Conclusion

The medico-legal aspect of priapism and its associated diagnostic and therapeutic interventions remains important in our litigious society. The physician should explain to the patient the natural history of the disease and the extremely high risk of developing erectile dysfunction, early or late, despite active or no intervention. Discussion should include the advantages and potential disadvantages of the various treatment alternatives, as well as the risks associated with no treatment at all....

Transport

Testosterone is a lipophilic molecule and its solubility in blood is limited. Only 2 of circulating T is free, non-bound to transport proteins, able to diffuse into cells, and immediately available for biologic action. Approximately 60 of circulating T is bound with high affinity to sex hormone binding globulin (SHBG), and 38 is loosely bound and transported by albumin. The free fraction of T (FT, 2 ) and the albumin-bound fraction ( 38 ) have been termed bioavailable testosterone (BT), since...

Collagenase

Mechanism of action Collagen degradation. The use of collagenase was initially demonstrated in vitro by Gelbard et al. in 1982 36 . An obj ective improvement in 64 of patients (n 20) was demonstrated within four weeks with collagenase injections. However, a decade later in 1993 37 , they reported their findings from a double-blind trial of collagenase injections in 49 men. Following stratifying patients based on a severity of curvature, a statistically significant improvement was noted in...

References

1 Holstege G, Georgiadis JR, Paans AM, et al. Brain activation during human male ejaculation. J Neurosci 2003 23(27) 9185-8193. 2 Levin RJ. The mechanisms of human ejaculation a critical analysis. Sex Rel Ther 2005 20 123-131. 3 Giuliano F, Clement P. Physiology of ejaculation emphasis on serotonergic control. Eur Urol 2005(in press). 4 Waldinger MD, Schweitzer DH, Olivier B. On-demand SSRI treatment of premature ejaculation pharmaco-dynamic limitations for relevant ejaculation delay and...

Sympathetic Skin Response SSR

Measurement of heart beat variation and the sympathetic skin response are generally accepted and now standardized investigation methods to demonstrate involvement of the autonomic nervous system, e.g. in diabetes, although the SSR method evaluates the sympathetic nervous system. SSR is infrequently used in the diagnostic evaluation of male ED, or in planning treatment for male ED. The method makes use of a somatic afferent sympathetic reflex, via which the activation of sweat gland secretion in...

Apomorphine SL

The history of apomorphine dates back to 1869 when its first synthesis from morphine was reported by Mathiessen 15 . The dopaminergic activities of apo-morphine were first published in the mid 1960s when it was successfully administered in Parkinson's disease to suppress refractory motor oscillations 16 . Apomorphine was formerly used as an emetic in the treatment of poisoning to prevent absorption of orally ingested poisons. The erection-inducing effect of apomorphine in humans was first...

ED Minimizing Maneuvers Nervesparing surgery

Nerve injury can occur at four time points during radical retropubic prostatectomy at the time of urethral dissection, during lateral pedicle division, during dissection along the base of the prostate, and at the time of seminal vesicle dissection. Nerve trauma is classically thought of as occurring with cautery, ligation or avulsion however, overly aggressive traction may lead to neuropraxia, and even this temporary trauma may result in structural sequelae in the corporal bodies that may limit...

Introduction

Our understanding of the etiology and risk factors for erectile dysfunction (ED) has grown immensely over the past twenty years. Masters and Johnson 1 (1970) suggested that most cases of impotence were psychogenic, while Helen Kaplan (1974) estimated that erectile failure was psychogenic in 90 of cases and organic in 10 of cases 2 . However, the introduction of modern diagnostic tools in the area of sexual medicine revealed that vascular, neurologic, endocrinal, and other factors, contribute...

Corpus Cavernosum Electromyography CCEMG

This procedure is used in the measurement of the reflex latency time of the BCR and pudendal, somatosensory-evoked potentials. This method has a considerable shortcoming in that it only checks the integrity of the somatic penile nervous system and does not allow any statement in terms of auto-nomic penile innervation, the system that is mainly responsible for the induction of erection (parasym-pathetic nervous system) and detumescence (sympathetic nervous system). The greatest obstacle to...

Potassium amino benzoid Potaba Glenwood

Potaba is historically used in dermatologic patients particularly scleroderma, dermatomyositis, and pemphigus. Mechanism of action Increasing activity of mono-amine oxidase in tissues, a subsequent decrease in serotonin levels, and thus a reduction in fibro-genesis, with subsequent decreased scar tissue formation. The use of potassium amino benzoid was described initially by Zarafonatis in 1959 25 . A large, pooled European study in 1978 involving 2653 patients, reported a 57 success rate with...

Tamoxifen citrate Nolvadex Astrozenica

Mechanism of action The potential benefit is based on its effect on the release of transforming growth factor beta (TGF-P) from fibroblasts, and blocking the TGF-P receptor sites, resulting in decreased fibrogenic activity. This was first introduced by Ralph et al. in 1992 28 , at a dose of 20 mg given twice a day for three months in 36 patients. The results demonstrated a reduction in pain in 80 of patients (n 29), reduction in curvature in 35 of patients (n 13), and a decrease in plaque size...

Secretion

T secretion follows a daily rhythm with highest T levels in the early morning hours, gradually declining to reach the lowest levels in the early evening. The biologic significance of this diurnal rhythm has not been established, and dissipates with aging. It is usually recommended to measure T in the early morning hours to avoid an erroneous diagnosis of hypogo-nadism, on the basis of the physiologically lower T levels in the afternoon. Two recent papers questioned this recommendation because...

