Effect of α-Blockers on Erectile Dysfunction in Patients complaining of lower Urinary Tract Symptoms Due To Benign prostatic Hyperplasia Thesis submitted in partial fulfillment of the requirements For the Master degree in Urology By Ahmed Mohamed Abdallah Mohamed M.B.B.Ch UNDER SUPERVISION OF Prof.Dr. Mohamed Salaheldin Professor of Urology Urology Department Cairo University Prof.Dr. Hisham Elghamrawy Assist. Professor of Urology Urology Department Cairo University Dr. Wael Magdy Elsaied Lecturer of Urology Urology Department Cairo University Cairo University- Faculty of Medicine Urology Department (2012) بس ا الرحم الرح س قحال سبحان عس الح ح عحملح ا ن ان العحس ابحح س صد ا العح س سورة البقرة آيت)32( Thanks to "ALLAH" who inspired me the will and effort to complete this work. I wish to express my supreme gratitude and appreciation to Prof. Dr. Mohamed Salaheldin, professor of urology, Cairo University who gave me a lot of his valuable time for support and guidance in preparation of this work and for whom no words of gratitude are sufficient. I am indebted to Dr. Hisham Elghamrawy, assistant professor of urology, Cairo University for his unconditional support and sincere piloting. I do honestly wish to extend my deepest appreciation and sincere gratitude to Dr. Wael Magdy Elsaeid, lecturer of urology, Cairo University who inspired me the spirit of research and granted me close supervision, precious aid and extreme help. And finally, many thanks to Dr. Mohamed Ahmed Azouz, consultant of urology-Cairo university hospital. Dr. Ahmed Mohamed Shelbaia, consultant of urology – Cairo university hospital for endless support. CONTENTS NO. PAGE 1 ABSTRACT. Ι 2 LIST OF FIGURES. Π 3 LIST OF TABLES. IV 4 LIST OF ABBREVIATIONS. VI 5 INTRODUCTION. 1 6 ANATOMY OF THE PENIS. 3 7 PHYSIOLOGY OF PENILE ERECTION. 12 8 EVALUATION OF ERECTILE DYSFUNCTION. 26 9 THE USE OF α-BLOCKERS IN TREATEMENT OF 50 BENIGN PROSTATIC HYPERPLASIA. 10 DRUGS AFFECTS MALE SEXUAL FUNCTION. 63 11 PATIENTS AND METHODS. 81 12 RESULTS. 88 13 DESCUSSION. 102 14 SUMMARY. 108 15 REFERENCES. 110 16 ARABIC SUMMARY. ABSTRACT OBJECTIVES & AIM OF THE WORK: To study the effect of α- blocker (TAMSULOSIN HCl) on erectile dysfunction in married men patients who suspected to have benign prostatic hyperplasia. METHODS: Our study was a prospective randomized study in one to one fashion conducted upon 60 patients, all of them are married, between May 2010 and May 2011, the patients under the study were attending out patient clinic of the New Kasr Al-Aini Teaching Hospital and Students Hospital, Cairo University complaining of lower urinary tract symptoms either obstructive, irritative or both and erectile dysfunction. History was taken from all patients; all patients were examined by digital rectal examination and abdominal examination. We performed pelvic ultrasound, serum P.S.A estimation (patients with P.S.A more than 4ng/ml will do TRUS and biopsy), other routine investigations and uroflowmetry to all patients. Assessment of sexual function changes was by the IIEE (International Index of Erectile Function) and penile Doppler ultrasound. RESULTS: A significant statistical improvement was detected in the erectile function score and intercourse satisfaction score with significant improvement in total IIEF beside the improvement in the IPSS (International Prostatic Symptom Score). While orgasmic function score showed significant worsened, the sexual desire and overall satisfaction score showed no difference between both groups. KEY WORDS: Tamsulosin HCl- α- blocker - BPH – LUTS- Erectile dysfunction - IIEF I LIST OF FIGURES Figure Page 1 Cross section of the penis. 3 2 Arterial supply of the penis. 7 3 Venous drainage from the corpora cavernosa. 9 4 The mechanism of penile erection. 13 5 Blood flow and intracavernous pressure changes 14 during the seven phases of penile erection and detumescence 6 Schematic representation of the regulation of 16 contractile tone of penile smooth muscle by adrenergic mechanisms. 7 Schematic representation of the processes leading 18 to penile smooth muscle relaxation. 8 Schematic representation of the mechanisms 20 involved in penile smooth muscle relaxation by the cGMP pathway. 9 Schematic representation of the mechanisms 21 involved in penile smooth muscle relaxation by the cAMP pathway. 10 Functional classification of impotence. 26 11 The RigiScan device chart. 37 12 Collateral circulation of penis by color duplex 40 ultrasound. 13 Artist's conception of the changes in diameter and 41 flow waveform in the cavernous arteries induced by intracavernous injection of prostaglandin E1 as demonstrated by duplex ultrasound. 14 This tracing depicts four simultaneous variables 42 obtained during the third phase of dynamic infusion cavernosometry and cavernosography. II 15 Pharmacologic arteriography. 