Penis and Urethra Disorders of Function

Penis and Urethra Disorders of Function

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.

Keywordserectile dysfunction (ED); phosphodiesterase type 5 (PDE5) inhibitor; Peyronie disease; premature ejaculation (PE); priapism; retrograde ejaculation

34.1 Erectile Dysfunction

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].

34.1.1 Pathophysiology

ED is generally classified as psychogenic and organic, but in most cases, it is combination of both. Psychogenic Erectile Dysfunction

Psychogenic ED frequently coexists with other sexual dysfunctions, notably reduced libido and with major psychiatric disorders particularly depression and anxiety [1]. Organic Erectile Dysfunction Arterial Causes

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]. Venous Causes

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

  • Primary large venous leak draining the corpora cavernosa.
  • Traumatic injury to tunica albuginea (e.g. penile fracture).
  • Acquired shunt e(.g. after operative intervention for priapism).
  • Degenerative changes associated with old age, DM, and Peyronie disease. Neurological Causes

Disruption of the erectogenic neural pathways (central and peripheral) leads to the development of ED.

Causes of Central Neuropathy

There are a variety of causes of central neuropathy, among them are:

  • Multiple sclerosis (MS)
  • Cerebrovascular accidents
  • Malignancy (e.g. brain and spinal cord)
  • Parkinson disease
  • Multisystem atrophy
  • Spinal cord transection

Causes of Peripheral Neuropathy

There are a variety of causes of peripheral neuropathy, among them are:

  • MS
  • DM
  • Sacral cord injury and pelvic fracture
  • Radical pelvic surgery Hormonal Causes

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. Drugs

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).

34.1.2 Assessment Clinical History

  • A careful and sympathetic history is essential to determine that what a patient describes as ED is not some other sexual dysfunction.
  • Patients should be asked specifically about onset of symptoms, early morning erection, loss of libido, and ejaculatory disorders to establish the type of ED (psychogenic or organic).
  • Patients should detail past medical history of DM, hypertension, cardiovascular diseases, neurological diseases, pain or angulation of penis, history of trauma or pelvic surgery, drug history; history of smoking, alcohol intake, or substance misuse to establish a possible aetiology. Physicians should confirm any previous treatment for ED and the response.
  • Validated ED questionnaires such as the International Index of Erectile Function (IIEF) is useful to record objective evidence of severity of ED (Table 34.1).

Table 34.1 IIEF‐5 scoring: The IIEF‐5 score is the sum of the ordinal responses to the five items.

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

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

Physical examination should consist of a general abdominal, neurological, and cardiovascular examinations.

  • Blood pressure and signs of arteriopathy.
  • Body mass index (BMI) and waist circumference.
  • Secondary sexual characteristics.
  • Genital examination (i.e. note size of penis and testes, presence of penile plaque or angulation, phimosis, or hypospadias).
  • Evidence of previous trauma or pelvic surgery.
  • Penile sensation.
  • Bulbocavernosus reflex (i.e. squeezing the glans leads to contraction of the anal sphincter and bulbocavernosal muscles; this tests the integrity of S2–4).
  • Testicular examination: size, location, abnormality, or abscess.
  • Digital rectal examination (DRE): perineal sensation, anal reflex or tone, and prostate examination (if older than 50 years of age).

34.1.3 Investigations General Investigations

In most patients with ED, the following initial blood tests are recommended:

  • Fasting blood glucose and HbA1c.
  • Lipid profile.
  • Total testosterone level (tested for between 8 and 11 a.m.); if testosterone levels are subnormal, follicle‐stimulating hormone (FSH), luteinising hormone (LH), and prolactin levels should be performed. Other investigations can be done based on relevant history and examination findings (i.e. prostate‐specific antigen [PSA] and thyroid function tests). Specialised Investigations