Clinical Trial Design

In the past decade the concept of evidence-based medicine (EBM) has strongly influenced the research of PE. The results of PE drug clinical trials are only reliable, interpretable and capable of being generalized to patients with the disorder studied when conducted in well-defined and consistent populations, using a double blind placebo-controlled study design with consistent objective physiologic measures or sensitive, validated outcome assessment instruments as study endpoints 41 . Optimal...

Efficacy

Although apomorphine SL has shown statistically significant efficacy vs. placebo in the phase II III clinical program, the net benefit ratio (active efficacy minus placebo efficacy) with figures between only 11 and 13 , were not convincing at all 27,28 . This limited efficacy of apomorphine SL, especially in organic ED, was recently confirmed in 130 diabetic ED patients in whom apomorphine SL 3mg resulted in response rates of 22.9 vs. 17.3 for placebo 29 . Meanwhile several prospective studies...

Obesity

The prevalence of obesity is ever increasing, especially in developed countries. Increased weight (BMI 25.0-29.9) and obesity (BMI > 30.0 ) are seen as risk factors in as many as 85 of men with ED 416 . This is quite pertinent to ED because the insulin resistance that accompanies excess weight is a cause of decreased blood flow 417 . The observation that insulin receptor numbers can be restored to normal if insulin levels are decreased in obese patients suggests that the changes in receptor...

Diagnosis and Evaluation

Although no clear operationalized criteria exist for IE, given that most sexually-functional men ejaculate within about three to eight minutes following intromission, a clinician might assume that men with latencies beyond 20 or 30 minutes (and who experience consequent distress), or men who simply cease sexual activity due to exhaustion or irritation, qualify for this diagnosis 39 . Such symptoms, together with the fact that a man and or his partner decide to seek help for the problem, are...

Arteries

The ischiopudendal trunk originates on both sides from the internal iliac artery, giving off the obturator and inferior gluteal arteries and continuing as the internal pudendal artery. The internal puden-dal artery is the main trunk for arterial penile blood supply and, in radio-anatomical terms, is divided into the pelvic segment (origin-obturator foramen), ischiorectal segment (corresponds to Al-cock's canal in the obturator foramen) and the perineal segment (below obturator foramen). Their...

Epidemiology

Premature ejaculation is claimed to be the most common male sexual disorder, affecting 5-40 of sexually-active men 9 . It is believed that there is a higher frequency of PE in adolescents or young adults. Premature ejaculation is more frequently reported by men in East Asia (China, Indonesia, Japan, Korea and Malaysia), and less frequently by men in Middle Eastern and African countries (Algeria, Egypt, Morocco and Turkey). The European prevalence of PE is said to be between that of East Asia...

Hyperprolactinemia

Prolactin (PRL) is a large polypeptide mainly responsible for the regulation of lactation and involved in over 300 other functions. The release of PRL from the pituitary lactotropic cells is under tonic inhibitory control by the hypothalamus, primarily by the neurotransmitter dopamine. The secretion of PRL is stimulated by estrogens, and therefore, indirectly, by aromatizable androgens such as T. PRL has no known role in the physiologic control of human sexual behavior, except a possible...

Pathophysiology

Mechanistically, post-RP ED may be neurogenic, ar- teriogenic, venogenic, mixed vascular (arterio-venogenic) or psychogenic in etiology and is generally multi-factorial in nature. Neurogenic impotence, while obviously occurring after cavernous nerve interruption, may also occur transiently following cavernous nerve traction and or dissection. Even in the hands of expert nerve-sparing surgeons, temporary neural trauma may occur. It is believed that the primary mechanism of development of...

Anatomy of the Penis

The penis is composed of the paired corpora cavernosa and the single corpus spongiosum, which surrounds the urethra. In the mobile section, the corpora cavernosa communicate with each other through numerous pore-like junctions in the septum penis. The corpora cavernosa are characterized by a spongy tissue structure consisting of connective trabecular tissue surrounding the sinusoidal spaces. These spaces fill up with blood during erection and are lined with endothelial cells and the subjacent...

Combination Therapies

Various combinations of therapies have been evaluated and investigated as potential treatments for Peyronie's disease. A controlled study by Pieto Castro et al. 50 randomized 45 patients to receive vitamin E plus colchicine and or ibuprofen (placebo). Patients in the treatment group reported a higher percentage of pain relief, although the difference was not significant. Mirone et al. 51 examined two populations of patients with Peyronie's disease electromotive drug administration plus...

Clinical guidelines

Defining candidacy for Peyronie's disease surgery Correction of penile deformity due to Peyronie's disease is surgically challenging and is required in the minority of patients with this condition 1 . Surgery is considered only after stabilization of the fibrotic process. The committee recommends that men be considered candidates for surgical correction if they have had Peyronie's disease for at least 12 months and have had stable deformity (that is, no change in deformity) for a duration of at...

Phosphodiesterase5 Inhibitors Sildenafil Viagra Tadalafil Cialis and Vardenafil Levitra

The physiological basis of erection (Fig. 7.1) Pro-erectile impulses are generated in the parasym-pathetic erection centers of the limbic system and the hypothalamus, in particular in the paraventricu-lar nucleus and the medial preoptic area, which are the key regions for the central regulation of erection 25 . Perception of sexual (erotic) stimuli, such as visual, imaginary or tactile stimuli, activate a variety of receptors processing the stimulatory signals, which in turn are running via...

Hypogonadism

Many observations suggest that androgens play a critical role in human sexual behavior. Throughout life, the general pattern of their rise and decline cor responds to that of male sexual potency and activity. However the possibility of minimally-impaired sexual function in men with very low levels of testosterone (T), as well as the often disappointing results of T therapy used alone in men with sexual dysfunction and moderate hypogonadism, have cast doubt on the importance of androgens in...

