriogenic erectile dysfunction, the impaired penile perfusion is a component of the generalised atherosclerotic process. Common risk factors associated with arterial insufficiency include hypertension, hyperlipidemia, cigarette smoking, diabetes mellitus, blunt perineal or pelvic trauma, & pelvic irradiation (Goldstein et al 1984; Levine et al 1990; Rosen et al 1990) Diabetic men and older men Intimal proliferation, calcification and luminal stenosis Nicotine may adversely affect erectile function not only by decreasing arterial flow to the penis but also by blocking corporeal smooth muscle relaxation, thus preventing normal venous occlusion (Junemann et al 1987; Rosen et al 1991) Hypertension is another well-recognised risk factor for arteriosclerosis; a prevalence of about 45% has been noted in one series of impotent men (Rosen et al 1991) Drug - Induced Centrally acting sympatholytics Peripheral sympatholytic Alpha-adrenergic blocking Selective alpha-adrenergic Beta-adrenergic blockers Major tranquilizers or antipsychotics Alcohol in small amounts improve erection and sexual drive because of its vasodilatory effect and suppression of anxiety; however, large amounts can cause central sedation, decreased libido, and transient erectile dysfunction. Chronic alcoholism may result in liver dysfunction, decreased testosterone and increased estrogen levels, and alcoholic polyneuropathy which also affects penile nerve (Miller and Gold, 1988) Cimetidine, a histamine H2 receptor antagonist, act as an antiandrogen, prolactin level. Sexuality Facts Anatomy Drawings Male 1. Vas deferens 2. Bladder 3. Prostate gland 4. Urethra 5. Penis 6. Testicle 7. Scrotum Female - Internal 8. Fallopian tube 9. Ovary 10. Uterus (womb) 11. Cervix 12. Vagina Female - External 13. Clitoris 14. Labia majora outer lips 15. Urethra (opening) 16. Labia minora (inner lips) 17. Vagina (opening) 18. Anus (opening) Diagnosis of Dysfunction Symptoms Medical and Psychosexual history Physical examination Laboratory testing Symptoms Verbal Weakness Not strong Not working Nervous weakness Non Verbal Medical and Psychosexual History Early morning erection and erectile quality A history of peripheral vascular or coronary artery disease, diabetes, renal failure, tobacco and alcohol use, psychologic, neurologic, or chronic debilitating disease can direct further evaluation Radical pelvic surgery (prostatectomy, abdominoperineal resection), radiotherapy, pelvic trauma are often associated with impotence Psychometry and Psychologic Interview Organic / Psychogenic Characteristic Organic Psychogenic Onset Gradual Sudden Circumstances Always Situational Course Constant Varying Noncoital erection Poor Rigid Partner problem Same Specific to the partner Anxiety and fear + + Physical Examination Extensibility of the flaccid penis Sensation Bulbocavernosus reflex Axial rigidity Laboratory Testing Renal insufficiency, diabetes Hyperprolactinemia ( Thyroid) Generally serum testosterone and prolactin Serum lipids Platelet aggregation Special tests – CIS test – X-ray cavernosography – Rigi scan – Doppler study – Penile plethysmography Nocturnal Penile Tumescence Testing NPT - associated with REM sleep Normal parameters 4-5 / night > 30 mts > 30 mm at base > 20 mm at the tip RIGI scan not measure axial rigidity (500 gm) Axial Rigidity A bucking resistance of 500 to 550 g is considered minimum for vaginal penetration Penile tumescence may not always correlate with penile rigidity sufficient for vaginal penetration 50 gm CIS Test Inhibitory effect on phosphodiesterase Calcium channels Papaverine 7.5 - 60 mg Tanaka (1990) measured systemic papaverine levels after intracavernous injection and found significantly higher peripheral blood levels in patients with poor erectile response suggestive of veno-occlusive dysfunction Sexual Stimulation (Audiovisual and Vibratory) The triple drug combination : Papaverine, Phentolamine and PGE2 Contraindications : Sickle cell anemia, schizophrenia or a severe psychiatric disorder, severe nenous incompetence, or systemic disease Neurologic Testing Somatic Autonomic Autonomic Nervous System Heart rate variability and sympathetic skin response Platelet Aggregation Biochemical study : It has been suggested that penile hypercoagulability predisposes the patient to penile vascular changes and impotence. Thromboxane A2 is