  • Penile Doppler Ultrasound: a peak systolic blood flow of >30 cm s−1, an end‐diastolic velocity of <5 cm s−1, and a resistance index of >0.8 before and after intracavernosal injection of prostaglandin E1 (PGE1) is considered normal.
  • Nocturnal penile tumescence and rigidity testing: An objective record of nocturnal erection is made with two strain gauges fitted around the base and distal penis (Figures 34.1 and 34.2). A good or functional erection is with a minimum of 60% rigidity recorded on the tip of the penis that lasts for >10 minutes. A paper strip which records its expansion during sleep to demonstrate the presence of nocturnal erections, which can be useful for psychogenic ED (Figure 34.3).
  • Penile arteriography: In younger patients with trauma‐related ED or in patients considered for vascular reconstruction surgery.
  • Cavernosography: Intracavernosal contrast and artificial erection is used to determine evidence of venous leak. The pressure in the venous sinuses of the corpora can be recorded during an erection (Figure 34.4). Fluoroscopy shows whether the penile veins are being effectively closed during the phase of rigid erection (Figure 34.5).
Top: Diagram depicting a penis fitted with subcoronal strain gauges around the base for plethysmograph. Bottom: Graph of increased circumference vs. time depicting 2 fluctuating waves labeled subcoronal and basal.

Figure 34.1 Strain gauges fitted around the penis record nocturnal tumescence.

Photo displaying a paper strip with measurements (mm) used for denoting the expansion of the penis during sleep.

Figure 34.2 Paper strips can be used to denote expansion of the penis during sleep.

Photo displaying an apparatus used for psychogenic ED.

Figure 34.3 A continuous record is made of expansion and elongation of the penis during sleep.

Image described by caption.

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.

Image described by caption.

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).

34.1.4 Management

General measures should be considered before pharmacotherapy for ED.

  • Identify any reversible cause of ED (e.g. drug induced or hormonal abnormalities).
  • Correction of underlying disorder (e.g. good glycaemic control, correction of hyperlipidaemia, hyperprolactinaemia management, cessation of smoking, weight loss, and exercise).
  • Lifestyle changes and risk factor modification (e.g. exercise, weight reduction, and avoidance of precipitating factors) can improve ED but more importantly improve overall health and reduce cardiovascular risks.
  • All patients with significant cardiovascular disease need to see a cardiologist before ED treatment. Sexual activity is equivalent to walking a mile on a flat surface in 20 minutes or climbing two flights of stairs in 10 seconds.
  • Psychosexual therapy for patients with psychiatric disorders and younger patients with ED. First‐Line Medical Therapy Phosphodiesterase 5 inhibitors

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.

Key Features Sildenafil
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:

  • Headache
  • Flushing
  • Dyspepsia
  • Nasal congestion
  • Dizziness
  • Abnormal vision
  • Back pain
  • Myalgia





+ Mechanism of Action

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.

Image described by caption.

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. Pharmacokinetic and Side Effects of PDE5 Inhibitors

Key pharmacokinetic features are summarised in Table 34.2. Specific Considerations

  • Cardiovascular disease: there is no evidence that PDE5Is have a negative effect on these patients (i.e. do not increase infarction rates or negative effect on exercise testing).
  • Nitrates are absolutely contraindicated as the result in accumulation of cGMP which can lead to severe blood pressure drops and symptomatic hypotension.
  • All PDE5 inhibitors show some interaction with alpha‐blockers and may result is orthostatic hypotension Assessment of Non‐Responders

  • Establish that the patient is following appropriate instruction (i.e. ensuring adequate sexual stimulation and allowing for the medication to take effect before attempting sexual intercourse). Some PDE5 inhibitors have a reduced efficacy with high‐fat foods.
  • Appropriate dose has been used.
  • Check patient is using licenced medication and not buying from black market. Second‐Line Therapy Intracavernosal Injections

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).

Image described by caption.

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.

Adverse Effects

  • Penile pain (50%).
  • Prolonged erections (5%).
  • Fibrosis (2%).
  • Priapism (1%).


  • History of hypersensitivity to Alprostadil.
  • Men at risk of priapism.
  • Bleeding disorders (Sickle Cell disease). Intra‐urethral Alprostadil

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.