Hartmut Porst

The overwhelming success of sildenafil in the management of male erectile dysfunction (ED) encouraged both researchers and the pharmaceutical industry to enforce their endeavors in this special field of medicine. Meanwhile two further PDE-5 inhibitors tadalafil and vardenafil have joined sildenafil. Because they are not really distinguishable from sildenafil in terms of efficacy and side effects, but only from the pharmacokinetic profile, they are now directly competing with this very first...

Treatment of Post Radical Prostatectomy Erectile Dysfunction

Treatment of post-RP ED follows the same principles as for any other ED. The first therapeutic option is oral treatment with PDE-5 inhibitors (PDE-5i) or vacuum device, when there is a contraindication for the use of oral agents. Second-line treatment includes the intraurethral alprostadil suppository or intracavernosal injection therapy. When pharmaco-logic treatment does not restore the patient's erectile ability or there is a preference for a surgical treatment, penile implant may be the...

Candidates for androgen therapy

It is generally accepted in clinical practice that any male with any form of classical hypogonadism and inadequately low T for his age will require androgen therapy if hypogonadism occurred before the age of 50 213 . Even in men who have proceeded normally through puberty, and who experience no or only minor symptoms (e.g. fatigue, reduced libido), T therapy may be recommended, to prevent long-term sequelae such as osteoporosis 1 . Conversely, there is much debate concerning the validity of...

Selfadministered questionnaires

Sexual function symptom scales should be used routinely to assess functional level (e.g. ability to respond, level of interest) and to determine the impact of therapy. The most frequently used type of instrument is the self-administered questionnaire. As with all psychometric instruments, the fundamental requirements for psychometric validity include reliability and validity. Reliability refers to the consistency or replicability of data, while validity reflects the degree to which an...

Veins

Blood drained off from the sinusoidal spaces or directly from arteriovenous shunts is collected in the distal two thirds of the corpora cavernosa via a direct subtunical venous plexus, and is then transported further via the oblique emissary veins that perforate the tunica albuginea. Several emissary veins open into a circumflex vein, which originates ventrally between the corpus spongiosum and the corpus caver-nosum, and surrounds the corpus cavernosum like a hoop, finally opening into the...

Age

Although many men continue to function sexually into later age, epidemiologic studies confirm that the prevalence of ED increases significantly with age (see also Chapter 4). In the Massachusetts Male Aging Study (MMAS), 39 of men had some degree of ED at the age of 40 8 . The prevalence gradually increased to reach 67 at the age of 70. A strong relationship of patient age with both prevalence and severity of ED was also recently confirmed by a large-scale study of 2476 Spanish men 9 . In this...

Cavernsography

Non-ionic contrast agent is then added via a three-way stopcock, and after 50-100 mL of contrast agent, X-ray is performed in four different planes. This includes two anterior posterior projections with the penis bent upwards and downwards, as well as two lateral oblique projections using the urethrogram technique. Infusion is then stopped and 300-500 g of phenylephrine is injected intracavernosally to achieve detumescence. The butterfly cannula are removed after detumescence has occurred and...

And

The Standards Committee of the International Society for Sexual Medicine 2006 International Society for Sexual Medicine Published by Blackwell Publishing Blackwell Publishing, Inc., 350 Main Street, Malden, Massachusetts 02148-5020, USA Blackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK Blackwell Publishing Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, Australia The right of the Author to be identified as the Author of this Work has been asserted in accordance with...

Experimental techniques

The choice of research models will dictate what research techniques will be needed. If these are new methods for the investigator, there are many approaches to acquiring the necessary technical skills. Some may be relatively straightforward to learn on one's own, using the literature. However, it may save considerable time to visit labs using the techniques to learn the little details and learn to troubleshoot problems. Other techniques may require more formal training. Many courses on...

Renal insufficiency

Renal failure may result in ED in up to 50 of patients. Possible mechanisms for ED in patients with renal disease include vascular insufficiency, auto-nomic or sensory neuropathy, endocrine factors with decreased testosterone and elevated prolactin levels, significant anemia, zinc deficiency, associated diabetes, psychologic stress, and anti-erectile medications such as antihypertensives 48,49 . In pa tients requiring dialysis, occlusions of the cavernous arteries was found in 78 , and...

Integrated treatment for sexual dysfunction

Medical treatments alone are often insufficient in helping couples resume a satisfying sexual life. The term integrated is used to denote concurrent or stepwise combinations of psychologic and medical interventions. Too often, medical treatments are directed narrowly at a specific sexual dysfunction and fail to address the larger biopsychosocial issues. While medical therapies, especially for ED, are generally efficacious (50-90 ), approximately 50 of individuals fail to continue treatment....

Pharmacologic profile

Apomorphine is a central dopamine receptor agonist with effects on D1 and D2 receptors (dominantly on D2). Predominant sites of action are located in the paraventricular nucleus, stria terminalis, medial preoptic area, and amygdaloid nucleus 19,20 . Apomorphine-induced erections are both testosterone and NO dependent 21,22 , i.e. the erection-triggering effects of apomorphine diminish or may even be absent in the case of a clinically-relevant NO or testosterone deficiency withdrawal. Following...

Etiologic diagnosis

Drug-induced HPRL is the first etiology to consider. It is responsible for a significant proportion of HPRLs in men. Many drugs may increase PRL (Table 18.6). The most common are antipsychotic agents. Other medications include antidepressants, some antihy-pertensive agents, and drugs that increase bowel motility 251 . HPRL may also be secondary to hy-pothyroidism, renal insufficiency, cirrhosis, and chest injury (mild or moderate in all four conditions), and to any process compressing or...