a potent vasoconstrictor and a stimulus of platelet aggregation, which may contribute to hypercoagulability. Contrarily, prostaglandin I2 has exactly the opposite effect Penile Brachial Pressure Index A normal PBI connot be relied upon to exclude arterigogeic impotence. Indeed, attempts to correlate PBI and other more established techniques have been disappointing. Penile plethysmography (Penile pulse volume recording). This test is performed by connecting a 2.5 or 3 cm cuff to an air plethysmograph. The cuff is inflated to a pressure above brachial systolic pressure, which is then decreased by 10 mm Hg increments, and tracings are obtained at each level. Nonsurgical Treatment of Erectile Dysfunction Lifestyle change Change of medication Pelvic floor muscle exercise Hormonal therapy Oral agents Transdernal and intrauretheral medications Intracavernous injection Vacuum constriction device Lifestyle Changes Exercise, Diet, Smoking and Alcohol In rabbit experiments, the deleterious effect of a high-cholesterol diet on the cavernous smooth muscle was reversed several weeks after cholesterol was eliminated from the diet Long-distance bicycle riding is another risk factor that should be discussed Changes of Medication Methyldopa and reserpine Calcium channel blockers or angiotensin-converting Trazodone Pelvic Floor Muscle Exercise Electrical stimulation of the ischiocavernosus muscle, graded pelvic floor exercises with muscle training, and a home exercise program for lying, sitting, and standing positions for 4 months. The root of the penis. The corpora are shown in transverse section Sex Therapy In the 1970s, Masters and Johnson (1970) developed a sensate focus exercise program for sex therapy and treatment performance anxiety, inhibition, and guilt. Kaplan (1974, 1983) added personal or interpersonal conflicts. Vacuum Constriction Device The blood oxygen level in the corpus cavernosum is less Proximal to the ring is not rigid, which may produce a pivoting effect The penile skin may be cold and dusky, and ejaculation may be trapped by the constricting ring The ring can be uncomfortable or even painful Pharmacology of Penile Erection Increase the libido of patients (LADY PANT) Suppress mating behavior Suppressors ( prolactin) Phenothiazine Opiates Tricyclic antidepressents Clonidine Haloperidol Prazocin Methyldopa Serotonin Reserpine Fenfluramine Meprobomate Estrogens and drugs with antiandrogenic action, such as ketoconazole & cyproterone acetate. Many anticancer drugs. Erection Inducing Drugs Papaverine Nitroglycerine Phentolamine Phenoxy Benzamine Moxy Sylyte Verapamil Trazodone PGE LADY PANT L-Dopa Amphetamine Deprinyl Yohimbine Pergolide Apomorphine Nomifensine Trazodone Hormonal Therapy The long acting forms, testosterone cypionate and enanthate, are the drugs of choice for replacement therapy (Sustanon) The recommend dose is 200 mg intramuscularly every 2 to 3 weeks. Parenteral testosterone is given if free testosterone < 9 ng/dl Serotonergic Drugs Trazodone is a commonly prescribed mild antidepresant with a rare incidence of priapism A combination of trazodone and yohimbine Better nocturnal erections after trazodone. Sexual activity in the morning when the sedative effect is no longer a problem. Transdermal and Intrauretheral Medications Nitroglycerin paste Penile shaft (nitroglycerin) or glans penis (minoxidil & placebo) Increases in diameter and rigidity were measured with the Rigiscan divice, and arterial flow was evaluated by conventional Doppler sonography Minoxidil was shown to be more effective than nitroglycerin Treatment with yohimbine ointment was reported to be effective in patients with impotence of recent onset who had no major vascular alterations Sildenafil Mode of action Type 5 (PDE5) By selective inhibition of PDE5, sildenafil enhances cyclic GMP activity in the erectile tissue. It amplifies the vasodilatory effect of nitric oxide, which is produced naturally in the erectile tissue in response to sexual stimulation. Without sexual stimulation, therefore, sildenafil has no effect on erections Peak plasma concentration at 30-120 minutes The improvement in erectile function was dose related, with men on 100 mg doses scoring 100% higher Sildenafil gave a significant improvement in erectile ability and success at intercourse increased fourfold : this benefit was conferred