Prof. Dr.Mohamed Hamdy Abouel-Hassan

I 

- ERECTILE DYSFUNCTION - 

DIAGNOSIS AND TREATMENT 

Thesis Submitted In Partial Fulfillment Of The 

Requirements for MD degree in Urology 

BY 

A 

amid 

BCh, M Sc ( 

bilel 

Urol. 

) 

Supervised by 

Prof. Dr.Mohamed Hamdy A 

ahee, 

-R 

bouel-Hassan 

-- 

I/ o 

Professor of Urology, Faculty of Medicine, El-Minia University 

Prof. Dr. Mohamed A 

E 

Prof. & 

Head of Urology Dept., Faculty of Medicine 

Prof. Dr. H 

esham 

bdel-Malik 

Bacialiyay 

_Etassan 

Minia 

l. 

- 

Prof. of Urology, Faculty of :Medicine, Cairo University 

Prof. Dr. Ahmed A 

Prof. of Urology, Faculty of Medicine E 

bdel 

Faculty of Medicine 

El-Minia University 

- H 

amid 

2004 

l-Minia 

Away 

inett, 

Te. 

Ce. 

1A16. 

, 

University 

University

2 1c 

Z1) 

0 

O. 

• •

INDEX OF CONTENTS 

Acknowledgment RI 

List of Abbreviations IV 

List of Tables VII 

List of Figures 

INTRODUCTION AND AIM OF THE WORK 1 

REVIEW OF LITERATURE: 

DEFINITIONS Q 

AND 

CHAPTER 1: Anatomy and physiology 11 

UESTIONNIARES 

CHAPTER 2: Diagnostic work up of erectile dysfunction 51 

CHAPTER 3: Priapism, Peyrone's, and Rapid ejaculation 63 

CHAPTER 4: Treatment options for Erectile Dysfunction 91 

PATIENTS AND METHODS 118 

RESULTS 144 

DISCUSSION 183 

SUMMARY AND CONCLUSION 208 

REFERENCES 214 

Index of Questionnaires 255 

ARABIC SUMMARY 

4

Acknowledgment 

Firstly; all thanks and appreciations are to Allah, the most merciful and 

the most compassionate. 

I would like to thank Professor Mohamed Hamdy A 

Professor Urology, for giving me opportunity to do the study. 

I am deeply grateful to my supervisor, Professor Hesham Abdel-Hamid 

Badawy, Prof. of Urology, Faculty of Medicine, Cairo University for his 

support and guidance during this study and providing constructive 

comments and criticism. 

I wish to express my sincere gratitude to Professor Mohamed Abdel- 

Malik Hassan, Head of the Urology Dept, Faculty of Medicine, El-Minia 

University who provided me great supports and encouragement during this 

work. 

I express my truly special thanks to Professor A 

Ahmed 

Awad, Prof. Of Urology, Faculty of Medicine, and El-Minia University for 

his endless support and helping me to complete this study. 

I wish to express my gratitude to all the surgeons at University 

Urologists of Cleveland, Case Western Reserve University and Prof. Allen 

Seftel in particular for his endless support and advice to complete this 

work. 

My sincere thanks are due to my co-workers to create a scientific article 

and all the nurses at the Outpatient Department of Urology, E 

University hospital for their support. 

bou-Elhassan, 

bdel-Hamid 

Mamclouh, 

l-Minia 

2004-5

, 

ist 

of Abbreviations 

AVSS Audiovisual Sexual Stimulation 

ADAM Androgen Deficiency in Aging Men 

AFUD American Foundation for Urologic Disease 

BCRL Bulbocavemous Reflex 

BMI Body Mass Index 

BPH Benign Prostatic Hyperplasia 

CAD Coronary Artery Disease 

C 

CC Corpus 

CES-D Centers for the Epidemiologic Survey of Depression 

DICC 

CHF Congestive Heart Failure 

CVD Cardiovascular Disease 

CVA Cardiovascular Abnormalities 

DDCS 

avernosum 

Duplex-Doppler Color Sonography 

DH EA Dehydroepiandrosterone 

Dynamic Infusion Pharmacocavemosometry and 

Cavemosography 

DSM - IV Diagnostic and Statistical Manual — 

HT Dihydrotestosterone 

ED Erectile Dysfunction 

EF Erectile Function 

EM Electromyography 

E2 Estradiol 

IV 

IV

FSD , 

Female Sexual Dysfunction 

FSH Follicle Stimulating Hormone 

GTP G 

uanosine-Triphosphate 

HDL High-density lipoprotein 

HB Hemoglobin 

HCT Hematocrit 

ICI Intracavernosal Injection 

II EF International Index of Erectile Function 

IPPs 

Inflatable Penile Prosthesis surgery 

LH Luteinizing Hormone 

LVD Left Ventricular Defect 

MI Myocardial Infarction 

MMAS Massachusetts Male Aging Study 

MOD Male Orgasmic Disorders 

MS Moxisylyte 

NIH National Institute of Health 

NO Nitric oxide 

PGE1 

NPT Nocturnal Penile Tumescence 

NPTR Nocturnal Penile Tumescence and rigidity 

Prostaglandin E-1 

PSA Prostate-Specific Antigen 

PV Papaverine Hydrochloride 

PVD Pulmonary Vascular Disease 

REM Rapid Eye Movement

SHBG 

SSR! 

s 

U/ 

S 

SHIM 

Sex-Hormone Binding Globulin 

Sexual Health Inventory for Men 

TT Total Testosterone 

Selective Serotonin Reuptake Inhibitors 

TRUS Transrectal Ultrasound 

TU RP Transurethral Resection of Prostate 

Ultrasound 

VAS Visual Analogue Scale 

VED V 

acuum/ 

entrapment 

Device 

V I

LIST OF TABLES 

NUMBER TITLE PAGE 

TABLE 1 Questionnaire for assessment of Cardiac Risk factors 9 

TABLE 2 Grades of risk factors and it's managements 10 

TABLE 3 The Function of Penile Components During Penile Erection 13 —14 

TABLE 4 key Findings in the Evaluation of Priapism 65-66 

TABLE 5 Typical Blood Gas Values in priapism patients 68 

TABLE 6 

Shows different methods of diagnosis used for patients in this 

study 

TABLE 7 The S 

SRIs, 

122 

trade names, doses and patients numbers 142-143 

TABLE 8 The instruments, duration and patients numbers in73men 143 

TABLE 9 ED by age 145 

TABLE 10 ED by etiology and / or risk factors 145 

TABLE 11 Severity of ED presentation according to S 

HEVI 

score 146 

TABEL 12 The overall patients presentation in our series 148 

TABLE 13 Finding on clinical examination 149 

TABLE 14 

TABLE 15 

TABLE 16 

Patient's improvements and/or satisfaction. After sildenafil 

citrate 

Rigiscan finding in 53 men with history suggesting of 

Psychogenic ED 

The correlation between Rigiscan and U/S finding in 38 

Men 

TABLE 17 The results of 3 diagnostic methods used in 38 men, 157 

151 

152 

156 

VII

Rigiscan, 

buckles 

TABLE 18 The response to ICI ( 

and penile U/S finding 

n- 

47) 

- - 

TABLE 19 The local complications after ICI (n=153) 159 

TABLE 20 The ICI discontinuation by etiology (n=38 161 

TABLE 21 

TABLE 22 

TABLE 23 

TABLE 24 

The diagnostic outcome using penile Doppler ultrasound 

(n=106) 

The Table distribution of the buckle response according to 

etiology of ED assessed by penile U/S in the study population 

(n =106) 

Prevalence of hypogonadism among patients with low sexual 

drive 

The different treatment options for men with low libido and 

ED 

TABLE 25 Etiology of priapism (n=20) 175 

TABLE 26 Types of prostheses by treatment group 177 

TABLE 27 

TABLE 28 

TABLE 29 

Shows Etiology of ED by treatment group 

Shows the different verities of mechanical complication in our 

patients 

Shows response to treatment and instruments used were listed 

as fellow 

158 

162 

166 

171 

174 

179 

181 

182 

VIII

^^^

Introduction 

Erectile Dysfunction: The new paradigm 

Introduction and Aim of the Work 

The new paradigm in the office diagnosis and treatment of male sexual 

function extends beyond pure erectile function. The evaluation now includes 

a discussion of ejaculation, libido, erectile function (including any cardiac 

risk factors), and depression. The evidence for this new paradigm comes 

from several sources. 

In 1999, Laumann et al reported (Laumann, 1999) on a large series of 

patients from the United States National Health and Social Life Survey. He 

assessed the prevalence and risk of experiencing sexual dysfunction across 

various social groups and examined the determinants and health 

consequences of these disorders. He analyzed data from the National Health 

and Social Life Survey, a probability sample of 1749 women and 1410 men 

aged 18 to 59 years at the time of the survey a 1992 cohort of US adults. The 

main outcome measures were the risk of experiencing sexual dysfunction as 

well as negative concomitant outcomes. He found that sexual dysfunction 

was more prevalent for women (43%) than men (31%) and was associated 

with various demographic characteristics, including age and educational 

attainment. Women of different racial groups demonstrated different patterns 

of sexual dysfunction. Differences among men were not as marked but 

generally consistent with women. Experience of sexual dysfunction was 

more likely among women and men with poor physical and emotional 

health. Moreover, sexual dysfunction was highly associated with negative 

experiences in sexual relationships and overall well-being. Premature 

ejaculation was the most common male sexual dysfunction. Decreased libido


and male erectile dysfunction were less common. The results indicated that 

sexual dysfunction was an important public health concern, and emotional 

problems likely contributed to the experience of these problems. 

Patients with ED were 2.6 times more likely to report depressive symptoms 

than men with BPH alone. Additionally, patients with depressive symptoms 

reported lower libido than other patients. They concluded that ED was 

associated with high incidence of depressive symptoms, regardless of age, 

marital status, or comorbidities. Patients with ED have a decreased libido 

compared with control subjects. In addition, patients with depressive 

symptoms have a lower libido than patients without depressive symptoms. 

Patients with ED and depressive symptoms are more likely to discontinue 

treatment for ED than other patients with ED 

It is estimated that at least 10 to 20 million American males suffer from 

erectile dysfunction. The most recent and comprehensive epidemiological 

report, the Massachusetts Male Aging Study (Feldman, Goldstein, 

Hatzichristou et al, 1994), asked men between the ages of 40 to 70 years to 

categorize their erectile function as either completely, moderately, 

minimally or not impotent. Fifty-two percent of the sample reported some 

dysfunction. This study demonstrated that erectile dysfunction is an age 

dependent disorder; "between the ages of 40 -70 years the probability of 

complete impotence tripled from 5.1% to 15%, moderate impotence doubled 

from 17 to 34% while the probability of minimal impotence remained 

constant at 17%." By age 70, only 32% portrayed themselves as free of 

erectile dysfunction.

Aim of the Study 


This study will aim at finding of different etiology and/or Risks factors for 

Erectile Dysfunction, outlining the different diagnostic modalities and 

finally evaluating the most suitable treatment option for Erectile 

Dysfunction. 

3

Definition 

Review of literature 

For years, the terms impotence and erectile dysfunction had been used 

interchangeably to denote the inability of a man to achieve or maintain 

erection sufficient to permit satisfactory sexual intercourse [ K 

(1989)] 

rane 

et al. 

Social scientists objected to the impotence label, because of its pejorative 

implications and lack of precision [Rosen and Leiblum (1992) 

The NTH Consensus Development [N 

Conference 

Conference (1993)] advocated that erectile dysfunction be used in place of 

the term impotence and defined it as: 

IH 

Consensus 

The inability of the male to achieve an erect penis as part of the overall 

multifaceted process of male sexual function. This definition de-emphasizes 

intercourse as the sine qua non of sexual life and gives equal importance to 

other aspects of male sexual behavior 

The Diagnostic and Statistical Manual- IV (DSM-IV). The American 

Psychiatric Associations Nomenclature Manual (1994) offers the following 

diagnostic criterion set for Male Erectile Disorder: 

A. Persistent or recurrent inability to attain, or to maintain, 

until completion of the sexual activity, an adequate erection. 

B. The disturbance causes marked distress or interpersonal 

difficulty. 

C. The erectile dysfunction is not better accounted for by another 

Axis I disorder (other than a Sexual Dysfunction) and is not due 

exclusively to the direct physiological effects of a substance (e.g., 

a drug of abuse, a medication) or a general medical condition.

Review literature 

o 

DSM-IV also asks the clinician to make three additional specifications 

1-Lifelong 

versus Acquired • 

2-Generalised versus localized • 

3-Due to Medical Factors, Psychological Factors or, Combined Factors. 

The definition offered by the NIH consensus panel is used most 

Commonly for daily and practical a 

still think of ED as the inability to maintain or sustain an erection 

during coitus. N 

The definition allows for a broader 

interpretation of erectile dysfunction, allowing both the clinician 

IH 

and patient greater latitude in the diagnosis and treatment of this 

disease entity. 

Questionnaires: 

pplication, 

It is clear that questionnaires can capture certain desired aspects of 

sexual function. Indeed, the US regulatory agencies accepted a questionnaire 

(IIEF, International Index of Erectile Function, [Rosen RC et al (1997)] as 

evidence of effects during the sildenafil trials. However, for these 

questionnaires may be too cumbersome or burdensome to be of practical 

value. Nonetheless, these questionnaires are useful and provide a 

mechanism of capturing a large amount of patient data. Thus, it is suggested 

that implementation or inclusion in daily office practice be considered, in 

spite of the constraints of the modern day primary care practice paradigm. 

SHIM: The sexual health inventory for men (SHIM) is an abridged and 

slightly modified version of the IIEF [Rosen et al (1999)]. This simpler 

version allows the clinician to assess male ED with great security. This brief 

5 —question questionnaire is user —friendly, is short (a highly desired 

although_clinicians 

f

Review ( 

feature), and validated, and thus quite appropriate for the evaluation of male 

ED. This questionnaire is most often completed by the patient in the exam 

room or waiting room prior to the interview. The SHIM is appended, and is 

scored as follows: 

Score 22-25 no ED 

Score 17-21 mild ED 

Score 12-16 mild to moderate 

Score 8-11 moderate 

Score 0-7 severe ED (in my experience consider psychogenic ED, or is seen 

after radical prostatectomy or pelvic surgery) 

The SHIM gives a severity index, a common vocabulary and has supplanted 

vascular testing in many cases. The SHIM, however, is not predictive 

outcome of Low libido. 

The ADAM questionnaire, authored by Morley [Morley et al (2000)], is 

relatively easy to administer and to use. The ADAM questionnaire is 

considered positive for low libido if there is a yes response to q 

no response to question 7, or a yes response to any other 3 questions. It 

appears that this questionnaire is sensitive, but not very specific for 

hypogonadism. The major shortcoming, that is not a questionnaire issue, but 

rather a conceptual issue, is that of the definition of low libido. Depression/ 

Depressive Symptoms: 

While there are many questionnaires available to assess depression, we have 

used the second version of the Beck Depression Inventory ( 

BDI-II) 

, 

uestionl, 

21 

- 

l 

iterature 

a 

[Lasa L, 

et al (2000)], as well as the CES-D (Centers for the epidemiologic survey of 

depression [Sheehan et al (1995)] instruments. These are relatively short, 

straightforward and completed by the patient. They provide excellent 

6

t 

P; 

I 

-i 

_10 

t / t 

0 4 

• 


quantitative 'data. The issue resides in the area of depressive symptoms, 

which are reflected by reaching the "abnormal" threshold for depression 

upon using these questionnaires, but not reaching the threshold for overt 

depression. At present, the standard treatment recommendations offered by 

the practicing mental health professional should be utilized for depressive 

symptoms. 

Ejaculation: There is 1 questionnaire at present that has been utilized in 

sexual medicine circles to assess ejaculatory dysfunction, in particular in 

men who have prostatic symptoms. This questionnaire, the DAN-PSS, 

Danish Prostate Symptom Score, does have some clinical utility .A new 

questionnaire to assess ejaculatory function has been developed by Rosen et 

al and may be more robust in capturing the specifics of the ejaculatory 

disorder, is it rapid, delayed, painful, etc [Rosen et al (2003).]. 

Questionnaires for rapid ejaculation are on the horizon. The "IPE", Index of 

Premature Ejaculatory, is an instrument in development. This instrument 

examines the level of distress, increased ability to control ejaculation, or 

improved sexual satisfaction, in men with rapid ejaculation [Symonds 

(2002)]. 

The clinical utility of these questionnaires is still under review. 

EDITS: The area of sexual function treatment satisfaction has become the 

subject of interest. The EDITS (Erectile Dysfunction Index of Treatment 

Satisfaction, [Althof et al (1999)] is one such tool. The EDITS has a partner 

version and is thus quite useful in that regard. Other instruments, such as the 

Sear (Self Esteem, Confidences and relationship satisfaction [Althof et al 

(2003)] have been developed and address specific relationship issues. The 

7

Bottom Line: Q 

tiesticnnaires 


may be too cumbersome for the average 

clinician. They serve a useful purpose, in that they provide a mechanism to 

quantitative certain aspects of, in this case, sexual behavior. If the clinician 

is not comfortable with a certain topic in this arena, then the questionnaires 

are extremely helpful in providing an assessment tool .Emerging concept of 

ED as a predictor of cardiovascular disease. While the association of 

cardiovascular risk factors, such as hypertension and ED is known, data 

appear to be emerging that supports ED as a potential risk factor for 

cardiovascular disease. While the public health implications are significant, 

the data are still emerging and are thus evolving. Having said that, there is 

still ample opportunity to intervene 

Assessing the cardiovascular risk prior to instituting erectogenic 

therapy 

The erectogenic agents, and in particular the oral PDE5 inhibitors, have 

created an aura of uncertainty with respect to cardiovascular safety inasmuch 

as they are mild peripheral vasodilators. 

Guidelines were developed which allow the clinician to categorize the 

individual patient cardiovascular risk profile and provide guidance with 

respect to proceeding to direct erectogenic treatment or further cardiac 

evaluation. Essentially, the patient is classified based on cardiac risk factors 

as outlined in the table I 

be offered, or further stratification is needed. 

. Based on this assessment, erectogenic agents can 

Cardiovascular disease risk assessment-questionnaire (table 1) [DeBusk R., 

(2000)] 

8

Review o/ literature 

Table (1) shows Questionnaire for assessment of Cardiac Risk factors 

Low Risk Intermediate Risk High Risk 

Asymptomatic, 3 major risk 

factors for CAD, excluding 

gender 

Unstable refractory 

angina 

Moderate, stable angina Uncontrolled 

-, 

. . 

hypertension 

Mild, stable angina Recent MI ( 6-8 wk) 

LVD/CHF ( 

NYHA 

class 

II) i 

Noncardiac squeal of 

atherosclerotic disease 

(e.g.. CVA, PVD) 

Mild valvular disease 1 

LVD/CHF (NYHA 

class I) - 

class III/IV) 

Recent MI (

xtiaj'actiOity 

reeliine 

fitit. 

ED 

or 

Clinical Evaluation 

Cardiovascular 

assessment and 

Restratification 

Figure (1) :grades of risk factor and it's managements 

Table ( 2 ) shows grades of risk factors and it's managements 

Grades of risk Management Recommendations 

Low risk 

Intermediate 

risk 

High risk 

Review 0 

literature 

Defet-sextiataelivit 

• 

-Pow* 

. 

f. 

: 

-- 

until Stabilization of 

Primary care management. Consider all first-line therapies 

Reassess at regular intervals (6-12 mo) 

Specialized cardiovascular testing (e.g., ETT, echo) 

Restratification into high risk or low risk based on the Based on 

results of cardiovascular assessment. 

Priority referral for specialized cardiovascular management. 

Treatment for sexual dysfunction to be deferred until cardiac 

condition stabilized and dependent on specialist 

recommendations 

Cardiac 

! 

, 

c0, 

nilition 

10 

--

1-1 Male Sexual Anatomy 

A- Gross anatomy of the penis 

Shaft of Penis 

A. Corpus C 

avernosum 

1-Chapter 

(two) 

1 

Revielv 

1. Two large columns of erectile tissue on penile dorsum 

2. Columns separated by septum of fibers 

B. Tunica albuginea 

1. Bands together the two columns of corpus c 

C. Lacunar space (Space of Smith) 

1. Surrounds tunica albuginea 

2. Intralacunar smooth muscle found within space 

D. Corpus spongiosum 

1. Located on ventral side (underside) of penis 

2. Does not contribute to penile rigidity 

3. Contains urethra 

Glans Mead) of Penis Innervations 

a- Sensation 

1. Pudendal nerve supplies dorsal nerves to penis 

b- Erectile function 

2. Parasympathetic input (excitatory) 

a. Nervi erigentes runs adjacent to prostate gland 

b. Parasympathetic nerves join at hilum of penis 

c. Nerves course through corpus cavernosa 

3. Sympathetic input (inhibitory) 

avemosa 

of literature 

Sympathetic nerves supplied by thoracolumbar plexus 

11

Vascular Supply of the Penis 

1-Arterial inflow 

1. Supplies glans penis and shaft of penis 

2. Branches of deep internal Pudendal arteries 

2-Venous drainage 

1 - 

Superficial 

a. Common penile artery 

b. Bulbar artery 

c. Dorsal artery 

d. Urethral artery 

e. Cavernosal artery 

penile veins 

2 - Superficial dorsal vein 

3 - Intermediate penile veins 

Emissary vein 

Circumflex vein 

Deep dorsal vein 

3. Deep penile veins 

a. H 

b. C 

ilar 

avernosal 

vein (Santorini's Plexus) 

vein 

B-Functional Anatomy of the Penis 


The penis is composed of three cylindrical structures, the paired corpus 

cavernosum and the corpus spongiosum, which houses the urethra, covered 

by a loose subcutaneous layer and skin. The flaccid length of the penis is 

controlled by the contractile state of the erectile smooth muscle and varies 

considerably, owing to emotion and outside temperature. In one study, the 

erect length of the penis measured from pubopenile junction to the meatus 

12

was 8.8 t 

m 


flaccid, 12.4 cm stretched, and 12.9 cm erect, with' neither a 

man's age nor the size of the flaccid penis accurately predicting erectile 

length (W 

essells 

et al, 1996). In another study, the author concluded that 

about 15% of men have a downward curve during erection; erection angle is 

below horizontal in one fourth of men; and shorter erection lengths in the 

range of 4.5 to 5.75 inches occur in 40% of men (Sparling, 1997). Regarding 

penile morphology and erection, a study shows that during erection, the 

penile buckling forces are dependent not only on I 

ntracavernosal 

pressures 

but also on penile geometry and erectile tissue properties. Therefore, in 

patients with normal penile homodynamic but without adequate penile 

rigidity, other structural causes should also be sought (Udelson et al, 1998). 

The functions of various components of the penis are listed in Table ( ). 

Table (3): The Function of Penile Components during Penile Erection 

Component i Function 

Corpora c 

avernosa 

Tunica albuginea (of 

corpora c 

muscle 

Ischiocavernosus 

avernosa) 

Smooth muscle 

Bulbocavernous 

Supports corpus spongiosum and glans 

Contains and protects erectile tissue 

Provides rigidity of the corpora cavemosa 

Participates in veno-occlusive mechanism 

Regulates blood flow into and out of the sinusoids 

Pumps blood distally to speed up erection 

Provides additional penile rigidity during rigid 

erection phase 

muscle Compresses the bulb to help expel semen 

Corpus spongiosum Provides a pressurized narrow chamber to allow 

13

Component - 

Glans 

Tunica Albuginea 

Der 

1-Function 

expulsion of semen from urethra 

) 

7 1- 

11' 

/ 

x11. 

•ti 

r 1 

- 

: 

, 

t 

: 

ultte: 

_ttl 

. 

ell l 

i 

d 

4: 

43-r 

S. 

C 

n i 

rrric 

. 7 

. 

- A 

, W 

rFel 


Acts as a shock absorb cushion to lessen the 

impact of penis on female organs 

The tunica affords great flexibility, rigidity, and tissue strength to the penis 

(Hsu et al, 1992) (Fig.1). The tunical covering of the corpora cavernosa is a 

bilayered structure with multiple sublayers. Inner-layer bundles support and 

contain the cavernous tissue and are oriented circularly. Radiating from this 

inner layer are intracavernosal pillars acting as struts, 

ka. 

. 

. 

. 

orpud 

-{ 

c 

a 

r t 

Figure (2): shows a transverse section in the penis with three corpora. [From Catalona 

ins. 

1988] 

tititif 

r 

i 

: 

ire. 

V. 

. 

tl 

Hit 

17411: 

i 

Jr 

TiC 

14

Review of l 

Augmenting the septum that provides essential support to the erectile tissue. 

Outer-layer bundles are oriented longitudinally, extending from the glans 

penis to the proximal crura; they insert into the inferior pubic rami but are 

absent between the 5- and the 7-o'clock positions. In contrast, the corpus 

spongiosum lacks an outer layer or intracorporeal struts, ensuring a low- 

pressure structure during erection. Figure 45-1 Cross section of the penis 

shows the intracavernous pillars supporting the erectile tissue and the inner 

circular and outer longitudinal layers of the tunica albuginea. The 

longitudinal layer is absent between the corpus cavernosum and the 

spongiosum. (From Lue TF, Akkus E, and Kour NW: Physiology of erectile 

function and dysfunction. Campbell's Urology Update #12 1994; 1-10.) 

The tunica is composed of elastic fibers that form an irregular, latticed 

network on which the collagen fibers rest. The detailed histologic 

composition of the tunica varies depending on anatomic location and 

function. Emissary veins run between the inner and the outer layers for a 

short distance, often piercing the outer bundles in an oblique manner. The 

cavernous artery and the branches of the dorsal artery that give additional 

blood supply to the corpus cavernosum, however, take a more direct route 

and are surrounded by a periarterial soft tissue sheath. The latter structure 

protects the arteries from occlusion by the tunica albuginea during erection. 

The outer tunical layer appears to play an additional role in compression of 

the emissary veins during erection. It also determines, to a large extent, the 

variability in tunical thickness and strength (Hsu et al, 1992). At the 7- 

o'clock position, the tunical thickness is 0.8 ± 0.1 mm; at the 9-o'clock 

position, 1.2 ± 0.2 mm; and at the 11-o'clock position, 2.2 ± 0.4 mm. At the 

3-, 5-, and 1-o'clock positions, the measurements are nearly identical in 

iterature 

15

Review c f literature 

mirror-image fashion. (Differences at specific locations have been found to 

be statistically significant.) 

The stress on the tunica before penetration has been measured as 1.6 ± 0.2 x 

10 7 N 

/ 

m 

2 

at the 7-o'clock position, 3.0 ± 0.3 x 10 7 N 

position, and 4.5 ± 0.5 x 10 7 N 

/ 

m 

2 

/ 

m 

2 at the 9-o'clock 

at the 11-o'clock position. The strength 

and thickness of the tunica correlate in a statistically significant fashion with 

location. The most vulnerable area is located on the ventral groove (between 

the 5- and the 7-o'clock positions), which lacks the longitudinally directed 

outer-layer bundles; most prostheses tend to extrude here (Hsu et al, 1994). 

Corpora Cavernosa, Corpus Spongiosum, and Glans Penis 

The corpora cavernosa comprise two spongy, paired cylinders contained in 

the thick envelope of the tunica albuginea. Their proximal ends, the crura, 

originate at the undersurface of the puboischial rami as two separate 

structures but merge under the pubic arch and remain attached up to the 

glans. The septum between the two corpora c 

but is complete in some species, such as the dog. The corpora c 

intracavernous 

avernosa 

is incomplete in men 

supported by a fibrous skeleton that includes the tunica albuginea, the 

septum, the i 

ntracavernous 

pillars, the i 

ntracavernous 

avernosa 

are 

fibrous framework, 

and the periarterial and perineural fibrous sheath (Goldstein and Padma- 

Nathan, 1990; Hsu et al, 1992). Bitsch and coworkers (1990) believe that the 

framework adds significant strength to the tunica albuginea. 

Within the tunica are the interconnected sinusoids separated by smooth 

muscle trabecula surrounded by elastic fibers, collagen, and loose areolar 

tissue. The terminal cavernous nerves and helicine arteries are intimately 

associated with the smooth muscle. Each corpus c 

avernosum 

is a 

conglomeration of sinusoids, larger in the center and smaller in the 

16

periphery. In the flaccid state, the blood slowly diffuses from the central to 

the peripheral sinusoids and the blood gas levels are similar to those of 

venous blood. During erection, the rapid entry of arterial blood to both the 

central and the peripheral sinusoids changes the intracavernous blood gas 

levels to those of arterial blood. In a canine study, Azadzoi and associates 

(1995) demonstrated that subtunical oxygen tension in the penis is consistent 

with arterial blood whereas the oxygen tension in the central portion of the 

corpus c 

avernosum 

is consistent with venous blood, and they suggest that a 

shunting mechanism may exist in canine penis.The structure of the corpus 

spongiosum and glans is similar to that of the corpora cavernosa, except that 

the sinusoids are larger; the tunica is thinner in the spongiosum (with only a 

circular layer [see earlier]) and is absent in the glans. 

Arterial Supply 

The main source of blood supply to the penis is usually through the internal 

pudendal artery, a branch of the internal iliac artery .In many instances, 

however, accessory arteries exist, arising from the external iliac, obturator, 

vesical, and femoral arteries, and may occasionally become the dominant or 

only arterial supply to the corpus cavernosum (Breza et al, 1989). Damage to 

these accessory arteries during radical prostatectomy or cystectomy may 

result in vasculogenic ED after surgery [Kim ED et al, (1994)]. 

17

5. 

04( 

CCIV) 

- 

Ccgpc4. 

1 

C, 

Aveln 

Arterial supply of the penis 

1 t 

h•P 

urtsr 

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re-ction) 

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el. 

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en, 

it 

Review ( 

Figure (3,): Penile arterial supply cross section of the penis [Devine CJ Jr, Angermeier 

KW (1994) from, Campbell's urology update # 2004]. 

After giving off a branch to the perineum. The three branches of the penile 

artery are the dorsal, the bulb urethral, and the cavernous arteries. The 

cavernous artery is responsible for tumescence of the corpus cavernosum 

and the dorsal artery for engorgement of the glans penis during erection. The 

bulbourethral artery supplies the bulb and corpus spongiosum. The 

cavernous artery enters the corpus cavernosum at the hilum of the penis, 

trfy 

. 

xr; 

( 

24-. 

? 

Vliterature 

18

whet 

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the two crura merge. Distally, the three branches join to form a 

vascular ring near the glans. Along its course, 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 penis 

Cross S 

Venous drainage of the penis 

Figure (4): Shows longitudinal section of venous drainage of the p 

Angermeier KW (1994)] 

The venous drainage from the three corpora originates in tiny venules 

leading from the peripheral sinusoids immediately beneath the tunica 

albuginea see fig. (4), these venules travel in the trabecula between the 

ectbn 

enislfrom 

Devine CJ Jr, 

Lymphatic drainage of the penis: The penis drains into the inguinal lymph nodes. 

These nodes may be divided into a superficial and deep group, which are separated by the deep 

fascia of the thigh (fascia lata). In relation to the external pudendal, superficial inferior epigastric, 

and superficial circumflex iliac vessels, the superficial nodes lie at the saphenofemoral junction. 

At the saphenous opening (fossa ovalis) in the fascia l 

ata, 

the greater saphenous vein joins the 

19

The skin and subcutaneous tissue 


. Multiple superficial veins run subcutaneously and unite near the root of 

the penis to form a single (or paired) superficial dorsal vein, which in turn 

drains into the saphenous veins. Occasionally, the superficial dorsal vein 

may also drain a portion of the corpora cavernosa. 

The pendulous penis 

The emissary veins from the corpus cavernosum and spongiosum drain 

dorsally to the deep dorsal, laterally to the circumflex, and ventrally to the 

periurethral veins. Beginning at the coronal sulcus, the prominent deep 

dorsal vein is the main venous drainage of the glans penis, corpus 

spongiosum, and distal two thirds of the corpora c 

avernosa. 

Usually, a single 

vein, but sometimes more than one deep dorsal vein, runs upward behind the 

symphysis pubis to join the periprostatic venous plexus. 

1. The infrapubic penis. Emissary veins draining the proximal corpora 

cavernosa 

join to form cavernous and crural veins. These veins join 

the periurethral veins from the urethral bulb to form the internal 

pudendal veins. 

2. The veins of the three systems communicate variably with each other. 

Variations in the number, distribution, and termination of the venous 

systems are common. 

1-2 ED Prevalence and Medical Risk Factors 

It is estimated that at least 10 to 20 million American males suffer from 

erectile dysfunction. The most recent and comprehensive epidemiological 

report, the Massachusetts Male Aging Study (Feldman, Goldstein,


Hatzichristou et al, 1994), asked men between the ages of 40 to 70 years to 

categorize their erectile function as either completely, moderately, 

minimally or not impotent. Fifty-two percent of the sample reported some 

dysfunction. This study demonstrated that erectile dysfunction is an age 

dependent disorder; "between the ages of 40 -70 years the probability of 

complete impotence tripled from 5.1 % to 15%, moderate impotence doubled 

from 17 to 34% while the probability of minimal impotence remained 

constant at 17%." By age 70, only 32% portrayed themselves as free of 

erectile dysfunction. 

After the data were adjusted for age, men treated for diabetes (28%), heart 

disease (39%) and hypertension (15%) had significantly higher probabilities 

for erectile dysfunction than the sample as a whole (9.6%). Men with 

untreated ulcer (18%), arthritis (15%) and allergy (12%) were also 

significantly more likely to develop erectile dysfunction. Although erectile 

dysfunction was not associated with total serum cholesterol, the probability 

of dysfunction varied inversely with high density lipoprotein cholesterol. 

Certain classes of medication were related to increased probability for total 

erectile dysfunction. The percentage of men with complete dysfunction 

taking hypoglycemic agents (26%), antihypertensive (14%), vasodilators 

(36%), and cardiac drugs (28%) was significantly higher than the sample as 

a whole (9.6%). Various psychotropic medications including the 

antipsychotic medications, tricyclic antidepressants and the selective 

serotonin reuptake inhibitors have been shown to cause erectile dysfunction 

(Segraves, 1998). Finally, cigarette smoking increased the probability of 

total erectile dysfunction in men with treated heart disease, hypertension or 

21

1. 

3-Pathophysiologv 


untreated arthritis. It similarly increased the probability for men on cardiac, 

antihypertensive or vasodilator medications. 

Physiology 

of Erectile Function 

The penile erectile tissue, specifically the cavernous smooth musculature 

and the smooth muscles of the arteriolar and arterial walls, plays a key role 

in the erectile process. In the flaccid state, these smooth muscles are 

tonically contracted, allowing only a small amount of arterial flow for 

nutritional purposes. The flaccid penis is in a moderate state of contraction, 

as evidenced by further shrinkage in cold weather and after phenylephrine 

injection. Sexual stimulation triggers release of neurotransmitters from the 

cavernous nerve terminals. This results in relaxation of these smooth 

muscles and the following events (Fig.5): 

Figure (5) The mechanism of penile erection A in the flaccid. B in the erect state


1. Dilatation of the arterioles and arteries by increased blood flow in both 

the diastolic and the systolic phases 

2. Trapping of the incoming blood by the expanding sinusoids 

3. Compression of the subtunical venular plexuses between the tunica 

albuginea and the peripheral sinusoids, reducing the venous outflow 

4. Stretching of the tunica to its capacity, which encloses the emissary veins 

between the inner circular and the outer longitudinal layers and further 

decreases the venous outflow to a minimum 

5. An increase in intracavernous pressure (maintained at around 100 mm 

Hg), which raises the penis from the dependent position to the erect state 

(the full-erection phase) 

6. A further pressure increase (to several hundred millimeters of mercury) 

with contraction of the I 

schiocavernosus 

muscles (rigid-erection phase) 

7. The angle of the erect penis is determined by its size and its attachment to 

the puboischial rami (the crura) and the anterior surface of the pubic bone 

(the suspensory and funiform ligaments). In men with a long heavy penis 

or a loose suspensory ligament, the angle usually will not be greater than 

90 degrees, even with full rigidity. 

Corpus Spongiosum and Glans Penis 

The homodynamic of the corpus spongiosum and glans penis are somewhat 

different from those of the corpora cavernosa. During erection, the arterial 

flow increases in a similar manner; however, the pressure in the corpus 

spongiosum and glans is only one third to one half of that in the corpora 

cavernosa because the tunical covering (thin over the corpus spongiosum 

and virtually absent over the glans) ensures minimal venous occlusion. 

During the full-erection phase, partial compression of the deep dorsal and 

23


During the full-erection phase, partial compression of the deep dorsal and 

circumflex veins between Buck's fascia and the engorged corpora c 

contribute to glanular tumescence, although the spongiosum and glans 

essentially function as a large arteriovenous shunt during this phase. In the 

rigid-erection phase, the. Ischiocavernosus and B 

cavernosum, 

Italiano 

ulbocavernous 

avernosa 

muscles 

forcefully compress the spongiosum and penile veins, which results in 

further engorgement and increased pressure in the glans and spongiosum. 