Preoperative considerations

Patients are admitted to the hospital either the evening before or the morning of the operation. The shorter the hospital stay, the smaller the risk of contracting infections from hospital contamination. The urine culture should be negative at the time of surgery 14,55 . Antibiotic prophylaxis is used routinely. Intravenous administration of the first dose of the antibiotic should be completed at least one hour before the skin incision to ensure having adequate serum concentrations of the...

Diagnosis of Hypoactive Sexual Desire

The diagnosis of HSD is not difficult if the clinician asks directly about desire or interest for sexual activity. Most patients identify with ease a change in their usual pattern, and this is the way in which the condition is identified most of the time in clinical practice. Sometimes, it is necessary to investigate the indicators of sexual desire, which, although not as direct as the expression of desire, are often good clinical indicators. Table 13.5 shows a list of clinical indicators of...

Cavernosometry

The technique, involving use of a 27-30 g needle, is used to inject varying g (microgram) doses of PGE1 (Caverject ), or a triple drug mixture, approximately 5-15 min before the actual investigation. The penile shaft is then draped with a sterile, perforated drape. Patients who are sensitive to pain receive 1-2 cm3 of a 1 local anesthetic containing lidocaine, which is infiltrated prior to insertion of the 19 g butterfly needle. The butterfly needles should be applied vertically to the penis...

Contraindications

The absolute contraindication for T therapy is the suspected or documented presence of prostate cancer or breast cancer 212 . Although there is no evidence that T or any other androgen initiates prostate cancer, it is generally accepted that T therapy may accelerate an already existing prostate cancer. Relative contraindications and cautions include severe congestive heart failure for concern of fluid retention, and polycythemia, severe sleep apnea, severe lower urinary tract symptoms,...

Closing Comments

The diagnosis lifelong or acquired PE in daily clinical practice is not difficult and can be achieved with a careful medical and sexual history. Detailed evaluation with questionnaires or stopwatch is not required. Pivotal to the management of PE is the recognition that PE is a condition defined by the IELT and the dimensions of control, satisfaction and bother. Reliance on patient self-report is associated with a high level of false-positive diagnosis of PE, and consequential inappropriate...

Daily treatment with selective serotonin reuptake inhibitors

Daily treatment can be performed with paroxetine 20-40 mg, clomipramine 10-50mg, sertraline 50-100mg, and fluoxetine 20-40mg 19,45,46 (Figure 16.2) Paroxetine appears to exert the strongest ejaculation delay, increasing IELT approximately 8.8-fold over baseline 44 . Ejaculation delay usually occurs within five to10 days, but may occur earlier. Adverse effects are usually minor, start in the first week of treatment, gradually disappear within two to three weeks and include fatigue, yawning, mild...

Foreword

It is a mystifying paradox that among the most important functions of the human body, sexuality has drawn more public attention than any other, yet sexual function is one of the last areas to receive the careful attention of medical scientists. Many studies have shown that sexual health is a very important element of overall health and quality of life. Yet in both the developed and the developing worlds, social taboos and religious restrictions surround human sexuality. In some places,...

Introduction and History

Impotence, or in modern terms erectile dysfunction (ED), has afflicted human males since ancient times, if not since the very beginning of human existence. External supports intended to aid the inadequate erection, a precursor of the modern prosthesis, were known in the Ancient World. In the Roman theatre, actors wore oversized cases made of leather or wood, which were fastened to the actors' hips to produce the appearance of a large penis. These external devices originated in China and Japan....

Conclusions

The application of penile revascularization procedures even in highly selected patients performed by well-trained experienced surgeons results in a variable and unpredictable outcome. The precise mechanism by which these procedures yield their potential benefit has not been fully elucidated. In the 2005 update of the AUA ED guideline, narrow criteria were chosen for outcome evaluation. These criteria were well-circumscribed arterial occlusive disease without obvious cavernous myopathy. Only...

Vacuum constriction device VCD

VCD is probably the oldest described tool for treatment of ED. Cookson and Nadig (1993) reported long-term efficacy and high satisfaction rate for non-selected patients and couples treated with VCD 73 . However Dutta and Eid (1999) reported a dropout rate of 65 and most patients reported stopping the treatment within a mean of four months 74 . Raina et al. published one the few papers on the subject VCD and post-RP erectile dysfunction 75 . To assess the efficacy of VCD following RP they...

Gene Therapy and ED

Basic science research on erectile physiology has focused on the pathogenesis of ED and has provided convincing evidence that ED is predominantly a disease of vascular etiology. The oral phosphodi-esterase-5 (PDE-5) inhibitors are uniformly recommended as first-line therapy because of their convenience and high rate of efficacy in a diverse population of ED patients. Unfortunately, not all ED patients benefit from PDE-5 inhibitor therapy, and the development of new approaches, including gene...

Retrograde Ejaculation Etiology and risk factors

Antegrade ejaculation requires a closed bladder neck and proximal urethra. Retrograde ejaculation (RE) may be caused by anatomic, neurologic, pharmaco-logic, or idiopathic factors 113-116 . Anatomic causes Anatomic causes include congenital (urethral valves, congenital defects of the hemitrigone, congenital dysfunction of the hemitrigone, or bladder exstrophy), or acquired (urethral stricture, bladder neck resection or fibrosis, and transurethral or open prostatectomy). Neurologic causes These...

Cardiovascular function

Steroids and vascular risk factors Premenopausal women suffer significantly less from cardiovascular disease than men, and traditionally it has been thought that the relationship between sex steroids and cardiovascular disease is predominantly determined by the relatively beneficial effects of estrogens, and by the relatively detrimental effects of androgens on lipid profiles 101 . Nevertheless, the vast majority of cross-sectional studies in men are not in agreement with this assumption they...

