34 Sarfraz Ahmad1 and Nick Watkin2 1 Aberdeen Royal Infirmary Hospital, Aberdeen, Scotland, UK 2 St George’s Hospital, St George’s University of London, London, UK Functional disorder of penis and urethra are quite prevalent. These include erectile dysfunction (ED), ejaculatory disorders, priapism, and Peyronie disease. ED is usually multifactorial and requires careful evaluation and management decisions. This ranges from oral pharmacotherapy to insertion of a penile prosthesis. Ejaculatory disorders, especially premature ejaculation (PE) can cause considerable distress to both patient and partner. Effective management of PE requires behavioural or psychotherapy and pharmacotherapy (e.g. local anaesthesia and oral serotonin reuptake inhibitors). Priapism is an acute urological emergency, and a prompt diagnosis and management is required to avoid irreversible damage to erectile tissues. Peyronie disease is a benign inflammatory condition but can cause penile curvature and ED significantly limiting sexual function. Keywords erectile dysfunction (ED); phosphodiesterase type 5 (PDE5) inhibitor; Peyronie disease; premature ejaculation (PE); priapism; retrograde ejaculation Erectile dysfunction (ED) is defined as persistence or recurrent inability to attain or maintain a penile erection for satisfactory sexual performance. ED is a common male sexual disorder. According to the Massachusetts male ageing study, in men between ages of 40 and 70 years, mild ED was found in 17%, moderate ED in 25%, and severe ED in10% [1]. ED is generally classified as psychogenic and organic, but in most cases, it is combination of both. Psychogenic ED frequently coexists with other sexual dysfunctions, notably reduced libido and with major psychiatric disorders particularly depression and anxiety [1]. Arterial insufficiency is a major factor in pathogenesis of organic ED. The arteriopathy usually develops secondary to diabetes mellitus (DM), hypertension, hyperlipidaemia, and smoking, lack of exercise, and obesity or metabolic syndrome. Rarely posttraumatic arterial obliteration or fistula can also lead to ED. ED is found in nearly 50% of patients with coronary arterial disease and precedes cardiac symptoms by an average of three years [2]. In the rigid phase of erection, the venous outflow from the penis is shut off by nervous stimulation and kinking of the veins as they pass through the tunica albuginea. Failure of this venous outflow causes a venous leak, leading to ED. Common causes of a venous leak are Disruption of the erectogenic neural pathways (central and peripheral) leads to the development of ED. There are a variety of causes of central neuropathy, among them are: There are a variety of causes of peripheral neuropathy, among them are: Hyperprolactinaemia causing ED is found in about 5% of men. Men reporting lack of libido may have low levels of testosterone. Other endocrine causes include hyper‐ or hypothyroidism, Cushing disease, and hypogonadism. Antihypertensives (e.g. beta‐blockers, angiotensin‐converting enzyme [ACE] inhibitors), diuretics (e.g. thiazides), statins, amiodarone, antidepressants (e.g. tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin reuptake inhibitors), finasteride, cyproterone acetate, luteinising hormone releasing hormone (LHRH) analogues, anticonvulsants (e.g. phenytoin, carbamazepine), and anti‐Parkinson drugs (i.e. levodopa). Table 34.1 IIEF‐5 scoring: The IIEF‐5 score is the sum of the ordinal responses to the five items. Total score; 22–25 = No ED, 17–21 = Mild ED, 12–16 = Mild to moderate ED, 8–11 = Moderate ED, 5–7 = Severe ED. Physical examination should consist of a general abdominal, neurological, and cardiovascular examinations. In most patients with ED, the following initial blood tests are recommended: Figure 34.1 Strain gauges fitted around the penis record nocturnal tumescence. Figure 34.2 Paper strips can be used to denote expansion of the penis during sleep. Figure 34.3 A continuous record is made of expansion and elongation of the penis during sleep. Figure 34.4 The pressure in the corpora is recorded during erection while fluid is injected under pressure. Two needles are placed in the corpora. Through one needle saline is infused, to which PGE1 and contrast medium is added; the second needle measures the pressure. PGE1 prostaglandin E1. Figure 34.5 Using radio‐opaque fluid, leakage of contrast medium during erection can be detected. 