Smooth Muscle Physiology 

Spontaneous contractile activity of cavernous smooth muscle has corpus 

Mandrek (1994) demonstrated spontaneous been recorded in 

vitro and in vivo .In isolated strips of rabbit mechanical activity with a 

frequency of 6 to 30 contractions per minute accompanied by fluctuations in 

membrane potential. Stimulation of the tissue with tetraethylammonium 

chloride and norepinephrine produced strong tonic contractions with relative 

electrical silence. In a human study, Y 

arnitsky 

and colleagues (1995) found 

two types of electrical activity recorded from the corpus c 

spontaneous and activity-induced. Levin and coworkers (1994) reported that 

in vitro spontaneous contractile activity is correlated with a phasic increase 

in intracellular calcium and a biphasic change in the N 

ADH/ 

NAD 

avernosum: 

ratio, 

suggesting an initial increase and then a decrease of intracellular energy. 

and coworkers (1998) suggested that phasic contraction of the penis 

is through the enzyme N 

a-K-ATPase 

and the resting tone is mediated by the 

endothelium through the release of prostaglandin Fla. Field stimulation 

results in a decrease in tension and intracellular calcium at low frequencies 

and an increase in tension with increased intracellular calcium at high 

frequencies. In general, the response to pharmacologic agents correlates with 

the change in intracellular calcium: for example, phenylephrine produces

Nerves in penis (dorsal 

penile nerve, lesser 

n 

cavernous greater 

cavernous nerve) send 

messages T 

O 

erve, 

Iscral 

pie 

4S 

o 

Sacral 

messages to penis 

lextas 


muscle contraction and an increase in intracellular calcium, whereas 

nitroprusside causes the opposite. In a study of myosin isoforms in smooth 

muscle cells in the corpus c 

avernosum 

penis, DiSanto and associates (1998) 

reported that the corpus cavernosum smooth muscle cells possess an overall 

myosin isoforms composition intermediate between aorta and bladder 

smooth muscles, which generally express tonic- and phasic-like 

characteristics, respectively. Further studies of isoforms changes may 

uncover the increased contractility or impaired relaxation of the cavernous 

smooth muscle in pathologic conditions. 

Figure (6): Neuroanatomy and Neurophysiology of Penile Erection [Walsh P 

Campbell's urology update 2004] 

Sacral plexus: 

S2 to S4 

a 

Brain 

t o S 

acral 

reas 

send e 

plexus 

nessi3ges 

welds 

C, 

1982 

25

Peripheral Pathways 

The innervations of the penis is both autonomic (sympathetic and 

parasympathetic) and somatic (sensory and motor) (Fig.6). From the neurons 

in the spinal cord and peripheral ganglia, the sympathetic and 

parasympathetic nerves merge to form the cavernous nerves, which enter the 

corpora c 

avemosa 

and corpus spongiosum to effect the neurovascular events 

during erection and detumescence. The somatic nerves are primarily 

responsible for sensation and the contraction of the Bulbocavemous and 


muscles. 

Autonomic Pathways 

The sympathetic pathway originates from the 1 1 th thoracic to the 2nd 

lumbar spinal segments and passes through the white r 

arni 

to the 

sympathetic chain ganglia. Some fibers then travel through the lumbar 

splanchnic nerves to the inferior mesenteric and superior hypogastric 

plexuses, from which fibers travel in the hypogastric nerves to the pelvic 

plexus. In humans, the T10 to T12 segments are most often the origin of the 

sympathetic fibers, and the chain ganglia cells projecting to the penis are 

located in the sacral and caudal ganglia (de Groat and Booth, 1993). 

The parasympathetic pathway arises from neurons in the i 

cell columns of the second, third, and fourth sacral spinal cord segments. 

The preganglionic fibers pass in the pelvic nerves to the pelvic plexus, where 

they are joined by the sympathetic nerves from the superior hypogastric 

plexus. The cavernous nerves are branches of the pelvic plexus that 

innervate the penis. Other branches of the pelvic plexus innervate the 

rectum, bladder, prostate, and sphincters. The cavernous nerves are easily 

damaged during radical excision of the rectum, bladder, and prostate. A 

clear understanding of the course of these nerves is essential to the 

nterrnediolateral


damaged during radical excision of the rectum, bladder, and prostate. A 

clear understanding of the course of these nerves is essential to the 

Stimulation of the pelvic plexus and the cavernous nerves induces erection, 

whereas stimulation of the sympathetic trunk causes detumescence. This 

clearly implies that the sacral parasympathetic input is responsible for 

tumescence and the thoracolumbar sympathetic pathway is responsible for 

detumescence. In experiments with cats and rats, removal of the spinal cord 

below L4 or L5 reportedly eliminated the reflex erectile response but 

placement with a female in heat or electrical stimulation of the medial 

preoptic area produced marked erection (Root and Bard, 1947; Courtois et 

al, 1993). Paick and Lee (1994) also reported that apomorphine-induced 

erection is similar to psychogenic erection in the rat and can be induced by 

means of the thoracolumbar sympathetic pathway in case of injury to the 

sacral parasympathetic centers. In man, many patients with sacral spinal 

cord injury retain psychogenic erectile ability even though reflexogenic 

erection is abolished. These cerebrally elicited erections are found more 

frequently in patients with lower motoneuron lesions below T12 (Bors and 

Comarr, 1960). No psychogenic erection occurs in patients with lesions 

above T9; the efferent sympathetic outflow is thus suggested to be at the 

levels T11 and T12 These authors have also reported that, in patients with 

psychogenic erections, lengthening and swelling of the penis are observed 

but rigidity is insufficient. 

It is, therefore, possible that cerebral impulses normally travel through 

sympathetic (inhibiting norepinephrine release), parasympathetic (releasing 

NO and acetylcholine), and somatic (releasing acetylcholine) pathways to 

produce a normal rigid erection. In patients with a sacral cord lesion, the 

27


cerebral impulses can still travel by means of the sympathetic pathway to 

inhibit norepinephrine release, and NO and acetylcholine can still be 

released through synapse with p 

ostganglionic 

parasympathetic and somatic 

neurons. Because the number of synapses between the thoracolumbar 

outflow and the postganglionic parasympathetic and somatic neurons is less 

than the sacral outflow, the resulting erection will not be as strong. 

Somatic Pathways 

The somatosensory pathway originates at the sensory receptors in the penile 

skin, glans, and urethra and within the corpus cavernosum. In the human 

glans penis are numerous afferent terminations: free nerve endings and 

corpuscular receptors with a ratio of 10:1. The free nerve endings are 

derived from thin myelinated A 5 and unmyelinated C fibers and are unlike 

any other cutaneous area in the body (Halata and Munger, 1986). The nerve 

fibers from the receptors converge fto 

bundles of the dorsal nerve of the 

penis, which joins other nerves to become the pudendal nerve. The latter 

oim 

S 

t 

enters the spinal cord via the roots to on spinal neurons and 

interneurons in the central gray region of the lumbosacral segment 

2— 

S4 

(McKenna, 1998). Activation of these sensory neurons sends messages of 

pain, temperature, and touch by means of spinothalamic and spinoreticular 

pathways to the thalamus and sensory cortex for sensory perception. The 

dorsal nerve of the penis used to be regarded as a purely somatic nerve; 

however, nerve bundles testing positive for nitric oxide synthase (NOS), 

which is autonomic in origin, have been demonstrated in the human by 

Burnett and colleagues (1993) and in the rat by Carrier and coworkers 

(1995). Giuliano and associates (1993) have also shown that stimulation of 

the sympathetic chain at the L4—L5 level elicits an evoked discharge on the 

elminate 

28



Review o 

dorsal nerve of the penis and stimulation of the dorsal nerve evokes a reflex 

discharge in the lumbosacral sympathetic chain of rats. These findings 

clearly demonstrate that the dorsal nerve is a mixed nerve with both somatic 

and autonomic components that enable it to regulate both erectile and 

ejaculatory f 

unction. 

Onuf 

s nucleus in the second to fourth sacral spinal 

segments is the center of somatomotor penile innervations. These nerves 

travel in the sacral nerves to the pudendal nerve to innervate the 

contraction of the B 

Ischiocavemosus 


and B 

ulbocavernous 

muscles. Contraction of the 

muscles produces the rigid-erection phase. Rhythmic 

ulbocavernous 

muscle is necessary for ejaculation. 

Depending on the intensity and nature of genital stimulation, several spinal 

reflexes can be elicited by stimulation of the genitalia. The best known is the 

reflex, which is the basis of genital neurologic examination 

and electro physiologic latency testing. Although impairment of 

and I 

the significance of obtaining B 

a 

dysfunction assessment is controversial. 

schiocavemosus 

ulbocavernous 

muscles may impair penile erection, 

reflex in overall sexual 

A variety of neurotransmitters, including dopamine, or epinephrine, and 

serotonin (5-hydroxytryptamine [ 

5-HT] 

) 

, 

have been identified in the 

hypothalamus. It has been suggested that dopaminergic and adrenergic 

receptors promote sexual function and that 5-HT receptors inhibit it 

(Foreman et al (1989). 

In summary, these structures are responsible for the three types of erection: 

psychogenic, reflexogenic, and nocturnal. Psychogenic erection is a result of 

audiovisual stimuli or fantasy. Impulses from the brain modulate the spinal 

erection centers ( 

T11— 

L2 

and S2—S4) to activate the erectile process. 

f 

- l 

iterature 

29


Reflexogenic erection is produced by tactile stimuli to the genital organs. 

The impulses reach the spinal erection centers; some then follow the 

ascending tract, resulting in sensory perception, whereas others activate the 

autonomic nuclei to send messages through the cavernous nerves to the 

penis to induce erection. This type of erection is preserved in patients with 

upper spinal cord injury. Nocturnal erection occurs mostly during rapid-eye- 

movement (REM) sleep. PET scanning of humans in REM sleep shows 

increased activity in the pontine area, the a 

rnygdalae, 

and the anterior 

cingulate gyrus but decreased activity in the prefrontal and parietal cortex. 

The mechanism that triggers REM sleep is located in the pontine reticular 

formation. During REM sleep, the cholinergic neurons in the lateral pontine 

tegmentum are activated, whereas the adrenergic neurons in the locus 

coeruleus and the serotonergic neurons in the midbrain Raphe are silent. 

This differential activation may be responsible for the nocturnal erections 

during REM sleep. 

Neurotransmitters 

Peripheral Neurotransmitters 

Flaccidity and Detumescence a-Adrenergic nerve fibers and receptors have 

been demonstrated in the cavernous trabecula and surrounding the cavernous 

arteries and norepinephrine has generally been accepted as the principal 

neurotransmitter to control penile flaccidity and detumescence (Hedlund and 

Andersonl985; 

Diederichs et al, 1990). Receptor binding studies have 

shown the number of a adrenoceptors to be 10 times higher than the number 

of 13 adrenoceptors (Levin and Wein, 1980). Currently, it is suggested that 

sympathetic contraction is mediated by activation of postsynaptic —la alb -, 

30

Review of l 

and A 1 C -adrenergic receptors (Christ et al, 1990; Traish et al, 1995) and 

modulated by c 

presynaptic -adrenergic receptors (See), controversial 

effect. NO, nitric oxide; VIP, vasoactive intestinal. Polypeptide. (Saenz de 

Tejada et al, 1989b). 

c, 

Endothelin, a potent vasoconstrictor produced by the endothelial 

cells, has also been suggested to be a neurotransmitter for 

detumescence (Holmquist et al, 1990; Saenz de Tejada et al, 1991). In 

addition, other vasoconstrictors such as thromboxane A2, prostaglandin F 

leukotrienes, and angiotensin II have been proposed (Hedlund H et al, 1989; 

Azadzoi et al, 1992; Kifor et al, 1 

997) 

. 

In 

summary, the maintenance of the 

intracorporeal smooth muscle in a semicontracted (flaccid) state probably 

results from three factors: intrinsic myogenic activity (Andersson and 

Wagner, 1995), adrenergic neurotransmission, and endothelium-derived 

contracting factors such as prostaglandin Fla and Endothelin. On the other 

hand, detumescence after erection may be a result of cessation of NO 

release, the breakdown of second messengers by PDEIs, or sympathetic 

discharge during ejaculation. 

Erection 

Acetylcholine has been shown to be released with electrical field stimulation 

of human erectile tissue (Blanco et al, 1988). Traish and coworkers (1990) 

reported the density of muscarinic receptors in cavernous tissue to range 

from 35 to 65 f 

10 f 

mol/ 

mg 

mol/ 

mg 

protein and in endothelial cell membrane from 5 to 

protein. However, IV or intracavernous injection of atropine has 

failed to abolish erection induced in animals by electrical neurostimulation 

(Stief et al, 1989) and in men by erotic stimuli (Wagner and Uhrenholdt, 

1980). Although acetylcholine is not the predominant neurotransmitter, it 

iterature 

l 

a 

31 

,

nonadrenergic/ 

noncholinergic 


does contribute indirectly to penile erection by (1) presynaptic inhibition of 

adrenergic neurons and (2) stimulation of the release of NO from endothelial 

cells (Saenz de Tejada et al, 1989a). 

Most researchers now agree that NO released from 

(NANC) neurotransmission and from the 

endothelium is the principal neurotransmitter mediating penile erection. NO 

increases the production of cGMP, which in turn relaxes the cavernous 

smooth muscle (Holmquist et al, 1991; Kim N et al, 1991; Pickard et al, 

1991; Burnett et al, 1992; Knispel et al, 1992; Trigo-Rocha et al, 1993,). 

NO and cGMP in Relaxation of Smooth Muscle 

NO was first described in 1979 as a potent relaxant of peripheral vascular 

smooth muscle, with an action mediated by cGMP (Gruetter et al, 1979). 

Subsequently, endothelium-derived relaxing factor was identified as NO or a 

chemically unstable nitroso precursor (Ignarro et al, 1987; Palmer et al, 

1987). NO is synthesized from endogenous 1 

inhibited by N-substituted analogues of 1-arginine, such as N 

arginine, N 

-nitro-l-arginine, 

hemoglobin. 

and N 

-amino-l-arginine. 

-arginine 

by NOS, which can be 

-methy1-1- 

NO is inactivated by 

There are three distinct forms of NOS (neuronal [nNOS or NOS-1], 

macrophage and other immune cells [iNOS or NOS-2], and endothelial 

[eNOS or N 

OS-3] 

) 

. 

that increase intracellular C 

The NOS-1 and NOS-3 forms are activated by agents 

a 

2+ 

concentration, including the vasodilators 

acetylcholine and bradykinin. The NOS in immune cells is induced not by 

Ca 

2 

+ 

but by cytokines. NOS have multiple regulatory sites, including binding 

sites for nicotinamide-adenine dinucleotide phosphate (NADPH), flavin 

adenine dinucleotide (FAD) and flavin mononucleotide (FMN), and 

32

tetrahydrobiop 

amino acid sequence. 

/ terin. 

Review o 

The three forms of NOS display about 50% identity in 

In the penis, the NO that is released from nerve endings or endothelial cells 

diffuses into smooth muscle cells, where it activates soluble guanylyl 

cyclase, producing cGMP. The mechanism by which intracellular cGMP 

promotes smooth muscle relaxation has not been settled. The most likely 

mechanism is the activation of cGMP-specific protein kinase, resulting in 

the phosphorylation and inactivation of myosin light-chain kinase, thereby 

causing dissociation of myosin and actin and smooth muscle Relaxation 

(Draznin et al, 1986). Both cGMP and cGMP-specific protein kinase may 

also activate potassium channels, causing hyperpolarization and closure of 

voltage-dependent calcium channels and a decrease in intracellular calcium. 

signaling 

Independent of cGMP, a study also demonstrated that NO may stimulate the 

opening of N 

a-K-ATPase 

and thus cause hyperpolarization (Gupta et al, 

1995). A considerable number of studies suggest that cGMP is a more potent 

relaxant of smooth muscle than cAMP. The increased levels of cGMP in 

response to neurotransmitters are caused by activation of soluble or 

particulate forms of guanylyl cyclase in the cell. The soluble guanylyl 

cyclase is a heterodimer whose subunits have molecular weights of 

approximately 77.5 KD (a) and 70.5 kDa (b) (Chinkers and Garbers, 1990). 

A study of cGMP-dependent protein kinase I—deficient mice clearly shows 

that cGMP/cGMP—protein kinase I is the main physiologic signaling 

pathway for penile erection and it cannot be substituted by the c 

pathway (Hedlund P et al, 2000).see figure below 

lliterattire 

AMP-

Regulation Sof 

o 

Effect 

Neurons or 

endothelium 

Sadorsky 

mOoth-Muscle 

fTDE5 

Relaxation: 

Inhibitors 

c 

GTP protein 

Nitric 

oxide 

Guanylyl Cydase 

ATP 

P KG 

ADP. 

P 

• 

inhibitors 

Dt5 

It. , 

ail. h 

t 

• 

i/ 

. 

/ 

•. 

c 

c' 

. / 

. 

. 

• . 

Prat 

t 2 

001155: 

115-12S. 

/ 

PDE54 

. 5 

-Gtvl1. 

Grop 

p 

— 

. 

* 

, 

' 

-RELAXATIOff 

protcin 

lower 

•• 

• 

OF 

VASCULAR • 

.SMOOTH MUSCLE 

Figure (7): Regulation of Smooth- Muscle Relaxation 

Cef 


Other investigators believe that vasoactive intestinal polypeptide (VIP) may 

be one of the neurotransmitters responsible for erection. V 

relaxation is reportedly inhibited by the NO synthesis N 

blocker 

which has led Y. C. Kim and colleagues (1995) to suggest that NO 

arginine, 

generation is involved in VIP-stimulated smooth muscle relaxation. In a 

colocalization study, acetylcholine, VIP, and nNOS appear to be colocalized 

in parasympathetic neurons (Hedlund P et al, 1999). Thus, they may act 

synergistically to induce erection through inhibition c 

of 

acetylcholine and release of NO by VIP, as suggested by Aoki and 

- P 

t 

• 

i 

IP-induced 

-co-nitro-l- 

activity by 

associates (1994). Other potential candidates include a relaxing factor 

working through a K + channel (Okamura et al, 1998), a non-NO, cGMP- 

dependent pathway (Reilly et al, 1997a), and prostaglandins (Adaikan et al, 

1988; Saenz de Tejada et al, 1989b). 

34

Phosphodiesterase 

During, 

the return to the flaccid state, cGMP is hydrolyzed to G 


MP 

by the 

highly specific cGMP-binding PDE type 5 (PDE5). The PDE superfamily 

comprises 11 families of proteins that are encoded by at least 17 genes 

(Fisher et al, 1998; Soderling, et al, 1998; Fawcett et al, 2000). Each PDE 

contains a conserved catalytic region, which is approximately 275 amino 

acids long and is located in C 

the portion of the protein. The Nterminal 

portion contains regulatory domains that differ among the PDEIs, 

cGMP; 

including c 

alcium/ 

calmodulin 

localization domains, and phosphorylation sites. 

-tenninal 

binding sites, cGMP binding sites, membrane 

Of the 11 PDE isozyme families, only PDE5, -6, and -9 are specific for 

cGMP as a substrate. PDE1, -2, -3, - 10, and -11 hydrolyze both c 

and PDE4, -7, and -8 hydrolyze C 

only ( Fisher et al, 1998; 

Soderling et al, 1998; Fawcett et al, 2000). Although PDE2, -3, and -4 are 

also found in the corpus cavernosum, they do not appear to play a significant 

role in physiologic erections when compared with PDE5 (Ballard et al, 

1998). However, the significance and the possible interactions of the PDEIs 

in the penis have yet to be determined. 

In addition to corpus cavernosum, where three i 

AMP 

sofolins 

AMP 

and 

of PDE5 have been 

cloned, many other tissues have been reported to express PDE5, including 

platelet, lungs, cerebellum, spinal cord, skeletal muscle, heart, placenta, 

pancreas, intestine, aorta, and adrenal gland (Yanaka et al, 1998; Lin et al, 

2000). Although one might expect the PDE5 inhibitor sildenafil to have 

wide-ranging side effects, in clinical trials these have appeared to be limited 

to the retina (from inhibition of PDE6) and cardiovascular and

gastrointestinal systems (e.g., blurred v 

tuberoinfundibular 

indigestion) (Goldstein I et al, 1998). 

ision, 

Central Neurotransmitters and Neural Hormones 


headache, facial f 

A variety of neurotransmitters (dopamine, norepinephrine, 5-HT, and 

oxytocin) and neural hormones (oxytocin, Prolactin) have been implicated in 

regulation of sexual function. It is suggested that dopaminergic and 

adrenergic receptors may promote sexual function and that 5-HT receptors 

inhibit it [Foreman et al, (1989)]. 

Dopamine 

There are many dopaminergic systems in the brain with ultrashort, 

intermediate, and long axons. The cell bodies are located in the ventral 

tegmentum, substantia nigra, and hypothalamus, one of which, the 

system, secretes the dopamine into the portal hypophysial 

vessels to inhibit Prolactin secretion (Ganong, 1999a). Five different 

dopamine receptors have been cloned (D 1 to D 5), and several of these exist 

in multiple forms (Ganong, 1999b). In men, apomorphine, which stimulates 

both D 1 and D2 receptors, induces penile erection that is unaccompanied by 

sexual arousal (Danjou et al, 1988). Dopamine agonists (apomorphine and 

pergolide) and dopamine uptake inhibitors (nomifensine and bupropion) 

have been reported to enhance sexual drive in patients (Jeanty et al, 1984). 

In animal studies, selective activation of D 2 -dopaminergic receptors by the 

systemic administration of agonists such as apomorphine and quinelorane 

increases sexual behavior, and this effect can be counteracted by centrally 

acting antagonists. 

lushing, 

36

Serotonin 


Raphe nuclei of the brain stem and project to a portion of the hypothalamus, 

the limbic system, the neocortex, and the spinal cord (Ganong, 1999a). 

Currently, there are 5-HT 1-7 receptors that have been cloned and 

characterized. Within the 5-HT-1 group, there is 5 

subtypes. Within the 5-HT-2 group, there 5 

is 

There are two 5 

subtypes, 5-HT-5 A and B ( 

-HT-5 

-HT-2 

-HT-1 

Ganong, 

A, B, D, E, and F 

A, B, and C subtypes. 

19996). General 

pharmacologic data indicate that 5-HT pathways inhibit copulation but that 

5-HT may have both 5 

-HT— 

containinL 

, neurons 

have their cell bodies in the 

midline facilitatory and inhibitory effects on sexual function, depending on 

the receptor subtype, the receptor location, and the species investigated (de 

Groat and Booth, 1993). 

Norepinephrine 

The cell bodies of the norepinephrine-containing neurons are located in the 

locus coeruleus and AS c 

atecholaminergic 

cell group in the pons and 

medulla. The axons of these noradrenergic neurons ascend to innervate the 

paraventricular, supraoptic, and paraventricular nuclei of the hypothalamus, 

the thalamus, and neocortex. They also descend into the spinal cord and the 

cerebellum. Central norepinephrine transmission seems to have a positive 

effect on sexual function. In both humans and rats, inhibition of 

norepinephrine release by c 

ionidine, 

a a2 - 

adrenergic 

agonist, is associated 

with a decrease in sexual behavior, and yohimbine, a a 2 -receptor antagonist, 

has been shown to increase sexual activity (Clark et al, 1985). B Blockers 

have also been implicated in sexual dysfunction, probably because of their 

central side effects such as sedation, sleep disturbances, and depression.

Opioids 

iterature 

Review of l 

Endogenous Opioids are known to affect sexual function, but the mechanism 

of action is far from clear. Injection of small amounts of morphine into the 

MPOA facilitates sexual behavior in rats. Larger doses, however, inhibit 

both penile erection and yawning induced by oxytocin or apomorphine. It is 

suggested that endogenous Opioids may exert an inhibitory control on 

central Oxytocinergic transmission (Argiolas, 1992). 

Oxytocin 

Oxytocin is a neural hormone secreted by the neurons into the circulation. 

Besides the posterior pituitary gland, o 

xytocin-secreting 

neurons are also 

found in the neurons projecting from the paraventricular nuclei to the brain 

stem and spinal cord and, thus, oxytocin can also function as a 

neurotransmitter. The blood level of oxytocin is increased during sexual 

activity in humans and animals. It produces yawning and penile erection 

when injected into the paraventricular area in rats. It has been suggested that 

calcium is the second messenger mediating oxytocin-mediated penile 

erection. Because neurons in the paraventricular area have been shown to 

contain NOS, and NOS inhibitors prevent apomorphine- and oxytocin- 

induced erection, it is suggested that oxytocin acts on neurons whose activity 

is dependent on certain levels of NO (Vincent and Kimura, 1992; Melis and 

Argiolas, 1993). 

Prolactin 

Increased levels of Prolactin suppress sexual function in men and 

experimental animals. In rats, high levels of Prolactin decrease the genital 

reflex and disturb copulatory behavior. It is suggested that the mechanism of 

38


prolactin's action is through inhibition of dopaminergic activity in the 

MPOA and decreased testosterone level. In addition, Prolactin may have a 

direct effect on the penis through its contractile effect on the cavernous 

smooth muscle (Ra et al, 1996). 

1.4- Patho s hvsiolo of Erectile Dysfunction ED 

Pathogenesis of vasculogenic ED 

Data from the literature report a strong correlation between ED and 

cardiovascular diseases ( CVD ).Impairments in the homodynamic of 

erection have been shown in patients suffering from coronary artery disease 

(CAD) ( Feldman et al ,1994 ); );Melman & Gingell ( 1999 ); Greenstein et 

al ( 1997 );Bernardo ( 2001 );Bush (2001 );Montorsi et a 

infarction (Feldman et al (1994)); Dhabuwala et al (1986); K 

l( 

1994 

loner 

) ,myocardial 

(2003) 

and peripheral vascular disease (Feldman et al (1994); Melman & Gingell 

(1999); Sullivan et al (2001).Besides, several authors demonstrated that the 

incidence of abnormal penile vascular findings significantly increases with a 

history of systemic vascular risk factors such as treated and untreated 

hypertension, dyslipidemia, obesity and cigarette smoking (Feldman et al 

(1994; Chung et al (1999); Sullivan et al (2001); Mannino et al (1994); 

impaiiment 

McVary et al (2001). On the other hand, a similar significant correlation has 

been described between ED and vasculars, anti-hypertensive drugs, cardiac 

medications and oral hypoglycaemic agents [Menihardt et al (1997)]. 

(1) Erectile dysfunction and cardiovascular diseases 

Since ED is a common problem in men suffering from CVD, penile erection 

may herald a systemic vasculopathic state such as ischemic heart 

disease. In addition, the coexistence of coronary artery disease (CAD) and 

39

Review o 

sexual dysfunction in middle-aged and older men is common, and the 

prevalence of ED among patients with coronary artery disease is very high 

(Kim et al (1991) ). Greenstein et al. (1997) demonstrated a statistically 

significant correlation between erectile function and the number of coronary 

vessels involved; patients with one-vessel disease had more numerous and 

firmer erections with fewer difficulties in achieving an erection, than men 

with two or three vessels disease. 

Recently, we studied a population of 246 consecutive male patients 

presenting with acute angina pectoris (mean age: 62.3 yrs; range 33-86) who 

underwent a morphological and function evaluation of the coronary arteries 

by means of a coronary angiography (Montorsi et al (2002). Erectile 

dysfunction prevalence in this series of patients was 48%. According to the 

ED severity classification proposed by Cappelleri et al. (1999), the enrolled 

patients were subdivided into four groups. Forty-nine% of the men 

complained of severe ED; moderate ED was reported by 18% patients; mild 

to moderate ED was described by 18% and 15% of the men complained of 

mild ED. Coronary angiography showed that 44 out of the96 patients (46%) 

suffering from ED had a three vessels disease; 22/96 (23%) had two 

diseased coronary arteries diseased; 30/96 (31%) patients had a stenosis in 

only one coronary artery. Among the 44 patients who showed occlusive 

disease in three vessels (46%), twenty-six (59%) reported severe ED; four 

patients (9%) did report moderate ED; seven men (16%) presented mild to 

moderate ED and seven men (16%) had mild ED ;. Instead, among the 22 

patients who showed occlusive disease at two vessels (23%), 9 (41%) 

reported severe ED; three patients (14%) did report moderate ED; four men 

(18%) presented mild to moderate ED and six men (27%) had mild ED 

r 

- l 

iterature 

40

Review of l 

(Montorsi et al (2002) ). This study confirmed that ED prevalence in patients 

suffering from CAD conditioning ischemic heart disease is significant; on 

the other hand coronary arteries angiography showed a close correlation 

between number of arteries disease and severity of the ED. 

Arterial insufficiency is most commonly the result of progressive systemic 

atherosclerosis. Atherosclerotic lesions are characterized by the proliferation 

of SMC and deposition of lipids in the vessels wall (Davies (1991)). Arterial 

occlusive disease, especially in the hypogastric-cavernous bed, can decrease 

the perfusion pressure and arterial flow to the corpora c 

avernosa, 

iterczture 

therefore 

decreasing the rigidity of the penile shaft (Udelson et al (1998 )Common 

risk factors associated with arterial insufficiency include, as already 

described, hypertension, hyperlipidemia, cigarette smoking, and diabetes but 

also blunt perineal or pelvic trauma and pelvic irradiation. 

Laboratory and clinical studies have demonstrated that the dysfunctional 

degree associated with ED cannot be predicted exclusively by the arterial 

homodynamic abnormalities (Azad7oi & Goldstein (1992); Azadzoi et al 

(1995); Azadzoi et al (1990)). Chronic cavernous arterial insufficiency 

seems to affect some structural components in erectile tissue, such as 

corporal SMC and endothelial cells, thereby impairing normal corporal 

smooth muscle relaxation. Smooth muscle cells represent the structural basis 

for sinusoidal relaxation; studies have suggested that vasculogenic ED may 

be related to corporeal dysfunction, rather than simply impaired cavernosal 

arterial flow (Krane et al (1989); Saenz de Tejada et al (1989)). Structural 

alterations in smooth muscle cells can then be due to local low cavernosal 

oxygen tension. Systemic atherosclerosis seems to potentially determine 

hypoxia of the erectile tissue associated with focal abnormalities which 

41

egin alterations in the intracellular organelles ( 

e. 

g. 

Review o 

lose of mitochondria, 

myofibers and inclusion bodies, etc.) that finally induce a reduction in the 

percentage of SMC, with a proportional increase in the collagen amount of 

extracellular matrix. 

(2) Erectile dysfunction and Hypertension 

Hypertension affects blood vessels by shear stress, which can lead to 

endothelial abnormalities such as an altered production and activity of 

vasoactive substances. It has been proposed that in hypertension the 

increased blood pressure per se dose not induce an impairment of erectile 

function; therefore, it is thought that the resultant dysfunction could be 

caused by the associated arterial stenotic lesions (Hsieh et al (1989)). 

Recently animal studies demonstrated that hypertension induced important 

morphologic changes in cavernous tissue, characterized by an increase in the 

vascular smooth muscle proliferative score, trabecular SMC content in the 

cavernous spaces but also by a larger amount of perivascular collagen type 

III and higher fibrosis score. Authors suggested that compliance of the 

corpora cavernosa. Moreover, the increase in extracellular matrix expansion 

seemed to affect not only the interstitium but also the neural structures of the 

penis (i.e. perineurium and endoneurium of the amielinic nerves) finally 

resulting in a modification of the correct relaxation mechanism for penile 

tumescence. This analysis also suggested a relationship between 

morphologic changes and the degree of arterial hypertension. 

(3) Erectile dysfunction and Cigarette smoking 

Cigarette smoking is an important independent modifiable risk factor and it 

appears to have a deleterious effect on penile homodynamic integrity. 

f 

literature 

42

Review 

of literature 

Mannino and co-workers (1994) showed an Odds Ratio (OR) of 1.4 for 

smokers vs. non-smokers. Parazzini et al. (2002) furthermore demonstrated 

an OR of 1.7 and also that the risk of ED increases with duration of the 

habit. Indeed, the prevalence of ED vs. non-ED was 27.8 vs.59% for an 

exposure to smoking shorter than 20 years long; on the contrary with a 

smoking exposure longer than 20 years the relative risk was 72.2 v 

(ED vs. non ED, respectively) (Feldman et al (1994)). Cigarette smoking 

showed also to increase the age-adjusted risk of ED in addition to increasing 

the relative risk for antihypertensive medications, cardiac drugs and 

systemic illness as diabetes mellitus (50% versus 45.4% of complete ED, 

smokers vs. non-smokers respectively) (Feldman et al (1994)). 

More recently, McVary et al. (2001) reviewed the literature concerning the 

impairment of quality of life ( 

QOL) 

due to cigarette smoking. The authors 

reported that there are strong parallelisms and shared risks among smoking, 

CAD, atherosclerosis and ED. Clinical and basic science studies provide 

strong indirect evidence that smoking may affect penile erection by the 

impairment of endothelium dependent smooth muscle relaxation. They also 

confirmed that the association of ED with risk factors such as CAD and 

hypertension appears to be amplified by cigarette smoking. Smoking may 

increase the likelihood of moderate or complete ED 2-fold. The prevalence 

of ED in former smokers was no different from that of individuals who had 

never smoked, implying that smoking cessation may decrease the risk of ED. 

From a path physiological point of view, nicotine may inhibit smooth 

muscle function or the neurovascular mediators, such as prostacyclin, 

causing many types of homodynamic alterations. Atherosclerotic changes 

have also been suggested to be one of the chronic effects of nicotine. 

s, 

41% 

43

Hypercoag, 

ulability 

veno-occlusion 

and increased platelet a 

ggregation, 


the release of fatty 

acids and catecholamins, or a direct toxic effect on the vascular endothelium 

has also been considered as possible mechanisms. Recently, literature data 

showed that smoking may act as a risk factor for ED by reducing High 

Density Lipoprotein (HDL) and increasing fibrinogen concentrations. As 

previously reported by the MMAS (Feldman et al (1994)), low HDL was a 

predictor for the development of ED. These issues suggest that ED may 

share a similar pathogeneses with other forms of vascular disease. 

(4) Veno-Occlusive erectile dysfunction 

One of the most common causes of organic ED is corporal v 

insufficiency. Corporal v 

eno-occlusive 

pathology characterized ED owing to 

venous insufficiency with adequate arterial inflow. Indeed, as the trabecular 

SM relax and fill with blood, I 


eno-occlusive 

pressure and volume increase; 

develops through stretching and compressive forces by 

"expandable" trabecular tissue on subtunical venules (Udelson et al (1998); 

Saenz de Tejada et al (1991)). The percentage of trabecular SM content in 

the corpus cavernosum showed a significant tight positive correlation with 

the function of the corporal v 

eno-occlusive 

mechanism (Wespes et al 

(1991)). Furthermore, SMC content depends on the correct oxygen tension 

at the tissue level. 

The pathphysiological mechanisms of venogenic ED or structurally based 

corporal v 

eno-occlusive 

dysfunction appear to be related to elevated 

corporeal connective tissue content and fibrosis (Wespes et al (1991)). 

Furthermore, venogenic ED is also frequently characterized by atrophy of 

the trabecular smooth muscle cells with increased fibrous connective tissue 

(Nehra et al (1996)). Corporeal fibrosis induced by venogenic impairment is 

44

arteriogenic 

most likely related to c 

hronic 


ischemia, which in turn frequently results in 

abnormalities in collagen synthesis and degradation (Wespes et al (1991)). 

This damage limits the ability of the smooth muscle to relax within the 

corpora, resulting in reduced sinusoidal dilation. Regarding c 

oxygen tension, patients with mild/moderate venous leak are probably 

different physiologically from those with severe venous leak. Brown et al. 

demonstrated a low c 

avernosal 

oxygen tension value both in patients with 

ED or severe venous leakage concept of corporeal fibrosis 

secondary to chronic ischemia and low c 

avernosal 

oxygen tension as a 

mechanism for both arteriogenic and venogenic ED ( Wespes et al (1991 ) . 

Rarely, venogenic ED may be the result of the congenital presence or 

development of excessively large venous channels through the corpora 

The impairment of mechanical properties of the tunica a 

cavemosa. 

. 

lbuginea 

avernosal 

described 

in patients with Peyrone's disease may also result in an inadequate 

compression of the subtunical and emissary vein, f 

1.5 -Pathophysiology of erectile dysfunction in the aging male 

inally 

leading to an ED. 

Age alone is a statistically significant (p

Review o 

t 

. literature 

abnormalities of the h 

sex milieu may significantly affect the quality 

of penile erections and this aspect has raised a lot of interest with regards to 

ormoneS 

its role in the aging population. The process of aging may affect all the 

pillars of the erectile process including nerves, arteries, veins, cavernous 

tissue and hormones; however, the evidence of the a 

ging-induced 

damage to 

these structures reported in the literature has been certainly influenced by the 

availability of techniques able to identify a certain from of damage and this 

is why the vascular and endocrinological abnormalities affecting the male 

erectile system seem to have a first line role with this regard. 

Age related smooth muscle dysfunction has long been recognized in the 

respiratory (Benet & Melman (1995)), gastrointestinal and cardiovascular 

(Geokas et al (1985) systems. Aging also affects the genitourinary tract and 

is associated with lower urinary tract symptoms and sexual function (Kinsey 

et al (1948) in both men and women understood .Atherosclerosis-induced 

arterial insufficiency is a common clinical problem in the elderly and 

remains the leading cause of death in the adult population. 

The abdominal aorta and its branches, especially the bifurcation of the iliac 

arteries, are involved earliest and most severely by atherosclerotic lesions 

[Rose G. (1991) .Atherosclerosis of the aorto-iliac arterial bed can 

potentially compromise the blood supply of lower genitor-urinary tract. For 

example atherosclerosis disease of the pudendal and cavernosal arteries has 

been shown to be the major cause of ED in the elderly patients [Krane et al 

(1989). Major risk factors for atherosclerosis such as hypertension, 

hypercholesterolemia, smoking and diabetes [keil et al ( 1992 ) have also 

been found to be associated with smooth muscle degeneration and are 

absolutely much more frequent in the aging male population [Bireman et al ( 

46

veno-occlusive 

1991). In animal models, a 

therosclerosis-induced 


pelvic ischemic can 

produce function and structural alterations in detrusor (Johnstone et al 

(2000)), which parallel the age-related changes in bladder and cavernosal 

smooth muscle in humans. Therefore there has been an increasing interest in 

the possible role of atherosclerosis-induced ischemic in lower urinary tract 

symptoms and ED of the elderly. 

There are numerous studies showing that atherosclerosis and subsequent 

tissue ischemia does affect significantly both the arterial inflow to and the 

mechanism of the corpora cavernosa (Azadzoi and Goldstein 

(1992). The severity of arterial occlusion has also been correlated with the 

decreased proportion of smooth muscle in the corpus cavemosum. The 

decrease in smooth muscle content of the corpus c 

with the im 

paiiiiient 

avernosum 

is associated 

of cavernosal expandability and subsequent veno- 

occlusive dysfunction .These animal studies have thus identified the 

association between veno-occlusive dysfunction of the corpora cavernosa 

and corporeal fibrosis. 