Surgery

Several authors have reported the use of surgically-induced penile hypo-anesthesia via selective dorsal nerve neurectomy, or hyaluronic acid gel glans penis augmentation, in the treatment of lifelong PE refractory to behavioral and or pharmacologic treatment 71,72 . This is based on the hypothesis that some men with PE have penile hypersensitivity. In selective dorsal neurectomy, several branches of the dorsal nerve of the penis are severed. The exact role of selective dorsal nerve neurectomy...

Diagnosis of hyperprolactinemia in men with sexual dysfunction

Some precautions are critical to avoid false HPRLs resulting from stress (especially from venepuncture) and meals. Blood sampling must be performed fasting, following a 20-minute rest in a quiet place. Any elevated PRL level must be checked again, if possible following catheter insertion 20 minutes before sampling, and after discontinuation of any drug likely to increase PRL (Table 18.6). In case of discrepancy between high serum PRL and a pattern of non-endocrine sexual dysfunction, the...

New PDE5 inhibitors

DA 8159 is a new PDE-5 inhibitor from a South Korean pharmaceutical company with a selectivity that is similar to sildenafil with a Tmax of 1.0-1.5 h and a T1 2 of 11-13h. This new PDE-5 inhibitor was recently investigated in a large multicenter, double- blind placebo-controlled home trial for 12 weeks, in doses of 100 and 200 mg, in 319 men with ED 18 . As shown in Fig. 9.2, the SEP 3 rates reached nearly 70 , against only 17 at baseline. Side effects > 5 were flushing and headache. TA-1790...

Serotonin receptor agonists

Generally speaking, serotonin (5-hydroxytrypta-mine, 5-HT) receptors are attributed inhibitory effects in the erectile mechanism, but the serotonin receptor subtypes 5-HT1C 2A and C are suggested to facilitate both erection in male and female sexual proprioceptive behaviour 12-14 . There were two 5-HT2C agonists in preclinical or clinical phase I IIA investigations named RSD 992 and YM 348, with no results being reported so far. The pro-erectile effects of RSD 992 were blocked by the 5-HT2A C...

Special populationsfeatures with selfinjection therapy

According to the literature and my own experience, self-injection therapy can be performed even in men on warfarin or phenprocoumon-containing antico agulants, without increasing the risk of bleeding ecchymosis 67 . The literature does not show any increased risk with self-injection therapy in patients who have received kidney or heart transplants 68 . Both in the literature and in own patient populations, ED patients with diabetes are revealed at increased risk of fibrosis and painful...

Prevalence of hyperprolactinemia in other sexual dysfunctions

Routine determination of serum PRL in men consecutively seen for hypoactive sexual desire without ED (n 53), anorgasmia retarded ejaculation (n 74), and premature ejaculation (n 124) 210,249 found no HPRL in the two former sexual dysfunctions. However Schwartz etal. 250 reported on some male HPRLs revealed by isolated hypoac-tive sexual desire or anorgasmia. In contrast, serum PRL was mildly elevated (20-35ng mL) in 13 men with premature ejaculation (10 ). This was not the cause of sexual...

Questionnaires

Physicians who are not facile with the specifics of the ED office evaluation may turn to questionnaires to aid in the diagnosis. Questionnaires are not mandatory in the evaluation of male ED, but often serve as an important adjunct to the proper diagnosis. Prior to, or in addition to, being seen by the physician (and as a significant part of the history), it is advised that the patient fill out a questionnaire to delineate the extent of the erection problem. There are several questionnaires...

Postoperative management

Most patients are discharged on the first day after surgery and intravenous antibiotics are stopped at that time. At home, patients are usually prescribed one week of oral quinolones. Patients are instructed to start activating and deactivating the implant as soon as the local pain has subsided enough to allow this. In most cases this takes place during the first follow-up visit appointment seven to ten days after surgery. Sexual activity is not allowed until six weeks after the procedure, when...

Conclusions on PDE5 inhibitors

As described in the extension to this chapter, all three PDE-5 inhibitors are very effective and safe and can be applied to nearly all ED patients, with the exception of those under nitrate or NO donor medications and those suffering from very severe eye diseases (retinitis pigmentosa and NAION). In terms of efficacy they are not really distinguishable, although it might quite often happen in the daily routine use of these drugs that one PDE-5 inhibitor produces better erections in an...

Treatment

Controlling the blood sugar is the essential first step. Decreasing the blood sugar by itself will correct certain metabolic abnormalities, but the use of insulin sensitizers will further increase blood flow by decreasing insulin resistance. Then comes the treatment of the related factors, such as hypertension, obesity, and any diabetic complications. The treatment of diabetic ED should begin with a review of potential risk factors in the patient, but also in the partner and the relationship...

Technique and complications of selfinjection therapy

In order to overcome the reservations and to increase the acceptance of patients on the one hand, but to decrease at the same time the complications of self-injection therapy on the other hand, a thorough instruction of the patients in a proper technique and use of ultra-thin needles is mandatory. According to the experiences of the authors it takes, in many patients, at least two teaching sessions before the patient is sure that he has mastered this technique correctly and avoids potential...

Transurethral alprostadil PGE1 with MUSE Medicated Urethral System for Erection

A new alprostadil preparation using transurethral application with a small single-use applicator was introduced in 1994, and later on developed as MUSE (Medicated Urethral System for Erection) for market approval in US, 1996 (VIVUS, USA) followed by many other countries worldwide 70 . Although the transurethral application route seemed at first glance to be preferable to self-injection therapy the outcome and especially direct comparative trials to intracavernously-applied alprostadil...

