Sexuality and erectile dysfunction
Sexuality and penile erectile function
Sexuality is a complex concept encompassing far more than the simple sexual act. Sexuality in fact includes the physiological, behavioural and relational aspects of human sexual life, which are variously influenced by psychological factors (e.g. sexual fantasies, desire, arousal, psychosexual orientation, and the choice of the sexual object), as well as social and organic (vascular, nervous, and endocrine) factors.
From a functional point of view, a normal penile erection may be defined as an erection which permits the penetration of a lubricated vagina without additional assistance. Concerning the erectile mechanism, the haemodynamic changes in the penis require a high degree of central and peripheral nervous coordinated control and an unaffected endocrine system.
The penis consists of two paired and elongated spongelike bodies, the corpora cavernosa. These are ventrally joined to the corpus spongiosum and are covered by a tough fibroelastic sheath, the tunica albuginea, which has both structural and functional purposes. The corpus spongiosum surrounds the urethra and distally forms the glans (1).
The erectile tissue of the corpora cavernosa is composed of sinusoidal spaces, also named lacunae, covered by endothelial cells. The lacunae are lined by trabecular tissue, whose ultrastructure consists of an intricate network of both smooth muscle cells and fibroblasts joined by collagen and elastin. The trabeculae have a structural and contractile function (1).
Arterial inflow to the penis is supplied by the helicine arteries which branch out from the two deep cavernosal arteries. When the penis is flaccid, the helicine arteries are contracted. During erection arterial relaxation causes an increase in blood flow and a consequent enlargement of the lacunar spaces. The structural elasticity of the trabeculae allows the increase in penile size from the flaccid to the erected state (1). Blood drainage from the corpora cavernosa is guaranteed by the circumflex and emissary veins which end in the deep dorsal penile vein.
The innervation of the penis involves both the autonomic and the somatosensory nervous system. The sympathetic fibres arise from the thoracolumbar centre of erection (T12–L2) and reach the penis through the hypogastric plexus and the pelvic, cavernous and pudendal nerves. The parasympathetic and somatic fibres have their origin in the sacral centre of erection (S2–S4). The efferent parasympathetic fibres along with the pelvic nerves, also named nervi erigentes, reach the erectile tissue through the cavernous nerves. Somatosensory innervation is provided by the pudendal nerve with afferent fibres from the penile and perineal skin (the afferent branch of the sacral spinal reflex pathway of erection), and with efferent fibres directed to the perineal striated musculature of the pelvic floor (bulbocavernosal and ischiocavernosal muscles) (1).
An erection occurs as a consequence of haemodynamic changes in the penile state induced by peripheral integration of one or more neurological stimuli. Erections are produced by the spinal centres which can be activated by genital sensory stimulation and by pathways from the brain.
Sexual stimuli are classified into two types: psychic stimuli such as visual, auditory, olfactory, and tactile stimuli, and internal imagery (imagination/fantasy), which are dependent on the brain, and reflexive stimuli that are dependent on touch and which can be effective without the brain. Both central and peripheral neurological stimuli are able to promote an erection. Obviously, psychic stimuli will increase the sensitivity to reflexive stimuli and vice versa (2).
Central erotogenic stimulation promotes sexual arousal, a subjective state which stimulates the subject to search for sexual stimulation and sexual intercourse (2).
The limbic system is the central neural substrate of sexuality as it is for other appetitive functions. Other brain areas involved in erectile control include the preoptic region, the lateral hypothalamus, the tegmentum, and the anterior part of the cyngulate gyrus (2). The brain exerts both excitatory and inhibitory modulations on the spinal mechanisms involved in erectile regulation, but some central brain areas maintain a constant inhibitory control on erection via the sympathetic pathway. The sensitive stimuli and the psychogenic activity activate specialized sites of both thalamus and hypothalamus, inducing a psychogenic erection via the inhibition of the sympathetic thoracolumbar erection centre (T12–L2) and via a reduction of the adrenergic tone in the penis.
In addition to psychogenic erections, direct physical stimulation of the penis and perineal skin induces a reflexogenic erection by activation of the sacral spinal reflex pathway. The erectile response is the result of an inhibition of the thoracolumbar sympathetic centre of erection (T12–L2), a stimulation of the parasympathetic centre of erection (S2–S4), and the activation of both parasympathetic and nonadrenergic-noncholinergic (NANC) pathways (Fig. 188.8.131.52).
Sleep-related erections occur during rapid eye movement (REM) sleep; however, the precise physiological mechanism involved in sleep-related erections is not thoroughly understood (Fig 184.108.40.206).
The endocrine system contributes to penile erection. Androgens are the hormones mainly involved in erectile physiology. Prenatal and perinatal brain androgenization is the prerequisite for normal male sexual function in rodents, and androgens are necessary for sex maturation in mammals (3).
In adult men androgens maintain male sexual behaviour (3); lack of testosterone frequently produces loss of libido and erectile dysfunction (3). In hypogonadal men testosterone replacement therapy increases sexual interest and facilitates sexual behaviour (3).
Sleep-related erections are androgen-dependent, (4) being impaired in hypogonadal men and being restored by testosterone replacement therapy (3). Erections induced by visual erotic stimuli are not affected by lack of testosterone (3).
The sites of androgen action are the limbic system of the brain (especially the anterior hypothalamus), and probably the spinal cord (where reflexes serving erection and ejaculation are androgen-dependent), and the penis.