The significant role of cavernosal oxygen tension in maintaining a normal 

smooth muscle to connective tissue ratio suggests a possible role for 

nocturnal penile tumescence (NPTs) in oxygenation of the corpus 

cavemosum. Nocturnal erections occur during rapid eye movement (REM) 

sleep from intrauterine life to late senescence and are still poorly understood. 

They are believed to represent a spontaneous mechanism for oxygenating 

the corpora cavernosa and maintain the liability of c 

avernosal 

tissue 

(Moreland et al (1995); these erections are particularly at risk for 

deterioration in the aging male. Aging has been shown to decrease the 

frequency, duration and degree of these erections; Karacan et al (1978). 

47


Although it has been widely accepted that impairment of NPT is caused by 

ED, it is known that decrease of NPT has been found in potent men as a 

function of aging. It is an interesting hypothesis that NPT may serve to 

periodically oxygenate the corpus cavernosum and that an age-related 

disease in the quality and number of NPTs can indirectly affect erectile 

function by not exposing the penis to sufficient oxygen. Rather than ED 

leading to impaired NPTs, a decreased frequency of NPTs may also 

compromise erectile function. 

The endocrine milieu does play a significant role in the regulation of erectile 

function. In men, several hormonal systems show gradual decline during 

aging, represented by a decrease in their bioactive hormone concentrations. 

"Andropause" is characterized by a gradual decline in serum total and 

bioavailable testosterone, due to a decrease in testicular Leydig cells number 

and in their secretory capacity, as well as by an age related decrease in 

episodic and stimulated gonadotropins secretion . Both cross sectional and 

longitudinal (Vermeulen (1991) studies have shown that in healthy males, 

mean serum total testosterone levels decrease by about 30% between ages 

25-75 years, whereas mean serum free testosterone levels decrease by as 

much as 50% over the same period. The steeper decline of free testosterone 

levels is explained by and age-associated increase in sex hormone binding 

globulin capacity (Morley et al (1993)). It has recently become clear that not 

only testosterone decreases with age but also serum Estradiol and estrone. 

Finally, the third endocrine system that gradually declines its activity with 

aging is the growth h 

ormone/ 

insulin 

like growth factor axis. 

In summary, it seems reasonable to hypothesize that the ED of aging is the 

result of atherosclerosis induced cavernosal ischemic leading to cavernosal 

48

Revicw 

of literature 

fibrosis v 

and dysfunction. Abnormalities in l 

circulating 

of hormones controlling sexual organs, especially testosterone, most 

eno-occlusive 

probably play a significant role at least in some patients. Besides, in a 

men a delayed penile erection is associated to a reduction of penile rigidity 

and sensitivity, with an elongation of the refractory time and less frequent 

NPTs. 

1.6 -Androgen deficiency and erectile dysfunction 

Androgens are essential in the maintenance of libido and have an important 

role in the regulating penile smooth muscle function in man .1 n the penis , 

androgen deprivation leads to smooth muscle cell apoptosis , a relative 

increase in connective tissue content, and a consequent reduced relaxation of 

the erectile tissue [ (Brown et al (2000 );Mills et al (1996 );Baskin et al 

(1997 )].It has been demonstrated that andro gens are essential in the 

maintenance of the of nitric oxide —mediated erectile activity in the rat 

[Traish et al ( 1995) ;Reilly et al ( 1997 )].Indeed, both testosterone and its 

metabolite, 5 alpha dihydrotestosterone , stimulate neuronal NO-synthase ( 

NOS ) gene expression and increase amount of NO produced by the corpus 

cavernosum and penile arteries during erection ( Reilly et al ( 1997). 

Recently, Adverse et al demonstrated that I ED patient's low free 

testosterone may correlate, independently, regardless of age, with the 

impaired relaxation of the cavernous endothelial and corporeal smooth 

muscle cells to a vasoactive challenge; thus, patients with ED may present 

subtle endocrine changes that can produce change in the e h 

parameters of erection. 

Data from the literature suggest that profound hypogonadism results in 

abolition of erections associated with rapid eye movement sleep, whereas 

omodynamic 

evels 

ging, 

49


wake, erotically stimulated erectile function may be preserved [Aversa et al 

(2000)].In addition; low androgen levels are associated with a decrease in 

the frequency of sexual thoughts and intercourse. The adverse effect of the 

volume of the ejaculate and semen quality are well recognized 

% 

/ 

yr. 

Dehdroepiandrosterone 

.Hypogonadism in the age group with highest incidence of ED (middle age 

and beyond) is higher than initially suspected [Burris et al (1992)]. 

Further more Feldman et al., using longitudinal data from the Massachusetts 

Male Aging Study. recently showed that total testosterone declined cross- 

sectionally at 0.8 % /yr of age within the fellow-up data, whereas both free 

and albumin-bound testosterone declined at about 2 %/yr [ 

(1991a )].On the other hand ,the same fellow-up data showed that sex 

hormone-binding globulin increase cross-sectionally at 1.6 

( 

DHEA) 

. 

DHEAS-sulfate 

Vermeulen 

(DHEAS ), cortisol 

and estrone showed significant longitudinal declines , whereas 

dihydrotestosterone (DHT ), pituitary gonadotropins and PRL rose 

longitudinal (Feldman et al (2002)). A 

hn 

et al (2000) reported that of the sex 

hormone levels, the change in free testosterone correlated most closely with 

aging and had the closest correlation with sexual activity. 

However, in men with ED the prevalence of reduced serum testosterone 

levels is generally low (6%) (Aversa et al (2000); Ahn et al (2000)). In other 

words, hypogonadism rarely seems to be the main, much less the only, 

etiologic factor in ED (Aim et al (2000); Crook (1999); Morales et al (1997). 

50

CHAPTER: 2 


DIAGNOSTIC WORK UP OF ERECTILE DYSFUNCTION 

Philosophy of patient assessment 

Before considering appropriate investigations for a man who presents with 

erectile dysfunction, it is important to consider what the objectives of that 

assessment are. 

The first objective of patient assessment is to confirm the diagnosis .This is 

best done by means of a detailed sexual history 

The second objective of patient assessment is to ascertain the severity of the 

problem. This can be performed objectively with questionnaires (e.g.IIEF) 

or it can be ascertained from the history 

The third objective is to identify treatable conditions that may be relevant to 

the etiology of the ED .Such conditions might include diabetes, 

hypertension, hyperlipidemia, or hypogonadism. 

Some of these conditions will be identified during history and examination 

while all others will require special investigations. 

The fourth objective is to identify patients who have causes of ED which 

might be amenable to specific treatment e.g. 

Vascular anomalies amenable to reconstructive surgery 

Endocrine abnormalities amenable to therapy 

Psychogenic component amenable to therapy 

Given these objectives; there is a basic assessment that should apply for 

every patient. 

Specialist investigation is appropriate in selected cases only 

51

1-Basic assessment 

Review o 

The fundamentals of assessment for any patients are the history, the physical 

examination and special investigations. 

(A) Sexual history 

It is important to clarify exactly what the patient, symptoms are .Some men 

confuse disorders of erection with disorders of ejaculation or orgasm or 

desire. 

The basic elements of the sexual history are as follows: 

• Nature of the problem 

• Psycho-social context of the problem 

• Chronology of the problem 

• Severity of the problem 

• Definition of patient's needs and expectations 

(B) Medical history 

In addition to the sexual history a full medical history is important. Known 

risk factors for organic erectile dysfunction are as follows: 

• Ageing 

• Hypertension 

• Arteriosclerosis 

• Diabetes mellitus 

• Smoking 

• Depression 

• Dyslipidemia 

• P 

elvic/ 

Perineal/ 

penile 

trauma or surgery 

/ 

- l 

iterature

• Neurological 

• Endocrine disease 

• Prescription and recreational drugs 

(C) Psychogenic versus organic ED 


It is often helpful to try and differentiate those patients with primarily 

organic erectile dysfunction from those patients with primarily psychogenic 

erectile dysfunction (although it is recognized that both etiologies play a 

significant part in the majority of patients). 

Erectile dysfunction of organic origin usually has a gradual onset, is usually 

constant, usually affects non-coital erections and may occur under all 

circumstances. 

Erectile dysfunction of a primarily psychogenic o 

origin onset and 

may be situational with varying degrees of ED under different 

circumstances. For instance it is not unusual in men with primarily 

psychogenic ED for them to be able to achieve a fully rigid non-coital 

erection. 

Another useful point in history, is the presence or otherwise of nocturnal or 

early morning erections. If these are present and of normal strength then a 

primary diagnosis of psychogenic erectile dysfunction is more likely. 

(D) Physical examination 

Physical examination does usually not need to be complete. The most 

important aspects of the physical examination are listed below: 

• Complete genital examination 

fte 

n 

53


• Examination for secondary sexual characteristics (Gynecomastia , 

body hair distribution, fat distribution) 

• Blood pressure measurement. 

The value of rectal examination, peripheral vascular examination and 

neurological examination is controversial. In the majority of patients they 

are unnecessary. However if there are other symptoms within the history that 

suggest a problem either with the urinary tract, the neurological system or 

with the vascular system, then an appropriate focused examination is 

appropriate. 

2- Laboratory 

work up 

The following investigations should be performed in all patients: 

• Fasting blood glucose 

• Fasting lipid profile 

• Serum testosterone 

• Serum Prolactin 

These investigations will be discussed in detail below: 

Fasting blood glucose 

Diabetes mellitus is one of the commonest causes of ED and it I important to 

identify when present. 

• In some patients diabetes is unrecognized prior to the diagnosis of ED. 

• It is now clear that urinalysis is inadequate as a screening test for 

diabetes. 

• The appropriate diagnostic test for diabetes in 2003 is a fasting blood 

sugar. 

Fasting lipid profile 

• It is now clear that ED is often a marker for atherosclerosis. 

54

• Risk factor for atherosclerosis include d 

,smoking, and hyperlipidemia 

iabetes, 

Review of l 

iterature 

hypertension 

• Is in increasingly clear that in a proportion of men with ED there is 

previously unrecognized hyperlipidemia. 

• Therefore a fasting lipid screen should be performed 

• The most important features of this are the ratio of HDL to L 

short, high level of HDL are c 

risk of atherosclerosis. 

Testosterone 

zood 

while high levels of LDL promote 

• A serum testosterone will assess the hypothalamic/pituitary/gonadal 

axis 

• It is important that the testosterone assay is undertaken in the morning 

since there is a diurnal variation in serum level. 

• The is controversy as to the most appropriate testosterone assay ( total 

,free, and % free testosterone ) but a consensus does exist that at least 

one of these assays should be performed. 

• Serum testosterone is secreted episodically by the testicular Leydig 

cell 

• 98 % of testosterone is bound to plasma proteins with the majority 

being either to albumin or sex hormone binding globulin 

• only 2 % of total testosterone is unbound or free 

• B 

ioavailability 

bound serum testosterone 

testosterone include both the free and the albumin 

• I t is possible to measure either the total or the free or the bioavailable 

testosterone 

DL. 

In 

55

• The relative value of these three assays is unclear 

Review o 

• While the pickup rate for hypogonadism is relatively low, the test is 

justified in that testosterone replacement represents a potentially 

reversible form of ED 

Prolactin 

• Although h 

yperprolactinarnia 

important diagnosis to make. 

is a rare cause of male ED .it is an 

• Hyperprolactinamia is usually due to a Prolactin —secreting tumor of 

the anterior pituitary 

• Clinical features suggesting hyperprolactinamia are Gynecomastia , 

galactorrhoea and ED 

• In some cases of hyperprolactinamia the serum testosterone is slightly 

• % 

low but this is not invariable 

hat 

.t 

number of conditions cause a marginal rises in the serum Prolactin 

are not thought to be pathogenic in terms of ED .Such conditions 

include hyperthyroidism . Stress, chronic renal failure, liver disease 

and Varity of drugs including Methyldopa, Opiate, and 

Metoclopromide. 

Special investigation 

A-Endocrine evaluation 

1- If the serum testosterone and Prolactin are normal then further 

endocrinological evaluation is usually unnecessary. 

llileranire 

56

Review o 

f 

literature 

2- If either of these tests is abnormal then they should both repeated. At the 

same time a serum FSH should also be performed 

3- ED can occasionally be due to the thyroid disease .If there is clinical 

suspicion of this then a thyroid h 

oiiiione 

and serum TSH are appropriate. 

4- If the serum Prolactin is significantly raised then CT and N 

the pituitary 

Gland is appropriate. 

B-Vascular Testing 

In the last 1980 and early 1990 vascular testing was undertaken in all 

IRI 

scan of 

patients .It is now clear that this is unnecessary for the fast majority. The 

current indication is. 

A-Selection of patients for vascular surgery 

B-Medico-legal reasons 

C-Patient request 

I-Color 

Doppler scanning of the penile vasculature 

Penile Doppler ultrasonography is able to detect the presence of 

vasculogenic dysfunction and it is also able to differentiate between arterial 

compromise v 

and 

study as originally described by Lue et al, ( 

eno-occlusive 

incompetence. Criteria for penile Doppler 

1985) 

j, 

included cavernous artery 

PSV, cavernous artery dilation and visualization of arterial pulsation. 

Recently, PSV was found to be a more reliable parameter, the proposed cut — 

off value of PSV varies from 25 — c 

40 [Benson et al, (1993)]. The large 

range of values may be may be due to many different reasons such as 

m/ 

s 

57


anatomical variants [Jarow et al, (1993)] .as well as the timing and location 

of sampling. 

EDV reflect the I 


pressure, Different EDV measurements 

(range c 

5-9 have been selected as the value above which the diagnosis 

of venous leak is made .However it has been observed that in some patients 

m/ 

s) 

who have attained an EDV of c0 

only partial rigidity is achieved .On 

some reversal is only transient or observed unilaterally. In most n 

individuals, the E 

L" 

! 

m/ 

s, 

is usually high early (5-10 or even up to 25 min. in 

some patients .On the other hand the PSV, usually occurred immediately at 

any time within the 5 min. after PGE1 injection, but in some, this occur later 

at approximately 25 to 35 min.post injection [ 

Chiou, 

oiinal 

el al, (1998)]. Venous 

leak should only be diagnosed late when there is persistently high EDV late 

in the examination (at 15 min. or later after injection). Another cause for 

wide variability in the velocity reading is the location of sampling .it is now 

generally preferred that, patients be sampled near the base of the penis. 

Studies has shown that reading are more accurate at this site .It is also to 

keep the Doppler a 

ngle 

at < 60 degree at this point. [ 

The following methodology is usually used 

Seung 

et al (1956]. 

a- The test should be performed following an injection of a smooth muscle 

relaxant such as prostaglandin El 

b -High frequency linear array transducer (5-10 MHZ) provides the best 

images. 

c- The examination should be p 

erformed 

in a warm and darkened room 

d- A challenge of 10 mcg of prostaglandin E 1 with genital stimulation and 

visual erotic stimulation is considered to be the best initial challenge. 

58

Interpretation of the results 


-A peak systolic velocity (PSV) of less than 25 cm/sec suggests penile 

arterial insufficiency [Lue et al, (1985)], 

-PSV more than 35 cm/sec is considered normal 

-The diagnosis of penile veno-occlusive dysfunction should be considered 

when the PSV is greater than 30 cm/sec and the end diastolic velocity is 

more than 5 cm/sec 

2-Dynamic infusion pharmacocavernosometry and cavernosography 

( 

DICC) 

v 

• This is a test designed to assess function. 

• It is now only indicated in patients who are suspected as having a site- 

eno-occlusive 

specific venous leak where vascular surgery is considered a treatment 

option. 

• Such cases might include patients with primary (congenital) erectile 

dysfunction, a history of penile fracture, perineal or pelvic trauma, or 

Peyronie's disease. 

(3) Penile arteriography 

• Selective pudendal arteriography is reserved for those cases, which 

are being considered for vascular reconstruction in which color 

Doppler scanning has demonstrated arterial insufficiency. 

• These are usually young men with a history of pelvic or perineal 

trauma. 

59

Nocturnal Penile tumescence and Rigidity Testing (NPTR) 

Review of l 

A cycle of sleep erections in men aged 20-40 years was characterized by 

Ohlmeyer .Aserinsky and Kleitman first described rapid eye 

movement(REM) sleep in 1953 and later recognized that nocturnal erections 

seemed to correspond with REM periods during normal sleep [ Aserinnsky 

and Kleitman (1953 ) 

associates suggested that m 

NPT 

assessment of ED [Fisher et al, (1965)] 

] 

It was not until 1965 that Fisher. Karacan and their 

onitoring, 

can be a valuable resource in the 

• Most men achieve an erection four to five times during the night. The 

presence of normal nocturnal erections is strongly suggestive of a 

psychogenic etiology. 

• In 2003, the device most commonly used for NPT studies is the 

Rigiscan device that measure tumescence and rigidity at both the base 

and the tip of the penis. 

• In research studies, Rigiscan monitoring is widely used to assess the 

efficacy of oral therapy during visual sexual stimulation. 

• The normal measurement that is used under these circumstances is the 

period of time during which the base rigidity exceeds 60%. 

• The NPT test takes advantage of the natural sleep-related erections 

found in potent men during rapid eye movement (REM) sleep. The 

primary goal of NPT testing is to distinguish organic etiology from 

psychogenic causes of ED. 

NPT testing and the introduction of the portable Rigiscan for home use in 

1985 still have some controversies, particularly regarding the lack of 

standardized parameters and limited clinical trials. 

Limitations of NPT 

irerature 

60

Review o 

f 

literature 

The basic assumption of NPT testing is that the presence of nocturnal 

erections indicates the capacity to have awaking erection with sufficient 

rigidity for vaginal penetration. Wasserman and associates agree that NPT 

monitoring is a useful aid in differentiating organic from psychogenic 

impotence, but they stress that it has never been validated independent of the 

NPT measurements themselves. Other groups caution that NPT may not 

always be a true indication of erectile potential in erotic and sexual 

circumstances [Morales a et al (1990)]. 

Another concern regarding NPT is that organic factors may, in fact, alter 

NPT in the patient with psychogenic impotence. Previously, a 

results have been demonstrated in 15-20% of patients with no identifiable 

evidence of organic impotence indicating that subtle, undetectable 

physiological factors may be operating in the patients [Karacan et al, 

(1978)]. It has also been noted that dreams containing anxiety, aggression 

and other negative content are associated with abnormal NPT results. 

Another factor that has been shown to affect NPT adversely is depression. 

Studies by colleagues Roose and [Roose et al (1982)] and by these and 

colleagues have reported on patients with major depression exhibiting a 

reversible loss of NPT which was restored when the depression was 

successfully treated. 

A decrease in the number of tumescence [Jovanovich et al (1969)] episodes, 

total tumescent time and decreased quality of erections on the first night of 

sleep laboratory testing, has given rise to the concept of a 'first n 

ight 

bnormal 

effect'. 

Although wearing the NPT device is unnatural and could presumably 

interfere with normal sleep, resulting in false NPT readings, a first night 

effect was not revealed in two recent studies of normal, healthy volunteers 

using the Rigiscan device [Levine et al, (1994)]. 

61


Home monitoring devices, such as the Rigiscan, have the additional 

drawback of the inability to assess the adequacy of sleep. Conditions such as 

sleep apnea, periodic leg movements, and nocturnal myoclonus can 

negatively affect NPT and thus a diminished NPT result may not be 

indicative of abnormal erectile function [Pressman et al (1989)]. Whereas 

Bradley has suggested that disturbed sleep impairs the appearance of a 

spontaneous erectile event, Schiavi has demonstrated that a full erection may 

not occur in normal potent males despite a normal sleep pattern [Schiavi et 

al (1977)]. More recently, Morales and associates studied 18 impotent men 

by formal NPT testing during a morning nap session [Morales et al (1994)]. 

16 of the 18 patients (89%) experienced REM sleep and four patients did not 

experience tumescence during the nap. All four of these patients did not 

experience nocturnal erections on two separate sessions.. 

A final criticism of NPT monitoring is that radial measures of rigidity, as 

provided by the Rigiscan, may not be accurate when compared with axial 

measures of rigidity. 

Cilurzo et al (1992) suggest the following for normal NPT parameters. 

• Achieving 4-5 erectile episodes per night 

Mean duration of erectile episodes greater than 30 

minutes 

• Increase in circumference of greater than 3 cm at base 

and 2 cm at tip during erectile episodes 

Greater than 70% maximal rigidity at both tip and base 

during erectile episodes 

62

Chapter -3 

Definitions 

A-PRIAPISM 


Priapism is a pathological persistent penile engorgement and/or erection 

that continues hours beyond, or is unrelated to, sexual stimulation. 

Typically, only the corpora c 

avernosa 

are affected. For the purposes of this 

guideline, the definition is restricted to only erections of greater than four 

hours duration. Priapism requires prompt evaluation and may requite 

emergency management. 

Classification of Priapism 

A. Ischemic ( 

Veno-Occlusive, 

low flow) priapism is a nonsexual, persistent 

erection characterized by little or no cavernous blood flow and abnormal 

cavernous blood gases (hypoxic, hyperbaric, and acidotic). It is a medical 

emergency and the most common form of priapism.The corpora cavernosa 

are rigid and tender to palpation. Patient typically report pain. A variety of 

etiologic factors may contribute to the failure of the detumescence 

mechanism in this condition. Resulting to resolution of ischemic priapism is 

characterized by the penis returning to a flaccid, nonpainful state. However, 

in many cases, persistent penile edema, ecchymosis and partial erections can 

occur and it may mimic unresolved priapism. Resolution of priapism can be 

verified by measurement of cavernous blood gases or blood flow 

measurement by color duplex ultrasonography. 

B .Nonischemic (arterial, high flow) priapism is a nonsexual, persistent 

erection caused by unregulated cavernous arterial inflow. Cavernous blood 

gases are not hypoxic or acidotic. Typically the penis is neither fully rigid 

63

nor painful. Antecedent trauma is the most commonly described e 


Nonischemic priapism does not e 

require treatment. 

Resolution of nonischemic priapism is characterized by a return to a 

completely flaccid penis. 

C .Stuttering (intermittent) priapism is a recurrent form of ischemic 

priapism in which unwanted painful erections occur repeatedly with 

intervening periods of detumescence. This historical term identifies a patient 

whose pattern of recurrent ischemic priapism encourages the clinician to 

seek options for prevention of future episodes. Priapism associated with 

sickle-cell disease is classically described as ischemic, although rare 

exceptions of high —flow priapism in patients with sickle-cell disease .The 

pathophysiology of high-flow priapism is not known. The authors reported 

frequent self-limited priapistic episodes; mostly occurring during sleep that 

last less than 3 h. Priapism associated with sickle-cell disease was unusual 

before the puberty and in keeping with previously reported 6 % prevalence 

of priapism in children with sickle-cell disease (Tarry et al 1 

was significantly associated with low hemoglobin F levels as well as high 

Platelets counts and over one —fourth of those who had suffered priapism has 

some degree of impotence. 

III. Evaluation of the Priapism Patient 

The diagnosis of priapism is self-evident in the untreated patient. The 

evaluation of priapism should focus on differentiating ischemic from 

nonischemic 

mergelii 

priapism (Table 4). Once this differentiation is made, the 

appropriate management can be determined and initiated. The evaluation of 

the patient with priapism has three components: patient history, physical 

examination and laboratory/radiologic assessment. 

987) 

. 

priapism 

tiol 

, ) 

gy. 

64

AUA GUIDE LINE FOR PRIAPISM EVALUATION AND 

TREATMENTS 

Recommendation 1: 


In order to initiate appropriate management, the physician must determine 

whether the priapism is ischemic or nonischemic. 

A-Patient History 

Understanding the history of the episode of priapism is important because 

the history and etiology may determine the most effective treatment. 

Historical features that should be identified are: 

1 .Duration of erection 

2. Degree of pain (ischemic priapism is painful while nonischemic priapism 

usually is not) 

3. Previous history of priapism and its treatment 

4. Use of drugs that might have precipitated the episode. Drugs that have 

been associated with priapism are: antihypertensive; and other psychoactive 

drugs; alcohol, marijuana, cocaine and other illegal substances; and 

vasoactive agents used for intracavernous injection therapy such as 

alprostadil, 

papaverine, and prostaglandin El, p 

hentoleamine 

and others. 

5. History of pelvic, genital or perineal trauma, especially a perineal straddle 

injury 

6. History of sickle cell disease or other hematologic abnormality 

Penile pain 

- 

Table (4): key Findings in the Evaluation of Priapism 

Finding Ischemic priapism Nonischemic priapism 

# 

1 

0 

65

# 

Abnormal cavernous blood 

gases 

Blood abnormalities and 

hematologic malignancy # 0 

Recent intracavernous 

vasoactive drug injections * 0 

Chronic, well-tolerated 

tumescence without full 

rigidity 

# 

* # 

Perineal trauma 01 


Usually present 0 Seldom present * Sometimes present 

Physical examination 

The genitalia, perineum and abdomen should be carefully examined. In 

patient with priapism, the corpora c 

avernosa 

0 

are affected while the corpus 

spongiosum and the glans penis are not. In patients with ischemic priapism, 

the corpora c 

avemosa 

are often completely rigid. In patients with 

nonischemic priapism, the corpora are typically tumescent but may not be 

completely rigid ( 

( 

Tablel) 

. 

reveal evidence of trauma or malignancy. 

Laboratory Evaluation 

Abdominal, pelvic and perineal examination may 

The laboratory evaluation of patients with priapism should include a 

complete blood count (CBC) with special attention to the white blood count 

WBC) 

, 

white blood cell differential and platelet count. Acute infections or 

hematologic abnormalities that can cause priapism, such as stickled red 

1 

66


blood cells, leukemia and platelet abnormalities, may be suggested or 

identified by the CBC. 

The reticulocyte count is often elevated in men with sickle cell anemia. 

Hemoglobin electrophoresis identifies the presence of sickle cell disease or 

trait as well as other hemoglobinpathies. Because hemoglobinpathies are not 

confined to African-American men but may be found in Caucasian men, 

especially of Mediterranean desert (e.g., thalassemia), a reticulocyte count 

and hemoglobin electrophoresis should be considered in all men unless there 

is another obvious cause of priapism. However, in an emergency setting, 

hemoglobin analysis may not yield result in a timely fashion. In such cases, 

screening for sickle cell disease or trait should be performed by either the 

sickled test or examination of a peripheral smear, preferably with 

consultation by a hematologist and subsequent confirmation using 

hemoglobin electrophoresis. 

tiv. 

, 

Screening for psychoactive drugs and urine toxicology may be performed (if 

suspected) because standard doses of antidepressants and other psychoactive 

drugs, as well as overdoses of legal and illegal drugs, may cause priapism. 

Blood gas testing and color duplex ultrasonography are currently the most 

reliable diagnostic methods of distinguishing ischemic from nonischemic 

priapism (Table). Blood aspirated from the corpus cavernosum in patients 

with ischemic priapism is hypoxic and therefore dark, while blood from the 

corpus c 

avernosum 

in patients with nonischemic priapism is normally 

oxygenated and therefore bright red. Cavernosal blood gases in men with 

ischemic priapism typically have a pot of < 30 mm Hg, a Pco2 of > 60 mm 

and a pH< 7.25. Cavernous blood gases in men with nonischemic 

priapism are similar to the blood gases of arterial blood. Normal flaccid

Noi 


penis cavernous blood gas levels are approximately equal to those in normal 

mixed venous blood. Typical blood gas values are shown in Table. (5) 

Table (5): Typical Blood Gas Values 

Source Pot (mm Hg) Pco2 (mm Hg) pH 

Ischemic priapism 

(cavernous blood) 

Normal arterial blood 

(room air) 

mal mixed venous 

blood (room air) 

Radiological evaluation 

A. Color Duplex Ultrasonography 

< 30 > 60 90 < 40 7.40 

40 50 7.35 

Color Duplex Ultrasonography may be utilized as an alternative to 

cavernosal blood gas sampling to differentiate ischemic from nonischemic 

priapism .Patients with ischemic priapism have little or no blood flow in the 

cavernosal arteries , while patients with nonischemic priapism have normal 

to high flow velocities in the cavernosa; arteries . Ultrasonography will 

reveal the absence of any significant blood flow within the corpora 

cavernosa. It may also be performed as a screening test for anatomical 

abnormalities, such as cavernous artery fistula or pseudoaneurysm, in men 

who already have the have the diagnosis of nonischemic priapism. These 

abnormalities are most often due to straddle trauma or direct scrotal injury 

and are, therefore, ultrasonography should be performed in the lithotomic or 

68

Review o 

frog leg position, screening in the perineum first and then along the entire 

shaft of the penis 

B. Penile Autobiography 

Penile Autobiography may be used as an adjunctive study to identify the 

presence and site of a cavernous artery fistula (rupture helicine artery). Since 

color duplex ultrasonography has largely supplanted arteriography for the 

diagnosis of the cavernous artery fistula, arteriography is usually only 

performed as a part of an embolization procedure. 

In summary, the laboratory and radiological tests that should be considered 

in the diagnostic evaluation of priapism are. 

Laboratory tests 

-CBC 

-Reticulocyte count 

-Hemoglobin electrophoresis 

-Urine analysis 

-Blood gas testing 

Radiological tests 

-Penile Duplex Ultrasonography 

-Penile A 

Recommendation 2: 

rteriography 

In patients with an underlying disorder, such as sickle cell disease or 

hematologic malignancies, systemic treatment of the underlying disorder 

should not be undertaken as the only treatment for ischemic priapism .The 

lliterature 

69


ischemic priapism requires ICI treatment, and this should be administered 

concurrently. 

Ischemic priapism is a compartment syndrome and thus requires ICI 

sympathomimetics drugs .In patients with an underlying disorder, such as 

sickle cell disease or hematologic malignancies, ICI treatment of the 

ischemic priapism should be provided concurrently with appropriate 

systemic treatment for the underlying disease. The ischemic cases reported 

in the literature resolved in o to 37 % of patients with sickle cell disease 

managed only with systemic treatments ( transfusion , hydration ,oxygen and 

alkalization ) while much better resolution were achieved with therapies 

directed at the penis . There are few published reports on patients with 

hematologic disorders other than sickle cell disease. Three of 4 patients with 

hematological malignancies treated with pheresis procedures expererinced 

resolution of the priapism, but only 3 of 15 treated with other 

chemotherapies resolved. Moreover, many of the treatments successes with 

systemic therapy after very prolonged periods of ischemia and may represent 

the end results of the natural history of ischemic priapism rather than a true 

treatment-related resolution. Even without treatments, all priapism will 

resolve but with ED may be compromised .Review of the published cases of 

ischemic priapism managed with systemic treatments alone found that 7 of 

20 (35 %) patients had ED. Thus. While systemic treatments may ultimately 

prove to be effective. The current data suggest that any delay in the direct 

treatment (i.e. ICI treatment) of the penis is not justified. 

Recommendation 3 

Management of ischemic priapism should progress in a step-wise fashion to 

achieve resolution as promptly as possible .Initial intervention may utilize 

70

therapeutic aspiration (with or without irrigation) or i 

of sympathomimetics. 


ntracavemous 


injection 

If ischemic priapism persists following aspiration /irrigation, ICI of 

sympathomimetics drugs should be performed, Repeated ICI of 

sympathomimetics drugs should be performed prior to initiating surgical 

intervention 

Vasoactive properties of sympathomimetics drugs confer on these agents 

the potential to relive priapism by facilitating detumescence mechanism. 

Review of the literature reveals significantly higher resolution of priapism 

following sympathomimetics injection with or without irrigation (43 to 81 

%) than aspiration with or without irrigation alone (24 to 36 %).The risk of 

post-priapism ED also appears to be lower when sympathomimetics agents 

are employed. 

Therapeutic aspiration is often the first maneuver employed following 

insertion of scalp vein (19 Or 21 gauge) needle into the corpus c 

for diagnostic purposes. This procedure lowers intracorporeal pressure thus 

facilitating subsequent ICI .Priapism resolved in 36 % of patients with 

ischemic priapism treated with aspiration alone. Other studies have shown 

resolution of priapism in 24 % of patients treated with aspiration plus 

irrigation. Due to the limitations of the literature, the panel believes that this 

difference is not real and the efficacy of the aspiration with or without 

irrigation is approximately 30 %. The physician should be prepared to 

continue treatment with administration of a sympathomimetics agent if 

therapeutic aspiration, with or without irrigation, fails to relieve 

priapism.The value of aspiration as an adjunct to sympathomimetics 

avernosum 

71



The use of surgical shunts for the treatment of ischemic priapism shouid be 

considered only after a trial of ICI of s 

should not be considered as first —line therapy [Hinman el al., ( 

ympathomimetics 

a surgical shunt 

decision to initiate surgery requires the failure of nonsurgical interventions. 

However, deciding when to end nonsurgical procedures and proceed with 

surgery will depend on the duration of the priapism.For ischemic priapism of 

extended duration, response to ICI of sympathomimetics become 

increasingly unlikely. Phenylephrine is less effective in priapism of more 

than 48-hour duration because ischemia and acidosis impair the 

intracavernous smooth muscle response to the drugs [Broderick and 

Harkaway (1994)]. Under such anoxic conditions, phenylephrine procedures 

poorly sustained phasic contractile responses. In particular, ICI of 

sympathomimetics agents after 72 hours offers a lower chance of successful 

resolution and a surgical shunting procedure often is required to reestablish 

the circulation within the corpora cavemosa. 


A c 

avernoglanular 

(corporoglanular) shunt should be the first choice of the 

shunting procedures because it is the easiest to perform and has fewest 

complications. These shunting procedures can be performed with large 

biopsy needle (whinter) or a scalpel (Ebbehaj) inserted percutanously 

through the glans. It can also be performed by a excising a piece of the 

tunica albuginea at the tip of the corpora c 

avemosum 

1998) 

. 

The 

(Al-Ghorab) 

.Proximal shunting using the Quackels or Grayhack procedures may be 

warranted if more distal shunting procedures have failed to relieve the 

priapism. 

74

Al-Ghorab 


Of the three methods of the cavernoglanular (distal) shunt, excision of both 

tips of the corpora cavemosa (Al-Ghorab) is the most effective and can be 

performed even if the other two procedures fail. In most cases, shunts will 

close with time. However, long-term potency of the shunt may lead to 

erectile dysfunction (Kulmala et al (1995)). Shunting procedures evaluated 

during analysis of evidence included distal shunts (e.g. winter, Ebbehaj, and 

procedures); c 

the (corporospongiosal) shunt 

(i.e. Grayhack procedure). The limited data preclude a recommendation of a 

avemospongious 

greater efficacy for one procedure over another based on accurate outcome 

estimates. The summary data generated by the Panel show resolution rates of 

74% for Al-Ghorab, 73% for Ebbehoj, 66% for Winter, 77% for Quackels, 

and 76% for Grayhack procedures. Erectile dysfunction rates are higher for 

the proximal shunts, Quackels and Grayhack, (about 50%) than for the distal 

shunts (25% or less). However, patient selection and time to treatment may 

be the main explanation for these differences. Each surgical shunting 

procedure may have its own constellation of adverse events. Assessing the 

literature was difficult due to the fact that patients frequently received 

multiple treatments and therefore, it was difficult to ascertain the treatment 

that produced adverse events. 

A distal shunting procedure is generally successful in re-establishing penile 

circulation in cases other than those with severe distal penile edema or tissue 

damage. In these cases, more proximal shunting procedures may be 

considered, and a shunt can be created between the corpus c 

the corpus spongiosum (Quackeis). Alternatively, a proximal shunt such as 

between the corpus c 

avernosum 

avernosum 

and 

and the saphenous vein (Grayhack) is 

75


performed. These procedures are time consuming and technically 

challenging. Reports of serious adverse events include urethral fistula and 

purulent c 

avernositis 

following the Quackels shunt [Ochoa Urdangarain and 

Hermida Perez (1998)] and pulmonary embolism following this shunt 

procedure [Kandel et al (1968). 


Oral systemic therapy is not indicated for the treatment of ischemic priapism 

The literature contains no data supporting the use of oral sympathomimetics 

treatment for ischemic priapism. Although not priapism, prolonged erections 

due to injection therapy may show some response to oral terbutaline 

treatment. Two randomized controlled trials examined the use of oral 

terbutaline in patients with prolonged erections of less than 4-hour duration 

following pharmacologic stimulation of an erection. Despite the lack of 

statistical significance, meta-analysis showed a trend suggestive of possible 

benefit. A summary of uncontrolled trials showed a 65% resolution rate... 

There is no evidence for the efficacy of oral pseudo ephedrine in the 

treatment of either prolonged erections or priapism. 

VI. Nonischemic Priapism 

Nonischemic (high-flow) priapism is an uncommon form of priapism caused 

by unregulated arterial inflow. This condition may follow perineal trauma 

that results in laceration of the cavernous artery. However, may patients 

have no apparent underlying cause? Panel summary data found spontaneous 

resolution to be the outcome of untreated nonischemic priapism in up to 

62% of the reported cases with an associated complaint of erectile 

difficulties in one third of patients. 

76

B- RAPID EJACULATION 


Rapid ejaculation, the generally accepted diagnostic label for this 

disorder, has been known by other names, including ejaculation praecox, 

early, premature or uncontrolled ejaculation. Not only are the names 

confusing but accurate and scientific diagnostic criterion sets are equally 

illusive. By combining the criterion sets of I 

CD-10 

with DSM-IV, rapid 

ejaculation is diagnosed along four dimensions: 1) ejaculatory latency; 2) 

voluntary control; 3) presence of marked distress or interpersonal 

disturbance and; 4) the exclusionary criterion that the symptoms are not due 

to another mental, behavioral or physical disorder. According to I 

ejaculation must occur "within 15 seconds of the beginning of intercourse." 