Adverse Effects

  • Local pain (35%).
  • Dizziness with possible hypotension (1.9–14%).
  • Urethral bleeding (5%).
  • Penile fibrosis and priapism (<1%).
  • Urinary tract infections (0.2%). Vacuum Erection Device Principle

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. Adverse Effects

  • Penile pain.
  • Inability to ejaculate.
  • Petechiae or bruising.
  • Penile numbness.
  • Skin necrosis (can be avoided if patients remove the constriction ring within 30 minutes). Third‐line Therapy: Penile Prostheses

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:

Left: Diagram of a penis inserted with semi‐rigid prosthesis into corpora cavernosa. Middle: A Hegar’s dilator. Right: A penis inserted with small-Carrion prosthesis.

Figure 34.8 Insertion of semi‐rigid prosthesis into corpora cavernosa.

Image described by caption.

Figure 34.9 ‘DuraPhase’ penile prosthesis (Euro Surgical Ltd).

Image described by caption.

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:

  • Infection (5%).
  • Erosion (5%).
  • Mechanical failure (4%).

34.2 Premature Ejaculation

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:

  1. The seminal vesicles contract rhythmically to pump up.
  2. Peristaltic contractions of the vas deferens eject a small volume of semen containing sperm through the common ejaculatory ducts.
  3. This is followed by contraction of the seminal vesicles which squirt the sperm‐rich fraction of semen into the prostatic urethra.
  4. At the same time the bladder neck closes and the external sphincter relaxes, preventing the sperm from flowing back and expelling it down the urethra, assisted by the contractions of stage 5.
  5. Rhythmical contractions of the bulbospongiosus muscle take place.
Diagrams illustrating the mechanism of ejaculation. The left diagram has lines marking vas deferens, seminal vesical, and internal sphincter. The right diagram has lines marking seminal vesical fluid and spermrich fluid.

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.

34.2.1 Aetiology Biological Factors

  • Penile hypersensitivity
  • Hyperexcitable ejaculatory reflex orabnormal reflex activity of ejaculatory system (e.g. 5‐hydroxytryptamine (5‐HT) receptor sensitivity.
  • Inflammation or infection of prostate.
  • Abnormal hormone level (e.g. testosterone).
  • Side effect of some drugs (e.g. antihypertensive).
  • Nervous system damage (e.g. surgery or trauma). Psychological Factors

  • Fear (often stems from previous experience of PE).
  • Stress, anxiety, or relationship problems.
  • Early sexual experience.
  • Reduced frequency of sexual intercourse.

34.2.2 Classification of Premature Ejaculation

  • Lifelong PE: onset from the first sexual experience and remains so during life. Characterised by ejaculation before vaginal penetration or <1–2 minutes IVELT and usually caused by genetic or neurological factors. In most cases pharmacotherapy is required (see below).
  • Acquired PE: gradual or sudden onset following normal ejaculation experiences. Characterised by short IVELT and caused by medical or psychological disorders. Management includes psychotherapy and pharmacotherapy.
  • Natural variable PE: inconsistent and irregular early ejaculations, a normal variation with men having PE occasionally. IVELT 3–8 minutes. Reassurance and psychotherapy is mainstay of management.
  • Premature‐like ejaculatory dysfunction: subjective perception of consistent or inconsistent rapid ejaculation during intercourse and IVELT 3–30 minutes (normal to prolonged). Reassurance and psychotherapy is needed; this group should not be considered to have manifestations of true medical pathology.

34.2.3 Assessment

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.

34.2.4 Management

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. Behavioural and Nonpharmacologic Therapy

The following behavioural and nonpharmacological measures should be use as first‐line therapy, except in lifelong PE.

  • Psychosexual counselling and education: Efforts to relieve underlying performance pressure on the male.
  • Sex therapy instruction in the stop‐start manoeuvres: The partner stimulates the penis until the urge to ejaculate, at which point stimulation is stopped until the sensation subsides, and then resumed [8] or a modified version, the squeeze‐pause technique (i.e. similar to stop‐start, but the partner squeezes the glans until the urge subsides). It is usually applied in three cycles before preceding to orgasm.
  • Second attempt at coitus: If another erection can be achieved shortly after an episode of PE, ejaculatory control may be much better second time.
  • Masturbation: This can teach the patient to recognise the signs of increased sexual arousal and how to keep his level of sexual excitement below the intensity that elicits the ejaculatory reflex [9].
  • Exercises: The aim of pelvic floor muscle exercise is to restore erectile function by strengthening the bulbocavernosus and ischiocavernous muscles.
  • Treat ED and genitourinary infection. Pharmacologic Therapy Topical Anaesthetic Agents

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.