120 ml of contrast were injected into one corpus cavernosum at 3 ml s−1. The corpora have both filled, but not the corpus spongiosum and glans (normal). Subtracted image towards the end of the injection shows no satisfactory tumescence, due to venous leak from the penile root with numerous veins draining into the right iliac venous system (arrow). General measures should be considered before pharmacotherapy for ED. Three phosphodiesterase 5 (PDE5) inhibitors are approved by for treatment of ED (Table 34.2). All of these agents have shown successful efficacy in management of ED [3, 4]. However, these agents cannot initiate erection, and hence, require sexual arousal to facilitate erection. Table 34.2 Key characteristics of PDE 5 Inhibitors. Source: Adapted from European Association of Urology (EAU) guidelines. In the smooth muscle lining (of the trabecular network of the cavernosal tissue) of the penis, PDE5 enzyme hydrolyses cyclic guanosine monophosphate (cGMP) to 5 cGMP (Figure 34.6). PDE5 inhibitors prevent this hydrolysis, and hence, results in prolonged smooth muscle relaxation, increased arterial flow, and penile erection. Figure 34.6 Mechanism of action of PDE5 inhibitors. NOS enzyme cleaves L‐arginine to L‐citrulline and NO. NO stimulates guanylate cyclase which results in conversion of GTP into cGMP. The cGMP causes reduction in intracellular Ca++ producing smooth muscle relaxation and hence erection. PDE5 rapidly convert the cGMP into an inactive form, 5GMP. PDE5 inhibitors prevent this conversion and hence facilitate erection. cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate; NO, nitric oxide; NOS, nitric oxide synthase; PDE5, phosphodiesterase type 5. Key pharmacokinetic features are summarised in Table 34.2. Alprostadil, a synthetic PGE1, is used as a second‐line agent for treatment of ED. It results in corporal and glandular smooth muscle relaxation by increasing cyclic adenosine monophosphate (cAMP) (Figure 34.7). Figure 34.7 Mechanism of action of PGE1 stimulates adenylate cyclase which results in conversion of ATP into cAMP. The cAMP causes reduction in intracellular Ca++, producing smooth muscle relaxation and hence erection. ATP adenosine triphosphate; cAMP, cyclic adenosine monophosphate; PGE1 prostaglandin E1. Alprostadil is the only drug approved for intracavernous treatment of ED. Usually, the starting dose is 5 μg, but the dose can be increased up to 20 μg. The first injection is conducted by a professional as training. The needle is inserted into the corpus cavernosum on the lateral aspect of the mid‐penile shaft at a 90º angle. The erection appears after 5–15 minutes and lasts according to the dose injected. Efficacy is reported in >70% of patients with ED. A specific formulation of Alprostadil in a medicated pellet (medicated urethral system for erection [MUSE]) is approved for use in ED [5]. The dose ranges from 125 to 1000 μg. With intra‐urethral Alprostadil, erections sufficient for intercourse are achieved in 30–70% of patients. A vacuum erection device (VED) consists of three components: a vacuum chamber, pump, and a constriction band. It provides passive engorgement of the corpora cavernosa, together with a constrictor ring placed at the base of the penis to retain blood within the corpora. Satisfaction rates range between 27 and 94%. However, because of adverse effects, the long‐term use of VEDs decreases to 50–64% after two years. A penile prosthesis may be considered in patients who do not respond to pharmacotherapy or who prefer a permanent solution to their problem. The two currently available classes of penile implants are: Figure 34.8 Insertion of semi‐rigid prosthesis into corpora cavernosa. Figure 34.9 ‘DuraPhase’ penile prosthesis (Euro Surgical Ltd). Figure 34.10 ‘Dynaflex’ flexible penile prosthesis (Pfizer American Medical Systems). Prosthesis implantation has one of the highest satisfaction rates (92–100% in patients and 91–95% in partners) [6]. Patients must be warned that they will have a floppy glans and will need exchanging of the device after 10 years. Insertion of a penile prosthesis can be associated with the following complications: Premature ejaculation (PE) is the most common sexual disorder in men younger than 40 years of age. However, 30–70% of males can be affected by PE at one time or another. PE is a condition in which the entire sexual process of arousal, erection, ejaculation, and climax occur more rapidly, often in just a few minutes or even seconds, leaving the partner unsatisfied. The International Society of Sexual Medicine defines it as ‘a male sexual dysfunction characterised by ejaculation which always or nearly always occurs before or within about one minute of vaginal penetration; and the inability to delay ejaculation on all or nearly all vaginal penetrations; and negative personal consequences such as distress, frustration and/or the avoidance of sexual intimacy’ [7]. The ejaculatory latency is measured by the intravaginal ejaculatory latency time (IVELT), defined as the time between vaginal intromission and ejaculation. The mechanism of ejaculation (Figure 34.11) requires five coordinated functions: Figure 34.11 The mechanism of ejaculation. The smooth muscle fibres in the neck of the bladder and seminal vesicles are alpha adrenergic. Diabetic neuropathy, sympathectomy, alpha‐blocking drugs for hypertension, or surgical injury to the sympathetic chain or presacral nerve will prevent contraction of the vesicles and closure of the bladder neck. Prostatectomy or bladder neck incision should not affect contraction of the seminal vesicles, but the semen will tend to flow back into the bladder rather than squirt out from the urethra (i.e. retrograde ejaculation). Prostatectomy may inadvertently injure and obstruct the common ejaculatory