Stopstart method

In the first step of the stop-start process, the penis is manually stimulated until the man is fairly highly aroused at which point stimulation is stopped. When his arousal subsides, stimulation recommences and continues until a high level of arousal is again achieved when stimulation is stopped. This sequence is repeated at least four times before stimulation continues to ejaculation. The process is repeated three or more times a week. The aim is to increase the duration of stimulation the man...

General considerations for the three PDE5 Inhibitors

For a better understanding of differences among, and comparisons between the three PDE-5 inhibitors, some terms frequently used in publications have to be explained. IC50 is defined as the concentration of a PDE-5 inhibitor required to reduce the activity of PDE-5 by 50 . The IC50 values provide an overview of the clinical efficacy of a PDE-5 inhibitor. Generally speaking the lower the IC50 values the more potent and therefore more effective a compound is for this enzyme. Regarding the clinical...

The Phosphodiesterase PDE System

Currently the PDE system includes 11 families, with a total of more than 50 splice variants (iso-forms) 34-40 . The distribution and density of PDEs varies among the different tissues. The PDEs catalyze the breakdown of either cGMP or cyclic adenosine monophosphate (cAMP), which are both second messengers with specific physiologic functions. By hydrolyzing the phosphodiesterase bond of cAMP or cGMP, these second messengers are converted to the biologically-inactive monophosphates, resulting in...

Intraurethral alprostadil

Intraurethral delivery of alprostadil was first introduced by Padma-Nathan et al., in 1997, who claimed an overall efficacy rate of 44 for post-RP ED 77 . Raina et al. in a retrospective study, reported a 48 rate of significant improvement in all domains of the Sexual Health Inventory for Men (SHIM) after a mean of 2.2 years in 27 patients with post-RP ED treated with intraurethral alprostadil, although seldom reaching pre-operative scores, and 52 of patients had discontinued after a mean of...

Drug induced ED

Several classes of medications and recreational drugs have been linked to the manifestation of ED (Table 5.3). This list is not meant to be inclusive of all medications that could cause ED. Drugs exhibit their adverse effects either through central inhibitory neuroendocrine mechanisms and or local neu-rovascular actions, or they have an impact on the hormonal milieu (testosterone, prolactin). Psy-chotropic medications may exert their inhibitory effects through their effect on central...

Hypogonadismagonadism

In male rats, castration or the administration of androgen synthesis inhibitors, like cyproterone acetate, disrupt and ultimately eliminate copulatory behaviors and penile reflexes progressively over time. They also shrink androgen sensitive peripheral tissues (e.g. penis and prostate). Although the degree of disruption depends on the amount of androgen synthesis inhibition that is induced (e.g. moderate following low doses of cyproterone acetate to total disruption following castration), the...

Female orgasm the urethragenital reflex and the consequences of paced copulation

It is not known whether female rats experience anything like orgasm during sex. However, like males, they display a genital reflex, called the urethro-genital reflex that is reminiscent of the orgasmic response in women. This reflex can be induced and studied in isolation by applying a mechanical stimulation to the urethra of anesthetized, spinalized female rats. The urethro-genital reflex includes rhythmic contractions of the vagina, uterus, and the anal sphincter, as well as the striated...

Pharmacodynamics

The term pharmacodynamics covers all actions of a drug on the different body organs, and in turn on their functions (for example blood pressure, heart rate, vision). The pharmacodynamic interactions of any drug are influenced by the number of receptors available in the target organ and the affinity of the compound for the receptors in question. So for example it was just recently reported that varde-nafil has, with 85 , a clearly higher proportion of high-affinity components to the PDE-5...

Future therapies

Selective androgen receptor modulators The discovery and development of selective androgen receptor modulators (SARMs) provides the opportunity to design molecules that are not only orally active, but that target androgen receptors in different tissues to elicit the specific desired activity 223 . The desired activity profile of novel SARMs is described in Table 18.5. An ideal SARM for the treatment of primary or secondary male hypogonadism would have the following profile orally active, with a...

Self Injection Therapy

The demonstration by Virag in 1982 that intracav-ernous (IC) injection of papaverine produced a fully-rigid erection in normal males, introduced a new route of administration in the clinical management of pharmacologic agents for the treatment of erectile failure 1,2 . Intracavernous injection of a vasoac-tive agent that readily produces erection has greatly simplified the multidisciplinary diagnostic investigations and management of erectile dysfunction (ED). Three groups of drugs are...

Erectile Dysfunction

It is estimated that 10 of all men presenting with erectile dysfunction suffer the condition as a result of surgical procedure typically, radical pelvic surgery 25 . Major discrepancy exists in the literature regarding postoperative potency rates, with spontaneous erectile function cited as occurring in 30-80 of patients 26 . Thus, despite the advent of nerve-sparing techniques a significant percentage of men continue to suffer from erectile impairment following this operation. It is estimated...

Phosphosdiesterase Type 5 inhibitors

The efficacy of PDE-5i for the treatment of post-RP ED has only recently been studied. Sildenafil is the most studied PDE-5i in this subgroup of patients. However, despite this there does not exist data from a multi-center, randomized, placebo-controlled study evaluating sildenafil in patients with post-RP ED. Montorsi and McCullough found eleven studies in a systematic research on MEDLINE and CANCERLIT (1998-2004) with discrete data sets of post-prostatectomy patients with erectile dysfunction...