DSM-IV 

is equivocal on duration, stating that "ejaculation occurs with 

minimal sexual stimulation before, on, or shortly after penetration." I 

makes no mention of voluntary control, while DSM-IV notes that ejaculation 

occurs "before the person wishes." Both nosologies require the man to be 

distressed ( 

ICD-10 

offers a time frame of six months; no specific time frame 

is defined in DSM-IV). Lastly, both I 

CD-10 

and DSM-IV require the 

clinician to make a judgment regarding the independence of this condition 

from other mental, behavioral or physiological disorders. 

Additionally, the DSM-IV requires the clinician to make three additional 

judgments: whether the dysfunction is lifelong or acquired, it is due to 

psychological or combined biological and psychological. The distinction 

CD-10, 

CD-10 

77


between the lifelong and acquired may ultimately prove to be the most 

helpful in clarifying the etiology of the dysfunction. It may turn out that a 

subgroup of lifelong rapid ejaculators has a biological vulnerability but not 

those with acquired symptoms. The later begs the clinician to be interested 

in the forces that generated the new symptom and may reflect recent 

psychosocial stressors or be a consequence of a medication or surgery. For 

instance, acquired rapid ejaculation is often a consequence of erectile failure. 

Men develop performance anxiety regarding their erectile reliability and 

hurry intercourse thinking that they have limited time to "complete the act." 

With this mindset, an additional dysfunction appears and men become even 

more anxious about sexual interactions. 

Prevalence 

A recent study of sexual behavior in the United States (Laumann et al., 

1999) employed area probability sampling to obtain a sample of 3442 

persons aged 18-59 who completed a standard interview. Twenty-nine 

percent of the men in this sample complained of ejaculating too quickly. It 

is unclear whether these complaints would meet diagnostic criteria as sexual 

dysfunctions. 

Kaplan (1983) reviewed the research literature and reported a somewhat 

higher prevalence of 36-38% for the incidence of rapid ejaculation. 

However, earlier studies placed the prevalence of rapid ejaculation between 

22% ( 

Shapiro, 

1943) 

Etiological Considerations 

and 38% (Gospodinoff, 1989). 

For years the prevailing opinion was that rapid ejaculation was a 

psychological or learned condition. However, a series of biological 

78

Review a 

ff 

literature 

investigations has begun to unravel the physiological undeipinnings of the 

ejaculatory process, leading theorists to speculate about organic 

contributions to this disorder (Gospodinoff, 1989). 

It is generally agreed that dopaminergic drugs enhance and serotonergic 

drugs impair several measures of sexual behavior and ejaculations in 

humans, monkeys and rats (Hendry et al., 2000). Giuliani et al., (2002) 

reported that a selective D2 agonist, systemically administered, produced 

premature ejaculation which could be counteracted by a D2 antagonist. On 

the other hand, administration of serotonin 5-HT1B or 5-HT2 antagonists 

may reverse the effects of serotonergic inhibition from either the anterior 

lateral hypothalamus or the nucleus paragigantocellularis in the ventral 

medulla. 

Proposing a biological vulnerability toward rapid ejaculation, Faniullacci 

et al, (1988) suggested that increased penile sensitivity and a constitutionally 

more rapid Bulbocavernous reflex may predispose men to develop this 

dysfunction. This speculation was supported by controlled studies by Xin et 

al., (1996) who speculated that rapid ejaculators have a heightened sensory 

response to genital stimulation and an inability to maintain the sympathetic 

dampening that maintains ejaculatory control. 

Waldinger (1998) adds a further interesting dimension to the biological 

etiology of primary rapid ejaculation by observing that 91% of a small 

sample of primary rapid ejaculators had a first degree relative who also 

suffered from this disorder. Based on this observation Waldinger speculates 

that genetic factors may contribute to the development of rapid ejaculation. 

The psychophysiological data of Rowland et al., (2000) comparing rapid 

ejaculators and normal controls have demonstrated that rapid ejaculators 

79


take substantially longer to ejaculate with masturbation in comparison to 

intercourse (1.5 vs. 4.5 minutes) a difference not observed in the control 

group. Rapid ejaculators also experienced less enjoyment from their orgasms 

than controls and were more vulnerable to penile vibratory stimulation, with 

no differences noted between in the two groups with visual stimulation 

alone. Rowland et al. also concluded that rapid ejaculators either ejaculate 

prior to full sexual arousal or, alternatively, they underestimate their level of 

somatic arousal. 

Other organic factors that may cause rapid ejaculation include trauma to 

the sympathetic nervous system during surgery for aortic aneurysm, pelvic 

fracture, Prostatitis and urethritis. Additionally, drug withdrawal from 

narcotics or trifluoperazine has been associated with this symptom. 

The psychological theories of rapid ejaculation postulate that the 

lowered ejaculatory threshold stems from anxiety regarding either 

unresolved fears of the vagina, hostility toward women, frequency of sexual 

behavior, interpersonal conflicts with a particular partner or conditioning 

patterned on early hurried sexual experiences with prostitutes or hasty 

lovemaking in the backseat of a car. Once established, performance anxiety 

was thought to maintain the rapid ejaculatory pattern (Althof et al, 1995). 

Anxiety is not a singular concept; it is employed to characterize at least 

three different mental phenomena. Anxiety may refer to a phobic response, 

like being fearful (i.e., afraid of the dark, wet, unseen vagina). It may also 

refer to affect, the end result of conflict resolution where two contradictory 

urges are at play (i.e., the man is angry at his partner but feels guilty about 

directly expressing his hostility). And it may refer to preoccupation with 

sexual failures and p 

poor As the man contemplates his next 

sexual opportunity, anxiety leads to avoidance of future sexual interactions. 

erfonnance. 

80

Review of l 

McCarthy (1998) suggests that performance anxiety has two discrete 

dimensions: a cognitive component where the man watches himself, thus 

removing himself from awareness of his arousal level, and an emotional 

component consisting of fear of failure. Performance anxiety per se does not 

generally cause the initial episode of rapid ejaculation; however, it is 

pernicious in maintaining the dysfunction. 

Psychological Intervention 

Since the early 1970's, an array of individual, conjoint and group therapy 

approaches employing behavioral strategies such as stop-start, the squeeze 

technique, progressive sensate focus exercises, masturbatory exercises and 

"quiet vagina" with the female astride have evolved as the treatments of 

choice for rapid ( 

ejaculation 1995) 

The stop-start procedure involves the man repeatedly being brought to 

Althof, 

high levels of excitement, initially by hand or mouth stimulation, and 

stopped prior w ejaculation (Semans, 1956). This pause allows the man's 

arousal to decrease and thereby delays orgasm. This exercise is repeated 

several times after which the man is permitted to ejaculate. Subsequently, 

Masters and Johnson (1970) modified the procedure and renamed it the 

"squeeze technique." The modification requires that stimulation be stopped 

but that he or his partner squeezes the glans penis. This results in delayed 

ejaculation, often accompanied by partial loss of erection. 

Sensate focus exercises are designed to heighten the man's awareness of 

his arousal level and to decrease performance anxiety by lessening the 

demand characteristics of a sexual experience. In a slow, graduated fashion 

the man and his partner take turns g 

iving, 

and receiving pleasure. Initially, 

iterature 

81

o 

Review literature 

the touching is restricted to non-genital/non-breast stimulation; upon 

achieving comfort these areas are also pleasured. 

"Quiet vagina" is an elaboration of the stop-start maneuver that involves 

intercourse. The woman sits astride or lays on top of the man and, without 

any thrusting or movement, envelopes his penis in her vagina. This aim of 

this exercise is to desensitize the man to the wet, warm sensations of the 

vagina. After the man can master "quiet vagina" for a prolonged period of 

time, movement is slowly introduced and controlled by the female. The man 

directs her to stop when his excitement approaches the ejaculatory threshold. 

The couples sit/lie quietly until his excitement decreases, whereupon they 

resume the exercise with the man eventually ejaculating. 

McCarthy (1998) delineates three foci of a cognitive-behavioral 

psychotherapeutic approach: 1) challenging self-defeating ideas about 

sexuality and women and replacing them with facilitating thoughts about 

ejaculatory control as well as the role of sexuality and intimacy; 2) learning 

the behavioral skill of identifying the point of ejaculatory inevitability, the 

stop-start technique and alternating intercourse positions and thrusting 

movements; and 3) establishing a cooperative, intimate and satisfying 

relationship. 

It is now known that the impressive initial post-treatment success rates 

ranging from 60% to 95% (Masters & Johnson, 1970) are not usually 

sustainable. Three years after treatment, success rates dwindle to 25 % 

(Hawton 1992). This data suggests that clinicians have failed to develop 

long-tea 

n strategies that allow patients to maintain their initial therapeutic 

gains the efficacy of periodic treatment sessions to maintain control after the 

termination of the original treatment has not yet been evaluated. 

f 

82

Self Help Techniques 

ivien 

Review of l 

have resorted to wearing multiple condoms, applying desensitization 

ointment to the penis, repeatedly masturbating prior to intercourse, not 

allowing partners to stimulate them or distracting themselves by performing 

complex mathematical computations while making love to overcome rapid 

ejaculation. These tactics, however creative, curtail the pleasures of 

lovemaking and are generally unsustainable as well as unsuccessful. 

Pharmacological Treatment of Premature Ejaculation 

Clinicians are aware that several classes of drugs impede or eliminate 

orgasm. These include MAO-inhibitors, tricyclic and serotonergic 

antidepressants and a newly developed compound referred to as SS- cream. 

Double-blind, placebo-controlled studies with Clomipramine and the major 

selective serotonin reuptake inhibitors (SSRI), using strict dosages in 

carefully selected populations, have repeatedly demonstrated that these 

agents are efficacious in delaying ejaculation. However, when subjects 

discontinue the medication, improvements are lost, and in general 

ejaculation latencies return to baseline. Side effects of these medications are 

generally mild, dose related and tend to diminish with time; dry mouth, 

headache, drowsiness and gastrointestinal upset are most frequently 

( 

observed et al, 1995 and McMahon, 1998) 

To determine which of the major selective serotonin reuptake inhibitors 

Althof 

were most effective in delaying orgasm, Waldinger et al (1998) performed a 

head-to-head study between Fluoxetine, f 

luvoxamine, 

iterature 

Paroxetine and 

Sertraline in treating rapid ejaculation. He found that Paroxetine induced the 

longest delay in ejaculation, followed by Fluoxetine and Sertraline. No 

clinically significant delay in ejaculation was noted with fluvoxamine. 

83

C-PEYRONIE'S DISEASE 


Peyronie's disease is an acquired inflammatory condition of the penis 

associated with penile curvature and, in some cases, pain. It primarily affects 

men between 45 and 60 years of age, although an age range of 18 to 80 years 

has been reported. If left untreated, Peyronie's disease may cause fibrotic, 

nonexpansile thickening of relatively discrete areas of the corpora tunica, 

typically resulting in focal bend, pain or other functional or structural 

abnormalities of the erect penis. Many cases resolve without treatment. 

Medical therapies, including antioxidants (such as vitamin E and potassium 

amino benzoate) and corticosteroids injected directly into the plaque, lack 

adequate scientific support. Surgery remains a mainstay when conservative 

measures fail. 

Peyronie's disease was first described in 1704. It is named for 

Francois de la Peyronie, who, in 1743, described a patient who had "rosary 

beads of scar tissue to cause an upward curvature of the penis during 

erection." The penile curvature of Peyronie's disease is caused by an 

inelastic scar, or plaque, that shortens the involved aspect of the tunica 

albuginea of the corpora c 

avernosa 

during erection [Ehrlich (1997)]. In 

approximately one third of patients, the scarring involves the dorsal and 

ventral aspects of the shaft. Such offsetting plaques may cause the penis to 

be straight but shortened or to have a lateral bend (Figure). The 

circumference of the shaft may also be reduced, resulting in an erect penis 

that is flail at the site of the constriction, firm proximal to the constriction 

and soft distally [Elrlich (1997)]. 

The first symptom of Peyronie's disease may b focal pain with erection, new 

curvature with erection or inability to penetrate as a result of curvature or 

distal flaccidity [Williams and Green ( 1980 ) ].' Some patients who do not 

84

Corpus c 

Corpus s 

ponglosum 

Tunica a 

avemosum 

Corpus s 

pongiosum 

Buck's fasda 

lbuginea 

Corpus c 

Tunica a 

avernosum 

Buck's f 

ibuginea 

asd 

Corpus s 

pongiosum 

Corpus c 

a 

avernosum 

A 

Fibrous plaque 

Fibrous plaque 


have pain with erection have tenderness on palpation of the Indurated 

plaque. 

Figure (12): Penile curvature associated with P 

normal erection. (B) P 

eyronie's 

eyronie's 

disease. (A) Anatomy of a 

disease. Penile cross-section showing plaque between the 

corpora (C) Penile curvature. Fibrous plaque prevents uniform lengthening as erection 

occurs. As the rest of the corpus cavernosum and corpus s 

bends toward the involved area. 

pongiosum 

lengthen, the penis 

8

Potential Etiologies 

A number of authors believe that P 

trauma [Somers and Dawson ( 

1997) 

] 

. 

More 

eyronie's 


disease results, in part, from 

than 75 percent of patients with 

Peyronie's disease are between 45 and 65 years of age, when elasticity of the 

collagen of the penis has diminished. Many patients recall an episode of 

penile trauma, such as an invasive procedure, blunt trauma or injury during 

intercourse, at the site of subsequent plaque formation. Up to 47 percent of 

patients with Peyronie's disease also had another condition associated with 

loss of elasticity, such as Dupuytren's contracture or Ledderhose's disease 

(fibrosis of the palmer and plantar fascias, respectively) [Zarafonetis and 

Horran (1959)] Some authors [Levine and Lenting (1997)], suggest that 

either a single episode or recurrent episodes of flexion of the tunica 

albuginea may result in tears that bleed and form a clot, with subsequent 

fibrin deposition. Biopsy may demonstrate fibrin deposition and perivascular 

inflammation underlying the tunica albuginea and, occasionally, within and 

beneath Buck's fascia overlying the plaque [Morales and Bruce (1975)] 

Presentation 

Patients typically present with focal pain that occurs with erection, bent 

erection, presence of a hard mass and/or inability to i 

have 

secondary to flail penis distal to the lesion [Devine et al (1997)]. One half to 

two thirds of patients with P 

eyronie's 

disease describe pain as a symptom. 

Pain is associated with the inflammation generated by the active phase of the 

healing process, and it typically disappears as the inflammation resolves. It 

is believed to be the result of inflammation of the adjacent Buck's fascia, 

since the tunica albuginea itself has .no nerve fibers [Devine et al 1997)]. 

tercourse 

86

Clinical Course 


During the first year or so after formation of the plaque, while the scar in the 

tunica is undergoing the process of remodeling, penile distortion may 

increase, remain static or, as is most often the case in younger men, resolve 

and disappear spontaneously [Devine et al ( 

1997) 

] 

. 

In 

most patients the 

curvature remains static as the scar matures although, in some patients, it 

becomes worse as fibrosis ensues and the scar contracts. In 25 percent of 

these patients the scarring process progresses to calcification, and in 25 

percent of those it progresses to bone formation. 

After the scar has matured, the configuration of the tunica albuginea is 

unlikely to be changed by nonsurgical treatments Williams and Green 

(1980). However, many patients with advanced disease who have not sought 

surgical correction have been able to continue mutually satisfactory sexual 

intercourse with a partner. Approximately one third of patients with end- 

stage disease have a disabling curvature that requires surgical correction. 

Pain that occurs in conjunction with Peyronie's disease may also progress 

with the onset of new injuries to the corpora cavernosa occurring as a direct 

result of the patient's attempts to correct or compensate for the original 

defect during sexual intercourse [Van de (1997)]. One of the more common 

reasons for seeking treatment involves discomfort of the patient's partner 

during intercourse, which is associated with penile curvature. 

Diagnosis 

Indurated plaques may be palpated on physical examination of the penis. 

Such palpation may elicit pain if the disease is still in the inflammatory 

stage. Corroboration of Peyronie's disease may be obtained by having the 

8

patient p 

hOtograph 

hourglass shape or flail distal penis. 

Review o 

f 

literature 

the erect penis, demonstrating curvature, and an 

Radiographs of the penis may show calcification in 20 to 25 percent of 

patients with end-stage disease, and 25 percent of these patients have frank 

Peyronie's 

bone [Devine et al (1997)]. Doppler flow studies and results of dynamic 

infusion c 

avernosometry 

and cavernosography are normal both proximal and 

distal to the plaque, demonstrating that disparity in the erection is not 

associated with lack of blood flow at or beyond the lesion [Devine et al 

(1997)]. 

Treatment 

Despite numerous treatment options, there is no generally accepted, standard 

nonsurgical treatment for P 

eyronie's 

disease. Moreover, the success of 

treatment may be difficult to assess because 20 to 50 percent of patients with 

disease experience spontaneous T 

resolution. potential for 

improvement probably warrants delay of surgical correction for at least six 

to 12 months after diagnosis unless the plaque is calcified or the patient is 

completely incapable of sexual activity [Williams and Green (1980)]. 

Oral agents, particularly those with antioxidant properties, have been tried 

with limited success. Such agents include vitamin E [Rodriquez et al 

(1995)], potassium amino benzoate (Potaba), c 

and 

intralesional treatments include corticosteroids, parathyroid hormone, 

collagenase and verapamil (Calan) [Desanctis and Furey ( 

olchicines. 

his 

1967) 

] 

. 

Various 

Experimental 

modes of energy transfer, including ultrasound, radiation, laser therapy, 

short-wave diathermy and lithotripsy, have also been used Wahl (1997). 

However, all current published reports of these treatments have been 

compromised by l 

i 

mited-sample 

patient populations, lack of control 

populations, poorly characterized outcome parameters, inadequate follow-up 

88


perious and inconclusive results. It has been difficult, therefore, to determine 

which, if any, of the nonsurgical treatments may be effective. Caution 

should be used when recommending any of these experimental treatments. 

Vitamin E and Verapamil 

One possible medical regimen is 100 mg of vitamin E taken three times a 

day for a minimum of four months. Theoretically, this antioxidant will 

prevent further development of plaque, although studies have suggested that 

it is no more effective than placebo. 

Injectable v 

erapamil 

also has received some attention recently, although 

studies have either shown no statistical improvement over placebo or have 

been critically compromised by very small study size [Rehman et al (1998)]. 

Corticosteroid Injection 

The corticosteroid preparation used in the treatment of P 

varies, but two common regimens are d 

examethasone 

eyronie's 

disease 

(Decadron), in a 

dosage of 0.2 to 0.4 mg per plaque injected weekly for 10 weeks) [Desanctis 

and Furey (1967)], and triamcinolone hexacetonide (Aristospan 

Intralesional), in a dosage of 2 mg administered once every six weeks for a 

total of six injections. Courses of treatment have been repeated in some 

instances. A small syringe and a fine needle are used to inject the medication 

into the plaque and the tissues immediately adjacent to it. Local anesthetic 

agents are not used routinely because of the risk of injection into the 

vascular corpora. 

In a study [Van de (1997)] of 42 patients treated with triamcinolone, 33 

percent of patients had complete recovery or marked improvement in 

symptoms and signs during the course of treatment. 

89


Steroid injections are probably most effective during the initial formation of 

Peyronie's plaque, and success is limited with mature plaques. Patients are 

advised to abstain from sex during treatment to minimize further potential 

trauma to the penis. 

Surgical Management 

a number of surgical techniques are used for treatment of Peyronie's disease. 

The technique should be individually chosen for each patient. The optimal 

surgical approach considers penile rigidity, degree of curvature, shaft 

narrowing and erectile response [Levine and Lenting (1997)]. One 

commonly used surgical technique, the Nesbit procedure, involves excision 

of the plaque accompanied by "patch grafting" of the defect left by the 

excision. Graft material generally is taken from scrotal tunica vaginalis or 

nonhair-bearing skin from the forearm. Artificial graft material such as 

Cortex has also been used but with mixed results. These materials are 

generally less elastic and do not permit adequate stretch of the corpora 

during erections.Some authors have suggested that excision of a plaque may 

impair v 

erectile function It is recognized that the pathogenesis 

of PE is not only located in the plaque itself but involve the whole tunica 

enoocclusive 

albuginea .For this reason, some surgeons recommended incision of the 

plaque as a better choice than wide tunical excision. Other techniques 

include penile prosthesis and plication of the tunica albuginea. 

Excision of the plaque has been associated with complaints of diminished 

rigidity of erection and impotence following surgery. These problems have 

been attributed to damage of the erectile nerves during penile surgery. Thus, 

it is sometimes more practical to treat severe cases of Peyronie's disease with 

placement of an artificial penile prosthesis following incision and release of 

the plaque. 

90

CHAPTER: 4 

TREATMENT OF ERECTILE DYSFUNCTION 


Current approaches to the treatment of the ED are based on patient self- 

directed, goal-oriented modalities ,with patient satisfaction determining 

therapeutic success or failure .Introduced in 1998 ,sildenafil is already 

considered first line therapy for most men with ED , delegating the 

traditional therapies of Vedas , Injectable agents and intraurethral 

vasoactive devices to second line approaches .Surgical treatments are still 

reserved for patients who can not use or fail to respond to first and second 

line of treatments.[Canadian Urological Association Guidelines Committee 

(2002) ] 

. 

A- Oral drug therapy 

1-PDE5 Inhibitors: 

Mechanism of Action 

The PDE5 inhibitors enhance erectile function by maintaining 

sufficient cellular levels of c 

GMP 

in both the corpus c 

avemosum 

and its 

contributing vessels to dilate the corporeal sinusoids. This allows the influx 

of blood that supports penile erection. [Corbin and Francis (2002)] 

During sexual stimulation, NO is synthesized and released by 

endothelial cells and nonadrenergic/noncholinergic (NANC) nerves, see fig. 

(13). NO then diffuses into the smooth muscle cells of the penis. There, it 

activates a soluble guanylyl cyclase, which raises the intracellular 

concentration of cGMP, a secondary messenger of penile erection. PDE5 

inhibition causes a marked elevation of GMP triggers a series of other 

enzymatic reactions including activation of a protein kinase that ultimately 

reduces intracellular calcium levels, enhances smooth muscle relaxation, and 

91


produces penile erection. [Lue TF, (200)]. The PDE5 inhibitors have no 

effect on the penis in the absence of sexual stimulation, when concentrations 

of NO and cGMP are low [Lue ( 

TF, 

PDE5 Inhibitors: Pharmacodynamics Properties 

Selectivity and Effects on Vision 

200A 

The PDE5 inhibitors are highly selective for PDE5, but have varying 

degrees of selectivity for the other PDE isoenzymes in the body. [Corbin and 

Francis (2002)]. Selectivity is expressed as a value known as I 

the 

which is the concentration of drug in vitro that inhibits a given response by 

50% [Corbin and Francis (2002)]. The lower I 

the the greater the 

selectivity. A PDE5 inhibitor's selectivity ratio (i.e., the relative affinity of 

the drug for the PDE5 is enzyme versus another PDE) is also based on the 

10 50 value and may have clinical implications for its adverse event profile. 

For example, sildenafil is a relatively potent inhibitor of PDE6 (localized in 

the rods and cones of the retina), which may explain the color vision 

disturbances reported in up to 11% of men receiving sildenafil. [Padma — 

Nathan and Giuliano (2001] conversely, tadalafil is a weak inhibitor of 

PDE6 compared with either sildenafil or vardenafil and may account for the 

rare occurrence of color vision abnormalities (< 0.1%) with tadalafil. 

Tadalafil is a relatively potent inhibitor of P 

< 

-- 

DE1 

C 

50 

, 

1, which is localized in 

skeletal muscle and other tissues. However, the physiologic role and clinical 

relevance of PDE 11 inhibition in humans have not been defined. 

PDE5 P 

Inhibitors: Properties 

Administration of sildenafil with a high-fat meal reduces the C 

harmacokinetic 

about 29% and delays the time to achieve peak plasma concentration, or T 

by about 1 hour. . [ 

Padma 

ma 

C50, 

, 

nia 

by 

—Nathan H and Giuliano F (2001]. Clinically, this 

may result in a delayed onset of action for sildenafil. This d 

rug/ 

food 

92 

,


interaction is one of the likely causes for treatment failure of sildenafil in 

men who are unaware that this medication should be administered on an 

empty stomach for optimal efficacy. Similarly, taking vardenafil with a 

high-fat meal decreases Cthe 

ranging from 18% to 50% and delays r 

t 

by about 1 hour. [Rajagopalan, et al, (2003)], However, when vardenafil is 

max 

administered with a moderate-fat meal, no clinically significant effects on 

absorption were observed. The manufacturer of vardenafil states that the 

drug may be taken with or without food. [Bayer pharmaceuticals, (2003)]. 

Both the rate and extent of absorption of tadalafil are unaffected by the 

presence of high-fat food see figure (13), and therefore, this medication can 

be taken with or without food [Patterson et al (2001)] 

The p 

han 

acokinetic 

- n 

profiles of sildenafil and vardenafil are similar. 

Sildenafil onset of action has been reported as early as 14-20 minutes with a 

median of 60 minutes, whereas the earliest onset reported with vardenafil is 

16 minutes with a reported median of 25 minutes. The half-lives of sildenafil 

and vardenafil are 3 to 5 hours and 4 to 5 hours, respectively, resulting in a 

shortened period of responsiveness (about 4 to 5 hours) when compared with 

tadalafil [Boolell et al (1996)] the earliest onset of action t 

for 

reportedly occurred at 16 minutes with a median of 45 minutes. In contrast 

to sildenafil and vardenafil, tadalafil has a longer elimination half-life of 

[ 

] 

17.5 hours et al (2001 ) resulting in an extended period of 

responsiveness for up to 36 hours [Brock et al (2002 ) Ports and 

Padma-Nathan 

colleagues [Porst et al (2003)] examined the clinical effects of tadalafil in 

348 men and determined that at 24 hours 53% of intercourse attempts were 

successful in the treatment group versus 29% for men receiving placebo. 

The clinical effects of tadalafil continued to be evident at 36 hours after 

dosing with 59% of intercourse attempts b 

eing, 

. 

adalafil 

i 

m) 

has 

successful in men receiving 

, 

93

[ 

Hellstorm 

Review o 

f literature 

tadalafil compared with 28% in the placebo group. The longer duration of 

action with tadalafil has the potential for increasing flexibility for engaging 

in sexual intercourse by removing the time constraints associated with the 

shorter-acting PDE5 inhibitors. This significantly changes the sexual pattern 

paradigm, in that couples no longer have to plan for intercourse within 4 

hours of taking a PDE5 inhibitor. In another study, a greater number of men 

taking tadalafil successfully completed sexual intercourse at 4- to 12-, 12- to 

24-, and 24- to 36-hour time intervals. [Brock et al (2002)]. 

Efficacy and Tolerability 

Efficacy in General Populations 

Based on noncomparative clinical study data, efficacy for the three 

PDE5 inhibitors for the treatment of ED is comparable. Because direct 

clinical comparisons of these agents have not been conducted to date, no 

conclusions can be drawn about the relative efficacy of the PDE5 inhibitors. 

In one 12-week, randomized, placebo-controlled study with sildenafil 50 

mg, 65% of intercourse attempts were successful in sildenafil-treated 

patients compared with 20% of men receiving placebo [Padma —Nathan et al 

(1998 ) ] Results from another 12-week efficacy study with tadalafil showed 

that successful intercourse rates were 61% and 68-75% in men receiving 10 

mg and 20 ing, 

Respectively, compared with 32% in those receiving placebo [Seftel et al 

(2003)]. In a clinical study with vardenafil, successful intercourse rates were 

65% for both 10 mg and 20 mg compared with 32% for placebo at 12 weeks 

et al (2002)]. Therefore, clinical evidence suggests that 

approximately two thirds of men receiving a PDE5 inhibitor will be able to 

have successful intercourse on a per-dose basis. 

94

Tolerability 


Noncomparative clinical data also suggest that tolerability is similar 

among the three PDE5 inhibitors [Morales et al (1998)] the most frequently 

occurring adverse effects associated with sildenafil, tadalafil, and vardenafil 

include flushing, headache, dyspepsia, and nasal congestion or rhinitis. This 

adverse event profile is typical of agents having vasodilator action. Back 

pain and myalgia have reportedly occurred with sildenafil at higher than 

recommended dosages and with tadalafil at dosages of 10 mg and 20 mg. In 

the case of tadalafil, pain associated with these Conditions was generally 

reported as mild or moderate in severity, generally occurred 12 to 24 hours 

after dosing, and typically resolved within 48 hours without medical 

treatment 

In general, very few patients discontinue treatment because of side effects, 

which tend to dissipate with time; headache, myalgia, or back pain can 

usually be managed by taking acetaminophen, aspirin, or nonsteroidal anti- 

inflammatory agents. 

Efficacy and Tolerability in Special Populations 

Men with Diabetes 

ED is three times more common in men with diabetes than in those 

without diabetes and affects approximately 50% of men with diabetes during 

their lifetime. Whether this is related to oxidative stress, tissue fibrosis, or 

some other factor is unknown. Furthermore, ED occurs 10 or 15 years earlier 

in men with diabetes than in their age-matched peers without diabetes [ 

and A 

neuropathy, 

lthof 

(2000)]. A correlation between H 

bA 

ic 

Seftel 

levels, peripheral 

and ED in men with diabetes has been demonstrated in one 

study by Seftel, and colleagues [Seftel and A 

lthof 

(2000)]. The higher the 

95

HbA l 

c 

levels, the lower the mean erectile function domain s 


cote 

based on 

the IIEF scale. Low erectile function domain scores were also present in men 

with peripheral neuropathy, who tended to be relatively young. Vascular 

neurologic complications render men with diabetes more resistant to ED 

treatment. The PDE5 inhibitors, however, appear to improve erections in 

men with diabetes and ED. In one study by Rendell and colleagues, 

[Renndel et al (1999-2003) ] 

, the percentage of men who responded 

positively to the Global Assessment Question (GAQ)—Did the treatment 

improve your erections?—was 56% for the sildenafil group versus 10% for 

the placebo group. 

Men with Cardiovascular Disease 

The PDE5 inhibitors have mild systemic vasodilator properties that 

may result in h 

omodynamic 

effects such as transient changes in blood 

pressure and heart rate. However, oral therapy for ED with PDE5 inhibitors 

is safe and effective in most patients with established cardiovascular disease 

or risk factors [ K 

loner 

et al (2003)]. Because patients with cardiovascular 

disease frequently receive multiple drug therapy to control angina, 

hypertension, and other cardiovascular conditions, potential drug 

interactions between PDE5 inhibitors and agents used for cardiac 

management are especially important. For example, the concomitant use of a 

PDE5 inhibitor with organic nitrates such as nitroglycerin has the potential 

to produce clinically significant hypertensive effects. Therefore, this 

combination is contraindicated K 

[ PDE5 INHIBITORS AND NITRATES 

loner 

- et 

al (2003)]. 

The cardiovascular effects of Sildenafil are summarized in table (6). 

This PDE5 inhibitor is a safe and effective option for most men with ED and 

CVD, provided they are not taking nitrates. Because the combination of 

96


Sildenafil and nitrates may produce severe hypertensive effects, Sildenafil is 

absolutely contraindicated in m 

e: 

-. 

taking any form of organic nitrates 

including amyl nitrate [ Azarbal,B.et al., (2000) ].Dietary forms of nitrates 

do not contribute significantly to circulating levels, so they are save to take 

with Sildenafil [ Cheitlin et al ( 

1999) 

] 

. 

In 

emergency situations when nitrates 

are deemed necessary,24 h should elapse following administration of 

Sildenafil or Vardenafil before a nitrate is administrated .Nitrates can be 

safely administered 48 h after the first dose of Tadalafil K 

[ 

PDE5 INHIBITORS AND A 

THERAPY 

NTIHYPERTENSIVE 

loner 

et al (2003) 

In general, the administration of PDE5 inhibitors causes little or no 

augmentation of the hypertensive effects of standard antihypertensive 

agents. Effects are similar in patients receiving single or multiple 

antihypertensive therapies. According to analysis of data from several 

placebo-controlled phase 3 studies of interactions, no difference in the 

incidence of adverse cardiovascular events in patients taking tadalafil with 

or without commonly prescribed antihypertensive medications was observed 

[ 

Kloner 

et al (2003)]. In addition, no statistically significant differences were 

observed between the tadalafil and placebo groups in mean changes in blood 

pressure from baseline in patients taking two or more antihypertensive 

agents. 

With respect to efficacy, when sildenafil was given to patients with 

ED who were taking multiple antihypertensive agents, 71% of men in the 

sildenafil group reported improved erections compared with 18% of those in 

the placebo group ( 

p= 

. 

0001) 

[Mancia, (2002 ) ]. Similarly, when tadalafil 

was administered to men with ED who were receiving antihypertensive 

agents, analysis of seven randomized, double-blind, placebo-controlled trials 

97

Review of l 

over a 12-week period showed improved erections based on the I 

et al., (2002)]. 

IEF 

ileraltire 

[Brock 

Tadalafil also increased the rate of successful intercourse attempts, as 

assessed by SEP (Question 3). At the 20-mg dose, the percentage of 

successful intercourse attempts was 65% compared with 24% of men in the 

placebo group [Brock et al., (2002)]. Furthermore, tadalafil was well 

tolerated in this patient population with the most frequently occurring side 

LNTERACTION 

effects being headache, dyspepsia, back pain, and flushing. These occurred 

about as frequently in men taking multiple antihypertensive drugs as in the 

general population of men with ED. There are limited data available on the 

efficacy of vardenafil in patients with ED who are receiving 

antihypertensive medications. 

WITH ALPHA BLOCKER 

Alpha blocker originally developed to lower BP by reducing systemic 

vascular resistance, a 

selective receptor inhibitors (alpha- 

Mockers) are used primarily for the treatment of benign prostatic hyperplasia 

lpha 

r 

adrenergic 

(BPH). Because many men with ED have comorbid hypertension and BPH, 

they are likely to receive concomitant tadalafil and alpha-blocker therapy.A 

study of the potential for a homodynamic interaction between tadalafil and 

doxazosin, a 

and indicated for the treatment of both BPH and 

hypertension, showed that tadalafil 20 mg produced mean maximal post 

s - 

blocker 

baseline reductions in standing SBP and standing and supine DBP that were 

significantly greater than those with placebo during treatment with 

doxazosin 8 mg. However, tadalafil 20 mg did not produce a significantly 

greater reduction in mean maximal post baseline supine SBP than placebo 

produced. 

98

Review ( 

Tadalafil should be used with caution in patients receiving doxazosin. 

[Data on file, Lilly ICOS LLC]. 

Concurrent administration of the alpha-blocker doxazosin 4 mg and 

sildenafil 25 mg to patients with benign prostatic hyperplasia produced mean 

additional reductions in supine BP of 7 mm Hg systolic and 7 mm Hg 

diastolic. Concurrent administration of higher doses of sildenafil and 

doxazosin 4 mg, led to infrequent reports of patients developing symptomatic 

postural hypotension within 1 to 4 hours of dosing. 

Because simultaneous use of sildenafil and alpha-blockers may lead to 

symptomatic hypotension in some patients, patients should not take doses of 

sildenafil higher than 25 mg within 4 hours of taking an alpha-blocker. 

[Viagra ® (sildenafil) prescribing information. New York: Pfizer Inc; 2002.]. 

Incorrect use of a PDE5 inhibitor 

Incorrect use of a PDE5 inhibitor may lead to treatment failure. To reduce 

the potential for incorrect use, patients initiating such therapy for ED should 

be advised that adequate sexual stimulation is needed to trigger the cascade 

of drug-induced events leading to erection. 

Although the majority of patients respond to treatment after 1 or 2 doses of 

medication, some patients may need 7 or 8 attempts before they are 

successful. They should be encouraged not to give up before they have had a 

sufficient number of trials and used the maximum tolerated dose of 

medication.' A review of logs for 654 patients with ED enrolled in 6 double- 

blind, placebo-controlled, flexible-dose studies from 1996 to 1998 found that 

the cumulative probability of achieving intercourse success increased from 

54% on the first attempt to 86% (plateau) after approximately 8 attempts. 

In the case of sildenafil, the drug, may be taken with food; however, onset of 

action may be delayed. It is, therefore, preferable to take sildenafil on an 

21 

iterature-l 

99

empty stomach (or at least not after a h 

igh-fat 


meal) and no more than once 

L 

daily et al (2001)1 Addressing other risk factors for ED, such as 

removing the patient from medications that cause ED; treating sleep 

sadovesky 

disorders and other potentially exacerbating conditions; reducing stress; 

counseling the patient to limit or quit smoking, alcohol, and other 

recreational drug use; and educating the patient and his partner about the 

factors that can exacerbate ED, may help to improve treatment outcomes 

with PDE5 inhibitors.. 

Prevalence and Causes of Dissatisfaction of Oral Therapy 

Shortly after sildenafil became available, treatment responses and overall 

satisfaction rates were measured in a short-term study involving 308 

patients. Almost half of the patients (49%) indicated that sildenafil did not 

meet their expectations, even though 65% of patients reported being satisfied 

with the level of sexual function it allowed them to achieve (Jarow et al 

1999). However, this number fell to 41% for men who were more severely 

affected. This result was consistent with those of other sildenafil studies, 

which indicated a lower level of efficacy in men with severe ED at baseline 

(Hatzichristou 2000, Jarow 1999). Similarly, sildenafil efficacy and 

satisfaction with sildenafil treatment were considered inadequate by 39% of 

patients in another cohort who took the drug for 2 months in 1998 (Virag 

1999). S 

ildenafil 

was subsequently chosen as the sole treatment for ED by 

only 32% of those patients (Virag 1999). 