ducts. History should include medical and sexual history and to ascertain which classification the patient is in. Specific questioning on the duration time of ejaculation, degree of sexual stimulus, impact on sexual activity and quality of life (QoL), drug use or abuse, situational PE (under specific circumstances or with a specific partner), and any coexisting ED. Latency estimation by patient self‐estimated IVELT is sufficient to establish classification. Stopwatch‐measured IVEPT can also be used. Patient reported outcome questionnaires can also be used; however, lack sufficient evidence (e.g. PE Diagnostic Tool and the Arabic Index of PE are two of the more popular questionnaires). Physical examination including general, neurological, and genitourinary examinations to establish underlying conditions. While laboratory investigations are tailored around further investigating underlying conditions. Any serious primary medical condition should be treated, as should any accompanying ED. To achieve the best outcome, the female partner should be included in the treatment and counselling sessions. The following behavioural and nonpharmacological measures should be use as first‐line therapy, except in lifelong PE. Use of topical desensitising agents (e.g. lignocaine and prilocaine) for PE can reduce the sensitivity of the glans penis, thus delaying ejaculation. Usually are used with condoms to prevent vaginal absorption leading to vaginal numbness. Topical lignocaine‐prilocaine cream has shown significant increase in the IVELT in various randomised, double‐blind, placebo‐controlled trials [10]. Patients are advised to use the cream (5%) for 20–30 minutes prior to intercourse. SS‐cream is a topical anaesthetic agent made from herbal extracts. It is known to increase the vibratory threshold and hence can improve PE. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants have had good efficacy for PE. These include paroxetine, citalopram, fluoxetine, fluvoxamine, sertraline, and clomipramine. Dapoxetine is the only on‐demand medication licenced for PE; it is a potent short‐acting SSRI with quick absorption (Tmax = 1.3 hours) and rapid clearance (half‐life: 95% clearance rate after 24 hours). On‐demand Dapoxetine has been evaluated in various trials and has shown promising results in the management of PE [11]. PDE5 inhibitors can increase confidence, the perception of ejaculatory control, and overall sexual satisfaction in patients with PE and ED; however, there is limited evidence on their efficacy for PE alone [12]. Retrograde ejaculation is defined as ‘failure of adequate closure of the bladder neck during ejaculation resulting in propulsion of ejaculate into the bladder’. Common causes of retrograde ejaculation are: Anatomical disruption of bladder neck Neurological damage Congenital causes Other causes Medications (e.g. alpha‐blockers) Presence of >10–15 sperms per high power field in post‐intercourse or orgasm confirms the diagnosis of retrograde ejaculation. Retrograde ejaculation is not known to have any adverse health effects. However, for patients with infertility due to retrograde ejaculation, the following options can be considered: Overall success of medical therapies is 50–60%. If medical therapies are not successful, for in‐vitro fertilisation, sperm can be retrieved from post‐ejaculatory urine. First the urine is rendered alkaline by giving the patient sodium bicarbonate 6 g every 4 hours for 24 hours beforehand. The bladder is emptied, and after ejaculation, the patient can ‘urinate’ before withdrawing, or the voided urine is centrifuged and placed in a plastic cup over the cervix or injected into it Artificial insemination using the husband’s semen is seldom worthwhile when his sperm is of poor quality, and before embarking on any programme, it needs to be understood by everyone involved that it can take multiple attempts before pregnancy is achieved if at all, even with normal semen. The greatest tact and care is necessary when setting up such a service, for the recurring monthly disappointment demands great sympathy. ‘Anejaculation is the complete absence of an antegrade or retrograde ejaculation’. Orgasm and ejaculation constitute the final phase of the sexual response cycle. There are three basic mechanisms involved in normal antegrade ejaculation: emission, ejection, and orgasm [13]. Ejaculatory dysfunction can result from disruption at any point in this cascade of events. True anejaculation is always connected with central or peripheral nervous system dysfunctions or with drugs (Table 34.3). Table 34.3 Causes of anejaculation. Anorgasmia is defined as the inability to reach orgasm. The causes of anorgasmia are usually psychological but may be related to drugs or reduced penile sensation (e.g. peripheral neuropathy). Mainstay of management is psychotherapy; however, neurological investigated may be required in selected patients. Drug treatment for anejaculation due neuropathy is not very effective. Priapism is the presence of a persistent, prolonged (>4 hours), painful or painless erection of the penis unrelated to sexual