Lignocaine‐Prilocaine Cream

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.

Severance‐Secret (SS) Cream

SS‐cream is a topical anaesthetic agent made from herbal extracts. It is known to increase the vibratory threshold and hence can improve PE. Oral Medication

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].

34.3 Retrograde Ejaculation

Retrograde ejaculation is defined as ‘failure of adequate closure of the bladder neck during ejaculation resulting in propulsion of ejaculate into the bladder’.

34.3.1 Aetiology

Common causes of retrograde ejaculation are:

Anatomical disruption of bladder neck

  • Post‐transurethral resection of prostate [TURP]or open prostatectomy
  • Post‐bladder neck incision
  • Trauma to bladder neck
  • Transurethral resection of ejaculatory ducts due to obstruction

Neurological damage

  • Retroperitoneal lymph node dissection
  • Spinal cord injury
  • DM neuropathy

Congenital causes

  • Bladder extrophy
  • Spina bifida
  • Ectopic ejaculatory ducts

Other causes

Medications (e.g. alpha‐blockers)

34.3.2 Presentation

  • Typically a patient presents with dry orgasm or low (<1 ml) ejaculate volume and cloudy urine (first voided urine post‐intercourse or orgasm).
  • Infertility

34.3.3 Diagnosis

Presence of >10–15 sperms per high power field in post‐intercourse or orgasm confirms the diagnosis of retrograde ejaculation.

34.3.4 Management

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:

  • Sympathomimetics: For example, ephedrine and pseudoephedrine 30 minutes before intercourse. Due to sympathomimetic effects, these medications close the bladder neck and facilitate antegrade ejaculation.
  • Tricyclic anti‐depressants: Such as Imipramine have mixed sympathomimetic and anti‐cholinergic effect.

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.

34.4 Anejaculation

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.

34.4.1 Aetiology

True anejaculation is always connected with central or peripheral nervous system dysfunctions or with drugs (Table 34.3).

Table 34.3 Causes of anejaculation.

Neurological causes
Spinal cord injury cauda equina lesions
Retroperitoneal lymphadenectomy
Colorectal or pelvic surgery
Multiple sclerosis
Parkinson disease
Autonomic neuropathy
Others Alcohol excess

34.4.2 Anorgasmia

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.

34.4.3 Management

Drug treatment for anejaculation due neuropathy is not very effective.

  • In all these cases, especially in men with spinal cord injuries, vibrostimulation (i.e. the application of a vibrator to the penis) is the first‐line therapy.
  • In patients not responding to vibrostimulation, electroejaculation is the therapy of choice. Electroejaculation involves an electric stimulation of the periprostatic nerves via a rectal probe.
  • When electroejaculation fails or cannot be performed, sperm retrieval from the seminal ducts may be achieved by:

    • Sperm aspiration from proximal vas deferens
    • Seminal tract washout

  • In case of failure of sperm retrieval, epididymal obstruction or testicular failure must be suspected. If there is clinical suspicion of possible ejaculatory duct obstruction, transrectal ultrasonography or vasography may be required.

34.5 Priapism

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.

34.5.1 Pathophysiology

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.

34.5.2 Aetiology and Classification

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. Low‐Flow (Ischemic) Priapism

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 :

  • Thromboembolic disorders: Sickle cell anaemia, leukaemia, multiple myeloma, thalassaemia, fat emboli, and haemodialysis.
  • Neurogenic: Spinal cord injury, autonomic neuropathy, anaesthesia, syphilis, cauda equine syndrome, lumbar disc herniation, spinal stenosis, cerebrovascular accident, and brain tumour.
  • Drugs: Intracavernosal injection of PGE1 (rare <1%) or with PDE5 inhibitors combination injections (up to 35%), alpha‐blockers, anti‐depressants, anti‐psychotics, anticoagulants, antihypertensives, hormones, and recreational drugs.
  • Regional or metastatic infiltration from cancer.
  • Infections (toxin‐mediated) scorpion sting, spider bites, rabies, or malaria. High‐Flow (Nonischemic) Priapism

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. Stuttering (Recurrent or Intermittent) Priapism

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.