Side effects and contraindications

The side effects commonly observed with yohimbine can mostly be traced back to the partially increased sympathetic activity anxiety, nausea, restlessness, agitation, sleeplessness tachycardia, palpitations, rarely diarrhea, manic symptoms 4,7,9 . In addition, after yohimbine, either increases or more infrequently decreases in blood pressure were reported, which may become of clinical relevance if hypertensive patients are taking this medication. In 25 hypertensive patients who had not been...

Pharmacologic treatment of premature ejaculation

Pharmacologic modulation of ejaculatory threshold represents a novel and refreshing approach to the treatment of PE and a radical departure from the psy-chosexual model of treatment, previously regarded as the cornerstone of treatment. The introduction of SSRIs has revolutionized the approach to, and treatment of, PE. Selective serotonin reuptake inhibitors encompass five compounds citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline with a similar pharmacologic mechanism of action....

Mechanisms of action

It has been well described that the physiologic effects of DHEA are related to its peripheral conversion to the downstream sex steroid hormones, which then act on nuclear steroid receptors to exert their effects 270,273,274 . The ability for the conversion of active hormones in the peripheral tissues, where the hormone will be active, is called intracrinology. This phenomenon has been outlined for sex steroids very well by the work of Labrie 275,276 . Different peripheral tissues are able to...

Visual Sexual Stimulation VSS

Visual sexual or erotic stimulation is an investigation method that has been used for many years in the diagnosis of ED. It is usually combined with intracav-ernous injection of vaso-active substances, say during Doppler duplex ultrasound, to achieve a maximum erection response and thus to be able to draw conclusions on the maximum relaxation ability of the corpora cavernosa. VSS facilitates relaxation of the cavernosal tissue and overcomes potential psychogenic barriers toward the creation of...

Summary

The patient (and partner) histories are the key toward the successful diagnosis of male ED. ED is highly prevalent in men with a variety of medical diseases, including depression, and is often confused with ejaculatory disorders. The clinician should have a high index of suspicion when evaluating men with these medical diseases for ED. The clinician must also be aware of the psychologic aspects of male ED, with a referral to a sex or marital therapist indicated as necessary. Finally, there is...

Premature Ejaculation

Although premature ejaculation (PE) is considered the most frequent self-reported male sexual dysfunction, there is a lack of a universally accepted definition 5 . This has led to a wide range of prevalence estimates and the development of proposed guidelines for the use of the varied psychologic and pharmacologic therapeutic interventions 6 . Premature ejaculation may affect the level of sexual satisfaction of both men and or their partners. However, few studies have examined the impact of PE...

General reviews on animal models

Relevance of nonhuman animal studies to the understanding of human sexuality. Scand J Psychol 2003 44 293-301. Beach FA. Sexual behavior in animals and man. The Harvey Lectures 1950 43 259-279. Bitran D, Hull EM. Pharmacological analysis of male rat sexual behavior. Neurosci Biobehav Rev 1987 11 365-389. Dornan WA, Malsbury CW. Neuropeptides and male sexual behavior. Neurosci Biobehav Rev 1989 13 1-15. Everitt BJ, Bancroft J. Of rats and men The comparative approach to male...

Topical alprostadil Alprox

Topical alprostadil (Alprox -TD) in doses of 100, 200 and 300 g was investigated against a placebo in two multicenter pivotal phase 3 trials involving 1732 patients with mild to severe ED 20 . The demographics of the study population showed diabetes in 21 , hypertension in 44 , RRP in 12 , CAD in 21 , and nitrate or a-blocker medication in 16 . The SEP 3 data obtained after 12 weeks of treatment as shown in Fig. 9.3, indicate a clearly inferior efficacy if compared to PDE-5 inhibitors, whose...

Psychotherapy

A number of different psychotherapeutic approaches to PE have been described, but their efficacy have not been evaluated in properly controlled and adequately powered trials, and the different therapeutic modalities have not been compared in formal studies. It is likely that only some men seeking treatment for PE require in-depth psychotherapy. In spite of hard evidence on the efficacy of psychotherapy, behavioral retraining is still often practiced by sexologists. Behavioral treatment is...

Rhokinase inhibitors

A variety of research findings emphasize the role of Rho-kinase in the regulation of the corpus cavernosum smooth muscle tone, i.e. maintaining con traction and thereby preventing erection 29,30 (Fig. 9.4, see also Chapter 3, p.36). It has been shown that Rho-kinase expression and activity is clearly up-regulated, both in diabetes and hypertension and in hypoxemic conditions 31,32,33 . In the animal model Rho-kinase inhibitors were able to ameliorate ED 34,35 . Recent studies performed in...

Responsibility of hypogonadism

Sexual function of men with severe organic hypogonadism Data accumulated in such men show that T is required for pubertal acquisition of gender characteristics as well as adult sexual behavior and functional capacity, including libido, ejaculation, and spontaneous erections. Administration of T during placebo-controlled studies demonstrated that sexual desire and arousal are T-dependent 13,29,30 and represent the main impact of T on sexual function of men. The frequency of sexual activity...

Therapeutics and the Molecular Pathology of Peyronies Disease

How do these mechanisms correlate with current therapeutic treatment of this disease There are two basic categories of pharmacotherapeutics that have been used in Peyronie's disease anti-oxidants and collagen synthesis inhibitors. As described briefly above, it has been hypothesized that oxidative damage may be causal in the initiation and progression of tissue fibrosis 20 . Presently, non-surgical options for the treatment of Peyronie's disease are based on anecdotal experiences with studies...

Hypoactive sexual desire disorder

There are no randomized clinical trials of psychologic intervention with hypoactive sexual desire disorder (HSDD). Clinical wisdom suggests that four dynamics are generally associated with psychologic HSDD. These include depression, anger, sexual arousal patterns that are not available within the present relationship (e.g. sexual arousal to a partner of another gender, sado-masochistic wishes), and relationship discord. By stabilizing mood, diminishing hostility and improving relationship...