stimulation or desire for more than four hours. Priapism is the result of persistent engorgement of the corpora cavernosa of the penis, developing as a result of disturbance in the mechanism that controls normal penile detumescence. In most cases, the corpus spongiosum and glans penis remain flaccid. Failure of detumescence is associated with hypoxia, acidosis, and glucopaenia, causing impaired smooth muscle contraction resulting in thrombosis and necrosis after 24 hours. Priapism is idiopathic (primary) in more than half of all patients; the remainder it is secondary to other diseases or conditions (see below). Three subtypes of priapism are well described. It is an acute urological emergency (e.g. penile compartment syndrome) resulting from veno‐oclusion. A patient usually presents with a painful rigid erection with little or low cavernosal arterial blood flow. Low‐flow priapism accounts for 95% of all priapisms. By 12 hours, the corporal interstitium is oedematous if left untreated and leads to destruction of the sinusoidal endothelium and exposure of the basement membrane with thrombocyte adherence at 24 hours. By 48 hours, thrombi are found in the sinusoidal spaces, and smooth muscle necrosis with fibrosis has ensued. Common causes are : Usually related to trauma (i.e. pelvic or perineal), resulting in laceration of the cavernosal artery leading to a high‐flow fistula between the artery and the sinusoidal spaces and aberrant and unregulated arterial blood flow. There is usually a two‐ to three‐week period between the initial trauma and the priapism presentation. Intracorporeal blood is well oxygenated, and hence, it is less likely to cause injury to erectile tissues. Patient present with painless semi‐rigid erection. Characterised by repetitive and painful episodes of prolonged erections. The erections are self‐limiting with the frequency and duration of episodes varying. Nonetheless, single episodes can develop into a major period of ischaemic priapism. Causes are similar to low‐flow priapism, however, it is more commonly seen in patients with sick cell disease. This is a urological emergency as such no delay in initiating management, which has a stepwise approach for priapism >4 hours to try and attain detumescence and preserve potency, whereas for priapism >72 hours is to relieve the erection and if present associated pain as at this point potency is lost. Therapeutic aspiration is considered to be the first manoeuvre (after diagnostic aspiration). Via large‐bore needles (19 g) inserted into the corpora laterally (you can place two on either side), aspirate 20–30 ml of blood with or without normal saline irrigation, and the procedure is repeated until the aspirate is bright red. Aspiration achieves detumescence in approximately 30% of cases. If therapeutic aspiration fails, the next step is direct corporeal administration of a sympathomimetic agent, Phenylephrine, a selective α1 adrenergic agonist, has the best cardiovascular side‐effect profile and is thus recommended [14]. It is diluted with normal saline at a concentration of 100–200 μg ml−1 and given in 0.5–1 ml doses every 5–10 minutes for a maximum dose of 1 g for no more than 1 hour. Side effects include headaches, dizziness, tachycardia, hypertension, and arrhythmias. It can be expected to induce detumescence in 65–80% of cases if aspiration with or without saline irrigation is coupled with intracovernosal sympathomimetic or alpha‐agonist injections. Other medications used: etilefrine, ephedrine, epinephrine, norepinephrine, oral terbutaline, and metaraminol have been used; however, one must be cautious of the cardiovascular risks. For refractory cases not resolved by first‐line intervention within one hour of initiating treatment, prompt surgical intervention is required. The basic principle is to establish a shunt to drain trapped blood from the corpora by an opening in the tunica albuginea. Distal shunts establish a communication between the erect corpora cavernosa and either the glans penis. Figure 34.12 Incision to permit blood to flow from the corpora cavernosa into the glans. Figure 34.13 Trucut needle used to make a fistula between the corpora. If distal shunts are unsuccessful, proximal shunts can be used. Figure 34.14 Anastomosis between corpus spongiosum and cavernosum. Figure 34.15 Anastomosis between the saphenous vein and corpus cavernosum. Shunt procedures have combined success rates of 66–77%; proximal procedures are associated with the highest resolution rates but increased complications, particularly ED. Erectile dysfunction is a major complication of prolonged priapism, 90% of men with a priapism lasting >24 hours develop ED. It is for this reason that immediate penile prosthesis insertion, initially with a temporary malleable prosthesis, is often considered for failed shunting or late presentation (>48 hours) of priapism. This is not an emergency because there is no ischaemia. If initial aspiration of the corpus cavernosum reveals bright red blood, consider an arterial cause for priapism and institute the steps noted. Observation alone may be sufficient