34.5.3 Assessment

  • History and clinical examinations is vital in initial assessment and distinguishing between various types of priapism. Duration of erection, presence of pain, previous episodes, medication, trauma, and presence of any haematological illnesses should be elicited in the history. General examination as well as evaluation of the priapism to establish low (fully rigid or painful) or high (semi‐rigid or painless) flow.
  • A full blood count (rule out leukaemia). If Sickle Cell status is unknown, a haemoglobin S determination is useful. Platelet count and coagulation profile as well. Further investigations depend on the history.
  • Blood glass analysis of the corpus cavernosa aspirated blood is useful to differentiate between high‐ and low‐flow disease. Values similar to venous blood suggest a low‐flow priapism can also be hypoxic and acidotic and will be dark in colour. Values similar to arterial blood suggest high‐flow priapism; the colour will be bright red.
  • Radiological investigations are not usually required. However, if in doubt, colour flow penile Doppler imaging is the study of choice. Furthermore, in patients with high‐flow priapism, selective penile angiography (i.e. pudendal artery) can identify the site of the fistula before embolisation.

34.5.4 Management

  • Conservative measures: Immediate treatment include ice packs to the perineum and penis, asking the patient to walk upstairs, and masturbation.
  • Treatment of underlying cause: Treat the underlying cause whenever possible. Priapism secondary to Sickle Cell disease is treated with intravenous hydration, alkalization with bicarbonates, narcotic analgesia, and oxygenation to prevent further sickling. Exchange and transfusions may be required to increase the tissue delivery of oxygen. Management of Low‐Flow Priapism

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. Pharmacotherapy

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. Surgical Interventions

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

Distal shunts establish a communication between the erect corpora cavernosa and either the glans penis.

Percutaneous Distal Shunts

  • Winter shunt: using venflon or true cut needle to create a fistula between the glans and each corpora cavernosa body.
  • Ebbehøj shunt: using a scalpel‐blade, multiple tunical incision windows between the glans and each tip of the corpus are created percutaneously.
  • Lue shunt: a scalpel is paced vertically through the glans until fully within the corpora then rotated 90° (away from urethra as not to damage it) and pulled out (T‐shunt).

Open Distal Shunts

  • Al‐Ghorab shunt: excision of disc of corpus cavernosum tip.
  • Burnett shunt: a modification of Al‐Ghorab shunt, same excision is done then a dilator is inserted into the corpus (Figures 34.12 and 34.13).
Image described by caption.

Figure 34.12 Incision to permit blood to flow from the corpora cavernosa into the glans.

Image described by caption.

Figure 34.13 Trucut needle used to make a fistula between the corpora.

Proximal Shunts

If distal shunts are unsuccessful, proximal shunts can be used.

Open Proximal Shunt

  • Quackles shunt (i.e. corporospongiosal shunt): creating a communication between the corpus spongiosum and cavernosum (Figure 34.14).
  • Sacher shunt: same as Quackles, but bilateral Venous shunts
  • Grayhack shunt: the saphenous vein is anastomosed (end to side) to the corpus cavernosum (Figure 34.15).
Image described by caption and surrounding text.

Figure 34.14 Anastomosis between corpus spongiosum and cavernosum.

Image described by caption and surrounding text.

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. Penile Prosthesis

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. Management of High‐Flow 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. Conservative Management

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.

Selective Arterial Embolisation

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].

Surgical Management

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. Management of Stuttering Priapism

Focus is to prevent subsequent episodes, while the management of each individual episode is similar to that low‐flow priapism. Hormonal Manipulation

To down‐regulate the testosterone levels which suppress its action on penile erection.

  • Gonadotropin‐releasing hormone agonists or antagonists most efficacious and safe treatment in adults.
  • Antiandrogens (i.e. flutamide and bicalutamide) and oestrogens.
  • 5‐alpha‐reductase inhibitors.
  • Ketoconazole.

  1. Should not be used before reaching sexual maturation or if planning on conceiving.

  • Pseudoephedrine is first‐line treatment.
  • Etilefrine is successful in patients with Sickle Cell disease.