Intracavernous injection test combined with Dopplerduplex ultrasound

This specific diagnostic test in the hands of the urologist (or perhaps radiologist) should be thought of as an optional part of the evaluation. It is the optimal method of reliably diagnosing relevant disturbed arterial blood supply to the penis, and of obtaining an approximate idea of the relaxation capacity and thus cavernous function in practice. In addition, the drug-induced erection reveals possible cavernous deformations in Peyronie's disease such as cavernous notches, or deviations that...

Yohimbine

Yohimbine is the main alkaloid from the bark of the tree called Coryanthe johimbe K. Schum (yohimbehe tree), found particularly in central Africa. This tree belongs to the Rubiaceae family. The alkaloid was first isolated from the bark of the yohimbehe tree (hence the name) by L. Spiegel in 1896. The bark of this tree is still used today as the raw material for the various yohimbine preparations. Information on its use combined with papaverine in the treatment of ED was published as early as in...

Endothelial factors

Angiotensin The angiotensin I II system and the an-giotensin-converting enzyme play a role in the regulation of the cavernous smooth muscle tone 37,38 . Angiotensin II causes a dose-dependent contraction of the cavernous musculature, which can be blocked by specific AT1-receptor antagonists such as losartan, but not by AT2-antagonists. In patients with severe organic impotence in whom a penile implant was inserted, hypertrophied cells secreting angiotensin II have been detected in the corpus...

Populations for combination therapy and screening

Testosterone efficacy as monotherapy for ED is limited, because of the multifactorial nature of the pathophysiology of ED. Combination therapy with T and other ED treatments, such as PDE5i, may be valuable in certain subpopulations of patients. There is increasing evidence that combination therapy is effective in treating ED in patients where treatment failed with testosterone or PDE5i alone. Combination therapy may be particularly useful in men with type 2 diabetes and metabolic syndrome, who...

Recommendations for screening and therapy

Currently there is no basis for androgen therapy in older men, unless they have overt androgen deficiency with symptoms and low testosterone 2 . Testosterone levels needed for normal sexual function may vary between individuals. Some men may have normal sexual function even if their T levels fall into the age-adjusted lower normal range 221 . However, in patients with ED and or hypoactive sexual desire, T testing is recommended to screen for hypogonadism. T therapy is appropriate when clinical...

List of Contributors

President, ISSM Department of Obstetrics and Gynaecology National University Hospital Yong Loo Lin School of Medicine National University of Singapore 5 Lower Kent Ridge Road Singapore 119074 Singapore Jeanne L. Alexander MD, ABPN, FRCPC, FAPA, FACPsych Director, Northern California Kaiser Permanente Medical Group Psychiatry Women's Health Program Assistant Clinical Professor of Psychiatry, Stanford Medical School, PaloAlto, California Founder, Alexander Foundation for Women's Health 1700...

Male Sexual Function

Peripheral sexual reflexes (erection and ejaculation), copulatory behaviour (mounts, intromissions, Fig. 1.1 Incentive sequences for human and rat sexual behaviors. This model provides a conceptual way to denote classes of homologous or analogous behaviors between the species (and sexes). The behavioral stream moves from left to right, through appetitive, precopulatory, and consummatory phases of behavior. This conforms to the movement of animals from distal to proximal to interactive with...

Collaborations

Developing collaborative relationships can be extremely useful, or even essential for the new investigator, especially someone with a demanding clinical practice. Except in very large institutions, there are unlikely to be many other researchers in sexual medicine. Therefore, the most likely collaborators will be in related areas of cellular and molecular biology, physiology and pharmacology, endocrinology, or neuroscience, depending on the research topic. The collaborative arrangements can...

Availability of DHEA

DHEA had previously been banned by the Food and Drug Administration (FDA) in the USA until the passage of the Dietary and Supplemental Health and Education Act of 1994. Since then, it has been available over-the-counter in pharmacies and health food stores in most countries, including America. DHEA is classified as a food supplement and its production and distribution is not regulated by the FDA or any other agency. There is no pharmaceutical grade DHEA product and, therefore, no guaranteed...

Neurologic diseases

ED can occur as a result of various neurologic diseases or lesions. The hippocampus and paraventricu-lar nucleus and medial preoptic area are considered as the main centers regulating sexual drive and behavior 37,38 . Lesions at these areas may result in ED, depending on their severity. Central neurologic disorders frequently associated with ED include disorders at the level of the brain (e.g. multiple sclerosis, temporal lobe epilepsy, Parkinson's disease, stroke or Alzheimer's disease), or at...

Hypertension

Hypertension is a major risk factor for the develop ment of vascular ED. Muller et al. reported a very high incidence (85 ) of cavernous artery insufficiency in a group of 117 hypertensive patients 18 . Oaks and Moyer reported that 8-10 of hypertensive patients suffered ED at their initial diagnosis with hypertension 19 . In a more recent study Burchardt etal. reported a 68 ED incidence rate in treated hypertensive patients with 7.6 suffering from mild, 15.4 from moderate, and 45.2 from severe...

Vignette B

Susan, aged 30 and John, aged 45 have been married for seven years. One year ago John developed ED, which had a tremendous impact on his relationship with Susan. For the last three months their sexual life has become almost non-existent. Susan is certain that John is involved with another woman and that this is the source of his ED. She is angry when he attempts to initiate lovemaking, believing that he is no longer attracted to her. John has no awareness of the foundation of Susan's extreme...