as erectile function is usually unimpaired. Ice‐pack pressure or compression therapy to the perineum may be successful, especially in children. Patients who do not respond to conservative measures. High success rate (90%), with varying recurrence rates (7–27%), and a high preservation of sexual function rate (80%) [15]. In rare cases, surgical ligation of the fistula may be required. However, potential complications of this procedure include long‐term ED. For surgical ligation, a transcorporeal approach under colour Doppler guidance is adopted. Focus is to prevent subsequent episodes, while the management of each individual episode is similar to that low‐flow priapism. To down‐regulate the testosterone levels which suppress its action on penile erection. Majority are acquired but rarely can be congenital. Prevalence has been reported to vary from <1 to 10% [16, 17]. Assessment by medical and sexual history can establish the diagnosis, with an examination to exclude other causes and to document curvature. The only treatment modality for the congenital form is surgical correction with plication in adulthood, which has a high correction rate (67–97%) [18]. An acquired benign condition, resulting in various degree of penile curvature, secondary to formation of a fibrous plaque within the tunica albuginea of the penis. Prevalence rates are between 0.4 and 9% with most patients between 40 and 60 years of age [19]. The aetiology of Peyronie disease is unknown. Repetitive microvascular injury or trauma to the tunica albuginea (during intercourse) is the most widely accepted hypothesis [20]. This leads to bleeding into the tunica albuginea, resulting in inflammation and fibrosis. Common associated comorbidities and risk factors are: A prolonged inflammatory response results in the remodelling of connective tissue and formation of a fibrotic plaque. The fibrous tissue in Peyronie disease can affect any part of the tunica albuginea around the corpora cavernosa or the septum between them. When the fibrosis affects one side more than the other, or dorsal more than the ventral, the penis bends during erection (Figure 34.16). Figure 34.16 Peyronie disease. Two phases of the disease have been described [21]. Pain is present in 35–45% of patients during the early stages of the disease, and in 90% of men, it resolves within 12 months. With time, penile curvature is expected to worsen in 30–50% of patients or stabilise in 47–67% of patients, while spontaneous improvement has been reported in 3–13% of patients [21]. At first, there is pain on erection with a lump (the plaque) which may become tender. When the penis is erect, it bends to the side of the lump (Figure 34.17). Sometimes intercourse may be impossible. ED is seen in 40% of patients. Complex deformities can lead to significant shortening or indentation. Figure 34.17 Polaroid photographs taken by a patient of his bent erections in Peyronie disease. Conservative treatment of Peyronie disease is mainly for patients in the early stage of the disease where the plaque is not stable, the deformity still changing, and there is still pain. The role of conservative treatment in stable or chronic disease is not well established. No single drug has been approved by the European Medical Association for the treatment of Peyronie disease; only potassium para‐aminobenzoate (POTABA) has been classified as possibly effective by the FDA. POTABA is thought to exert an anti‐fibrotic effect through an increase in oxygen uptake by the tissues, a rise in the secretion of glycosaminoglycans, and an enhancement of the activity of monoamine oxidases. Treatment with POTABA may result in a significant reduction in penile plaque size and penile pain as well as penile curvature stabilisation [22]. Adverse effects of POTABA include nausea, anorexia, pruritus, anxiety, chills, cold sweats, confusion, and difficulty in concentration. These include vitamin E, tamoxifen, colchicine, acetyl esters of carnitine, pentoxifylline, and PDE 5 inhibitors. Vitamin E acts as a natural antioxidant and is commonly prescribed by the majority of urologists at because of its wide availability, low cost, and safety. However, it has not shown any significant improvement in pain, curvature, or reduction of plaque size. XIAFLEX® (collagenase clostridium histolyticum) is the first and only FDA‐ and EMA‐approved biologic therapy indicated for the treatment of Peyronie disease in men with a palpable plaque and a curvature of 30° or greater at the start of therapy. Investigation for Maximal Peyronie Reduction Efficacy and Safety Studies (IMPRESS) I and II examined the clinical efficacy and safety of collagenase Clostridium histolyticum intralesional injections in subjects with Peyronie disease. The meta‐analysis of IMPRESS I and II data revealed statically significant improvement in penile curvature and Peyronie disease symptom bother score was significantly improved in treated men [23]. Verapamil (a calcium‐channel antagonist) can result in modification of the inflammatory response and the inhibition of fibroblast proliferation in the plaques. Dosage: 10 