  1. Other treatments are available with limited evidence

  • PDE5 inhibitors: low doses of sildenafil and tadalafil have a paradoxical effect in alleviating and preventing stuttering priapism in idiopathic disease and in patients with Sickle Cell. Treatment should be started when the penis is flaccid and not during an episode.
  • Intracavernosal injections with an alpha agonist.
  • Terbutaline (beta‐2 agonist with some alpha agonist activity) used for alprostadil‐induced priapism and in patients with Sickle Cell disease.
  • Digoxin and gabapentin have also been used for idiopathic stuttering priapism.

34.6 Peyronie Disease

Majority are acquired but rarely can be congenital.

34.6.1 Congenital Peyronie Disease

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].

34.6.2 Acquired Peyronie Disease

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].

34.6.3 Aetiology

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:

  • DM.
  • Hypertension.
  • Lipid abnormalities.
  • Ischaemic cardiomyopathy.
  • ED.
  • Low testosterone.
  • Tympanosclerosis.
  • Smoking.
  • Excessive consumption of alcohol.
  • Dupuytren contracture (i.e. more common in patients with Peyronie disease affecting 9–39% of patients, while 4% of patients with Dupuytren contracture report Peyronie disease).

34.6.4 Pathogenesis and Natural History

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).

Diagram displaying a bent erect penis with shaded area labeled plaque.

Figure 34.16 Peyronie disease.

Two phases of the disease have been described [21].

  • The first phase is the acute inflammatory phase (active phase), which may be associated with painful erections, formation of a soft plaque, and penile curvature.
  • The second phase is the fibrotic phase (stable phase) with the formation of hard palpable plaques (which may be calcified), penile curvature, and disease stabilisation (no pain).

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].

34.6.5 Clinical Features

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.

  • Assessment and history must include duration of the disease, penile pain, any penile deformity, difficulty in vaginal intromission due to deformity, and associated ED.
  • Physical examination should include assessment of palpable nodules or plaque, its location, any tenderness, penile length, extent of curvature (e.g. self‐photograph, vacuum pump/pharmacological‐induced erection), and any other possibly related diseases such as Dupuytren contracture.
  • Investigations are seldom necessary. However, if required a Doppler ultrasound or a cavernosogram can delineate the plaque, but more importantly, it provides an assessment of vascular parameters. Magnetic resonance imaging (MRI) is helpful in complex deformities.
Image described by caption.

Figure 34.17 Polaroid photographs taken by a patient of his bent erections in Peyronie disease.

34.6.6 Management Nonoperative Treatment

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. Oral Agents

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.

Potassium Para‐aminobenzoate

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. Other Oral Agents

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.

Intralesional Treatment

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 Treatment

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

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

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. Surgical Treatment

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:

  1. Penile‐shortening procedures.
  2. Penile‐ lengthening procedures.
  3. Penile prosthesis. Choosing Surgical Options

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: Patients often perceive the loss of length as greater than it actually is [27]. It is therefore advisable to measure and document the penile length perioperatively, both before and after the straightening procedure.
  • ED.
  • Penile numbness.
  • Recurrence of curvature.
  • Potential for palpation of knots or stitches underneath the skin.
  • Need for circumcision at the time of surgery; penile degloving with associated circumcision (to prevent postoperative phimosis) is usually performed for all types of procedures. However, in cases where the foreskin is normal circumcision is unnecessary.

Penile‐Shortening Procedures

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).

Nesbit Procedure

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.

  • Complete penile straightening is achieved in >80% of patients.
  • Recurrence of the curvature and penile hypoesthesia (~10%) and the risk of postoperative ED is minimal [27].
  • Penile shortening is common in Nesbit procedure [27]. About 1–1.5 cm loss of penile length has been reported in nearly 85% of patients.
Diagram of Nesbit’s operation for Peyronie disease depicting the bent penis with 2 ellipses removed from the side opposite the plaque (left) and the sutured cuts (right).

Figure 34.18 Nesbit’s operation for Peyronie disease. A series of ellipses are removed from the side opposite the plaque.

Plication Procedures

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].

Image described by caption.

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 Procedures

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

Penile prosthesis implantation is typically reserved for the treatment of patients with Peyronie disease and ED not responding to pharmacotherapy.