Another factor that may influence the success of oral therapy is prior 

response to other medical therapies for ED. For instance, McMahon and 

colleagues assessed the response to sildenafil in 304 men, the majority of 

whom had previously been treated for ED, mostly by i 

injections (ICI) (McMahon 2000). The overall response rate for men taking 

ntracavernous 

100

Atter 


sildenafil was 68%, and adverse events were reported by 54% of patients. 

a mean of 1.3 months, 9% of sildenafil responders discontinued 

treatment because of intolerable adverse events. Among sildenafil 

responders, 48.5% discontinued the previous therapy and elected to use 

sildenafil instead, 32% decided to alternate between sildenafil and the 

previous treatment, and 19.5% simply discontinued sildenafil. Twenty 

percent of patients who discontinued sildenafil and returned to ICI cited a 

delayed response to the former as their main reason for doing so (McMahon 

2000). Sildenafil acts within 1 hour of intake, while ICI provides a response 

within 15 minutes of injection (Pfizer 2000, Fallon 1995). Other reasons 

given for resuming ICI therapy included superior rigidity (15%), sustained 

erection after ejaculation (10%), adverse events associated with sildenafil 

(35%), and the cost of sildenafil (McMahon 2000). 

However, the most common underlying cause of dissatisfaction and 

discontinuation cited by sildenafil users was a perceived lack or loss of 

efficacy. Other causes of treatment discontinuation included cost and 

decreased libido. Among the patients who renewed their prescription for 

sildenafil (62%) after the first follow-up visit and were available at the 

second follow-up visit, 22% had not renewed the prescription by the second 

visit, with 78% citing a lack of efficacy as the reason for discontinuing the 

drug. Other reasons given included cost (27%), media scare (19%), and 

adverse events (8%) (Madduri 2001). 

Inadequate dosing and failure to follow instructions regarding food intake 

and the timing of drug administration may be responsible for the lack of 

efficacy experienced by some of the men who would otherwise respond to 

sildenafil treatment (Hatzichristou et al., 2000). In a study conducted by 

101

Hatzichris'ou 


and colleagues (EAU 2001), 56% of patients who visited their 

clinic as sildenafil failures had used the drug incorrectly. Some patients had 

attempted intercourse too early after dosing or after a meal, while others did 

not receive sufficient sexual stimulation prior to attempting intercourse. 

About half of these patients responded to sildenafil after receiving 

appropriate dose titration and instruction. 

2 

- 

Yohimbine 

Yohimbine is an indole alkaloid derived from the bark of the Central African 

Paysinystalin yohimbine tree. It has been classified as an aphrodisiac for 

over a century, but it was only recently investigated in controlled trials. 

Yohimbine is a centrally and peripherally acting alpha-2-adrenoceptor 

antagonist (Grunhaus et al. 1989); it produces a rise in sympathetic drive by 

increasing noradrenaline release and the firing rate of c 

eiis 

located in 

noradrenergic nuclei of the central nervous system. A promising effect of 

yohimbine on psychogenic impotence was reported by Reid and associates 

(1987): a 62% response rate versus a 16% rate for placebo. Many studies 

have supported the original assessment of yohimbine as an erectogenic 

agent, although the optimal dose remains undetermined (Susset et al. 1989). 

Yohimbine has no effect on erectility when given intracavernosally 

(Brindley 1986). The adverse effects of yohimbine hydrochloride include 

anxiety, nausea, palpitations, fine tremor and elevation of diastolic blood 

pressure (Morales et al. 1995), but serious adverse reactions are infrequent 

and reversible (Ernst & Pittler 1998). 

3 -Trazodone 

Trazodone is an antidepressant that has been used empirically for the 

treatment of erectile dysfunction. In addition to its serotonergic activity, 

trazodone has also been demonstrated to have alpha-blocking properties. Its 

10')

4-Phentolamine, 

Phentolearnine, 

Review _ 

activity was initially found incidentally through anecdotal observations of 

improved libido and the development of priapism in men (Saenz de Tejada 

et al. 1991) and a woman taking trazodone for its antidepressant properties 

(Pescatori et al. 1993). The mechanism of trazodone has not been 

elucidated, but it is recognized that the drug acts centrally by increasing 

serotonin at the 5 

1987). 

-HT1c 

receptor through reuptake inhibition (Abber et al. 

which is a 

an antagonist, was 

suggested to be effective in an initial study by Gwinup (1988). Zorgniotti 

lphal/ 

alpha-2-receptor 

reported a 42% positive response in men with psychogenic or mild vascular 

impotence in 1993. In a trial by Goldstein and colleagues (1998), the drug 

was found to be free of major systemic side effects. P 

hentoleamine 

Piterature 

Q 

mesylate 

is now being examined in large multicenter studies in men with ED, and it 

will also be examined in women with female sexual dysfunction (FSD) 

(Goldstein et al. 1998). 

B- Topical 

drug therapy 

1-Nitroglycerin ( 

glyceryl 

trinitrate) 

, 

a nitric oxide donor, applied topically 

to the penis or the perineum has been shown to induce some degree of penile 

erection (Claes & Baert 1989). 

2-Papaverine gel applied topically to the penis has been shown to increase 

penile blood flow (Kim et al. 1995): it appears to augment reflex erections 

in patients with spinal cord injuries and may be of benefit in this population. 

3-Minoxidil is a vasodilator widely known for its capacity to reverse 

alopecia androgenetica, and it has also been investigated in the management 

of erectile dysfunction. 

103

Review O 

literature 

4-Topical prostaglandin El has also been investigated in the treatment of 

ED. Kim and McVary (1995) concluded, in a phase I placebo-controlled, 

non-blinded investigation, that topical prostaglandin E 1 appears to be safe 

and well tolerated after application to the genitals and significantly increases 

blood flow to the penis. 

C- T 

ransurethral 

drug therapy 

Padma-Nathan and co-workers (1994) reported that intraurethral 

a 

A 

administration of 500 elicits marked cavemosal smooth 

muscle relaxation. pellets measuring 1 x 1 mm are placed 2 to 

3cm into the distal urethra after voiding followed by massaging of the distal 

lprostadil 

lprostadil 

shaft. Approximately 20% of the medication absorbs into the corpus 

cavernosum via intercommunicating veins. The remaining 80% of the drug 

is absorbed into the systemic circulation, although 99% of it is metabolized 

on the first pass through the lungs (Padma-Nathan et al. 1994). 

D- Intracavernosal therapy 

I. Papaverine hydrochloride 

Papaverine is an opium derivative that increases intracellular cAMP via 

nonselective inhibition of phosphodiesterase. In this way, papaverine alters 

the membrane calcium channel function and increases the efflux from cells, 

resulting in a decline of intracellular calcium levels and subsequent smooth 

muscle cell relaxation (Wang & Large 1991). Papaverine relaxes all 

components of the penile erectile system, i.e. the penile arteries, the 

cavernous sinusoids and the penile veins (Kirkeby et al. 1990). The drug is 

relatively slow to clear from the corpora (Hakenberg et al. 1990). 

Various doses of papaverine have been used in the diagnosis and treatment 

of ED. At the University of Iowa, from 1986 to 1989. papaverine alone was 

f 

104

Revieiv 

of literature 

used for test injections, and 55% of 232 patients achieved satisfactory 

erectile response iat 

doses of 5 to 60 mg (Fallon 1995). Only 35% of 

356 patients combined from five studies using papaverine alone achieved 

full erection (Juneman & A 

nit. 

: 

al 

lken 

1989). In Virag and associates' follow-up 

study in 1980-1988, the average doses were 20+12 mg of papaverine for the 

psychogenic type and 40+25 mg of papaverine for the organic type of 

erectile dysfunction (Virag et al. 1991). 

Because corporal clearance of papaverine is relatively slow, papaverine 

tends to predispose to priapism (Fouda et al. 1989, Hwang et al. 1991). 

According to a literature review of agents, papaverine alone produced 

priapism in 9.5% of 2,134 patients, papaverine-phentolamine in 5.3% of 

2,914 patients, and PGE1 in 2.4% of 1,284 patients (Juneman & A 

1989). A lethal complication of papaverine-induced priapism has also been 

reported: when papaverine and phentolamine failed to produce adequate - 

erection, the patient injected a second dose, which resulted in priapism and 

death from massive pulmonary embolism (Hashmat et al. 1991). 

Fibrotic nodules were reported in 5.4% of 1,573 patients collected from 

different series using papaverine monotherapy and papaverine-phentolamine 

combinations (Juneman & Alken 1989).The solution of papaverine 

hydrochloride is acidic (pH 3 to 4), and the importance of this for the 

production of intracavernous fibrosis has been discussed (Seidmon & 

Samaha 

1989). 

2. Prostaglandin ( 

El 

is a natural constituent of many mammalian tissues (Piper 1973), and 

PGE1 

alprostadil) 

human cavernous tissue generates prostaglandins (Roy et al. P 

1984). 

known to have a variety of pharmacological effects: it produces systemic 

vasodilatation, prevents platelet aggregation and stimulates intestinal 

GE1 

lken 

is 

105

circulatory 


activity. It is of interest that it has a short duration of action and is 

extensively metabolized; as much as 80% may be metabolized upon one 

pass through the lungs, which may partly explain why PGE 1 seldom causes 

. side-effects 

Andersson et al. 1991). 

when injected intracavernosally ( 

Stackl 

et al. 1988, 

PGE 1 relaxes the isolated penile smooth muscle contracted by noradrenaline 

and PGF 2-alpha (Hedlund & Andersson 1985). It exerts its effect by 

activating adenylate cyclase via G-protein cleavage. 

The published reports on I 


use of PGE1 since 1986 (Ischii et 

al. 1986, Virag & Adaikan 1987) consist primarily of data derived from 

uncontrolled retrospective studies with different formulations. PGE1 has 

been used as monotherapy for erectile dysfunction in doses typically ranging 

from 1 to 40 ug. Earle and associates (1990) reported that patients with 

spinal cord injury are very sensitive and may respond to as little 1 or 2 i 

Hwang and co-workers (1989) treated 80 impotent men with a single 20 l 

injection of prostaglandin El, and their overall positive response rate was 

79%, while in patients with psychogenic and neurogenic impotence the 

response rate was 100%. 

Prolonged erection or priapism is seldom seen in PGE1 users. In a literature 

P 

A 

review of different agents, produced priapism in 2.4% of 1,284 

patients (Juneman & 1989.PGE1 monotherapy seems to result in a 

iken 

GE1 

very low incidence of fibrosis (Ravnik-Oblak et al. 1990, Gerber & Levine 

1991, Linet & Ogrinc 1996, and Porst 1996). The incidence of penile pain 

after the injection of P 

( 

Stackl 

GE1 

has varied in different series from 0 to 91% 

et al. 1988, Hwang et al. 1989, Earle et al. 1990, Schramek et al. 

1990, Linet & Ogrinc 1996). In most cases, however, the pain is mild. 

Gerber and Levine (1991) did not find any difference in pain incidence 

_t 

_t 

g. 

g 

106

ased upon the etiology. The e 

The pain is probably induced by a 

tiology 

lprostadil 


of pain has not been fully elucidated. 

itself, because PGE1 can 

sensitize the peripheral terminals of primary afferent nociceptors and, 

consequently, produce hyperalgesia (Ferreira 1983.). 

3. Phentolamine 

Phentolamine is a competitive a 

affinity for a 

lphal- 

lpha-adrenoceptors 

antagonist with similar 

and alpha2-adrenoceptors (Andersson et al. 1991). In 

addition, the drug may have a direct non-specific, relaxant effect on vessels 

(Taylor et al. 1965). Its plasma half-life is 30 minutes. Since a single 

intravenous phentolamine injection does not result in a satisfactory erectile 

response in most cases, the drug has been used in combination with other 

agents, primarily papaverine (Zorgniotti & Lefleur 1985, Juneman & Alken 

1989). 

4. Moxisylyte ( 

thymoxamine) 

Brindley (1986) showed that Moxisylyte produces erection when injected 

intracavernosally. It has been shown that Moxisylyte is less active than 

papaverine, but its main advantage is its safety (Buvat et al. 1989). 

M 

5. combinations 

The first combination used was papaverine combined with phentolamine, 

papaverine-phentolamine-PGE1 

ultidrug 

which has been extensively used since 1985 (Zorgniotti & Lefleur 1985). 

This combination has been more effective, especially for older men, than 

papaverine alone (Richter et al. 1990). A combination of three u 

( 

Tri-Mix) 

, 

was introduced in 1991 by 

Bennet and associates. They concluded that the synergism of agents reduces 

the amounts of individual drugs needed while improving erectile quality and 

reducing side effects. A randomized crossover study of 228 patients 

comparing the efficacy of T 

rimix 

with that of PGE1 alone and with a 

tugs, 

107


mixture of papaverine and phentolamine also revealed the superiority of 

Trimix (McMahon 1991). A long-term follow-up also showed a low 

incidence of priapism (1.7%), pain (3.5%) and scarring (4.2%) It has further 

been shown that the total dose and volume of the injected drugs is reduced 

when several vasoactive drugs are combined (Bennet et al. 1991, McMahon 

1991, Govier et al. 1993, Montorsi et al. 1993, Fallon 1995). 

6. Long-term results and acceptance of Intracavernosal therapy 

Many reports do not mention the initial acceptance rates, but after a trial 

injection at the office, some of the responders normally refuse injection 

treatment because of pain, inconvenience, lack of regular partner, etc. 

(Cooper 1991). Long-term follow-up has shown that the proportion of drop- 

outs varies from 11% to over 50 % (Virag et al. 1991, Gerber & Levine 

1991, Montorsi et al. 1993, Govier et al. 1993, Valdevenito & Melman 

1994): most reports do not have cover periods beyond 2 or 3 years, but those 

which have longer-term information show the retention rate of patients to be 

high (Virag et al. 1991). Many reasons for dropping out in the long term 

have been described: recovery of spontaneous erections, loss of interest, 

complications, disacceptance of the injection technique, etc. (Fallon 1995). 

There have been several reports in the literature of transient, partial or 

complete restoration of spontaneous coital or nocturnal erections in patients 

using self-injection (Virag et al. 1984, Aravena & B 

ustamente 

1986, Buvat 

et al. 1991, McMahon 1991). In conclusion, intracavernous injection therapy 

is often associated with the restoration of spontaneous erections in patients 

with psychogenic impotence, but is rarely seen in patients with organic 

impotence. 

108

E-Hormonal 

treatment 


Androgen substitution may improve ED in some patients with diagnosed 

hypogonadism (Krane et al. 1989). Improvements in mood and sexual 

function can be elicited in hypogonadic men by increasing the plasma 

concentrations of either testosterone (T) or dihydrotestosterone (DHT) 

(Kuhn et al. 1986). However, it has been demonstrated that, in hypogonadal 

men with impotence, the administration of testosterone alone results in 

improvement of erection in only approximately 60% of patients (Morales et 

al. 1997). Furthermore, there are some hypogonadal men in whom ED is 

more dependent on vascular risk factors than low testosterone levels 

(Morales et al. 1997). In elderly men, short-term studies on a small number 

of patients have been performed and have shown favorable effects on 

sexuality, well-being and muscular strength (Morley et al. 1993, Tenover 

1992). Kirby (1994) proposed that testosterone should not be used in 

eugonadal men with ED because it may enhance prostatic hyperplasia or 

promote the growth of prostate cancer. 

Because of the poor bioavailability of the drug, oral therapy with 

testosterone is less effective than parenteral testosterone in achieving normal 

serum testosterone levels and has a higher incidence of hepatotoxicity and 

adverse serum lipid effects (Krane et al. 1989, Morley & Kaiser 1989). New 

Transdermal formulations of testosterone and dihydrotestosterone as well as 

oral formulations without associated liver toxity have been developed 

(Wagner & Tejada 1998). 

Bromocriptine has been used successfully in men with hyperprolactinaemia- 

associated hypogonadism, with subsequent improvements in erectile 

dysfunction (Leonard et al. 1989). 

109

( 

Nadiu, 

F- Psychosexual therapy 


Psychosexual therapy for ED problems was introduced in the early part of 

this century with Freudian-style psychoanalysis. In 1970, a treatment 

program involving a combination of behavioral and psychotherapeutic 

elements was described, and a 70% success rate after 5 years of follow-up 

was reported (Barnes 1991). Nowadays, these methods have mostly been 

replaced by more behaviorally oriented therapy, which aims to reduce 

performance anxiety via programmed relearning of sexual behavior. 

Hartman (1998) concluded that psychosexual therapy is a feasible treatment 

option, with significant improvements in 50 to 80% of cases, but its long- 

term outcome is less favorable. 

Surridge and co-workers (1998) concluded that men with ED want to have a 

rigid penis, while they and their partners are less interested in having help 

with relationship issues, general sexual issues and life style issues. 

G. Vacuum Entrapment Devices (VED) 

The vacuum constriction device (VCD) works by a combination of the twin 

principles of vacuum and tension: the negative pressure (vacuum) device 

increases corporeal blood flow, thereby inducing an erection, which is 

maintained by a constriction ring (tension) around the base of the penis that 

decreases corporeal venous drainage. VCD was developed over 100 years 

ago. Dr. John King introduced the first device in 1874, and the first patent 

was issued for the device to Dr. Otto Lederer in 1917. It took over 100 years 

before the device was approved as a legal treatment option; O 

device ( 

ErecAid 

) 

TM 

was granted FDA permission in 1982 (Osbon 1983). 

It has been reported that erections have succeeded in 84-95% of cases 

et al. 1986, Cookson & Nadig 1993, Baltaci et al. 1995) and overall 

sbon&grave; 

s 

110

Review of literal lire 

satisfaction with the device has been slightly lower, 72 94% (Turner et al. 

1991, Vrijhof and D 

elaere 

( 

Complications are generally of minor nature: pain, either during the suction 

(20-40%) or caused by the ring (45%), is the commonest complaint, which is 

most frequently presented at the beginning of treatment (Turner et al. 1991). 

Pain on ejaculation has been reported by 3-16% of users, and an inability to 

ejaculate by 12-30% (Witherington 1989, Turner et al. 1991, Cookson & 

Nadig 1993). Petechiae on the penis have been reported by 25-39%, 

concurrent bruising by 6-20% (Cookson & Nadig 1993, Baltaci et al. 1995), 

and numbness as a major problem during erection by 5% (Cookson & Nadig 

1993). 

(H) SURGICAL TREATMENT OF ERECTILE DYSFUNCTION(ED) 

A- Penile Implants Surgery 

The first commercially produced devices were the outcome of prototypes 

investigated by urologists Small and Carrion. Clinical use began in the 

sixties and relied on simple implantable stiffening components inserted in 

the penis. Significant usage of such devices took place in the seventies. The 

items consisted of semi-rigid, rod-like objects which could be manipulated 

and set thus imparting significant rigidity for sexual function. They were 

mostly manufactured of electrometric coating materials with malleable or 

segmented articulated cores. Outwardly they resembled plastic cylinders 

stiffened by semi-flexible metallic or plastic elements at the center which 

imparted rigidity and allowed alterations of position. 

The intrinsic rigidity of the object has been associated with long term 

problems, specifically trauma to tissue at both the distal and the proximal 

end of the rods. Other problems are the result of proximity of the rods 

111

against large vessels and vulnerable p 

primarily from chi ° 

clic 

. 

, 

nile 


tissue. Morbidity results 

friction and trauma as opposed to frank failure of the 

rods or their accessories. In the seventies, several new patients emerged. 

Since the introductions of penile prosthesis implantation for treatments of 

male ED in the 1970s, the modifications and improvements of penile 

prostheses have remarkably improved the device's reliability, longevity, and 

the prosthetic surgery outcome [Shabsigh.1998]. 

By the late-eighties, the inflatable penile implant nevertheless dominated the 

market and the malleable prostheses had become minority products. At least 

four major manufacturers were active in the field; they distributed 

competing versions of such products throughout the late-seventies and 

eighties. At least three manufacturers are still active worldwide. 

Antibiotic Impregnation of Inflatable Penile Prostheses ( 

After investigations that identified the efficacy of coating prostheses with a 

combinations of rifampin and monocyclines to inhibit bacterial growth a 

new penile prostheses was developed that received Food and Drug 

Administration approval in May 2001. In the InhibiZone prosthesis tissue 

contacting surfaces are impregnated with quantifiable doses of rifampin and 

monocyclines that elute into the area surrounding the prosthesis 

postoperatively. 

Models 

Mechanical I 

rods: II (Timm Medical Technologies) prostheses 

have a series of polyethylene segments that articulate in a ball and socket 

) 

urra 

arrangement and are held in place by a central spring. A silicone membrane 

covers these devices, and they come in 2 width s 

izeszl0 

InhibiZone) 

mm and 12 mm. 

112


covers these devices, and they come in 2 s 

width mm and 12 mm. 

The standard iength of 13 cm is augmented by adding proximal and distal tip 

In 

extenders. 

Malleable rods (AMS 600, 650; Mentor Malleable; and Accuform) 

The AMS models consist of a wire core surrounded by polyester covering 

and silicone outer jacket. Model 600 has 9.5-mm and 11.5-mm width sizes, 

and the model 650 has 11-mm and 13-mm width sizes. Lengths range from 

12/20 cm and can vary with tip extenders. 

The Mentor Malleable and Accuform both have a silver wire backbone with 

a silicone elastomers outer coat and have widths of 9.5 mm, 11 mm, and 13 

mm. Cylinder lengths range from 14-27 cm. These prostheses are chosen for 

their simplicity of usage and durability due to fewer vital moving parts. 

Unitary inflatable penile prosthesis (Dynaflex [ 

1990, the Dynaflex model was introduced as a more robust replacement 

of the Hydroflex. It is a paired cylinder with all operating components 

contained within each device, and it consists of the distal tip, central 

chamber, and proximal reservoir. Rigidity is achieved by pumping 2-3 cc of 

liquid into the central chamber from the reservoir. Bending the cylinder 55 

degrees or more from horizontal operates a pressure switch to deflate the 

device and return fluid back to the reservoir. These cylinders come in 2 

widths 

11 and 13 m 

mzand 

a variety of lengths. 

Two-piece inflatable devices (Mark II [Mentor] and [ 

Ambicore 

These devices are marketed to improve the ease of surgical implantation by 

eliminating the need for reservoir placement in the abdominal region. These 

prostheses consist of 2 inflatable cylinders that are inserted into the corporal 

bodies and are connected to a pump-reservoir located in the scrotum. The 

detraction of these devices is the limited reservoir capacity of 15-20 cc, 

AMS] 

) 

izesz10 

AMS] 

) 

113

Review g 

which is available not only for cycling the 2 cylinders for full rigidity but 

also for allowing for flaccidity. As much as 5-10 cc of fluid is left in the 

cylinders during the flaccid state due to limited reservoir space. Patients with 

larger penises criticize these devices for insufficient volume to fully inflate 

the cylinders, and those with smaller penises complain of difficulty 

completely deflating the cylinders due to the limited reservoir capacity and 

resulting residual cylinder fluid. 

These prostheses should be considered for patients whom reservoir 

implantation is difficult or contraindicated, such as those who have 

undergone pelvic exenteration or renal transplant patients. 

Three-piece inflatable devices (Ultrex [AIMS], CX [ 

Alpha 1 [Mentor]) 

These devices tend to be more complex and consist of 2 inflatable cylinders 

placed in the corporal bodies, a small pump that resides in the scrotum, and a 

large fluid reservoir that is placed in the abdomen. Three-piece prostheses 

prove to be the most satisfactory devices because they produce the most 

natural appearing phallus in the inflated as well as the deflated states; they 

produce good rigidity even for larger penises; and they offer good flaccidity 

for social dress. In addition, the flaccid state of the 3-piece offers removal of 

pressure against the corpora and tunica albuginea. The A 

ANIS] 

, 

MS 

CXIVI 

iliterature 

[ 

A1VIS] 

, 

line offers the 

Ultrex model, which allows for girth and distal expansion, while the CX 

imparts girth expansion only. The CX line is most applicable to patients with 

scar tissue or if there is a tendency for penile curvature upon tumescence. 

The Bioflex cylinders from Mentor allow expansion in girth with minimal 

axial elongation. It proves to be very durable and is resistant to cylinder 

aneurysm formation. 

114

Indications: 


I-failure of all kinds of conservative therapy either first or second line 

2-Patients with sickle cell anemia who have stuttering priapism and/or 

cavernosal scarring also are potential candidates for inflatable penile 

prosthesis.. 

3-Men with Peyrone's disease, which is a fibrous scar of the tunica 

albuginea, who have penile curvature may benefit from inflatable penile 

prosthesis. 

2-Other 

Contraindications: 

1-Some have listed psychogenic ED as a contraindication for penile 

prosthesis implantation. 

2-The clinician also may consider the patient's reliability for follow-up care 

as well as manual dexterity. If the patient cannot operate his device, he must 

have a supportive and willing partner who can help. 

3-Patients with active/chronic infectious processes such as decubitus ulcers 

and venous stasis ulcers are at high risk for seeding their devices. 

Complications: 

1-After the prosthesis is placed, patients may experience modest penile 

shortening in the range of about 2 cm. This must be discussed with the 

patient and partner prior to any surgical intervention. 

issues that should be addressed include possible erosion of the 

device over time and the possibility of implant infection despite careful 

preoperative preventive means. 

3-An average infection rate ranges from 2-4% over a 2-year period with a 

national wider range of 0.6-8%. Most infections become evident within the 

first year. Some bacterial species, such as Staphylococcus epidermidis, can 

lie indolent for as long as 2 years before causing clinical signs of infection. 

115

PATIENTS AND METHODS 

Pcllients 

and M 

This study included.459 men attended the out patients urolog y clinic at 

Urology Dept.University Urologists of Cleveland, Case Western Reserve 

University ( 359 men ) and El-Minia University Hospital (100 men ) in the 

period from August 1999 to August 2004 .The mean age of these patients 

was 61 ± 9.6 years, and duration of erectile dysfunction was 4.1 ± 3 years. 

Selection criteria 

The 359 men who included in this study from University urologists of 

Cleveland signed a consent form to release their data base from their 

hospital charts and their data became available for clinical research.. 

All patients had ED , the duration of ED was at least 6 months for all 

patients to be included in this series , of these, 280 men were presented by 

ED alone, 69 men with ED and low sex drive, 73 with ED and premature 

ejaculation, 20 men with priapism, and 17 men were presented with 

Peyrone's disease. 

Exclusions criteria 

We excluded from this study 

1-Patient with history of spinal cord injury and ED 

2-Patient with a recent fracture pelvis and/or urethral injury ( vascular 

trauma and improved their erectile quality with time ). 

3-Patient with a well known neurologic disease 

4-Patient with major health problems like renal, liver and/or cardiac failure 

5-Patient with organ transplant surgery 

6-Patients with severe psychosis diagnosed by psychotherapists 

The following questionnaires were completed by all patients during the first 

visit and before physical examination in the w 

aitino, 

room: 

ethods 

11S

2--Identification 

1-Sexual Health Inventory for Men (SHIM) Questionnaire 

Patients and Methods 

This questionnaire is designed to have 5 questions (hat best describe ED 

patients, each question has several possible response from 1 

questionnaire was completed by the patient in the office during the first 

visit and prior to the interview .The SHIM score was appended and 

scored as follow. 

Score 22-25 ....................................... .no ED 

Score 17-21 ....................................... .mild ED 

Score 12-16 ...................................... .mild to moderate ED 

Score 8-11 .......................................... moderate ED 

Score 0-7 ........................................... .severe ED 

2-Androgen Deficiency in Aging Men (ADAM) Questionnaire 

A copy of ADAM questionnaire was appended, the ADAM questionnaire is 

considered positive if there is a YES response to the question no 1 and No 

response to question no 7, or YES response to any other three questions, see 

the i 

ndex_ 

3-CES-D (Center Epidemiology Society for Depression) and Beck for 

detection of men with depression 

We considered patients with ED positive for depressive symptoms if 

reported 14 with Beck inventory for depression. 

-During the interview a complete history taking were conducted in the form 

of 

1 -Personal history; including name, age, age of puberty, marital state 

libido problems. 

of the sexual dysfunction either erectile, ejaculatory and/or 

-5. 

This 

119


3-Analysis of Erectile Dysfunction problems either, Inability to achieve 

erection, week erection, inability to sustain erection and/or painful erection 

4- The following leading questions were applied for all 

A-if the patient has never been able to have intercourse or not (primary vs. 

secondary) 

B-do you wake with normal erection in the morning or night 

C-do you have erection with masturbation 

you lose the erection you have rapidly 

0-do 

E-do you have painful erection 

F-do you have an orgasm 

G-sexual relation ship 

5-History of current or previous medications 

6-Past surgical history 

7-List a 

ll 

your prior evaluation for current health problem 

Yes no 

Yes no 

Yes no 

Yes no 

Yes no 

Good fair poor 

8-Have you seen any other doctor for this problem, if you have, please list 

below the following; name of doctor ,evaluation done ,any treatment used 

and response to this treatment option 

9--Special habits 

Do you smoke? 

Yes 

120

If yes how many packs per day and its duration 

Do you drink alcohol? 

Yes no 

Do you use any creational drugs? 

Physical Examination 

Yes NO 


All patients are subjected to complete physical examination in the form of. 

A-Inspection of General Habits 

-Vital signs (pulse, blood pressure and temperature) 

-Examine the neck for goiters 

-Chest and heart examination 

-Any Gynecomastia 

-Any signs of excess anxiety or hyperactivity suggesting of an 

endocrine abnormalities. 

B-ESCUTCHEON: a- weight b- Height c- Body hair distribution. 

C-Inspection of external genitalia: Penis size pathology 

D-Digital Rectal examination (DRE) 

- Sphincteric tone 

- Bulbocavernous reflex 

- Evaluation of the prostate gland for cancer 

- Prostatitis 

E-Special tests 

a - neuro-sensory examination 

b- Penile sensation by pin pricks technique. 

c- Cremasteric reflex. 

Testis size pathology 

121

Diagnostic work up of the patients in this study 


A summary of diagnostic modalities used and number of patients were 

listed in table below 

Table (6): Shows different methods of diagnosis used for patients in this stud 

Modality of diagnosis Number of patients 

A-Laboratory tests in the form of 

1-Fasting and postprandial blood sugar 

2-Complete urine analysis and culture 

3- Liver function test,CBC and PSA 

4- Serum testosterone 

-TOTAL 

-FREE 

-% FREE 

5-Serum Prolactin,LH and FSH 

All patients 

B-Diagnostic Intracavernosal Injection test (ICI 47 

C- RIGISCAN TEST alone 15 

D-penile Doppler ultrasonography alone 68 

E-Both Rigiscan and Penile Doppler 38 

E-Dynamic infusion cavernosometry and 

cavernosography 

We requested these laboratory investigation during the first visit 

A-Fasting and postprandial blood sugar 

B-Complete urine analysis and culture when indicated in some cases 

55 

69 

69 

69 

64 

66 

20 

3 

122


C-Liver function test,CBC and PSA; clone in patients in who received 

testosterone replacement therapy before and 3-6 months from starting of 

treatments, also in patients with known history of liver disease 

E-Hormonal evaluation which included: 

1 - Serum testosterone 

Was done in cases in which the main presentation was decreased in libido, 

positive ADAM questionnaire associated with insufficient erectile quality 

for intromission, cases with testicular abnormalities either in size or 

consistency or in some cases with other endocrine abnormalities. 

All men had ED and completed these validated instruments (questionnaires) 

in the office prior to physical examination (SHIM, ADAM CES-D and 

BECK). All men had Serum testosterone levels drawn; we measured total 

testosterone (TT), free testosterone and % free testosterone. According to the 

definition of hypogonadism, any patient with total testosterone level below 

300 ng/ml and/or low levels of either free T < 2 .50 ng/ml (N= 2 .50-10 

n 

0 

or % free t < 0.62 ( range was considered as 

had a hypogonadism in our group .We also looked for the prevalence of 

ng/ 

ml) 

g/ 

ml 

depressive symptoms in these group of patients using the two questionnaires 

for depression (CES-D and BECK) .We also correlated low libido with 

hypogonadism . 

Exclusion criteria 

1-Patients were excluded if no serum testosterone level was drawn 

2-If the questionnaires were incomplete. 

3-Patients didn't received replacement therapy 

We offered testosterone replacement therapy for all patients in the form of, 

shots in 44, androgel in 14 and dermal patches in 11. 

. 

62-1. 

75ng/ 

d1)

The i 

ndicaiiuns 

for replacement therapy in these patients were 

1-Patients with ED and decreased serum total testosterone < 300 n 


2-Patients with ED and low bioavailable (free testosterone) and/or % free 

testosterone 

3-Patients with ED and low sex drive, positive ADAM questionnaire and 

with a total testosterone range between n 

300-1000 

emerging data support the need for T levels of 500 n 

sexual function (Seftel 2003 ). 

g. 

/ 

g/ 

m1 

g/ 

ml 

based on our 

dl for adequate 

In patients who received shots ,we started by 200 mg dose intramuscular 

then ,we measured the total serum testosterone levels one week after ,if the 

levels was > n1000 

,we titrated the dose or /and change to androgel or 

patches ,then we measured the serum total testosterone level one week post 

g/ 

d1 

injection and every 3 month after. All patients had PSA, CBC and liver 

functions drawn prior treatment and then every 6 months during the course 

of treatment. We did TRUS guided biopsy for 5 patients who showed 

elevated PSA during the course of treatments using the PSAD (the PSA 

velocity was > n0.75 

.per Year). 

We stopped T therapy if patient diagnosed with positive prostate biopsy, 

2/ 

d1 

patients showed abnormal liver enzymes and in patients showed significant 

CBC abnormalities. 

These tests were done in 69 patients in this study with mean fellow —up 

period 12 months (range from 6 to 24 months). 

In this group , in addition to treatment with testosterone therapy , we added 

the following adjuvant treatment ,sildenafil citrate in 20 patients ,ICI in 3, 

combined sildenafil citrate and I 

CI 

in 5 ,penile prosthesis in 3 ( 2 piece 700 

124


AMS Ambicore in 1 , 3 piece inflatable in 1 and Duraphase 1 

in these 

patients showed poor response to T therapy ( week erection spite of T 

therapy ). 

2- Serum 

Prolactin, LH and F 

SH 

We measured these hormones in 20 Patients in whom there were a 

significantly lower serum testosterone level ,in our study we did a complete 

hormonal assay for all men who had total testosterone < 200 n 

g/ 

ml, 

) 

. 

all 

in this 

study only 5 patients showed high Prolactin level ,3 presented by ED and 

vague symptoms like headache and vision abnormalities and on physical 

Intracavernosal 

examinations, Gynecomastia was seen in 1 patient ,that suggest 

hyperprolactinamia , 2 patients referred for treatment of ED from 

endocrinology center ,we did M 

a pituitary lesion in this study . 

IZI 

study in all five patients ,no one showed 

All patients were referred back to the endocrinology center for hormonal 

therapy to correct the endocrine abnormality first before starting ED therapy. 

B- Diagnostic 

Intracavernosal injection (ICI) Test. 

injection test (ICI) using three different active agents 

[ 

m 

prostaglandin El (Caverjet 10-20 papaverine hydrochloride 

(PV), and Trimix (a combinations of 5.88 ug /ml prostaglandin El + 0.6 

mg/ 

ml 

PGE1 

phentoleamine + 18 m 

modality in some patients j 

economic reasons). 

-Dose of drugs used:0 

penile 

g/ 

nil 

ug) 

] 

, 

papaverine), was used as a diagnostic 

ultrasonic was not available or for 

ml 1 ml 2 ml. 

. 

. 

5 

125


-Depending on the provisional diagnosis and the age of patients we never 

exceed 4 ml papaverine and 1 ml Trimix in all injected c 

Technique 

Patient lie supine, complete sterilization of the penile shaft and the ipsilateral 

upper medial part of the thigh, no basal tourniquet was used after injection 

of the vasoactive agent, using sterile gloves and 1 ml insulin syringe. We 

stretch the penile shaft toward the sterilized area of the thigh and inject the 

previously measured dose according to the provisional diagnosis and patient 

age , in the ipsilateral corpus cavernosum at any site from 2 to 10 positions. 

Maximal erection obtained after ICI was scored as; 

*Type -1 (full tumescence-no sustained rigidity, angle on the abdominal 

plane > 90 degree). 

*Type -2 (sustained partial erection, valid for intromission, angle =90 

degree). 


* Type 3 (sustained full erection, angle < 90 degree). [Antonio et al, (2002)] 

-We noticed the response after 5, 10, 15 min. post injection 

-In few cases response was noticed after one-hour. 

-Sexual stimulation was done in all cases. 

-A positive response -i.e. normal erectile rigidity of sustained duration- is 

presumed to exclude a major vascular disease. 

test used in 47 out of 459 patients in this study (10.2 % ) 

these 47 men in this group not underwent penile ultrasonic examination 

during the test. 

ase. 

; 

. 

; 

126

In ally patients, ICI of phenylephrine was done : 

the office and their penises return back to the d 

etumescence 

efore 


the patients leave 

state. 

(Intracavernosal injections of phenylephrine not done in 4 patients) 

ICI Complication 

The complications of ICI were classified as f 

1-early complications 

a- local complications 

1-pain 

2-hematoma 

B-systemic complications 

at site of injection 

3- Bleeding or e 

/and 

4-prolonged erection ( 4-6 Hs erection) 

I-Dizziness 

2-Hypotention 

3-Headache 

2--Late complications (in the therapeutic ICI patents) 

1- Fibrosis of the corpora cavernous 

2-Loss of effectiveness 

3-Penile shortness 

The above listed complications were applied for ta 

underwent ICI (47 ICI alone +106 penile U/S p 

cchymosis 

ollm; 

a: 

ients) 

] 

otal 

153 men who 

127

C- RIGISCAN Test 

Depending on their sexual history, h 

i: 

1nry 


of psychological troubles .All 

patients diagnosed by the psychologists and results of their depression scores 

using the C-DES and BECK inventory for suppression. 

Twenty one patients in this group underwent Penile Doppler Ultrasonic 

examination before or after doing the rig scan test. 

1-Be 

All patients underwent the following instruction 

sure to put a new batteries in the Rigiscan monitor each night before 

using. New batteries for the next two nights' sessions should be included in 

the carrying case. Open the door labeled battery compartment on the top of 

the monitor, removed old batteries and insert the new ones as you would for 

a portable radio. Direction the batteries terminals should face as shown on 

the bottom of the monitor's battery compartment. 

2-During the testing period, be sure to 

-_Not 

D-Not 

etc.) 