mg diluted to 10 nl, injected into the plaque every two weeks for 12 consecutive treatments. Several clinical studies have reported that intralesional verapamil may induce a reduction in penile curvature and plaque size. However, in a randomised, placebo‐controlled study, this benefit was not proven [24]. Similarly, intralesional steroid injections failed to show statistical significant benefits [25]. Topical verapamil (gel 15% applied twice daily) can improve penile curvature, plaque size, and penile pain, with significant improvement seen after nine months over three months, implying importance of a prolonged treatment [26]. Iontophoresis (also known as electromotive drug administration ([EMDA]) with verapamil 5 mg and dexamethasone 8 mg can improve penile curvature and plaque size. Shock wave lithotripsy (SWL) is thought to work either by directly damaging and remodelling of the penile plaque or as a result of increase vascularity or inflammatory reaction with increased macrophage activity, resulting in plaque lysis and resorption. SWL has not been shown to improve penile curvature and plaque size but provides improvement in penile pain. Traction and vacuum devices are thought to increase the activity of degradative enzymes, leading to a loss of tensile strength and ultimately solubilisation. Both these methods have shown some improvement in penile curvature. The aim of surgery is to correct curvature to allow satisfactory intercourse. Surgery is indicated only in patients with stable disease for at least three months. Stability of the disease is based on resolution of the pain and stability of the curvature. Three types of surgical options are considered for Peyronie disease: Choosing the most appropriate surgical intervention is based on penile length assessment, curvature severity, and erectile function status, including response to pharmacotherapy in cases of ED. Before surgery, a careful discussion with the patient is required focusing on following points: Penile‐shortening procedures include the Nesbit wedge resection and the plication techniques performed on the convex side of the penis (contralateral site to the Peyronie plaque). These procedures are the first treatment options for Peyronie disease in patients with adequate penile length and function, curvature <60°, and absence of more complex deformities (e.g. hour‐glass or hinge). The Nesbit procedure was first described for congenital penile curvature. Subsequently this procedure was successfully applied for management of Peyronie disease. This operation (Figure 34.18) is based on a 5‐ to 10‐mm transverse elliptical excision of the tunica albuginea (from convex side, that is, opposite the deformity) or approximately 1 mm for each 10° of curvature. The overall short‐ and long‐term results of the Nesbit operation are excellent. Figure 34.18 Nesbit’s operation for Peyronie disease. A series of ellipses are removed from the side opposite the plaque. The plication procedures (Figure 34.19) share the same principle as the Nesbit operation but are simpler to perform. They are based on single or multiple longitudinal incisions on the convex side of the penis (opposite side of deformity) sutured in a horizontal way, or simple plication is performed without incisions, but suture opposite side of the deformity to straighten the penis. Another modification has been described, the‘16 dot’ technique with minimal tension under local anaesthesia [28]. Figure 34.19 (a) Plication operation for Peyronie disease. Having made an artificial erection, a series of nonabsorbable sutures are placed on the opposite side (b) and when tied, straighten the penis. (c) When there is a dorsal plaque, the sutures are inserted after mobilising the corpus spongiosum. Penile‐lengthening procedure are the preferred treatment option for patients with Peyronie disease with inadequate penile length, curvature >60°, and presence of complex deformities Penile‐lengthening procedures (e.g. Lue procedure) are performed on the concave side of the penis (incisions of the plaque) and insertion of a graft to minimise penile shortening. A variety of grafting materials (e.g. autologous dermis, vein grafts, tunica albuginea, tunica vaginalis, allograft; cadaveric pericardium, cadaveric fascia lata, and synthetic grafts; Gore‐Tex, Dacron) have been reported. Plaque removal can cause venous leak and hence the grafting procedures are associated with ED in 25% of patients. Additionally long‐term failures results in reoperation in up to 17% patients [29]. Penile prosthesis implantation is typically reserved for the treatment of patients with Peyronie disease and ED not responding to pharmacotherapy. Late onset hypogonadism (LOH) is also called ‘andropause’; however, unlike menopause, the reduction of testosterone is a slow gradual drop. Incidence varies based on age, can be around 4% in those <30 years of age, 20% in men older than age 60, 30% older than age 70, and 50% in men older than 80 years of age [30]. LOH is also known as age‐associated testosterone deficiency syndrome and is defined as ‘a clinical and biochemical syndrome