34.7 Late Onset Hypogonadism

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].

34.7.1 Definition

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].

34.7.2 Pathophysiology

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].

34.7.3 Aetiology

Primary hypogonadism (testicular) causes low testosterone levels and impaired spermatogenesis, with elevated or normal LHRH, LH, and FSH levels.

  • Congenital: Chromosomal (e.g. Klinefleter syndrome [47 XXY]), Turner syndrome, disorders of sexual development giving rise to enzyme defects (e.g. 17‐α‐hydroxylase deficiency), androgen receptor defects (e.g. androgen insensitivity syndrome or 5‐α‐reductase deficiency), and condition leading to testicular atrophy such as undescended testes and more common cause, testicular tumours.
  • Acquired: Bilateral testicular atrophy (e.g. torsion, infection, trauma, autoimmune disease, toxins, alcohol), bilateral orchiectomy, chemotherapy, or radiotherapy.

Secondary hypogonadism (nontesticular or central) causes disruptions in the LHRH and LH secretions.

  • Congenital: Kallmann’s syndrome (most common), Prader‐Willi syndrome, and congenital adrenal hypoplasia.
  • Acquired: Hyperprolactinemia (e.g. prolactin secreting pituitary adenomas or drug induced [dopamine antagonises]) and hypopituitarism (e.g. pituitary tumours) surgical excision, or radiotherapy.

34.7.4 Risk Factors Increasing the Likelihood of LoH

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].

34.7.5 Clinical Features

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].

34.7.6 Diagnosis

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]:

  • Early morning (7–11 a.m.) total testosterone: Total testosterone level above 12 nmol l−1 (350 ng dl−1) does not require substitution. Patients with serum total testosterone levels below 8 nmol l−1 (230 ng dl−1) will usually benefit from testosterone treatment. If the serum total testosterone level is between 8 and 12 nmol l−1, repeating the measurement of total testosterone with SHBG to calculate free testosterone or free testosterone by equilibrium dialysis.

    Total testosterone levels of 8 nmol l−1 leads to a loss of libido and 8.5 nmol l−1 ED.

  • LH and FSH levels, in addition to serum prolactin if testosterone level <5.2 nmol l−1 (150 ng dl−1).
  • PSA, full blood coun, liver function tests, and renal function tests.
  • Equilibrium dialysis is the gold standard for free or bioavailable testosterone measurement. Free testosterone when the serum total testosterone concentration is not diagnostic of hypogonadism, particularly in men who are obese; a free testosterone level below 225 pmol l−1 (65 pg ml−1) can provide supportive evidence for testosterone treatment.

34.7.7 Treatment [31, 33, 35, 36]

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].

Flow diagram from bars labeled Symptoms or signs of hypogonadism to Measure morning total testosterone, to Low (<8 nmol l–1), etc. then to Monitor, Borderline (8–11 nmol l–1), to Investigate other causes, etc.

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

  • Breast cancer: due to peripheral aromatization of testosterone.
  • Prostate cancer: controversial, but should be avoided or used with caution in men with high risk of developing prostate cancer or PSA levels >4 ng ml−1.
  • Primary liver cancer.
  • Polycythaemia (haematocrit >50%).
  • Untreated obstructive sleep apnoea.
  • Untreated congestive heart failure or renal failure or liver failure.
  • Obstructive benign prostatic enlargement (unlikely, as lack of testosterone will likely cause involution of the prostate).

Side effects of testosterone replacement

  • Polycythaemia.
  • Headaches.
  • Depression.
  • Liver toxicity and obstructive jaundice.
  • Gynaecomastia.
  • Baldness.

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].

  • Full blood count every three to four months for first year, then annually to maintain haematocrit below 52–55%. Effects may be evident at 12 weeks and peak at one year.
  • Rectal examination and PSA every three to six months for first year, then annually.
  • Bone mineral density if abnormal before replacement therapy. Improvements can be detectable from six months and may continue for three years.

Various testosterone preparations are available (Table 34.4) and should be tailored around the patients’ needs and compliance.

Table 34.4 Testosterone replacement preparations.

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.
Aug 6, 2020 | Posted by in UROLOGY | Comments Off on Penis and Urethra Disorders of Function

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