43 16 Pharmacologic cavernosography. 44 17 Basic diagnostic work-up in patients with erectile 49 dysfunction. 18 Distribution of α1-adrenergic receptors in the 51 lower urinary tract. 19 Proposed theory of pelvic loss of NOS and NO for 54 LUTS/ED. 20 Autonomic hyperactivity- metabolic syndrome 55 theory of ED. 21 Atherosclerosis-Pelvic ischemia theory of ED. 57 22 Distribution of cases according to age. 89 23 Distribution of the primary etiology of erectile 90 dysfunction among both groups. 24 Baseline IPSS category of cases and controls. 91 25 Baseline erectile dysfunction category of cases and 93 controls. 26 IPSS category of α-blocker group before and after 95 treatment. 27 IPSS category of controls before and after 95 treatment. 28 Erectile dysfunction category of α-blocker group 96 before and after treatment. 29 Erectile dysfunction category of control group 97 before and after treatment. III w LIST OF TABLES No Page 1 The key-elements in Leiden Impotence 28 Screening Test (LIST). 2 International Index of Erectile Function 30 Questionnaire (IIEF). 3 IIEF score domains. 32 4 Prevalence of and risk factors for sexual 53 dysfunction in men with LUTS/BPH. 5 Incidence of sexual side effects in medical 58 therapies for LUTS/BPH. 6 Adverse events of tamsulosin HCl 61 7 Baseline characteristics of the studied patients. 88 8 Baseline characteristics of cases and controls. 89 9 Distribution of the primary etiology of ED 90 among both groups. 10 Baseline IPSS (total) and category of cases and 91 controls. 11 Baseline laboratory characteristics of cases and 92 controls. 12 Comparison of baseline erectile dysfunction 92 severity of cases and controls. IV 13 Comparison of baseline IIEF scores of cases 93 and controls. 14 Clinical characteristic of cases and controls. 94 15 Erectile dysfunction severity of cases and 96 controls. 16 IIEF score of cases and controls. 98 17 Uroflowmetry characteristics of cases and 99 controls. 18 Comparison of final IIEF scores of cases and 100 controls. 19 Correlation of IPSS scores and Testosterone 100 among the studied cases. 20 Correlation of erectile dysfunction and 101 Testosterone among the studied cases. V LIST OF ABBREVIATIONS BPH Begnin prostatic hyperplasia. LUTS Lower urinary tract symptoms. ED Erectile dysfunction. DHT Dihydrotestosterone. EJD Ejaculatory dysfunction. HD Hypoactive desire. NO Nitric oxide NOS nitric oxide synthase GTP guanosine-5"-triphosphate PG Prostaglandin. cGMP Cyclic guanosine monophosphate cAMP Cyclic adenosine monophosphate. VIP Vasoactive intestinal peptide NANC nonadrenergic, noncholinergic neurotransmitters. pO2 partial oxygen pressure PKC Protein kinase C TXA2 Thromboxane A2 SM Smooth muscles VI IFIS Intra-operative Floppy Iris Syndrome IPSS International Prostatic Symptom Score LIST Leiden Impotence Screening Test IIEF International Index of Erectile Function CIS Combined Intracavernous Injection and Stimulation PSV Peak Systolic Velocity EDV End-diastolic flow velocity CASOP cavernous artery systolic occlusion pressure PBI Penile Brachial Pressure Index MRA Magnetic Resonance Angiography NPT Nocturnal Penile Tumescence REM Rapid eye movement AVSS Audiovisual and Vibratory Stimulation PTR penile tumescence and rigidity MMAS Massachusetts Male Aging Study NHSLS National Health and Social Life Survey QOL Quality of life PSA Prostatic specific antigen α1 AR α1-adrenergic receptors BMI Body mass index CCB Calcium channel blocker DHEAS Dehydroepiandrosterone sulphate. VII INTRODUCTION INTRODUCTION Benign prostatic hyperplasia (BPH) is a pathologic process that contributes to, but is not the sole cause of, lower urinary tract symptoms (LUTS) in aging men. It is the most prevalent condition to affect men beyond middle age. It is estimated that 43% of men over the age of 65 suffer either lower urinary tract symptoms (LUTS) or a reduced flow rate. Of these patients, approximately one-half have a reduced quality of life as a result of this problem. With the growing life expectancy and absolute number of the elderly, studies on age- related diseases are becoming increasingly important. Recent evidence has looked at a relationship between LUTS/BPH and erectile dysfunction (ED), as these diseases is frequently seen concomitantly in the same aging male group. The association between these two diseases has also garnered attention as investigators have hypothesized a common pathophysiology to explain the assertion that they are causally linked. The link between ED and LUTS is also important for physicians to understand because the treatment of one may adversely impact the other disease. Almost all accepted therapies for LUTS (surgical or medical) can impact some of sexual health. 1 INTRODUCTION There was a several