associated with advancing age and characterised by symptoms and a deficiency in serum testosterone levels (below the young healthy adult male reference range). This condition may results in significant detriment in the QoL and adversely affect the function of multiple organ systems’ [31]. Production of testosterone decreases by 1–2% every year after the age of 40 years [32, 33]. Natural reduction in testosterone production by ageing testicles leads to an increase in LHRH and LH secretion from the hypothalamus and pituitary glands; however, there is lack of sensitivity to LH and the testosterone levels stay low. With time, the production of LHRH and LH also decreases. Furthermore, sex‐hormone binding globulin (SHBG) bind to testosterone, reducing availability of testosterone even further. SHBG levels increase with age, cirrhosis, hyperthyroidism, use of anticonvulsants and oestrogens, and in HIV infections. Testicular volume decreases by 15% between 25 and 80 years of age, with a 50% reduction of Sertoli and Leydig cells [34]. Furthermore, there is an age‐related reduction in seminal fluid production, sperm production with less motility, and increased abnormal morphology; however, sperm concertation remains constant lead to infertility or subfertility [34]. Primary hypogonadism (testicular) causes low testosterone levels and impaired spermatogenesis, with elevated or normal LHRH, LH, and FSH levels. Secondary hypogonadism (nontesticular or central) causes disruptions in the LHRH and LH secretions. Obesity and metabolic syndrome, DM, chronic illnesses especially steroid or opiate requirements (e.g. chronic obstructive lung disease and inflammatory arthritic), end‐stage renal disease on dialysis, HIV‐related diseases, cardiovascular disease, and pituitary lesions [31, 33]. Clinical features are a lack of testosterone, the most prevalent symptoms being loss of libido, ED, and hot flushes; others include loss of vigour and strength, decreased muscle mass, small testes, delayed puberty, decreased body hair, lethargy and fatigue, metabolic syndrome and increased body fat visceral obesity, decreased bone mineral density, osteoporosis, decreased vitality, depressed mood, reduced concentration and lack of sleep, infertility or subfertility, and reduced bone mineral density [31, 33]. History looking for the signs and symptoms and a general examination with a focused urological examination include a prostate examination. Investigation [31, 33, 35, 36]: Total testosterone levels of 8 nmol l−1 leads to a loss of libido and 8.5 nmol l−1 ED. Management is aimed to improve QoL through testosterone replacement. Symptoms in general will improve with testosterone replacement within three to six months, with longer replacement periods needed for improvement in bone mineral density. Therefore, treatment should not go beyond six months if symptoms do not improve and will require re‐evaluating the diagnosis. Figure 34.20 outlines the diagnosis and treatment of LoH [36]. Figure 34.20 Algorithm for diagnosis and treatment of late onset hypogonadism. DRE, digital rectal examination; FSH, follicle‐stimulating hormone; Hb/Hct, hemoglobin/hematocrit; LH, luteinising hormone; MRI, magnetic resonance imaging; PRL, prolactin; PSA, prostate‐specific antigen; SHBG, sex‐hormone binding globulin. Contraindications for testosterone replacement Side effects of testosterone replacement Regular follow‐up during treatment is essential to maintain a symptom‐free status. Testosterone replacement can improve libido after three weeks of initiation of replacement and plateau at six weeks; erectile function improvement can take up to six months, and overall improvement of symptoms might be evident by the first four weeks [33]. Various testosterone preparations are available (Table 34.4) and should be tailored around the patients’ needs and compliance. Table 34.4 Testosterone replacement preparations.
Penis and Urethra Disorders of Function
Abstract
34.1 Erectile Dysfunction
34.1.1 Pathophysiology
34.1.1.1 Psychogenic Erectile Dysfunction
34.1.1.2 Organic Erectile Dysfunction
34.1.1.2.1 Arterial Causes
34.1.1.2.2 Venous Causes
34.1.1.2.3 Neurological Causes
Causes of Central Neuropathy
Causes of Peripheral Neuropathy
34.1.1.2.4 Hormonal Causes
34.1.1.2.5 Drugs
34.1.2 Assessment
34.1.2.1 Clinical History
Over the past 6 months
1) How do you rate your confidence that you could get and keep an erection?
Very low
Low
Moderate
High
Very high
2) When you had erections with sexual stimulation, how often were your erections hard enough for penetration?
Almost never/never
A few times (<50% of the time)
Sometimes (about half the time)
Most times (>50% of the time)
Almost always/always
3) During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?
Almost never/never
A few times
(< 50%of the time)
Sometimes (about half the time)
Most times (>50% of the time)
Almost always/always
4) During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?
Extremely difficult
Very difficult
Difficult
Slightly difficult
Not difficult
5) When you attempted sexual intercourse, how often was it satisfactory for you?