for at least 6 months Indications Sildenafil restores erectile ability, but has not demonstrable effect on sexual desire or ejaculation Contraindications Severe hepatic impairment; a recent myocardial or cerebral infarction; blood pressure below 90/50 mmHg; hereditary degenerative retinal disorders, such as retinitis pigmentosa. Cardiac condition in whom the heart is so decompensated that it will not stand the effort of sexual exertion. Men under 18 years (Legal) Drug Interactions Cimetidine Erythromycin by 182%. If sildenafil is taken with one of these drugs, it is advisable to start the patient on half the standard dose. There is no known interaction between sildenafil and alcohol, antidepressants or antihypertension medication. Side-effect Frequency (%) Headaches 12.8 Flushing 10.4 Dyspepsia 4.6 Dizziness 1.2 Nasal congestion 1.1 Green blue tingeing of vision Increased sensitivity to light Blue red vision Muscle aches have been reported in patients who used more than recommended one dose a day Dosage and administration The standard dose of sildenafil is 50 mg, one hour before intended sexual activity. The dose can be increased to a maximum of 100 mg or reduced to 25 mg, depending on efficacy and toleration in the individual Safe, effective and easy-to-administer treatments, such as sildenafil, are not a panacea Patient’s partners should be involved in the decision, and the treatment should be prescribed with psychotherapeutic support. Erectile dysfunction is a multifactorial problem and a comprehensive approach is the key to management Definition Inability to maintain until penetration are ejaculation sooner than desired either before or after penetration Test Intra vaginal latency period Treatment Paroxetine (Paxitil) 10-40 mg 20 mg / OD / daily is the best Rx Fluox (Fludac, Prozac) 20 mg Chlomipramine 10 mg / 4 hrs prior or 25 mg daily / 1 year Verapamil, Trazadone Early Ejaculation (PME) PME treatment - Medical treatment Pelvic exercises - Muscle stimulator Surgical Treatment Penile implants Leu’s surgery 50 Watts 50/60 Hz Kamasutra Mallanath Vatsayana Nagera (South Gujarat) 350 AD Situational Constitutional : Ahar, Vihar, Aushad What is good for the whole body is good for sex Education : Whom, When, Why Whom “A Sapthathi Yavvana” When : “Prag yavvana” Why : Dharma, Artha, Kama, Moksha Samyak Bhoga = Sambhoga Sama bhog = Equal enjoyment by both the partners Anand (orgasm) = Bliss Vajroli mudra, Ashwin mudra (Pubococcygeous exercises) Foreplay - Verbal, body Masturbation (Upa mardan) Pani (Hand) Manthan (Movement) Oral sex (Aupershtaka) for elderly, obese Anal sex : Adho rut (S2 S3 Vagina, Rectum) Apadravya or Prathima (Dilldos, Dolls) Artificial penis Partner Satisfaction Masturbation, oral sex, artificial penis Lesbian / Homo : Venus and Saturn in the same house Multiorgasm What are the points to be noted in the case sheet of FS ? How does differs from the male case sheet ? Female Sexuality Desire S. grounding Lubrication in arousal = erection in Case sheet Female Male Desire Desire Lubrication Erection Penetration Penetration Orgasm Orgasm orgasm What is to be asked the history ? Dislike to wards partner History of surgery especially Bilateral Oophorectomy What are the signs ? Exclusion of several pelvic diseases What investigations ? Prolactin Estrogen Progesterone What are the treatments ? Hymenectomy if needed Psychotherapy Desire F.lobe tumors, Prolactin , Androgen after bilateral oophorectomy, dislike of partner Lubrication inadequate foreplay, infection, endocrinal (E ) P Penetration no penetration, partial penetration painful penetration, hymen, vaginismus. Partial penetration : vaginal anatomy, position - faulty Painful penetration : superficial, deep, scars, wounds, infection Orgasm = enough and nothing more Cerebrally encoded neuromuscular response at the peak of sexual arousal Early, delayed, impaired, absent (My husband is using me as a sleeping pill) (Wo to na ha kar chalgaye, mai thadapthi rohi) Multi orgasms : Physiological in Acquired art in Prof. Kothari Ji : Orgasm cannot be explained but must be experienced (like a sneeze) One must try to posess acceptable, respectable sexual behavior. EPOR Model EPOR Model Excitement phase Plateau phase Orgasmic phase Resolution phase - short absolute refractory period in the male during which rearousal is not possible Thank you