A-Take all your medication as prescribed 

B-Not to take sleeping medications or muscle relaxants 

C-Not to take alcohol or other drugs like marijuana 

to drink coffee, tea, or cokes after 3.00 P.M 

to attempt sexual activity (intercourse, oral sex, and m 

3-Sit comfortably on the edge of the bed or chair, Wrap the leg strip around 

the thigh of either leg with the opening pointing toward the body. I f you 

sleep on your right side, the monitor and strip should be secured to your 

asturbatiori, 

128

2-After treatment failure 


right thigh. The strip should be comfortably snug. Slide the Rigiscan 

monitor into the holster o 

the strip 

Interpretation of the results 

1- Nightly Erection Episodes 

2-Time OF Erection Episodes 

3-Changes in Tumescence 

4-Degree of Rigidity 

5-Oveall Summery 

Final diagnosis were interpreted as fellow 

1- Diagnosis suggesting psychogenic ED 

2- Diagnosis Suggesting Organic ED 

f 

Normal Borderline abnormal 

3- Borderline Diagnosis and advice to repeat the test. 

In this study, a total 53 patients, presented with a history of persistent ED at 

least 6 months duration, underwent a Rigiscan examination 

D-penile Doppler ultrasonography 

Using Urometrics Knoll /Midus penile ultrasound 7-10 MHZ, 106 patients 

underwent penile Doppler ultrasonography. Of these men, 38 men 

underwent Rigiscan study in addition to ultrasonic examination. 

Indications for penile ultrasonic in our study were 

1-To exclude organic ED in patients with history suggesting psychogenic 

129


3-For medico-legal issues in some patients who underwent penile implant 

surgery 

4- Patients presenting with priapism to differentiate ischemic from non- 

ischemic priapism in some cases 

Before the test, all patients were given a 10 mg of already prepared 

prostaglandin El (Caverjet) to induce pharmacological erection, we didn't 

take any measurement in the flaccid phase. The ultrasonic examination was 

performed in a peaceful environment using Knoll /Midus Gray scale 7-10 

MElz 

linear array transducer to scan all patients. The patients were scanned 

in the supine position and while the penis was in its anatomical position. 

Sampling of the peak systolic velocity (PSV) was done near the penile base 

the penis was initially examined for plaque or fibrosis, we didn't assess the 

penis in the flaccid state. The penis was assessed after pharmacologically 

induced erection using a 29 G needle. The rigidity of erection was assessed 

by asking for the patient's subjective opinion, and with clinical palpation for 

rigidity. 

The PSV was measured immediately when we noticed rapid onset rigidity, 

and at 5, 10 and 20 min. post-injection, the end-diastolic velocity (EDV) was 

recorded at approximately 15 to 20 min. post injection. The examination was 

performed for at least 20 min. post-injection or until reversal of diastolic 

flow was obtained, and/or there was persistent high EDV with no 

progression towards a high resistance waveform. Patients were considered to 

have normal arterial inflow if their > 

PSV 28 cm/sec. 

Arteriogenic impotence was diagnosed when the PSV > 28 cm/sec. 

130


Criteria used for diagnosis of venogenic impotence in our protocol scanning 

5, 10, 15 and 20 min.postinjection were as follow. 

1- PSV > 28 (no arteriogenic abnormalities). 

2-Well-Maintained EDV > 5 cm/sec 

3-Resistive index (RI) >0.75 

4-Time passed from injection should > 

be 15 m 

visual rating scale, it should be accompanied by transient rigidity 

5-Using, 

after self stimulation. 

PSV > 28 cm/ or normal arterial flow is required to diagnose venous leak, 

because in the presence of possible arterial insufficiency venous leakage 

in. 

could not be accurately assessed) and EDV > 5 cm/sec after 15-20 m 

injection. 

in 

from 

All patients were given from 1-2 shoots of 0.3 ml of phenyl-ephrine for 

detumescence before leaving the office with continuous measurements of 

blood pressure for post-injection hypotension. 

We rated the erectile quality during ultrasonic examination, what is so called 

Buckle test. 

Buckle results were classified as: 

1-Negative buckle: Inadequate rigidity (rigidity< 50 %) 

2-50-60 % buckle; inadequate rigidity (if rigidity was borderline and not 

sustained) 

3-Positive buckle; Unbending rigidity sustained for 20 min. (rigidity > 70 %) 

Flow metrics Ultrasonic results were classified as follow 

A-Non-vasculogenic ED 

B-Abnormal arteriogenic ED 

131

C-Abnormal venogenic ED 

D-Mixed ED (combined venous and arterial ) 

E-Dynamic infusion cavernosometry and c 

avernosography 


Only 3 patients in our series had this test , we got patients signed consent 

form before the procedure about the risk of the technique ,of these ,1 had ED 

after surgical treatment of refractory priapism, 2 patients who had ultrasonic 

diagnosis of venous leak and requested penile prosthesis surgery , only one 

patient showed venous leak ,the other 2 patients no abnormality were 

detected , 

TREATMENT OPTIONS FOR ED PATIENTS IN THIS STUDY 

A-During the first visit ,we provided all patients in this study a trial of oral 

medication in the form of PDE5 inhibitor in the form of sildenafil citrate ( 

50-100 mg ) ,provided that there was no contraindication for PDEI . 

Exclusions criteria in this g 

roup 

1-patients receiving any form of organic nitrate or other NO donors (such as 

nitroprusside) medication were excluded 

2-patients with history of unstable cardiac disease 

3-For patients who have had more than two risk factors, these patients 

underwent stress test and cardiac consultant before putting them on PDEI 

mg, 

4-patients with recent cardiac stroke (< 3 months) 

5-patients with recent cardiac surgery 

In this study we provided PDEI, for 300 hundred patients' .All patients 

received the same instructions regarding method of administration, risks and 

potential efficacy of PDEI. They were instructed to administer the initial 50 

dose on empty stomach and/or approximately 2 hours after meal (not 

132


fatty) and he is ready to go 1 hr after .Escalation to 100 mg was performed if 

the initial dosage was ineffective and there were no adverse effects. we 

considered treatment failure if there were no satisfactory response after 6-8 

tablets of 50 or/and 100 mg and after we be sure that the patients taken the 

drugs in a proper way .Follow up SHIM questionnaire were administered 

only after several attempts and with all dosage if not effective initially. 

Successful outcome was defined as improvements in the SHIM score from 

severe to moderate ,moderate to mild ,or return to normal sexual function ( 

SHIM score >21) . 

B-VED (Vacuum Entrapment Device) 

we provided VED device as a second line therapy for only 12 patients in our 

study, 4 of them were given the device upon their request, 3 patients after 

failed oral medication, 5 patients had contraindication for PDEI, all patients 

saw a video tape showing all the issues about the device and how it use 

before giving them the device and all of them had appointment with our 

nurse who demonstrated for them how the machine work . 

C 

- 

ICI 

Home Therapy 

Inclusions criteria for ICI home therapy 

1-Good response to ICI at time of the test, at least type 2-3 response in 2 

successive ICI 

2-Buckle positive or > 50 % rigidity on ultrasonic examination 

3-Mastering the technique of ICI at the office and with help of our well 

trained nurse 

4-Negative history of blood disease or/and crisis 

5-Good mental dexurity to handling the technique 

133


6-No major vascular disease diagnosed by penile Ultrasound for ED 

All patients who underwent to home ICI therapy first started the injection in 

the office under supervisions of a well trained nurse for at least 3-4 office 

injections. 

All patients signed a consent form describing the short and long t 

outcome complications of the ICI and all of them have been instructed to 

call the nurse or the resident on call in situation of prolonged erection 

(erection of more than 4 Hs). 

Thirty-nine patients met the inclusion criteria started the ICI home therapy in 

this study 

The outcome of treatment for those patients were classified as fellow 

1-spontonous improvement of ED with discontinuation of treatments 

2-subjective improvement of sexual function with ICI alone or with help of 

adding PDEI sildenafil citrate 50-100 mg 

3-loss of effectiveness or 

4-stop of ICI 

In patients who had stopped the treatments, the reasons behind these have 

been listed as follow (WHY STOPPED) 

1-needle phobia 

2-fear of complications 

7-ineffectivness 

3-presence of complications 

4-loss of partner 

5-improvement of ED 

6-Shift to another method 

of therapy 

e 

m 

134

Peyrone's Disease Patients 


In our Patients population of 459, 17 (3.7 %) Consecutive patients with PD 

presented for evaluation and describe their clinical presentation, physical 

examination findings, and treatments outcomes. 

At the first visit all patients filled out a specific ED questionnaire, detailing 

medical and sexual history, symptoms, and duration of disease. 

All patients were subsequently examined, evaluated and treated. 

There was no exclusions based on disease severity, duration, or patient age 

The diagnosis of PD was dependent on the existence of a palpable penile 

plaque and/ or penile curvature ( 

defoimity) 

. 

The degree of penile curvature was assessed and graded using a modified 

Kelami classification. 

*Grade -1 less than 30 degree 

* Grade -11 30-60 degree, 

*Grade 111 greater than 60-degree 

PD plaque dimension and location was assessed with duplex Doppler 

ultrasound in some patients. All patients were examined for Dupuytren's 

contracture. 

Medical treatments in the form of oral medication (Vit. E 800-1200 mg per 

day and C 

olchicines 

0.6 mg BID. were applied for all patients who had 

presented during the acute phase of disease with pain that is related or 

unrelated to sexual activity ( immature stage ,) and also for the rest of the 

patients even in the absence of pain ( upon their request ) ,so oral therapy 

were provided to all patients in this group for at least 6-8 weeks durations 

135


Topical 0.5 mg verapamil gel applied twice a day to the entire shaft for at 

least 3 months in only 5 patients and patients were instructed to leave the gel 

on for a minimum of 4 has prior to removal. Verapamil intralesional (No 

FDA approval) injections were administered in the form of once 

percutanously intraplaque injections of 10 mg verapamil every two weeks up 

to 6 injections (Levine, 1997) in 9 patients. 

Surgical treatment, were applied for 9 patients in this study including 7 

patients who failed both oral and intralesional injections and in 2 patients in 

whom they request surgical treatment from start and in whom severe erectile 

difficulty were reported. Surgical treatment in the form of Nesbit plication 

were applied to 4 patients, Surgical grafts alone were used in 2 I 

patients 

patients with multiple penile curvature, we used a combination of Nesbit 

plication and Surgical graft, we used SIS (Small Intestinal Submucosal) graft 

for covering the incised penile plaque and we implanted 3 piece inflatable 

700 AMS CXM in 1 patient upon his request. 

Technique of Verapamil intralesional injection 

1- While the patient was in supine position ,using 25 gauge needle 9 

we 

n. 

2 

inject 

10 cc of infiltrating anesthesia at the penile base i.e. we used a combination 

of long and short acting local anesthetic agents , 5 cc of 1 

0mg/ 

mi 

of 1 % 

H 

lidocaine + 5 cc Bupivacaine m5 

2-After 5 min. we start to inject 10 mg of verapamil 2.5 mg /ml at the plaque 

UL 

site, approximately 8-10 plaque punctures were performed at each setting 

3-We apply penile compression for 3-5 min. after injection 

g/ 

ml 

(136


Treatment response; Three questions were directed to all patients to 

determine, how pain, ED, and curvature response to treatment, overall 

satisfaction and side effects. 

Priapism patients group 

ultrasonography 

From our 459 total population group, 20 (4.4 ) patients with a mean age 

37.years (range from 22-66) presented with a history and finding of low 

flow priapism. Factors assessed were the duration of priapism, history of 

previous intermittent attacks, possible underlying causes (e.g. hematological 

disorders, medications or trauma), relation to sexual stimulation, presence or 

absence of pain, and any attempt at previous management. A complete blood 

screen and blood gases were assessed in corporal aspirates. Duplex 

was used in 8 impotent patients at their follow-up. Early 

and late complications were reviewed, and patients asked about their erectile 

function before priapism, and history of any recurrence. 

The median duration of priapism was 48 Hs (mean 4-240 Hs) ;presentation 

with priapism was delayed in 8 patients (>48 Hs );the threshold of 48 Hs 

was chosen because it was the median and because the irreversible 

ultrastructural changes would then already be established , 6 within 24-48 

Hs from injection of vasoactive agents, 3 men presented within 4-10 Hs and 

were reported a history of previous recurrence attacks of priapism and were 

reported a history of sickle cell disease ,of which 2 were reported a history 

of previous treatments in the form of distal and proximal shunt ,3 patients 

were presented within 2 Hs from the onset of the priapism. 

Two patients in this group gave a positive history of medication, 1 men 

developed priapism after taken a h 

igh 

dose of Nitroglycerine and the second 

137


one after high dose of trazodone therapy. For the 6 men who were 

presented after ICI, 3 were presented after ICI injection in our office and 3 

were referred to us from other centers. 

All patients were initially treated by the first line-therapy consisted of 

corporal blood aspiration, irrigation and injection of phenylephrine, 

with 

independently upon time of presentation 

Doses and administration of p 

henylephrine 

For ICI of phenylephrine in adult patients we followed the following steps 

1-phenyl ephrine was diluted in normal saline 0.9 %, we added 9 cm of 

normal saline to each ampoule of 10 m 

volume 10 cc with a concentration 1000 m 

cg/ 

ml 

g/ 

m1 

phenylephrine to got a total 

of phenylephrine 

2-we started by injection of I ml every 5 minutes for approximately 60 min. 

before deciding treatments failure 

Initial therapy was considered successful if there is no recurrence of 

priapism within the first 24 hours after the treatments and treatments failure 

were considered if there was no resolution after 60 min. of injection. 

For patients with sickle cell, additional treatments in the form of adequate 

hydration and Alkalinization were added to the initial therapy and; if this 

failed or if the priapism was prolonged various shunts were used. 

Penile prostheses were provided for 4 patients, 1 with sickle cell disease, 3 

transglanular 

refractory priapism-induced ED. Corporoglanular shunts using 

Winter shunt using a gun biopsy device to create a multiple 

channels between the corpora and corpus spongiosum was done in 2 patients 

in whom bilateral Corpora cavemosa shunting were done later (24h), in I 

patient we did bilateral corpora cavemosa shunt only. Penile U/S and 

Dynamic infusion cavemosography were done in some patients after 

treatments 

138

Penile prostheses patients 


The indications for all penile prostheses surgery were severe ED failed more 

conservative treatments including ICI and VED, .Negative urine analysis 

and cultures obtained in all patients and Penile U/S were done in some 

patients, not only for diagnostic purpose, but also for medico-legal aspect. A 

written consent was obtained from all patients before surgery ,prior to the 

procedure the risks and benefits were discussed with the patient in detail 

including infection and malfunction of the procedure .All patients saw a 

video tape before and after the procedure showing how to use the device 

,particularly for those who had 3 piece penile implant surgery. 

-Anesthesia; general 

-Antibiotic; Intravenous gentamycin 80 mg and vancomycin 1 gm 

Were given to all patients immediately before the incision 

-For irrigation: Polymixon B 50.000 IU and Bacitracin 500.000 units were 

used for irrigations. 

-Scrubbing: Both doctors and incision must be scrubbed for at least 10 min. 

-Indwelling TM 16 French urethral Foley's catheter applied to all patients after 

scrubbing and while the patient was sleeping. 

-Penoscrotal incision provided for most of our patients in this study , 

combined penoscrotal and suprapubic incisions applied only when there 

were difficulty to put the reservoir from the penoscrotal incision ,previous 

abdominal surgery that interfere with reservoir position, or/and to get the 

reservoir out in ex-plant surgery. 

139

New technique 


To avoid implants infection intraoperatively and decrease the risk of 

postoperative infection , we developed a new technique in the process of 

implants surgery called "pressure irrigation technique "; we used a special 

battery machine connected to one end with a 3.000 cc of normal saline 0.9 % 

irrigation bag to which we added 2 ampoules of Kanamycin and to the other 

end with a plastic tube for irrigation and suction , this machine was used as 

a pressure irrigation and suction at the same time ,the total time for this 

techniques was 20 minutes and used immediately after closure of the 

corporotomies and positioning of the pump . 

We left a post-operative drain in all patients who underwent 3 piece penile 

implants, ex-plant implant surgery, when Mulcahy salvage procedure was 

used and/or intraoperative bleeding, we don't use drains in patients who 

underwent 2 piece AMS Ambicore or Duraphase penile implants. 

Both drains and Foley's catheter removed in the next day following surgery. 

Intravenous antibiotics continued for one day after surgery and oral 

antibiotics for one month to all patients 

Mulcahy salvage irrigation (Implant Ex -Plant Surgery) 

The Mulcahy salvage irrigation was performed as follow; 

1-First irrigating the entire wound with approximately 500 cc of kanamycin 

antibiotic fluid. This was used to irrigate the pump site and the reservoir site 

as well as the corporal body extensively 

2- Next, half-strength hydrogen peroxide was utilized to irrigate in the same 

fashion, 

3-Full-strength betadine was utilized to irrigate. 

140


4-Next full-strength betadine was utilized a second time ;and then by 

reversing the previous order, half-strength hydrogen peroxide and then 

kanamycin irrigation solution were utilized once again. 

5-After Mulcahy salvage, all operative instruments, dressing, all solutions, 

syringes, gloves, urethral catheter and other instruments in the previous 

operative field should be discarded away from the field and all surgeons and 

nurse should be scrubbed again before starting the next procedure 

Penile prostheses surgery used in 43 patients (10.5 %) in this study. 

Mulcahy salvage was done in 3 cases, 1 presented with urethral erosion after 

2 week from the implant, we removed the 3 piece 700 A 

MS 

and we 

implanted 2 piece 700 Ambicore, 1 with aneurismal formation in the lt.sided 

cylinder, and the third one was status a few weeks post implantation of AMS 

700 CXM 3 piece inflatable penile prosthesis for Peyrone's disease and ED, 

the patients presented with complains of extrusion of the prosthesis through 

the urethra. 

Erectile Dysfunction and Premature (PE) ejaculation group 

From a total 459 population group in this study , seventy three (15.9 %) 

patients presented with symptoms of ED and secondary premature 

ejaculation of more than 6 months duration ,all had a secondary PE, we 

excluded all cases with primary ( long life ) PE ,we didn't have premature 

ejaculation questionnaires for this study and our diagnosis were completely 

dependant upon 

a-A basic medical history, including use of prescribed and recreational drugs 

B-Developmental history of the disorder, including whether the RE is global 

or situational, lifelong or recent in its development, 

141,


C-Detailed about the ejaculatory response, including the patient's subjective 

assessment of his intravaginal latency time 

d-The partner's assessment of the situation, included whether the partner 

suffers from female sexual dysfunction. Of these 73 men, 7 patients 

presented with PE secondary to using alpha blocker Alfuzosin and /or 

Tamsulusin (Uroxatral and Flomax ) ) , 10 patients reported history of anti 

depression medication ,10 patients gave positive history p 

of 

anxiety as diagnosed by our psychotherapists ,there is no obvious cause for 

the rest of the patients . All patients were referred to the psychotherapist to 

provide management. 

With follow up of their medical records, all patients were provided the 

following treatment 

1 -Non medical trial (treatments of the penis) 

Provided for all patients during the first visit after interview with a 

psychotherapist .All patients were provided a video tape showing the 

technique. 

Treatment of the patients penises was in the form of stop-start technique, 

squeezing technique, and Quit Vagina technique .All these kinds of 

treatments were demonstrated by video tapes and explained to all by our 

psychotherapists in a special will equipped room. 

2- Medical therapy options provided for our patients in this series was 

listed in table (8) 

erfoimance 

142

EMLA 

Table (8) shows the S 

SRIs, 


trade names, doses and patients numbers 

SSRIs Trade names No. Dose of drugs used 

Fluoxetine P 

Paroxetine P 

rozac_, 

axil 

Sertraline Zoloft 13/73 

2- Topical therapies 

Sarafem 33/73 20 Mg/day 

22/73 20 Mg/day 

25-200 M 

g/ 

day 

and /or 50 

mg 4-8 hrs pre-intercourse 

Topical anesthetic agents in the form of Lidocaine/prilocaine cream 

) was used in 7, Lidocaine cream 2.5% in 9 and prilocaine 2.5% in 

5 patients , 20-30 min. preintercourse After topical application, all patients 

were instructed to used these agents either with or without a condom., and 

the penis should be washed clean of any residual active compound before 

the intercourse to avoid diffusion of residual cream to vaginal wall ,we 

excluded patients who were either allergic themselves to these local 

anesthetic or had partners who were allergic to any of these components. 

3-Sildenafil citrate 50-100 mg were prescribed to 21 patients in this series, 

in addition to SSRIs 

Response to treatment and instruments used were listed as seen in table 

(8): Shows the instruments, duration and patients numbers in 73 m3n 

Drug used instruments duration measure No 

Fluoxetine 

Paroxetine 

143

hypercholesteremia 

RESULTS 

1 

. 

20-29 

< 19 

❑ 30-39 

❑ 40-49 

o 50-59 

❑ 60-69 

• > 70 

Results 

Follow-up was obtained in 459 patients who entered the study from a total 

curvature, 

20 

1029 men. Mean age was 6 

1+ 

/ 

-9. 

6 

years and duration of erectile dysfunction 

was 4.1+1-3 year. The commonest age at presentation was seen in age group 

between 50-59 years ,see figure and table 9 ,while men with age

Table (9): Shows the ED presentation by age 

Grouping No% from total 

>19 ys 5 1.1% 

20-29 ys 15 3.3% 

30-39 ys 51 11.1% 

40-49 ys 105 22.9% 

50-59 ys 125 27.2% 

60-69 ys 88 19.2% 

>70 ys 70 15.2% 

T able (10): Shows the ED by etiology and/or Risk factors 

Smoking 278 60.5 % 

High cholesterol 197 43 % 

Hypertension 183 40 % 

Obesity 42 28 % 

Diabetes M. 96 21 % 

History of MI 65 14. % 

History of stroke 27 5.8 % 

Results 

145

Uistory 

of MI 

65 14. °A 

Li 

• Hypertension 

Diabetes M. 

❑ Smoking 

❑ History of stroke 

■ High cholesterol 

❑ Obesity 

■ History of MI 

Figure (10): Shows ED risks factors in our series 

Results 

Using SHIM score criteria, the prevalence of ED in our series were listed in 

table (11). 

Erectile dysfunction according to SHIM score No c 

Inability to achieve erection (severe ED ) 152 33.1 % 

Week erection (moderate Ell) 189 41.2 °A) 

MILD ED 118 25.7% 

yo 

146

( 

73/ 

459) 

. 

Low 

Table (11): , 

S'hows 

severity of ED presentation according to S 

The ED severity by age at presentation using SHIM score in this series was 

listed in table (11) and also ( 

fig. severity of ED increased in our 

series as patients age got more elder, with much more severe ED by age > 

70. 

11) 

. 

the 

Figure (11): Shows ED severity by patient's age at presentation 

Regarding to the overall presentation of men in this study, the commonest 

presentation was El) alone (280/459), followed by premature ejaculation 

sex drive (69/459), priapism (20/459) and Peyrone's disease 

in 17 men. See table (12) and fig (12). 

TIIM 

Re2, 

1< 

i.

Table (12): Shows the overall patients presentation in our series 

Results 

ED alone 280 61 % 

ED and rapid ejaculation (RE) 73 16 % 

ED and low libido 69 15 % 

Priapism 20 4.3 % 

Peyrone's disease 17 3.7% 

Overall 459 100 % 

300 

250 

200 — 

150 

100 — 

50 

0 

c 

a) 

c - 

o 

o 

C6 

73 

2 

0 

C 

w 

_. 

— 

o 

Co 

-5 

o 

0 

- 

a - 

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- 

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= 

0 

c 

15 

o 

o 

' a 

E 

n 

. 

= 

-. 

a 

E 

co 

› 

, 

0 a) 

sa 

Figure (12): Shows the prevalence of sexual dysfunction in our series 

2 

a 

) 

148

Results 

ejaculation ,7 with ED Peyrone's disease and 20 were presented with ED 

and low sex drive „all patients were w 

evaluated a self-administered 

abbreviate version of the International Index of Erectile Function (SHIM ) 

questionnaire and ADAM questionnaire before and at completion of therapy 

to assess etiology of erectile dysfunction, level of sexual function, libido, 

and response to therapy with sildenafil citrate. Erectile function was 

measured before and 3-6 months of therapy, with a successful outcome 

defined as a level of improvement in their SHIM score and overall 

satisfaction rate. 

Follow-up was obtained in 285 of the 300 patients who entered the study. 

Overall satisfaction with sildenafil citrate for the entire patients population 

was 174 out of 285 (61 %), of these patients SHIM score was improved as 

follow, from severe (o-7 ) to moderate in 35/87 ( 41 % ) men ,from moderate 

( 8-11) to mild in 70/113 ( 62 %) and 69 / 85 ( 81 % ) men showed SHIM 

scores above 21.Response to prior therapies did not affect satisfaction. 

There was a significant positive correlation between baseline sexual function 

and response to sildenafil citrate, see Fig (13) but even patients with severe 

erectile dysfunction had a 41% satisfaction rate. 

Etiology of erectile dysfunction had a significant impact on satisfaction rate, 

with neurogenic causes of erectile dysfunction (diabetes, prostate surgery 

and so forth) having significantly lower rates than psychogenic or 

vasculogenic ED. 

it! 

, 

150

Table (14): Shows patients improvements and/or satisfaction. after s 

citrate using SHIM Score ( 

SHIM No =pre 

100% 

20% 

80% - 

60% 

treatment 

40% — 

0% 

svere 

no— 

number) 

No =post 

treatment 

No 

improved 

moderate mild 

ildenafil 

0 

Results 

Overall Satisfaction 

SEVERE 87 52 35 41 % 

MODERATE 113 43 70 62 % 

MILD 85 16 69 81 % 

OVERALL 285 111 (38.3 

% 

) 

174 (61 % 

) 

61.3 % 

❑ improved 

▪ after 

before 

Figure (13): shows improvement in erectile quality and/or satisfaction using SHIM 

questionnaire in patients before and after s 

ildenafil 

citrate therapy. 

151

RIGISCAN 

RESULTS 

From our total 459 patients' population, 53 (11.5 %) patients with a history 

that strongly suggesting psychogenic ED underwent a nocturnal penile 

tumescence and rigidity (Rigiscan) testing. Rigiscan results for these patients 

were as follow; see also t 

in 7, and abnormal in 24 

able< 

15) 

, 

normal Rigiscan finding in 22, borderline 

Table (15): Shows Rigiscan finding in 53 men with history suggesting of Psychogenic 

ED 

Rigiscan results No % 

Normal finding ( strongly suggesting 

psychogenic ED) 

22 41 .5 % 

Borderline ( mild organic ED) 7 13.2 % 

Abnormal finding (strongly suggesting 

organic ) 

24 45.3 % 

Overall 53 100 % 

Borderline Rigiscan results in this study were applied for all cases with; 

A-Normal tumescence and rigidity in only one episode of erections 

B-Tumescence more than 2.5 but still less than 3 cm at the base and/or < 

the tip in most of erectile episodes 

C-Axial rigidity between 50-65 % 

2 at 

152

T 

rip 

tuna 

cm 

riv 

100 

15 

5 

100 

4 

A 

S 

E 15 • 

tuna 

' 

S 

t 

SEa'rt 

• 

- . 

Results 

D-If the diagnosis of psychogenic ED was unclear after repeating the 

Rigiscan 

RigiScan 

Plus Session Graph 

Data for Session 2 

M 

Sampling Nocturnal 

Session Date: 12/17/2002 

Figure (14 ):Shows the Rigiscan finding in patients presented by history highly suggested 

of psychogenic ED ,penile Doppler ultrasonography support the same clinical diagnosis , 

in the above figure ,you can see the very long period of sustained erection more than 2 

hours erection with > 70 % rigidity at both tip and base ,tumescence also increase from 

baseline 4 and 5 cm at tip and base respectively to 7 and 8 cm during erectile episodes . 

ode: 

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Figure (15): Shows the Rigiscan finding in man with psychogenic ED; see normal penile 

rigidity, tumescence and frequency on both tip and base. 

hVt•: 

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Results 

Figure 16): Shows abnormal Rigiscan finding, abnormal rigidity, tumescence and time of 

erection 

Of these 53 men, 38 had penile Doppler ultrasound done after 

Intracavernosal injection of a pharmacological agent together with 

Rigiscan testing , abnormal Rigiscan finding (finding suggesting organic 

ED )were detected in 12/38 (31.6 % ) 

, 

• 

'tir 

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borderline results in 7/38 and normal 

Rigiscan finding were found in 50 % of patients ( 19/38 ) , Abnormal 

ultrasound finding were detected in 27/38 ( 71.1 % ) men and 11 ( 28.9 % ) 

men showed normal ultrasonic finding . Of the 27 patients with abnormal 

duplex ultrasound , only 5 had evidence strongly suggest of psychogenic 

impotence on Rigiscan finding and 6 had borderline and 16 had evidence 

• 

- 

: 

. 

155

of organic disease see table (17) . Of t 

hese, 

Results 

11 patients who had a normal 

duplex ultrasound finding (maximum velocity greater than 30 cm. per 

second), 7 of these patients had a normal nocturnal penile tumescence test, 1 

had borderline and 3 had abnormal finding. Based on this study 5 of 27 men 

with abnormal penile U/S had normal nocturnal penile tumescence test and 

other evidence of psychogenic impotence and 22 of 27 men with abnormal 

U/S had abnormal Rigiscan finding, see table (16). Therefore, an abnormal 

duplex ultrasound study should be interpreted cautiously if there is evidence 

of psychogenic impotence. In men with vasculogenic impotence there is an 

excellent correlation and cross-validation between maximum velocity on 

duplex ultrasound, and axial rigidity and on nocturnal penile tumescence. 

Table (16): Shows the correlation between Rigiscan and U/S finding in 38 men 

Diagnosis Rigiscan Ultrasound 

Psychogenic ED 12 /38 (31.6%) 11/38 (28.9 % ) 

Borderline and/or 

Mild organic 

7/38 (18.4 %) 3/38 (7.9 % ) 

Organic ED 19/38 ( 50 % ) 24 /38 ( 63.2 %) 

Overall 100 % 100 % 

Comparing the Rigiscan, buckle and penile ultrasonic finding in the 

diagnostic outcome of 38 men ,positive buckle were detected in 10 out of 11 

( 90.9 % ) men diagnosed as psychogenic ED using penile U/S and negative 

buckle in 5 out of 8 ( 62 % ) diagnosed as venogenic ED and 11 out of 16 ( 

68.8 ) as arteriogenic ED ,see Table (18). 

156

Table (17): Shows the results of 3 diagnostic methods used in 38 men, 

Diagnosis Penile 

Non- 

vascular 

ED 

Venogenic 

ED 

Arteriogeni 

c ED 

Vasculogen 

is ED 

Mixed 

vasculogeni 

c 

u/s 

Rigiscan, buckles and penile U/S finding 

Normal 

NPT 

Borderlin 

e 

Rigiscan 

1 Rigiscan 

Abnorma 

Positive 

buckle 

Negativ 

e buckle 

Results. 

50-60 % 

buckle 

11 7 1 3 10 1 0 

8 3 2 3 2 5 1 

16 2 3 11 3 11 2 

2 0 0 2 0 1 1 

1 0 1 0 0 0 1 

Overall 38 12 7 19 15 18 5 

There was a positive correlation (P< 0.05) using Pearson correlation test 

between the results of ultrasound and the Rigiscan in diagnosis of ED. 

The sensitivity of Rigiscan was 81.5%, and the specificity was 64% in the 

diagnosis of organic ED cases (ultrasound was used as the gold standard 

test), this means that the ability of Rigiscan to detect positive cases was 

higher than its ability to exclude negative cases in comparison to penile 

ultrasound. 

157

While there was a highly positive ( 

correlation using Pearson 

correlation test between the result of the Buckle test and the Ultrasound in 

the diagnqsis of organic ED. 

The sensitivity of the Buckle test was 81.5% in the diagnosis of organic ED, 

while its specificity w 

as 

90.9%. This means that the ability of the Buckle test 

to detect positive cases was similar to Rigiscan, while its ability to exclude 

1-For 

negative cases was much h 

igher 

than the Rigiscan (90.9% Vs 64%). 

Duplex ultrasound is used commonly to evaluate vascular function in 

A-IG 

impotent men. The is evidence, however, that some men with normal 

vascular function may have falsely abnormal duplex ultrasound results 

because of suppression of r 

anxiety 

Results of ICI G 

VET d 

Respoq 

iagpmtktests 

r9qp 

esponse 

1 

3 

40. 

005) 

to pharmacological stimulation due to 

In the 47 patients in whom we did not do penile Ultrasound , the response to 

ICI was, as follow, see table ( 18) , Type 1 results were detected in 25 /47 ( 

53.2 % ) , type -2 in 12/47 ( 25.5 ) and type-3 response in 10 /47 ( 21.3 %) , 

Table (18): Shows the response to ICI (n=47) 

Response NO % 

Type — I 25 53.2 

Type-2 12 25.5 

Type 

- 3 

10 21.3 

Resulis 

158

1 

B-IC! 

- e 

arly 

Complications in both groups (47 +106 =153) 

Results 

local complications ; The most common complications seen in this 

group of ICI injection were as follow , 21 out of 153 ( 13 % ) men were 

reported pain at site of injection during the test ,see table (19), of these 13 ( 

62 % ) men were received prostaglandin El injection alone .prolonged 

erection (> 4 Hs) were seen in 3 men( 1.9 % 

injection of p 

henyl-ephrine 

) 

in this study in whom post- 

was not done .Priapism was detected in 3 

patients in this study ,2 of them were diagnosed as had psychogenic ED 

.and 1 was in the honey moon period , see table (19). 

Table (19): Shows the local complications after ICI (n=153) 

Complications Number % from total (153 ) 

Pain 21 (13 with P 

Hematoma 2 1.3 

Bleeding or/and ecchymosis 1 0.7 

Prolonged erection (

Fierq 

Wsppto 

it 

Thirty- nine p 

pr 

7): Shows the local c 

ICI I 

aiiëtd§ 

: 

With 

Nme 

- 

omplicatioti, 

F 

Therapy; 

PGE1 (Caverjet) the mean time of using P 

after 

ICI (n = 1 

0 pain 

hematoma 

❑ bleeding 

(echymosis 

❑ prolonged 

erection 

5. 

3 

ED, met the inclusion criteria for ICI therapy w 

GE1 

der{ 

) 

Results 

was 23.3 months (range 10- 

48 month)], were invited to a control examination to find out the long-term 

outcome of this treatment and to evaluate the patients' overall satisfaction 

with their sexual life. Overall, 53.85 % of the subjects were satisfied with 

RA 

home therapy (21/39). 18 (46.15%) of the patients had discontinued 

PGE 1 therapy, 11.1% of the patients reported that their own spontaneous 

erections had improved during the PGE 1 injection , 4 patients ( 22.4 %) 

reported complications ,one with priapism ,two reported penile plaques 

(cavernosal fibrosis )and 1 reported penile numbness and shortness 

For those who discontinued the treatment the reasons for this discontinuation 

were as follow, see table (20). 

ith 

160

1-improvement 

2-fneffectivness 

prection 

RouNOE 

One 

anxiety ( 

(20): Shows the ICI discontinuation by etiology (n=39) 

TOle 

Reasons ( why stopped ) Number t 

of spontaneous 

(lack of experience or 

Result. 

s. 

'A) 

2 11.1 

3 16.6 

3-Needle phobia 2 11.1 

4-Fear of complications 2 1 1.1 

5-As a result of complications 4 22.2 

6-Loss of sexual interest 0 0 

7-Loss of partner 1 5.5 

8-Shift to another therapy 4 22.4 

Total 18 46.15 

4. 

0 

111 

penile Doppler ultrasound group 

and sixty patients underwent penile Doppler ultrasound in t 

study from February 1999 to August 2004. All patients were from our 

P 

c 

E 

. 

w 

(27.3 %) had normal Dqppler study with of more 

than 28 and persistent reversal of and all achieved erection 

deemed for adequate vaginal penetration remaining 77 men 

of 

llie, 

in/ 

s 

t4ese 

diagnosed as organic E 

and PSV > 28 c 

29/ 

109 

m/ 

s 

p, 

py 

Of 

21/109 ( 19.8 % 

) h 

a 

the 

< 5 c 

m/ 

s 

SV 

4i§ 

hp 

after 15 min. 

(venogenic ED , and 36/109 ( 34 % ) had PSV

Results 

cm/s (arteriogenic ED) see table (21) , 20/109 ( 18.9 % ) had PSV. < 28 

cm/s and EDV < 5 cm/sec (mixed vasculogenic ED) ,see also f 

19 

iguA 

- : 

: 

18 and 

Table (21): Shows the diagnostic outcome using penile Doppler ultrasound (n=106) 

Erectile function No 

Non-vascular ED 29 27.30% 

Abnormal arteriogenic ED 36 34.00% 

Abnormal venogenic ED 21 19.80% 

Mixed vasculogenic ED 20 18.90% 

Overall 106 100% 

162

Figure (18): Shows the ultrasonic results in 106 men underwent to Doppler 

ultrasonic examination in this series. 

No 0 Normal Erectile 

function (no 

vascular disease ) 

■ Abnormal 

arteriogenic ED 

❑ Abnormal 

venogenic 

❑ Mixed ED 

ED 

Results 

o normal penile U/S 

▪ vasculogenic ED 

Figure (19): Shows the penile Doppler results in 106 men presented with ED, 77were 

diagnosed with vasculogenic ED and 2 

9men 

were diagnosed With non-vasculogenic ED 

163

Dr. Frederic J. Levine 

25-Feb-1983. M 

SAMUM. 

JASOH, 

RI 8. 4 

. 2 

1 

PSY: 

9, 

Left C 

avernosal 

Left C 

avernosal 

A/ 

s, 

SE3I1 

It 

RI 8. , 6 

PSV: e n 

ils, 

43I1: 

It 

' 

:1 38, T 

8. mel 

EEP/ 

: 

Ater 

D2, 

/ 

s, 

Artery 

86-61 

OA-Jul-2982 

dB, none 

15:23 

3. AA, 102. 89-61 dB., none 

O 

EDV: 1 5: 31 

. 

eCi/ 

s, 

es-Jul-2842 

RI . 