Almost never/never
A few times (<50% of the time)
Sometimes (about half the time)
Most times (>50% of the time)
Almost always/always
Score
1
2
3
4
5
34.1.2.2 Physical Examination
34.1.3 Investigations
34.1.3.1 General Investigations
34.1.3.2 Specialised Investigations
34.1.4 Management
34.1.4.1 First‐Line Medical Therapy
34.1.4.1.1 Phosphodiesterase 5 inhibitors
Key Features
Sildenafil
(Viagra)
Vardenafil
(Levtra)
Tadalafil
(Cialis)
Avanafil
(Spedra)
Onset of action
30–60 min
30–60 min
60–120 min
15–30 min
Half‐life
2.6–3.7 h
3.9 h
17.5 h
4–5 h
Duration of Action
Up to 12 h
Up to 10 h
Up to 36 h
Up to 6 h
Available doses
25,50, 100 mg
5, 10, 20 mg
5, 10, 20 mg
50, 100, 200 mg
High fat meal efficacy effect
Decrease efficacy
Decrease efficacy
Not affected
Not affected
Side effects:
+
+
+
+
+
+
–
–
+
+
+
+
+
–
–
–
+
+
+
+
+
–
+
+
+
+
+
+
+
+
+
–
34.1.4.1.2 Mechanism of Action
34.1.4.1.3 Pharmacokinetic and Side Effects of PDE5 Inhibitors
34.1.4.1.4 Specific Considerations
34.1.4.1.5 Assessment of Non‐Responders
34.1.4.2 Second‐Line Therapy
34.1.4.2.1 Intracavernosal Injections
Adverse Effects
Contraindications
34.1.4.2.2 Intra‐urethral Alprostadil
Adverse Effects
34.1.4.3 Vacuum Erection Device
34.1.4.3.1 Principle
34.1.4.3.2 Adverse Effects
34.1.4.4 Third‐line Therapy: Penile Prostheses
34.2 Premature Ejaculation
34.2.1 Aetiology
34.2.1.1 Biological Factors
34.2.1.2 Psychological Factors
34.2.2 Classification of Premature Ejaculation
34.2.3 Assessment
34.2.4 Management
34.2.4.1 Behavioural and Nonpharmacologic Therapy
34.2.4.2 Pharmacologic Therapy
34.2.4.2.1 Topical Anaesthetic Agents
Lignocaine‐Prilocaine Cream
Severance‐Secret (SS) Cream
34.2.4.2.2 Oral Medication
34.3 Retrograde Ejaculation
34.3.1 Aetiology
34.3.2 Presentation
34.3.3 Diagnosis
34.3.4 Management
34.4 Anejaculation
34.4.1 Aetiology
Neurological causes
Spinal cord injury cauda equina lesions
Retroperitoneal lymphadenectomy
Colorectal or pelvic surgery
Multiple sclerosis
Parkinson disease
Autonomic neuropathy
Pharmacological
Antihypertensives
Antidepressants
Antipsychotics
Others Alcohol excess
34.4.2 Anorgasmia
34.4.3 Management
34.5 Priapism
34.5.1 Pathophysiology
34.5.2 Aetiology and Classification
34.5.2.1 Low‐Flow (Ischemic) Priapism
34.5.2.2 High‐Flow (Nonischemic) Priapism
34.5.2.3 Stuttering (Recurrent or Intermittent) Priapism
34.5.3 Assessment
34.5.4 Management
34.5.4.1 Management of Low‐Flow Priapism
34.5.4.1.1 Pharmacotherapy
34.5.4.1.2 Surgical Interventions
Distal Shunts
Percutaneous Distal Shunts
Open Distal Shunts
Proximal Shunts
Open Proximal Shunt
34.5.4.1.3 Penile Prosthesis
34.5.4.2 Management of High‐Flow Priapism
34.5.4.2.1 Conservative Management
Selective Arterial Embolisation
Surgical Management
34.5.4.3 Management of Stuttering Priapism
34.5.4.3.1 Hormonal Manipulation
34.6 Peyronie Disease
34.6.1 Congenital Peyronie Disease
34.6.2 Acquired Peyronie Disease
34.6.3 Aetiology
34.6.4 Pathogenesis and Natural History
34.6.5 Clinical Features
34.6.6 Management
34.6.6.1 Nonoperative Treatment
34.6.6.1.1 Oral Agents
Potassium Para‐aminobenzoate
34.6.6.1.2 Other Oral Agents
Intralesional Treatment
34.6.6.1.3 Topical Treatment
34.6.6.1.4 Shock Wave Lithotripsy
34.6.6.1.5 Traction and Vacuum Devices
34.6.6.2 Surgical Treatment
34.6.6.2.1 Choosing Surgical Options
Penile‐Shortening Procedures
Nesbit Procedure
Plication Procedures
Penile‐Lengthening Procedures
Penile Prosthesis
34.7 Late Onset Hypogonadism
34.7.1 Definition
34.7.2 Pathophysiology
34.7.3 Aetiology
34.7.4 Risk Factors Increasing the Likelihood of LoH
34.7.5 Clinical Features
34.7.6 Diagnosis
34.7.7 Treatment [31, 33, 35, 36]
Preparation
Oral (testosterone undecanoate)
Need to be taken with fatty foods, but as metabolised in the liver has lower efficacy with variable testosterone levels.
Intramuscular
Undecanoate is long‐acting injected every three months. Good level control, however, cannot withdraw if significant side effects develop.
Cypionate and enanthate are short‐acting injected every two to three weeks. Difficult to control levels, therefore, causes varying responses from improvement to no change in symptoms.
Transdermal
Daily use with good replacement of testosterone levels; causes skin irritation.
Sublingual and buccal
Daily use with good replacement of testosterone levels; causes local mucosal irritation.
Subdermal depot injections
Long‐acting injected every five to seven months. Increased risk of infections and extrusion of implants.
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