:1 S 

88, 

5 

O. 

NI 

PS 

) 

: 

1 

Left C 

avernosal 

Left C 

avernosal 

. 

6k/ 

s, 

Iss 

RI : 9. 98, 6 

PSV: 

O. 

6 

1n/ 

s, 

• 

811 

8I1 

Is , • 

: 

1 

EDV: 

. 79, T 

( 

8 

Artery 

D2, 

* 

kis, 

PA ' 

:1 . 89, T 

8. e 

EDV: 

Sn/ 

s, 

D2, 

Artery 

99-61 

81) 

-Ju1-2062 

' 

Jae-Jul-2 

138--61d13, 

CO-Jul-2082 

a, none 

1 5: 21 

' 

PA 

— 

none 

1 5: 3e 

— 

' 

— 

M 

— 

- - 

15136 

Results 

Figure (20): Shows Top Left, Lt. Cavernosal artery .disease with PSV 13 cm/sec. top 

RT, normal PSV (54 cm/sec), bottom Lt Mechanical errors, R 

Bottom 

cavernosal artery. With PSV 61 cm/sec 

t, 

normal 

— 

- 

- 

164

j 

r f - " 

:.1 

I. 

an. 

[ 

Lk 

: .1 

• 

• 

• r 

o 

I 

— 

ca. 

al 

D. 

cti 

1 + 

Llail 

A. 

a 

II :I . 

CON: 

a1 

' 

f 

Jt 

t 

J 

: 

41 

. 

e. 

a 7 

rpm 

P. 

% 

e 

-S 

1% 

. 

Ta7 . 

7/ 

Figure (21): Shows a 

) 

.r } 

LW" 

. 

-10 

r. 

1 

r 

- 

- 

C. - 

' • 

. 

7 

-I> 

- f _ 

1 

• 1 

r : ' 

trtir 1 

11911" 

. 

a. And 17 in the R 

rteriogenic 

t. 

Cavernosal 

1 1 

- 

ic" 

. 

. 

C. 

• 

7 

45117 

ti 

• 

. 

- 

NAN 

_ 

- 

H 

- 

▪ 

_ 

• I 

It 

C 

ap. 

m•rucasal 

P. 

- .11 h 

- 

e 

- 

•r 

I .I . T 

1 

tti 

. L 

-4 s 

Y 

K 

. 

S. 

a- 

r•-• 

I . 

- 

" 

1' 

111r 

- 

E 

o+ 

as 

a 

• 

'ffil! 

-I 

P, 

I 1r In 

•- 

I CL 

.P,.: . 

- 

. I } 

- 

, 

. 

. 

. 

. 

s 

f. 

• 

- 

a 

- 

Results 

and venogenic ED, PSV 23 c m / sec in Rthe 

a. EDV 13 cm/sec on the RT.and 19 cm/sec in the Lt 

Cavernosal a. 

t. 

oa 

nahaa. 

1 

- 

r■• 

1S 

YMtl 

5 

I : > 

be 

••• 

Cavernosal 

Using buckle criteria for diagnosis, 23 ( 79 % ) men out of 29 men (who 

diagnosed using ultrasound as non vasculogenic ED) were diagnosed as 

psychogenic ED , 27 /36 ( 75 % ) were diagnosed as buckle negative in 

arteriogenic ED men, 14/20 ( 70 % ) were diagnosed as buckle negative in 

venogenic ED men. in mixed (vasculogenic ED), 18/20 (90 %) were given 

negative buckle, See table 22. 

165 

• 

ZY

Results 

Table (22): Shows the Table distribution of the buckle response according to etiology of ED 

assessed by penile U/S in the study population (n =106) 

Diagnosis U/S Positive 

Non-vasculogenic 

ED 

buckle 

Buckle negative 50-60 

%BUCKLES 

29 23 (79.3 %) 2 ( 6.9 %) 4 ( 13.8 % ) 

Arteriogenic ED 36 6 (16.7 %) 27 (75 % 

) 

3 ( 8.3 % ) 

% 

Venogenic 20 4 (20 % ) 14 ( 70 ) 2 (10 % ) 

Mixed 

21 2 ( 8.5 ) 18 (85 .7 %) 1 ( 4.8 % ) 

vasculogenic 

There was a statistically significant (P

100.00% 

80.00% 

60.00% 

40.00% 

20.00% 

0.00% 

neagative 

buckle 

Results 

Figure (22): Histogram shows the percentage of etiologic categories of ED according to the 

penile Doppler results compared to positive buckle rating of erection :1=Non vasculogenic 

ED ,2=Arteriogenic ED ,3=Venogenic ED ,4= Mixed ED (n=106 men) 

1 2 3 4 

Figure (23 ):Shows the percentage of etiologic categories of ED according to the penile 

Doppler results compared to negative buckle rating of erections 

1 = 

Norma1, 

2= 

arteriogenic, 

3= 

venogenic 

, 4 =Mixed ED 

• 2 

• 3 

• 4 

167

So , negative buckle test diagnosed 27 ( 75 % 

penile U 

/ 

S 

) 

rnen 

out of 36 ( diagnosed by 

) as had arteriogenic organic disease ,and 14 ( 70 %) out 20 men ( 

diagnosed by penile U/S ) as had venogenic ED see again figure 23 . 

In these patients who had EDV < 5 cm/s and persistent inability to achieve 

erection we did cavernosogram in 3 patients prior penile prosthesis surgery, 

only 1 showed venous leak. 

Peyrone's disease patients 

In our patients population of 459 men, 17 (3.7 %) men with mean fellow—up 

period 36 months (range from 16-50 months), presented with complains and /or 

physical examination findings consistent with PD. All had ED .The prevalence 

of PD patients in our study was 17/459 ( 3.7 % ).The specific presenting 

complaint in this population was penile pain in 12 Patients ( 70.6 %) ,penile 

curvature in 1 

5. 

patients 

( 88 %) , a palpable penile plaque in all , and only 2 

( 11.8 %%) patients presented with Dupuytren's contracture in addition to 

penile plaque .The onset of disease was felt to be gradual in all patients ,2 

patients (11.8 % % ) attributed the onset of disease to a specific flaccid or erect 

penile trauma ,the trauma was described as an episode of pain during the 

reported activity. No patients had a history consistent with a full thickness 

tunica albuginea tear or penile fracture. Nine patients (52.9 %) reported normal 

erectile capacity (7 patients with aid of PDEIs), 10 Patients (58.8 %) reported 

pain with erections, of these 7 Patients reported that intercourse was possible, 3 

reported painful intercourse that compromised by penile deformity. 

On physical examination .all patients presented with a palpable penile plaque, 

15 patients presented with penile curvature (88 %).Of these 5/15 (33.3 %)) 

Resulis 

168

% 

) 

Results 

presented with lateral curvature, 8 (53.4 %).with dorsal curvature, and 2 (13.3 

with ventral curvature and 2 with mixed penile curvature. 

According to the modified Kelami classification, 5 men had Grade 1, 8 had 

Grade 11, and 4 had Grade 11 1. 

Response to treatments for Peyrone's patients 

Three men ( % 

17.6 ) reported some subjective improvement of pain related 

Peyronie, 5 ( 29.4 % ) men reported stabilization of condition and 9 ( 53 % ) 

(in whom surgery were indicated ) patients had subjective worsening of their 

erectile quality. Of the 9 patients treated with V 

substantial i 

mprovement, 

1 

erapamil 

injection , 2 had 

had complete resolution of their pain and.6 patients 

had no improvement at all ( improvement means no pain or feeling of softness 

of the plaque ).The mean fellow up for patients treated with oral therapy was 6 

week (range from 4-8 weeks ) ,for V 

erapamil 

injection , the mean fellow up 

was 12 weeks ( we used only 6 injections, once each 2 weeks ) . The four 

patients who treated with Surgical grafts ( 3 with SIS and 1 with Dermal graft ) 

reported reasonable response with no pain ,1 report mild penile curvature but it 

was able to get adequate erectile quality ,1 reported mild penile shortening (in 

whom we used both graft and Nesbit plication ), Nesbit plication was used as 

monotherapy ( no graft ) in 4 patients and in one patient we used SIS graft in 

addition to Nesbit., of these 4 patients ( Nesbit only ) 1 patients reported 

numbness in the immediate post operative period ( this patient had extensive 

dorsal penile plaque that need extensive dissection of the dorsal neurovascular 

bundle ) and resolve with time . All Nesbit p 

lication 

patients reported penile 

shortening from 0.5-2 cm after 18 months fellow —up, it was significant in only 

1 patient. No pain was reported in long-term fellow-up, and all were able to 

achieve intercourse without any subjective difficulty. In patient who received 

169

81% 

19% 

Results 

AMS 700 3 piece inflatable penile implant , he presented few weeks latter 

with post-implantation extrusion of the prosthesis with superadded infection ,in 

whom we do Mulcahy salvage and a Duraphase penile prosthesis was 

implanted with good response after 9 months fellow up. 

Results of ED and Hypogonadal (low sex drive) patients 

■ All 69 men had ED with an average SHIM score of 11±6. 

■ Using Beck inventory for depression only 19 % of patients with ED 

reported depressive symptoms, see fig (24). 

BECK positive for depressive symptoms n =69 

Figure (25): Show the prevalence of depression in 69 men with ED and low libido using 

BECK inventory for depression 

170

69 men 

CESD>16 

44% 

Figure (25): Shows prevalence of depressive symptoms among men with ED ( 

Using CES-D scores >16 for depression, 56 % of patients with ED were 

reported depressive symptoms, see fig (25) 

Regarding to the prevalence of h 

ypogonadism 

56% 

Results 

in our group, see also table (24), 

low T testosterone was noted in 13 /69 (19 %); low free T was 17 /64 (27%) 

and low % free was 11/ 66 (17 %).Low libido was noted in 97 % of men using 

ADAM questionnaire. The total numbers of men with hypogonadism are 26/69 

( 37.7 %), see Figgure 26 and table 23 

N-69) 

171

80 

70 

60 

50 

40 

30 

20 

10 

testosterone 

2 3 

I 1 FREE T %FREE T 

Results 

Figure (26): Shows prevalence of the hypogonadism using the TT, free T and % free T 

1= 

total, 

2-free, 3=% free testosterone (n=69 men) 

In this group ,serum PSA levels increased in 5 men ,prostate biopsy was 

positive in 2 out of them ( 2.9 % ) ,.liver function abnormalities in the form of 

abnormal liver enzymes were seen in 2 , 3 men showed low HCT and 2 

patients showed low HB level .we stopped T therapy in only 2 men who had 

positive prostate biopsy. 

172

Table (23): Shows prevalence of h 

Testosterone deficiency No 

ypogonadism 

11 

hypogonadism 

■ low libido 

Results 

among patients with low sexual drive 

% 

of hypogonadism in ED 

patients with low libido 

Total testosterone 13 /69 19 % 

Free T 17 / 64 27% 

% Free 11 / 66 17 % 

Total numbers of 

hypogonadal men 

Figure (27): Shows prevalence of h 

26 /69 37.7 % 

ypogonadism 

in men with low libido 

173

Results 

Regarding to treatments outcome of these group , out of 69 patients ,who 

received testosterone therapy ,see table (24), 32 men ( 46.4 %) showed a good 

response to T monotherapy therapy with no need for further medications , in 

the remaining 37 patients , 20 patients received sildenafil citrate ,good 

response was seen in 12 and 8 gave poor response to treatment ,3 patients 

received ICI therapy and showed a satisfactory response after 6 months of 

fellow up ,5 patients received a combination of sildenafil citrate and I 

CI 

,and 

in 3 patients penile implants surgery provided with good outcome ,finally 6 

men of these group received multi therapy . 

Table ((24): Shows the different treatment options given for men with low libido and ED 

(n=69) 

Type of therapy No O A 

Testosterone therapy alone 

(no more treatments 

needed.) 

Sildenafil citrate 50-100 

mg plus testosterone 

32 46.4 % 

20 28 % 

ICI plus testosterone 3 4 % 

Combined sildenafil and 

I CI plus testosterone 

5 7.2 % 

Penile prosthesis 3 4 % 

Multi-therapy 6 8.5 % 

174

These data support the concept that male ED must ' 

be 

broader scale evaluation of male sexual dysfunction .There is a significant 

Intracavemosal 

ncorporated 

Results 

into a 

prevalence of depressive symptoms, low libido and hypogonadism .ADAM 

score is sensitive, but not specific for hypogonadism 

Results of priapism patients 

All patients in this group had low flow pianism, no high-flow priapism was 

detected in our series .The median (range) duration of pianism was 48 (4- 

240) h and the main cause of priapism was, idiopathic in 9 men, after 

injection therapy in 6, 1 patient developed priapism after high 

dose of nitroglycerine (case report) and 1 after high dose of trazodone therapy 

See table (25) .Sickle cell-induced priapism diagnosed in 3 patients who 

presented with intermittent attacks of priapism. 

Table (25): Shows etiology of priapism (n=20) 

Cause of priapism Number % FROM TOTAL 

ICI 6 30 % 

Idiopathic 9 45 % 

Sickle cell disease 3 15 % 

Medication 2 7.5 % 

Initial therapy with aspiration, irrigation and phenylephrine injection was 

successful in 11 out of 20 % 

(55 patients, 3 of them presented within 2 Hs, 4 

out of 6 who presented within 24-48, 2 men after medication and two sickle cell 

) 

disease patients managed successfully as they presented shortly after their 

onset. 

175

Results 

Initial therapy failed in all cases presented after 48 Hs from the onset of 

priapism, and in 1 patient who presented within 24-48 Hs from onset of 

priapism. 

For the remaining 9 (45 % ) men who failed initial therapy, three pieces AMS 

CMX penile prosthesis was used in one who presented with refractory sickle 

cell-induced priapism, Proximal and distal bilateral c 

orporo-cavernosal 

shunts 

provided to 3out of 8 men who presented late after 48 Hs( 2 distal Winter 

shunts and 3 proximal corpora c 

avernosal 

shunts) .For the remaining 5 (5/8) 

patients ,Penile prostheses provided to 3 patients, two of them presented by 

refractory priapism -induced ED , in whom we putted a AMS Duna phase 

penile prosthesis in 1 and in the other two patients we implanted AMS CMX 

three piece inflatable in 1 and two piece AMS Ambicore in 1. 

In 2 patients we tried aspiration and irrigation together with injection of 

phenylephrine every 8 Hs, those men refused any kind of surgery including 

shunt procedures and then discharged with no more available information. 

In the long-term follow-up of 13 patients (mean 24.4 months) only 5 patients 

(38.5 %) reported preserved erectile function, and this was more likely in 

patients with brief priapism (< 48 h). The hospital stay was significantly 

shorter among patients with ICI papaverine-induced or brief priapism .Penile 

fibrosis was detected in 3 patients (2 treated with shunts surgery and 1 with 

initial therapy for sickle cell disease), and was significantly more common in 

those who presented with prolonged priapism or those who had treatment 

failure for priapism (after surgery).No reported cases of fibrosis detected in the 

ICI men who presented within 24-48 h. The impotent men evaluated by 

Doppler ultrasonography had severe echo-dense penile fibrosis and high end- 

176

Results 

diastolic velocities v 

suggesting incompetence. In 2 men with 

shunts, cavernosography showed extensive venous leakage irrespective of site 

of the shunt in 1 

patient. 

PENILE PROSTHESES PATIENTS 

eno-occlusive 

Forty three patients met the inclusions criteria for penile prosthesis surgery 

included in this study, the mean follow up in this group of patients were 24±4 

months. Non- treated 3 pieces inflatable penile prostheses provided to 19 

patients in this series ( A 

14 CXM and 5 AMS 700 Ultrex ) .The 

treated group , that is those who received a complete AMS 700 series prosthesis 

MS700 

with all InhibiZone components ,were used in 4 patients,2 piece inflatable 

InhibiZone 

penile prosthesis AMS Ambicore in 14 Patients , Semirigid Duraphase in 5 ,and 

alpha one mentor penile prosthesis used in only 2 .patients .see table (26).and 

fig .28. 

Table (26): Shows types of prostheses by treatment group 

Type of prosthesis used Number per-Cent 

3 piece inflatable 700 AMS 

CMX 

3 Piece inflatable 700 AMS 

Ultrex 

3 piece inflatable AMS 700 

2 piece inflatable AMS 

Ambicore 

14 32.5 % 

5 11.7 % 

3 

7 % 

14 32 .5 

Mentor alpha 1 2 4.6 

Semirigid mechanical Duraphase 5 1 1.7 

177

Results 

3 piece 

inflatable 700 

AMS CMX 

• 3 Piece 

inflatable 700 

AMS Ultrex 

❑ 3 piece 

inflatable AMS 

I 

700 

❑ 2 piece 

inflatable AMS 

Ambicore 

■ Mentor alpha 1 

nhibiZone 

Figure (28): Shows the different types of penile prostheses used 

Etiology by treatments group 

Malfunction of the penile prosthesis was the commonest etiology in our group 

followed by D.M and idiopathic ED.Refractory priapism was the etiology in 3 

,post prostatectomy in 3 

, 

postsystectomy 

in 1 „ in 1 case sickle cell priapism 

induced ED , see table (27) and fig (38) .malfunction of the device 2 ,

Table (27): Shows Etiology of ED by treatment group 

Etiology No Per-Cent 

Malfunctions 2 4.6 % 

Diabetes .M 5 11.6 % 

Hypertension 4 9.3 % 

Combined D.M and 

Hypertension 

6 14 % 

More than 2 risk factors 6 14 % 

Refractory Priapism 3 7 % 

Peyrone's disease 1 2.3 % 

Multiple sclerosis 1 2.3% 

Post-prostatectomy ED 3 7 % 

Post cystectomy 2 4.6 % 

Stroke 7 16.3 % 

Sickle cell disease 1 2.3 % 

Hypogonadal and ED 2 4.6 % 

Overall 43 100 % 

Results 

179

Results 

Paroxetine and/or Sertraline .We didn't do head to head study in this series to 

measure the response to SSRIs Jr the 21 men who received local anesthetic 

cream, only 9 gave a subjective improvements in their erectile quality with 

adequate vaginal penetration, 3 of them were reported mild penile numbness 

during and shortly after intercourse with no significant partner complaints . The 

instruments used, duration and response were listed in Table (29). 

Table (29): Shows response to treatment and instruments used were listed as 

fellow 

Drug used instruments Duration/month Response 

Fluoxetine Subjective and 

partner 

NO 

Total 

24 21 33 

Paroxetine Subjective 13 11 22 

Clomipramine Subjective 4 8 13 

Local anesthetic subjective 6 9 21 

182

DISCUSSION 

Discussion 

The new paradigm in the office diagnosis and treatment of male erectile 

dysfunction extends beyond pure erectile function. The evaluation now 

includes a discussion of ejaculation, libido, erectile function (including any 

cardiac risk factors), and depression. The evidence for this new paradigm 

comes from several sources. 

In 1999, Laumann et al reported (Laumann, 1999) on a large series of 

patients from the United States National Health and Social Life Survey. He 

assessed the prevalence and risk of experiencing sexual dysfunction across 

various social groups and examined the d 

eteiminants 

and health 

consequences of these disorders. He analyzed data from the National Health 

and Social Life Survey, a probability sample of 1749 women and 1410 men 

aged 18 to 59 years at the time of the survey a 1992 cohort of US adults. The 

main outcome measures were the risk of experiencing sexual dysfunction as 

well as negative concomitant outcomes. He found that sexual dysfunction 

was more prevalent for women (43%) than men (31%) and was associated 

with various demographic characteristics, including age and educational 

attainment. Women of different racial groups demonstrated different patterns 

of sexual dysfunction. Differences among men were not as marked but 

generally consistent with women. Experience of sexual dysfunction was 

more likely among women and men with poor physical and emotional 

health. Moreover, sexual dysfunction was highly associated with negative 

experiences in sexual relationships and overall well-being. Premature 

ejaculation was the most common male sexual dysfunction. Decreased libido 

and male erectile dysfunction were less common. The results indicated that 

183

Discussion 

sexual dysfunction was an important public health concern, and emotional 

problems likely contributed to the experience of these problems. 

The Massachusetts Male Aging Study, asked men between the ages of 40 to 

70 years to categorize their erectile function as either completely, 

moderately, minimally or not impotent. Fifty-two percent of the sample 

reported some degree of erectile dysfunction. This study demonstrated that 

erectile dysfunction is an age dependent disorder; "between the ages of 40 

-70 years the probability of complete impotence tripled from 5.1% to 15%, 

moderate impotence doubled from 17 to 34% while the probability of 

minimal impotence remained constant at 17%." By age 70, only 32% 

portrayed themselves as free of erectile dysfunction. Finally, cigarette 

smoking increased the probability of total erectile dysfunction in men with 

treated heart disease, hypertension or untreated arthritis. 

It similarly increased the probability for men on cardiac, antihypertensive or 

vasodilator medications. 

In our series , the severity of ED by age at presentation was increased as 

patients' age got more elder, with much more severe ED by age > 70 and 

age > 19 yr ,this results are comparable with the data obtained from MMAS 

study ,inspite of our limited number of patients population. 

In our series also, 33.l% of our patients were presented with complete 

(severe) ED, 42.2 % with moderate ED, and finally mild ED was diagnosed 

in 25.7 % regardless to the age at presentation. 

184

Discussion 

Kinsey et al were the first to report on the prevalence of sexual dysfunction. 

Data from this study of Kinsey revealed an increasing rate of ED with age 

.Based on interviews with 1.2000 men stratified for age, occupation and 

education, Kinsey reported the prevalence of ED as < 1 % in men under 19 

yr of age, 3 % under age 40, 7 % under 55, and 25 % 

by 7 

age 

Kinsey data was subsequently reanalyzed by Gebhard who found that 42 % 

of more than 5000 men interviewed had some degree of ED ( 

Johnson 1972). 

In our series the prevalence of ED among patients was increased with age 

from 1.1 % at 19 , 3.3 % at 20-29 yr,11.1 % at 30-39 , 22.2 % at 40-49 , 

27.2 % at age 50-59 ,then the presentation curve declined again from 19.2 

% at age 60-69 to 15.2 % at age > 70 Y. comparing our data with Kinsey 

data base ,our data were found to be comparable to this results obtained by 

Kinsey up to the age of 60 yr . 

Several other studies based on general populations are weakened by either 

sampling bias or inability to quantify the methods of data collection (Spector 

and Carey 1990). The results are widely variable and of questionable 

significance .Ard reported a 3 % incidence of ED among 161 couples 

married for more than 20 yr (Ard 1977). Frank reported that % 

40 of men 

married and sexually active with mean age 37 yr, had problems with either 

erection or ejaculation (Frank et al 1 

987) 

. 

Erectile 

0. 

Interstindy 

Gebhard 

and 

impairment in other 

studies range widely from 3 % to 40 % (Spector and l 

Carey 990).Morley 

reported that more than one-fourth of men aged 50 yr undergoing general 

health screening for ED (Morley 1988) .The relation between vascular 

disease and ED is well established. 

185

Both arterial insufficiency and c 

orporo-venoocclusive 

Junemann 

Discussion 

dysfunction (venous 

( 

1 

leak) are common causes of ED et al with a 

history of heart attack, peripheral vascular disease, and hypertension all have 

a higher incidence of ED when compared to general population. Myocardial 

infarction (MI) and coronary artery bypass surgery have been associated 

with ED in 657-64 %of patients (Wabrek and Burchell 1980).the incidence 

of MI in patients with ED is 12 % and 1 in 10 men with untreated 

hypertension have erectile difficulty (Oaks and Moyer 1972). 

Diabetes (DM) is also associated with a higher incidence of ED at all ages 

when compared to general populations. With its association 

microvasculopathy, between 35 % 

- 7 

5 

990) 

. 

Patients 

% of all men with DM experience ED 

(Oaks and 1 

Moyer fact 12 % of newly diagnosed diabetics have ED 

(Whitehead and Klyde 1990). It has been shown that the probability of ED 

972) 

. 

In 

increases with each vascular risk factor a patient possesses, including 

cigarette smoking, elevated cholesterol, DM and hypertension (Shabsigh et 

al 1991). 

In our study, in addition to age, the other risk factors among patients who 

diagnosed with ED were as follow, the prevalence of hypertension with or 

without treatment was 40 %, diabetes 21 % 

, hypercholesteremia with or 

without hyperlipidemia % 

43 heart disease in the form of stroke in 5 % and 

, 

myocardial infarction (MI) in 14 % of cases diagnosed with ED. 

In the MMAS, after the data were adjusted for age, men treated for diabetes 

(28%), heart disease (39%) and hypertension (15%) had significantly higher 

probabilities for erectile dysfunction than the sample as a whole (9.6%). 

Men with untreated ulcer (18%), arthritis (15%) and allergy (12%) were also 

significantly more likely to develop erectile dysfunction. 

186

Discussion 

Depression is another dimension that must be examined in she male, in that 

depression has a negative effect on male sexual function. Depression is 

associated with erectile dysfunction and perhaps low libido (Shabsigh et al 

1998) increased incidence of depressive symptoms in men with erectile 

dysfunction .Shabsigh et al Found that depressive symptoms were reported 

by 54% of men with ED alone vs. 21 % of men with BPH alone. Patients 

with ED were 2.6 times more likely to report depressive symptoms than men 

with BPH alone. Additionally, patients with depressive symptoms reported 

lower libido than other patients. They concluded that ED was associated 

with high incidence of depressive symptoms, regardless of age, marital 

status, or comorbidities. Patients with ED have a decreased libido compared 

with control subjects. In addition, patients with depressive symptoms have a 

lower libido than patients without depressive symptoms. Patients with ED 

and depressive symptoms are more likely to discontinue treatment for ED 

than other patients with ED. 

There is a clear association between depression and ED .Furthermore .it has 

been demonstrated that the successful treatment of the ED can significantly 

improved depression scale scores in men with ED and subsyndromal 

depression ((Shabsigh et al 1998). 

Thus, the new paradigm for male sexual function incorporates an evaluation 

of libido, depression, erectile function and ejaculation. 

The endocrine evaluation of male with ED is generally limited to the 

evaluation of a morning serum testosterone .The other, associated hormones, 

that are evaluated infrequently are serum Prolactin, and serum TSH. 

187

Discussion 

Historically, hypogonadism was thought to be a rare cause of male sexual 

dysfunction ( ED) .However , recent s 

data the significance 

prevalence of hypogonadism as men age and support a role of 

hypogonadism as a potential co-morbidity in ED .Moreover ,there is now 

recognition of the interrelationship between hypogonadism ,depression and 

male ED, underscoring the importance of the endocrine evaluation as a part 

of male sexual dysfunction evaluation paradigms ( Allen et al 2003) . 

In our study the prevalence of hypogonadism in patients presented with a 

low libido ( low sexual drive ) was 19% using TT < 300 n 

uppoit 

g/ 

dl 

( 2.8 % 

from total patients presented with erectile dysfunction ),27 % using 

bioavailable ( free ) testosterone and 17 % using percent free testosterone 

The reported incidence of endocrinopathy as etiology of ED is 1 % to 35 % 

( 

NTH 

Consensus Conference 1 

993) 

. 

Interestingly 

the incidence of low serum 

testosterone among men with ED is relatively small (6.6 %) ( 11 Mulligan 

et al 1988 ) .Most other studies show that ED has a clear association with 

aging, but no consistent correlation of total testosterone levels with ED had 

been identified ( Rhoden et al 2002 ) . The author's data suggest that 

testosterone level does play a role in sexual desire , frequency of nocturnal 

erections ,and frequency of intercourse ( Seftel 2003 ).Further , 

approximately 20 % of men complaining from sexual dysfunction have 

hypogonadism as measured by a subnormal serum testosterone level ( 

Manidouh 

et at 2003 ) .Shabsigh et al (2001) have shown a strong 

association of depression with male ED .In this study patients were screened 

for depressive symptoms using the Primary Care Evaluation of Mental 

Disorders and Beck Depression Inventory .Depressive symptoms were 

reported by Shabsigh in 26 ( 54 % ) of 48 men with ED alone ; 10 ( 56 % ) 

188

Discussion 

of 18 men with ED and BPH ; and 7 ( 21 % ) of 34 men with BPH alone . 

In our study, Depressive symptoms among men with L 

D and low sex drive 

were 56 % using CES-D score >16 and 19 % using Beck inventory for 

depression score >14. 

It is generally agreed upon that NPTR monitoring is one of the best available 

methods to objectively differentiate between organic and psychogenic 

etiology of ED ((Manouz et al 1993).Data analysis of Rigiscan monitoring, 

however, may be difficult to interpret for practicing physicians. A visual 

review of results based on a graphic printout or an assessments of the single 

best erectile events over the monitoring sessions may be utilized .Several 

NPTR patterns which have been associated with ED,where identified by 

Kaneko and Bradley ( Kaneko and Bradley 1986). 

These include dissociation of rigidity between the base and tip of the penis 

,uncoupling between rigidity and tumescence , a shortened duration of 

rigidity ,low amplitude rigidity and no rigidity and tumescence .Sohn et al 

have identified a strong correlation between Rigiscan finding and severity of 

ED based on the definition of the best erections the erectile events with the 

highest rigidity and greatest tumescence (Sohn et al 1 

9930. 

Another 

approach 

has been to select the best night of erectile activity, which has the highest 

Rigiscan measures. Shabsigh et al (1988) compared Rigiscan monitoring 

in 50 men with ED to results obtained from the penile U/S with 

intracavernosal injection of vasoactive drugs .They found abnormal Rigiscan 

results in men with vasculogenic ED , but differentiation between arterial 

and venous causes was more readily detected by duplex u 

with injection of vasoactive agents .The study of Shabsigh also found that 

ltrasonography 

189

Rigiscan testing was more sensitive than duplex u 

ltrasonogaphy 

Discussion 

evaluation of neurogenic causes of ED (Shabsigh et al 19988).In contrast 

,Kirkeby (1988 )found that Rigiscan results were normal in 11 of 26 patients 

with known neurological disorders that affect ED .McMahon and T 

(1999) evaluated the predictive value of patients history and correlated 

Rigiscan finding with results of color duplex Doppler ultrasonography in a 

retrospective study of 207 patients with ED ,They concluded that normal 

Rigiscan finding correlated with normal peak systolic velocity (PSV) in 85 

% ,resistive index in 94 %,but did not exclude organic ED -16 % of patients 

with normal Rigiscan were found to have organic ED .Abnormal Rigiscan 

correlated with abnormal PSV ,RI and had 4 % low false-positive rate. 

Intracavemosal 

pharmacological erection testing has also been compared to 

Rigiscan in several studies. Allen and Brendler (1988) found that the 

response to ICI testing did not distinguish psychogenic from organic ED 

Although Rigiscan can evaluation provided an accurate prediction of ICI 

results; however, the reverse was not true .They suggest that Rigiscan testing 

be performed before ICI testing to avoid unnecessary and inappropriate 

treatment of psychogenic ED.As with ICI ,penile ultrasound proved to 

unreliable in men with a history of psychogenic ED (Allen et al 1994).In a 

study of 40 men Allen et al compared duplex ultrasound to Rigiscan testing 

and found that anxiety and increased sympathetic stimulation resulted in 

inaccurate responses to pharmacological stimulation and duplex ultrasound 

measurements. They suggested that, Rigiscan testing should be carried out 

for appropriate treatments recommendations in men suspected of having 

psychogenic cause of ED. 

ouma 

in 

190

Discussion 

In our study ,53 men were underwent to Rigiscan monitoring, tests , normal 

Rigiscan finding suggesting psychogenic ED were diagnosed in 41.5% 

(22/53) ,abnormal finding suggesting organic ED in 45.3 %( 24/53) ,and 

borderline finding (mild ED) in 13.2 % (7/53). 

In our study, we found that there was a positive correlation (P< 0.05) using 

Pearson correlation test between the results of ultrasound and the Rigiscan in 

diagnosis of ED in 38 men who underwent to both penile U/S and Rigiscan 

The sensitivity of Rigiscan was 81.5%, and the specificity was 64% in the 

diagnosis of organic ED cases (ultrasound was used as the gold standard 

test), this means that the ability of Rigiscan to detect positive cases was 

higher than its ability to exclude negative cases in comparison to penile 

ultrasound. 

While there was a highly positive correlation (P

Recently, PSV was found to be a more reliable p 

off value of PSV varies i - 

om 

f 

'arameter, 

Discussion 

the proposed cut — 

25 — 40 cm/s [Benson et al, (1993)]. The large 

range of values may be due to many different reasons such as anatomical 

variants [Jarow et al, (1993)] .as well as the timing and location of sampling. 

End Diastolic Velocity reflects the Intracavernosal pressure, Different EDV 

measurements (range c 

5-9 have been selected as the value above which 

the diagnosis of venous leak is made [Patel et al (1993)]. However it has 

m/ 

s) 

been observed that in some patients who have attained an EDV of c0 

only partial rigidity is achieved .On some reversal is only transient or 

observed unilaterally. In most normal individuals, the EDV is usually high 

early (5-10 or even up to 25 min. in some patients .On the other hand the 

PSV, usually occurred immediately at any time within the 5 min. after PGE1 

injection, but in some, this occur later at approximately 25 to 35 min.post 

injection [Chiou el al (1998)]. Venous leak should only be diagnosed late 

when there is persistently high EDV late in the examination (at 15 min. or 

later after injection). Another cause for wide variability in the velocity 

reading is the location of sampling .it is now generally preferred that, 

patients be sampled near the base of the penis. Studies has shown that 

reading are more accurate at this site .It is also to keep the Doppler angle at 

< 60 degree at this point. [Seung et al (1994)]. 

Penile Doppler ultrasonography is able to detect the presence of 

vasculogenic dysfunction and it is also able to differentiate between arterial 

compromise and v 

eno-occlusive 

incompetence. Criteria for penile Doppler 

study as originally described by Lue et al (1990) included cavernous artery 

PSV, cavernous artery dilation and visualization of arterial pulsation. 

m/ 

s, 

192

Discussion 

Penile Doppler ultrasound was done in 106' men in this study, non 

vasculogenic ED was diagnosed in 29/106, arteriogenic in 36/106, 

venogenic in 20/106 and mixed Arterio-venous ED in 21 patients. 

The availability of an effective on-demand oral agent has had a tremendous 

impact on the management of ED (Rosen et al., 1998). Since the release of 

sildenafil citrate millions of prescriptions have been written and the 

traditional pattern of care for ED has been altered. This stud millions of 

prescriptions has been written and the traditional pattern of care for ED has 

been altered. this stud of a relatively small , unselected heterogeneous 

patient population reveals that sildenafil citrate is effective clinical practice 

The overall rate of patient satisfaction was 65 % ,even in patients with sever 

degree of ED ( SHIM score < 7) , the satisfaction rate were 41 % .This data 

base is similar to the success rate for sildenafil citrate in clinical trials by 

Moreles ( Moreles et al 1998) . 

The efficacy of various sildenafil citrate doses ,including 25 mg ,50 mg, and 

100 mg ,in improving ED was demonstrating in more than 3000 patients in 

21 American and European randomized double-blind placebo-controlled 

phase 111 trials lasting up to 6 months. A variety of study designs , 

including fixed dose , dose titration ,parallel, and cross over design were 

applied .the primary efficacy end point were question 3 ( ability to achieve 

an erection ) and 4 (ability to maintain an erection )in the IIFF( Rosen et al 

1997), which reflected the NIH definition of ED { 

Conference ,Dec 1 

992) 

. 

sildenafil 

NIH 

Consensus 

produced significantly greater 

improvement in erectile function then placebo in all 21 studies. Ther was a 

significant improvements in both the ability attain an erection (question 3) 

and ability to maintain an erection (question 4 of IIEF ) as measured by the 

193

Discussion 

erectile function domains of the IIEF in two pivotal American 

studies {Goldstein et al 1998) .in the flexible-dose study 69 % (94/138) of 

the sildenafil group indicated that they achieved erections sufficient for 

vaginal penetration on most to all occasions compared to 23 % of placebo 

group {(32/138) ( Padma-Nathan et al 1998).Additionally ,62 % (85/132) of 

patients receiving sildenafil citrate indicated that they maintained their 

erections after penetration in most to all occasions compared to 16 % 

(22/132) of patients receiving placebo. Overall, 59 % (81/137) of patients 

treated with sildenafil reported that they were able to both achieve and 

maintain their erections on most to all their occasions compared to 15 % 

(21/138) of placebo-treated patients (Goldstein et al 1998).the results were 

consistent regardless of age ,race ,baseline severity ,and etiology of ED . 

The most important observation in our study was the correlation between the 

baseline sexual function and response to treatment. As expected patients 

with high SHIM score ( mild to moderate ED) shoed better response ( 65 

and 81 respectively ) than patients with low SHIM score or sever ED ( 41 % 

) .The main drawback of our study is that we didn't observe the correlation 

between response rate to sildenafil citrate based on etiology of ED . 

Oral sildenafil and V 

for the treatment of ED .Although s 

EDs 

are two commonly used noninvasive modalities 

ildenafil 

is currently the most widely 

used approach and has an excellent overall success rate (60% to 85 %, a 

sustained portion of patients continue to have inadequate response (NIH 

Consensus Conference 2003). similar to other treatment options, VEDs have 

a reported success rate of 65 % to 90 % but, like oral medication, a 

significant number of patients have inadequate response to VEDs. In this 

194

Discussion 

study VEDs were provided for only 4 patients with no satisfaction rate 3 of 

them discontinue the device within 1-3 months. 

The availability of sildenafil, (Goldstein 1998) an effective oral 

Phosphodiesterase type 5 inhibitors approved for the treatment of erectile 

dysfunction (ED), has tremendously increased both the number of patients 

seeking treatment and the number of physicians rendering such treatment. 

When oral therapy fails, is contraindicated, or results in side effects, 

alternate therapies are available. Approved second-line therapies include 

vacuum-constriction devices,( Levine et al 2001 ) along with I 

and intraurethral administration of alprostadil.( Porst 1996 ) Transcutaneous 

medications ( McVary 1999) and new oral medications ( Wagner 2001 ) 

are under active investigation. Arterial (Goldstein et al 1994) and/or venous 

(Wespes 1994) procedures are available for highly selected individuals. 

However, despite widespread enthusiasm for minimally invasive 

approaches, there are many men whose ED is refractory to such therapy? 

These men, not infrequently, elect penile prosthesis insertion. 

Intracorporeal self -injection therapy is the best second-line drug therapy 

after oral therapy in the new algorithm of ED treatment. Moreover, the 

confirmed efficacy makes it first-line therapy for those patients in whom oral 

therapy is contraindicated or those who failed oral treatment. Prostaglandin 

E-1 is the best documented, and only FDA-approved Injectable vasodilator 

.Off —label combinations of either papaverine or phentolamine (Bimix), or 

papaverine, phentolamine, and prostaglandin E-1 (Trimix) have also been 

used in clinical practice. 


195

Discussion 

A report on 210 patients treated with a Trimix combination of papaverine 

(22.5 mg) ,pnentolamine (0.83 mg ) , and p 

rostaglandin-E-1 

(8.3 ug) showed 

an adequate erectile response in 81 % of patients with a low incidence of 

adverse effect (3.5 % pain , 

1. 

7 % priapism and 4.2 % fibrotic scaring ) 

(Govier et al 1993).A comparative study reported on the Trimix of 

papaverine (17.6 mg ), phentolamine (o.58 mg), and prostaglandin E-1(5.8 

ug ) versus prostaglandin in patients who had previously failed treatments 

with Bimix (Bechara et al (1996).An erection adequate for intercourse was 

observed 50 % of the Trimix —treated patients ,compared to 22 %of those 

patients treated with prostaglandin E-1 alone .Patients treated with Trimix 

( 

cavernosal 

combinations also reported a lower incidence of pain (12.5 vs. 41%).In a 

recent study on 766 responder to a questionnaire individuals ,76.2 % used 

prostaglandin E-1 ,19.5 % used Bimix of papaverine a 

3.7 % used Trimix of prostaglandin E-1 / 

papaverine 

nd/ 

phentolamine 

and 

/phentoleamine.Fourty 

percent of patients dropped out within the first 6 months of treatment . The 

reasons for drop out were inadequate penile rigidity, expense of the 

treatment, penile discomfort, or lack of spontaneity. Overall, 80 % of 

subjects were satisfied with intracorporeal therapy. 

In our study 39 men with ED who failed oral medication were underwent to 

ICI home therapy , the mean time of using PGE1 having been 23.3 months 

(range 0-48 months). Overall , 64.86 % of the subjects were satisfied with 

ICI home therapy ( 53.85 % continue therapy + 11.1 % spontaneous 

recovery) , 46.15% (18/39) had discontinued PGE1 home therapy, 11.1% 

(2/18) of the patients reported that their own spontaneous erections had 

improved during the PGElinjection , 4 patients ( 22.4 %) discontinued due 

to complications [one with priapism ,two reported penile plaques 

fibrosis )and 1 reported penile numbness and shortness].Needle 

196

Discussion 

phobia and fear of complications were the cause of discontinuation in 4 

(22.4 %), ineffectiveness (lack of experience or anxiety during the injection ) 

were the main cause of discontinuation in 3 patients. four patients shift to 

other therapy and in one patient ,loss of partner was the cause of stopping 

the ICI. Comparing our data with the results mentioned before, our overall 

satisfaction (63.86 %) was much less than the satisfaction rate obtained in 

these study (80 %), the reason for this may be they used a large dose of the 

PGE 1 I addition to using the Trimix in most of their patients, in our study all 

patients used Coverjet as home ICI, we started in all patients with 10 ug 

Coverjet in with titration of dose up to 20 ug per injection. we considered 

ICI failed if no response to Coverjet 20 ug ,we did not do a head to head 

study comparing the Coverjet with Timix or Bimix in our series. 

Multiple-component inflatable penile prostheses (IPPs) provide adequate 

penile girth, length, and rigidity, while allowing flaccidity when not needed 

for sexual activity. A penile implant is the only ED treatment that allows a 

man to obtain and maintain a rigid erection at any time and for any length of 

time. They are not cumbersome like vacuum-constriction devices, and they 

avoid the penile/urethral discomfort and unpredictable response that often 

occurs with Injectable or transurethral medications. Despite these 

advantages, many patients are reluctant to choose an implant because of the 

surgical procedure and its attendant risks, including subsequent device 

malfunction. Currently available IPPs have greatly improved mechanical 

reliability compared to earlier models. (Montague and Angermeier 2001) 

Many series have reported overall mechanical reliability rates for these 

devices. 

197

Discussion 

Implanted inflatable penile prostheses have demonstrated the capacity to 

produce s 

uital: 

le 

penile erections and good patient's satisfaction in long-term 

fellow up .The reliability of implants is excellent and the postoperative 

morbidity is low. .Although mechanical malfunction is the most frequent 

complication associated with intrapenile implantations, it can usually be 

resolved easily and recent technological advances have made prostheses 

even more reliable .Infection continues to be the most dreaded complication 

associated with the prostheses. Infections is associated with implanted 

inflatable penile prostheses are the most disastrous complication of this 

common treatment for ED .Fishman et al considered that hematological 

infection is less common and they believed that bacterial biofilm may allow 

infection to be quiescent for years before clinical demonstration ( Fishman 

et al 1987) .They reported that 56 % of prosthesis infections occurred within 

7 months of implantation ,36 % occurred between 7 and 12 months ,and 

only 2.6 % occurred after 5 years. In this study the infection rate within 60 

days was 2.3 % (1/43) and the infection rate within 1-5 years was 4.6 % 

(2/43). 

The innovation in design and the materials used for a penile prosthesis has 

translated into increased longevity. However, a major concern for patients 

and surgeons remains is the prosthesis infection, which occurs in 1% to 3% 

of virgin cases and 10 % to 18% of revision cases. Both of the major 

manufacturers of penile prostheses in the United States have introduced 

products that aim to reduce the chance of prosthetic infection. 

In our series the infection occurred in 1 patient within the first 90 days from 

implantation (2.3 %) and in 2 patients within 12-24 months (2.6 %). For the 

rest of patients we have a long term fellow up 4 yr ( 1-65 months ) ,only one 

patients developed persistent post implantation pain who didn't improved by 

198

the ordinary pain medication and we r 

remove the p 

rol 

The AMS 700 CX implants are i 

esis 

- l 

wised 

but no overt infection was detected . 

mpregnated 

Discussion 

the device for infection ,we 

with Minocycline and Rifampin 

to target staphylococci, the most common pathogen in penile prosthesis 

infections. Data from revision cases from May 2001 to September 2003 for 

InhibiZone and non-InhibiZone prostheses were reviewed ( Carson C 2004 ) 

.From 8754 revision cases, with implant times of 4-28 months, 5310 

(60.7%) were non-InhibiZone and 3444 (39.3%) were InhibiZone revision 

implants. The infection rate of 2.41% with non-InhibiZone revision cases 

was reduced to 1.36% with the use of InhibiZone devices (44% decreases in 

infection rate). 

A log term multicenter study of the AMS 700 CM three-piece inflatable 

penile prosthesis reported that mean device mechanical reliability plus or 

minus standard deviation was 92.1 % ±3.3 % after 3 years and 86.2 ± 4.6 % 

after 5 years. Postoperative infection and device malfunction developed in 

3.2 % and 17.5% of the cases, respectively (Carson et al 2000). Of the 207 

men interviewed by a neutral observer, 86 % 

still had an A 

MS 

700 CX 

penile prosthesis implanted, including 87.1% with erection suitable for 

coitus (Carson et al 2000). 

In 1998, Duboq and Dhabuwala's group compared five different types of 

devices and reviewed mechanical complication rates in 83 patients with two 

pieces and 283 with patients with three-piece inflatable penile prostheses for 

a mean time of 66 months. All device-related complications were secondary 

to fluid leakage. They noted that a trend toward all three piece prostheses 

being more mechanically reliable than the two piece; the Mentor Alpha - 

device had a higher cumulative proportional survival (0.957) than all other 

devices. (Dubocq et al 1 

998) 

. 

Prosthesis 

erosion is often a sign of device 

1 

199

Discussion 

infection, but device extrusions beneath the penile skin may occurs as an 

isolated phenomenon. Erosions are more common among semirigid devices, 

and in those with distressed tissues and vascular supply, as may be seen in 

brittle diabetes or 'redo' implants. Erosions have also been described as 

complication of urethral catheterization. Erosion presented as a late 

complication several months after implantations in 80 % of patients with 

indwelling urethral catheters, or who were using intermittent catheterization 

and who had a penile prosthesis. The incidence of these complications may 

be reduced by using inflatable rather than semirigid prostheses and by 

construction of a perineal or suprapubic cystostomy. 

OF the 43 men who underwent to penile prosthesis surgery in our series 

, major mechanical malfunction of the penile prostheses ,that need removal 

of the implants with or without redo, was the most common complication 

and seen in 6 patients out of 43 ( 14 %) ,of these , 2 (4.6 %) presented by 

postoperative urethral erosion 2 weeks after surgery and the implants were 

removed [the cause of erosions was oversized penile implant in land 

superadded infection with catheterization in 1], 2 with pump leak, 1 

reservoir leak and cylinder aneurysm was detected in 1 patient with 

AMS700CX 

three-piece penile prosthesis. Minor complication in the form 

of Pump malposition was seen in 2 patients in whom there were no need to 

remove the implant and we did repositioning of the pump within the 

scrotum. Comparing our results with the above mentioned results .we found 

that our results regarding the mechanical failure of the prostheses were 

comparable with that obtained by Carson et al (2000), our mean follow up 

was 24 ± 4 months which may be explain a little bit our low incidence rate 

(14%) comparing to that study by Carson group (17 %), another explanation 

may be due to limitation of the number of our patients population. numbers. 

200

100. 

000person-years 

Priapism is a ► 

clatively 

Discussion 

uncommon medical condition that is defined as a 

pathological prolonged erection or engorgement of the penis or clitoris that 

is unrelated to sexual desire .The condition is more common in men and 

typically involves the paired corpora cavernosa. although rare exceptions 

with involvement of the corporus spongiosum (Taylor WN 1980). 

The incidence of the priapism in general population has been evaluated by 

Eland et al (Eland et al 2001).These investigators conducted a population — 

based retrospective cohort study using a longitudinal observational data base 

from the patients records of group of general practitioners in the 

Netherlands. They found an overall incidence rate of 1.5 per 100.000 

person-years. The incidence rate in men 40 years old and older was 2.9 per 

(Eland et al 2 

001) 

. 

The 

authors acknowledged that not 

all patients with priapism will seek medical care and the reported data may 

be an underestimation of the actual rate in the general population. The 

incidence of priapism in special "at-risk" subpopulations is much higher. At- 

risk populations include men with cocaine drug use, advanced pelvic or 

hematologic malignancy, and those on antipsychotic medications [Compton 

and Miller ( 

2001) 

. 

Pohl 

et al (1986)] evaluated various etiologies for 

priapism in a study of 230 single case reports in the literature: idiopathic 

causes comprised one-third of the cases while 21% were attributed to 

alcohol abuse or medications, 12% to perineal trauma, and 11% to sickle- 

cell anemia (SCA). 

In our series, the prevalence of priapism in men with ED was 4.3 % , 

idiopathic causes were seen in about 45 % ( 9/20 ) , ICI in 30 % (6/20) 

,medication in 20 % and sickle cell disease in 5 % ( 

comparable with data obtained by Pohl group . 

3/ 

20) 

. 

these 

results are 

201

epiF 

Discussion 

For individuals on ICI therapy for ED, the incidence range or priapism 

, K 

les 

is from 1 % for those on P 

GE1 

and as high as 17 % for patients 

who receive ICI with papaverine [Linet and Ogrinc (1996).The most likely 

cause of prolonged erection as a result of ICI therapy is overdosage . 

In our series ICI were seen as a main etiology in 30 % of patients presented 

with priapism 4 of them received papaverine ICI. 

Priapism associated with sickle-cell disease is classically described as 

ischemic, although rare exceptions of high flow priapism in association with 

sickle-cell disease have been reported. The pathophysiology of high-flow 

priapism in patients with sickle cell-disease is not known. Fowler et al 

(1991) evaluated the incidence and prevalence of priapism in sickle-cell 

condition .The authors reported frequent self-limited priapismic episodes, 

mostley occurring during sleep , that last less than 3 h..Priapism associated 

with associated with sickle cell was unusual before puberty and in keeping 

with previously reported 6 % prevalence of priapism in children with sickle- 

cell disease (Tarry et al 1987).A similar study from Jamaica documented a 

42 % prevalence of priapism in sickle-cell disease (Emond et al 1980). 

In our series the incidence of Sickle-cell induced priapism was 5 % (3/20). 

Priapism is an emergency, which should be treated within 24-48 h to avoid 

irreversible ultra structural changes as a result of stasis and cavernosal tissue 

ischemia [Spycher ET AL, 1986]. Such histopathological changes are 

responsible for the high incidence of ED complicating low-flow priapism 

[Bertram et al, 1085)]. However, about a third of the patients had idiopathic 

priapism. The response to treatment and the long-term (Spycher et al, 1986) 

outcome were better for ICI-induced priapism; this was expected, as these 

? 

Cr

Discussion 

patients were aware of the possibility of priapism and therefore presented 

early. The, priapism was reversed easily and complete detumescence 

achieved with I 


a-adrenergic agonists. 

The AFUD Panel highly recommended first-line treatments (aspiration and 

irrigation) for low flow priapism of more than 4 h duration before 

undertaking more invasive surgical shunts and further suggested that these 

therapies have not shown a benefit in preserving potency when priapism has 

persisted beyond 72 h. (Berger et al 2001). 

In our series initial therapy was successful in 11 men out of 20 in whom the 

presentation were early ( 48 h); the 

threshold of 48 h was chosen because it was the median and because 

irreversible ultrastructural changes would then already be established 

[Spycher et al, 1986)]. Using this threshold, the response to treatment, 

hospital stay, long-term complications of penile fibrosis and ED were all 

significantly better in patients with brief priapism. A number of different 

surgical shunts for diversion of blood away from The corpus cavernosum 

has been described .The consensus among authorities is that, in general, 

distal corporospongiosal shunts should be undertaken before proximal 

shunts, however, there is no consensus regarding the choice percutaneous 

versus open surgical shunts .The authors prefer to start with a transglanular 

Winter shunt (Corporoglanular) using a gun biopsy device to create a 

multiple channels between the corpora and corpus spongiosum (Winter 

1977). If this technique is not successful, a large communication between the

Discussion 

corpus spongiosum and corpora cavemosa may be created by a modified Al- 

Ghorab shunt in which the distal tunica albuginea of the c 

corpora 

is removed through a transglanular incision. Proximal shunts have been 

described by a number of authors and are recommended if these shunt fail 

and absences c 

avernosal 

artery flow is assessed by Doppler sonography 

(Berger 2001).in our series we did Winter shunts in 2 cases and both were 

failed and patients needed more proximal shunts 24 h from the procedures. 

A few authors have advocated early use of penile prostheses in cases of 

refractory or recurrence priapism associated with corporal fibrosis and 

ED(Sundaram et al 1997) .In our study we did penile prostheses surgery for 

4 cases of refractory priapism-induced ED, one of them due to recurrence 

sickle cell priapism. 

Multiple conservative therapies for the treatment of Peyrone's disease have 

been offered with variable and poor response rates .A pilot study ( 1994 

)showed preliminary promising resulting treating plaque caused by 

Peyrone's disease .Lee et al. ( 1994 ) demonstrated that intralesional 

injection of verapamil hydrochloride directly into the plaque markedly 

reduce its size. Levine et al. (1994) used verapamil to dissolve Peyrone's 

plaque and reporting promising results .Finding in our study suggest that 

verapamil either intralesional injection or local cream results in a significant 

subjective improvement of pain related Peyrone's with no significant change 

in the degree of penile curvature , patient who failed to responded to 

intralesional injection of verapamil or whose angulations more than 45 

degree at presentation should considered a candidate for surgery either 

Nesbit placation with or without graft . So the mainstay treatment for PD 

correction remains surgery and is reserved for patients who fail conservative 

avemosa 

204

Discussions 

treatment options. z 

Several are required before surgical intervention is 

considered, including severe penile curvature which prevents intercourse, 

riteria 

stable and unchanged disease for at least 3 months, and severe penile 

shortening. 

The surgical approaches can be divided into 3 main categories: shortening of 

the convex side of the tunica albuginea (plication procedures or 

corporoplasty), lengthening the concave side of the tunica albuginea 

(incision or excision of the plaque and graft placement), and penile 

prosthesis implantation. When patients with PD have both penile deformity 

and ED, penile prosthesis implantation with or without excision or incision 

of the tunica with graft replacement is the standard of care. H 

Reddy 2000) 

The three major forms of male sexual dysfunction are ejaculatory 

dysfunction, ED, and decreased libido (hypoactive sexual desire disorder). 

While survey findings vary considerably, most epidemiological studies 

suggest that premature ejaculation (PE) (also known as early ejaculation or 

rapid ejaculation) may be the most common male sexual disorders. Data 

from the National Health AND Social Life Survey have revealed a 

prevalence of 21 % in men ages 18 to 59 in united states .Using various 

definitions ,other studies report prevalence ranging from less than 5 % ( 2 )to 

greater than 30 % 

( 5 ) . In this study the prevalence rate of PE is 16 % ( 

73/459 ) ,we excluded all patients presented to our clinics with primary PE ( 

life-long PE ). 

The exact etiology of the PE is unknown, p 

biogenic etiologies have been reported Current treatments are largely based 

sychologicaUbehaviorist 

ellstrom 

and 

and 

205

Discussion 

upon logical solutions (decreasing sensory input), behavioral modification 

therapies and pharmacological intervention. The diagnosis of PE is based on 

sexual history alone; several important sexual and psychological 

characteristics should be assessed. 

Another priority assessment should be determining whether ED is a 

concurrent problem .Many patients with ED develop secondary PE, perhaps 

due to either the need to intense stimulation to attain and maintain an 

erection or due to the anxiety associated with difficulty in attaining and 

maintaining an erection..PE may be improve in parents when concomitant 

ED is effectively treated .In our study we provide sildenafil citrate 50-100 

mg to 21 patients with secondary PE (with ED), most of them showed a 

satisfied subjective improvements in their erectile quality after 

improvements of their ED .Therapy for PE most likely will be needed on a 

continuous basis .There is no clear consensus as to S 

whether will effect 

an eventual cure of PE, allowing for discontinuation of the medication, or 

whether SSRIs will be required for life. The panel members' experience is 

that PE usually returns upon discontinuing therapy. Waldinger et al (1998) 

performed a head-to-head study between Fluoxetine, fluvoxamine, 

Paroxetine and Sertraline in treating rapid ejaculation. He found that 

Paroxetine induced the longest delay in ejaculation, followed by Fluoxetine 

and Sertraline. No clinically significant delay in ejaculation was noted with 

fluvoxamine .in this series we didn't perform a head-to-head study between 

Fluoxetine, fluvoxamine, Paroxetine S, 

and Clomipramine in 

treating our patients with rapid ejaculation ,but , by looking to the patients 

charts ,we found that Paroxetine induced the longest delay in ejaculation 

according to the subjective response of the patients included in this series, 

ertraline 

SRIs 

206

Discussion 

followed by Fluoxetine and Sertraline.this data was similar to the data base 

reported by Waldinger et al (1998) who performed a head-to-head study 

between Fluoxetine, fluvoxamine, Paroxetine and Sertraline in treating rapid 

ejaculation and he found that Paroxetine induced the longest delay in 

ejaculation, followed by Fluoxetine and Sertraline. No clinically significant 

delay in ejaculation was noted with fluvoxamine. 

Finally, several new, emerging areas are of interest. The first entails 

combination therapy of oral PDE5 inhibitors and T supplementation. 

Shabsigh et al demonstrated a marked increase in sildenafil success, when 

sildenafil was combined with T replacement therapy in hypogonadal men 

who had failed sildenafil monotherapy (Shabsigh et al (2003). Another 

interesting concept is that of erectile restorative therapy after radical pelvic 

surgery in the male. Padma-Nathan el demonstrated that nightly sildenafil 

for 9 months restored spontaneous erections after radical prostatectomy in 

27% or men vs. 4% placebo [Padma-Nathan, et al (2003)]. Apomorphine 

used in conjunction with sildenafil did not cause any additive negative effect 

to that expected from sildenafil alone, in an animal trial .Thus, combination 

therapies appear to hold promise to restore erectile function for the these 

patients. 

207

SUMMARY AND CONCLUSION 

Conclusion 

This study carried out upon 459 men with mean age 61 ± 9.6 who attended 

the out patients clinic at Urology Dept, University Urologists of Cleveland, 

Case Western Reserve University and Urology Clinic at El-Minia University 

Hospital in the period from August 1999 to August 2004, all patients had ED 

and completed the following questionnaires (SHIM for ED, ADAM for low 

sex drive and/or hypogonadism, Beck and CES-D for detection of depressive 

symptoms in men with ED and low sex drive). 

During the first visit, medical and sexual history obtained from all patients, 

physical examination carried out for all men in the office during the first 

visit. 

Laboratory evaluations in the form of complete urine analysis and culture 

used in some patients, fasting and post-prandial blood sugar in all patients, 

total, free and % free testosterone, done in men with ED and/or lows sex 

drive with positive ADAM questionnaire. 

Serum PSA, CBC and liver function tests measured before and 3-6 months 

after T therapy. 

Prostate biopsy carried out in 5 patients who developed high serum PSA 

during the course of T therapy {diagnosed by PSAD > n 

0.75 

Endocrine evaluation completed in 20 men who had very low serum 

g/ 

ml 

per year.), 

testosterone, abnormal testicular finding and symptoms and signs suggesting 

endocrine a 

bnoimalities. 

208

Diagnostic Intracavernosal injection (ICI) test used in 47 men with E 

Conclusion 

situation, where penile U/S was not available or in patients who were unable 

to pay the cost of the test. 

Diagnostic Penile U/S used in 106 men, Rigiscan in 53; Dynamic Infusion 

Cavemosography used in 3 men for detection of venous leak 

In this series 280 men presented by ED alone, 69 men had ED and low sex 

drive, 73 presented with ED and secondary premature ejaculation (PE), 20 

men with low flow priapism and 17 men diagnosed with Peyrone's disease. 

Cigarette smoking detected in 287 men; D.M in 96, hypertension with or 

without medication in 183 and finally hypercholesteremia and/or 

hyperlipidemia i 

diagnosed men. 

In this series ICI test diagnosed 25/47 men with type 1 (no erection), type 

n197 

12/38 and only 10/47 men diagnosed as type 3 (good rigid erection). 

Rigiscan used in 53 men, normal finding suggesting psychogenic diagnosed 

in 22/53, borderline cases in 7/53 and finding suggesting organic ED detected 

in 24/53. 

Using Penile Doppler ultrasound criteria in 106 men in this study, non 

vasculogenic ED diagnosed in 29/106, arteriogenic in 36/106, venogenic in 

20/106 and mixed Arterio-venous ED in 21 patients. 

In this series 300 men received sildenafil citrate 50-100 mg based on patient 

self-directed treatment, 39 men received ICI home therapy, VED tried in 12 

men, penile prosthesis surgery used in 43 men. 

D. 

In 

209

Conclusion 

Sixty nine men presented by low sex drive and/or positive symptoms score 

for hypogonadism, low serum T testosterone diagnosed in 19 % of men, low 

free T in % 

27 and low % free T in 17 %. 

Depressive symptoms among men with ED and low sex drive detected in 56 

% using CES-D score > 

16 and 19 % using Beck score > 

Forty three men in this series received penile prosthesis surgery; we used 

inflatable penile prosthesis in 36 patients, Duraphase in 5, Mentor in 2 men. 

The main etiology for penile i 

implants our series was ED complicated 

cardiac strokes, DM, men with more than risk factors followed by 

mechanical malfunction of the prosthesis. 

Pump leak, m 

alposition 

n 

onA erosion through the urethra were the most 

common complications in our series followed by infection of the prosthesis. 

Seventy three men with ED and premature ejaculation included in this study, 

all had ED, trial of oral therapy applied for all men in this group in the f 

of oral SSRIs and Clomipramine, topical anesthetic agents used in 21 

patients. We didn't have any questionnaires to assess the efficacy of 

treatments in men with PE, in 21 men we added sildenafil citrate 50-100 mg 

to oral SSRIs therapy, We didn't do head to head study in this series to assess 

patient's response S 

to but from our short term follow up we noticed 

that men who received sildenafil citrate in combination with SSRIs and men 

SRIs, 

who received Fluoxetine showed a better subjective improvements in their 

erectile quality than men who received Paroxetine and/or Sertraline. 

Medical treatment in the form of Vit D and C 

olchicines 

14 

og 

in 

applied for all men 

with Peyrone's disease during the first visit, topical verapamil gel in 5 men 

210

Conclusion 

and 9 men received intralesional verapamil injection .surczical correction of 

the curvature used in 9 patients using either Nesbit plication or grafts 

For the 20 men who presented with low flow priapism, we did aspiration and 

irrigation of corpora cavernosa with normal saline followed by injection of 

sympathomimetics ( phenylephrine ) agent in all patients , initial therapy 

were successful in 11 out of 20 men, for the remaining 9 men ,we used 

penile prostheses in 4 ,whinter shunts and corpora c 

avernosa 

shunts in 3 and 

in 2 patients we tried aspiration and phenylephrine injection several times 

with no response and both failed the initial therapy and discharged with no 

more further information . 

On conclusion 

• Erectile dysfunction is age related disease with increased severity as 

advanced age. 

- C 

igarette 

Smoking, Hypertension, DM, and cardiac stroke represent major 

risk factors in ED patients 

• We found a significantly higher incidence of depressive symptoms among 

men with ED, with significant correlation between ED, low libido, 

hypogonadism and depression... 

- S 

HIM 

security 

questionnaire allows the clinician to assess male ED with great 

• The CES-D questionnaire for depression is more sensitive than Beck 

inventory for depression in detection depressive symptoms among men with 

ED 

"ADAM questionnaire is sensitive, but not specific for hypogonadism 

• Low serum testosterone levels assume an increasingly important role in the 

office evaluation and management of male sexual function 

211

Conclusion 

• Sildenafil citrate is a highly effective oral agent for the treatment of erectile 

dysfunction in clinical practice 

• The best predictors for response to sildenafil citrate therapy are baseline 

sexual function and etiology of erectile dysfunction. However, we could not 

identify any patient characteristic that would predict absolute failure for 

sildenafil citrate therapy. Therefore, all patients with erectile dysfunction 

who do not have specific contraindications should be considered for 

sildenafil citrate therapy. 

•The ability of Rigiscan to detect positive cases was higher than its ability to 

exclude negative cases of ED in comparison to penile ultrasound. 

• The ability of Buckle test to detect positive cases was similar to 

Rigiscan, while its ability to exclude negative cases was much higher than 

the Rigiscan. 

• Buckle test can be used for the diagnosis of vascular ED in situations where 

ultrasound is not an option because of economic or unavailability of the 

instrument. 

• Penile Doppler ultrasound study provides a relatively non-invasive, safe, 

and cost-effective means of assessing of ED. 

• Low-flow priapism is a medical emergency and must be treated as early as 

possible with initial therapy which, in our series, was very successful in cases 

presented early within 24 hr 

• No role for oral therapy in the treatment of men with low-flow priapism? 

• Failure to maintain a complete detumescence in men with priapism lead to 

marked penile fibrosis which is the most significant risk factor responsible 

for refractory priapism-induced erectile dysfunction 

'21'2

Conclusion 

•Upon our limited experience the best treatment for delayed priapism after 

48-72 is penile prosthesis surgery to refractory priapism and post treatments 

ED 

•Initial treatment for Peyrone's disease (PD) is conservative, utilizing 

expectant and medical management. 

•Surgical therapy for PD is reserved for men with severe penile deformity 

that impedes sexual intercourse 

n•I 

patients with rapid ejaculation secondary to or associated with ED, PE 

may be improve in parents when concomitant ED is effectively treated 

•A penile implant is the only ED treatment that allows a man to obtain and 

maintain a rigid erection at any time and for any length of time. 

• Finally, The paradigm of ED must be extended to incorporate into a broad 

scale evaluation to help in determination of associated sexual co-morbidities 

during office evaluation of sexual dysfunction. 

213

1114411111311111

Althof 

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Res, 48: 69. 

sychosom 

iherl 

ncol 

244

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1379. 

Published 

lthof 

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avemosum 

254

- 

Patient's Name 

No sexual 

activity 

Almost never 

or never 

0 I 1 

Did not attempt Almost never 

intercourse 

0 

or never 

Did not attempt Extremely 

intercourse difficult 

0 1 

SEXUAL HEALTH INVENTORY FOR MEN (SHIM) 

From the Office of : 

1 

A few 

ti mes (much 

less than 

half the time) 

2 

A few 

times (much 

less than 


2 

Very 

difficult 

2 

Sometimes 

(about half 

the time) 

3 

Sometimes 

(about half 

the time) 

the time) 

3 

Difficult 

difficult 

3 

Date of Evaluation 

Patient Instructions 

Sexual health is an important part of an individual's overall physical and emotional w 

Erectile dysfunction, also know as impotence, is one type of very common medical condition 

affecting sexual health. Fortunately, there are many different treatment options for erectile 

dysfunction. This questionnaire is designed to help you and your doctor identify if you may be 

experiencing erectile dysfunction. If you are, you may choose to discuss treatment options 

with your doctor. 

Each question has several possible responses. Circle the number of the response that best 

describes your own situation. Please be sure that you select one and only one response for 

each question. 

Over the past 6 months: 

1. How do you rate your confidence that you could get and keep an erection? 

0 

Very low 

1 

Low 

2 

Moderate 

3 

High 

4 

Most times 

'(much more 

than half 

the time) 

4 

Most times 

(much more 

than half ) 

4 

Slightly 

difficult 

4 

ell-being. 

Very high 

2. When you had erections with sexual stimulation, how often were your erections hard enough for 

3. During sexual intercourse, how often were you able to maintain your erection a 

tter 

5 

Almost 

always 

or always 

you had 

5 

Almost 

always 

or always 

4. During sexual intercourse, how difficult was it to maintain your erection to completion of Intercourse" 

5. When you attempt sexual intercourse, how often was it satisfactory for you? 

i n 

tercourse 

5 

Not 

difficult 

Did not attempt Almost never A few Sometimes Most times Almost 

1 or never times (much (about half (much more always 

less than the ti me than half 

or always 


the time) 

2 3 4 5 

5

Androgen Deficiency in Aging Men (ADAM) 

Questionnaire 

1. Do you have a decrease in libido (sex 1 

drive)? 

2. Do you have a lack of energy?p 

J yes I I no 

i yes L no 

3. Do you have a decrease in strength, endurance both?r 

or yes I 1 no 

4. Have you lost height? 1 yes ❑ no 

5. Have you noticed a decreased enjoyment of life? II yes n 

6. Are you sad, grumpy, or both? yes n no 

7. Are your erections strong? yes p 

8. Have you noted a recent deterioration in your ability to play sports? ( 

i 

1 

yes❑ 

9. Are you falling asleep after dinner? 1 yes[ 

10. Has there been a recent deterioration in your work performance? 1 

- 

1 

yes 

i 

o 

no 

no 

I no 

no

DEPRESSION INVENTORY 

Instructions for Questions: Below is a list of ways you might have felt or behaved. Please tell h 

me 

felt this way during the past week. Please CIRCLE ONE number for each item. 

Rarely C 

ome 

esw 

often y 

i 

u have 

Occasionally Most 

or Of a or a or 

none little moderate all 

of the of the amount of the 

time ti me the time time 

less than 

1 day 

1-2 

days 

3-4 

days 

1. I was bothered by things that usually don't 

bother me ....................................................... 

0 1 2 3 

2. I did not feel like eating; my appetite was 

poor................................................................... 

0 1 2 3 

3. I felt that I could not shake off the blues 

even with help from my family or friends 

0 1 2 3 

4. I felt that I was just as good as other 

people.............................................................. 

0 1 2 3 

5. I had trouble keeping my mind on what I 

was doing....................................................... 

0 1 2 3 

6. I felt depressed.............................................. 0 1 2 3 

7. I felt that everything I did was an effort ..... 0 1 2 3 

8. I felt hopeful about the future...................... 0 1 2 3 

9. I thought my life had been a failure ........... 0 1 2 3 

10. I felt fearful ................................................... 0 1 2 3 

11. My sleep was restless .................................. 0 1 2 3 

12. I was happy................................................. 0 1 2 3 

13. I talked less than usual........................... 0 .1 2 3 

14. I felt lonely ................................................... 0 1 2 3 

15. People were unfriendly 1 0 1 _ 

_ 

5-7 

days 

2 3 

16. I enjoyed life .............................................. 0 1 2 3 

17. I had crying spells.......................................... 0 1 2 3 

18. I felt sad ....................................................... 0 1 2 3 

19. I felt that people dislike me ....................... 0 1 2 3 

20. I could not get "going" .............................. 0 1 2 3

CLEVELAND SLEEP HABITS Q 

(REPRINTED WITH PERMISSION DR K. S 

Age 

TROHL, 

Height Male 

Weight Female 

UESTIONARE 

AND IONSLEEP, LLP) 

Check answers that cover the past month or so... 

Do you snore? 

❑ Yes 

❑ No 

❑ Don't know 

If you snore: 

❑ Slightly louder than breathing 

❑ As loud as talking 

❑ Louder than talking 

❑ Very loud. Can be heard in adjacent r 

How often do you snore? 

❑ Nearly every day 

❑ 3-4 times a week 


❑ 1-2 limes a month 

❑ never or nearly never 

Has your snoring ever bothered other people? 

❑ Yes 

No 

= 

1 

Has anyone told you that you quit breathing 

during your sleep? 

Nearly every day 



-J 

[ - 

t= 

l 1-2 times a month 


coms. 

Date 

Site 

IC 

Time' 

. 

. 

❑ 

Race 

❑ Hispanic 

❑ American Indian 

1 have nodded off or fallen asleep while driving 

a vehicle... 

C 

Yes No 

1= 

= 

1 

I 

If yes, how often does it occur? 




❑ 1-2 times a month 


E= 

1 

El 

White 

Other 

❑ Black 

I feel I get enough sleep... 






I feel tired or fatigued after sleep... 






During my waking hours, I feel tired, fatigued 

or not up to par... 


❑ 3-4 times-a week 

❑ 1 -2 ti mes a week 


❑ never or nearly never

Do you have a high blood pressure? 

Do you take medicines for blood pressure or 

heart problems? 

No l 

Yes 

❑ 

Sometimes No 

[ 

Don't know 7 

Don't know 

It takes me more than half an hour to fall 

asleep 


71 

in 

Yes 

El 

I regularly get to sleep quite late-into the early 

morning hours 

Nearly every night 

n 

I I 

1 - 

ri 

1 

r _ 

I 

__! 

I I 

I w 

1 - 

1 

3-4 times a week 


1-2 times a month 

never or nearly never 

feel anxious about going to sleep. 

orry_qnd 

II 

I I 


1-2 limes a week 








have trouble unwinding. 





never or neatly never 

I've used sleeping pills or alcohol to help me 

sleep. 

Yes 

No 

If yes, how often 

I struggle to concentrate during the day. 



1 -2 ti mes a week 



I lose J 

even go limp, when I 

laugh, am surprised or get angry. 

n Nearly every day 

n 3-4 times a week 

I 1 

II 

II 

ontrol, 

n 1-2 times a week 


n never or nearly never 

7 

I get a strange crawling sensation in my legs 

along with an urge to move them. 

n Nearly every day 

I J 

h 

1 

I 3-4 times a week 

3-4 




Has anyone told you that your legs/arms move 

or jerk during sleep? How often? 

Nearly everyday 

times a week 


1 -2 time a month 


f often have nasal drip/sinusitis. 

Yes I I No 

I smoke cigarettes. 

Yes n No 

If yes, how many per day? 

c 

(20 

ig/ 

pack) 

I drink alcohol 

Yes I No 

If yes, how many drinks per d 

We thank you for your help. 

All responses are confidential. 

ay?

Do you have a high blood pressure? 

I 

Yes 

No 

Sometimes 

Don't know 

I regularly get to sleep quite late-into the early 

morning hours 

Nearly every night 

E7 

1 





It takes me more than half an hour to fall 

asleep 


E. 





I feel anxious about going to sleep. 






I worry and have trouble unwinding. 

1 



1-2 times c week 


never or neatly never 

I've used sleeping pills or alcohol to help me 

sleep. 

Yes 

n No 

I 

If yes, how often 

I struggle to concentrate during the day. 

Nearly every Coy 


El 

II 


1 1-2 times a month 


7 

Do you take medicines for blood pressure or 

heart problems? 

Yes 

No 

Don't know 

. 

. 

/ 

lose control, even go limp, when 

laugh, am surprised or get angry. 





17 

7 


I get a strange crawling sensation in my legs 

along with an urge to move them. 



1 -2 ti mes a week 

I 1-2 times a month 

7 never or nearly never 

7 

Has anyone told you that your l 

or jerk during sleep? How often? 

Nearly everyday 

pi 3-4 times a week 

it 


I I 

1-2 time a month 

Li never or nearly never 

- I often have nasal drip/sinusitis. 

7 Yesp 

❑ 

- 

i No 

I smoke cigarettes. 

Yes I I No 

If yes, how many per day? 

c 

(20 

icipack) 

I drink alcohol 

Yes I I No 

If yes, how many drinks per d 

ay) 

We thank you for your help. 

All responses are confidential. 

egs/ 

arms 

move

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Prof. Dr.Mohamed Hamdy Abouel-Hassan

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