Local control of erection
Table 220.127.116.11 Neurotransmitters and other substances involved as final neuroeffectors of erection and their role on penile smooth muscle and vasculature
Neurotransmitters and other substances
Effects on penile smooth muscle
In vivo demonstrated effects on penis
Calcitonin gene-related peptidea
Contraction (]]) (Contraction of cavernous arteries)
Relaxation (]]) (Relaxation of cavernous arteries)
No direct effect on smooth muscle
Erection via the NANC system
b Major effect on penis is smooth muscle contraction, since α-receptors are more prevalent than β-receptors in penile tissue.
Knowledge of neurotransmitters responsible for the local control of erection has recently been extended by the identification of NANC fibres, which are the final effectors of the nervous system in controlling erection. The activation of cholinergic fibres stimulates postganglionic NANC neurons to produce and release nitric oxide, which is the principal neurotransmitter involved in the promotion of penile erection. The sympathetic system exerts a constant negative control on erection by inhibiting postganglionic NANC neurons (1, 5).
Nitric oxide is released by both neuronal fibre endings and endothelial cells, but under physiological conditions neuronal nitric oxide plays the larger role.
Nitric oxide is a cleavage product whose synthesis from amino acid l-arginine is catalysed by nitric oxide synthase (NOS). Nitric oxide relaxes smooth muscle cells by increasing the synthesis of cyclic guanosine monophosphate (cGMP) via a direct stimulation of guanylate cyclase (6, 7) (Fig. 18.104.22.168). The cGMP activates protein kinase G, which then causes a reduction of transmembrane Ca2+influx, sequestration of intracellular Ca2+, and membrane hyperpolarization. All these events induce smooth muscle relaxation (1, 5). Residual cGMP is catabolized by phosphodiesterase 5 (PDE 5) (8).
It is noteworthy that testosterone has also a peripheral role on erections through the nitric oxide pathway by stimulating both neuronal NOS and PDE 5 activity (9).
Other substances, including neurotransmitters, hormones, prostaglandins, and other peptides are responsible for local control of erection. Particularly, prostaglandin E1 and vasoactive intestinal peptide (VIP) relax the smooth muscle, while substance P and prostaglandin F2-α cause it to contract (1, 5). Prostaglandin E1 induces smooth muscle relaxation by reducing intracellular Ca2+ uptake, as a result of the activation of adenylate cyclase and a consequent increase of intracellular cyclic adenylate monophosphate (cAMP), which activates protein kinase A (Fig 22.214.171.124; Table 126.96.36.199) (1, 5).
Erection and detumescence are haemodynamic events regulated by smooth muscle relaxation and contraction, respectively. Therefore, the tone of the corpora cavernosa smooth muscle is the major determinant in the control of the flaccid and erect penile state. The haemodynamic events involved in penile erection are as follows: (1) the resistance of intracavernosal arterioles decreases by relaxation of the cavernosal muscle cells; (2) the dilatation of the arterial bed (particularly helicine arteries) increases the arterial flow causing (3) the engorgement of sinusoids and the enlargement of lacunae; (4) these events cause an increase in penile tumescence and penile length; (5) the stretching of the poorly distensible tunica albuginea and the expansion of the lacunae activate a veno-occlusive mechanism with reduced venous outflow due to compression of the subtunical and emissary veins (1).
The mechanism of penile erection can be divided into five phases according to these haemodynamic events. Phase 1 (latent phase) is characterized by a two- to threefold increase in arterial perfusion with unchanged intracavernosal pressure. Phase 2 (tumescence phase) begins when progressive reduction of the venous outflow causes penile elongation and increase of intracavernosal pressure. Phase 3 (erection phase) is reached when intracavernosal pressure (approximately 90–100 mmHg) is just below systolic blood pressure, with a steady state of arterial inflow and a minimal venous outflow. Phase 4 (rigidity phase) is characterized by maximal rigidity, which is reached only after the pelvic floor muscles contract. During the rigidity phase intracavernosal pressure is higher than systolic pressure. After erotic stimulation ceases or ejaculation occurs, phase 5 (detumescence phase) takes place with a decrease of rigidity and tumescence as a consequence of reduced arterial flow and the inactivated veno-occlusive mechanism (1).
The penile erection is associated with an increased oxygen tension in penile tissues. In sinusoidal spaces, blood partial oxygen tension (pO2) is between 20 and 40 mmHg during the penile flaccid state; this increases to up to 90–100 mmHg during erection (10). The pO2 during the flaccid state could favour transforming growth factor β1 (TGFβ1) synthesis in the smooth muscle cells of the corpora cavernosa, followed by collagen and connective tissue synthesis and deposition (11). Alternatively, the oxygenation associated with erection might decrease the availability of TGFβ1 and collagen, thus erections could have a protective role on penile tissues.
Erectile dysfunction and sexuality
Erectile dysfunction had its first official definition in 1993: the inability to attain and/or maintain a penile erection sufficient to permit satisfactory sexual performance (Box 188.8.131.52) (12). According to this definition, satisfactory sexual performance is only achievable with a full erection, but this is a matter of opinion. A more recent definition is dated 2000 (13) and states that erectile dysfunction is the persistent or recurrent inability to attain, or to maintain until completion of sexual activity, an adequate erection. This second definition confirms a relationship between penile erection and sexual performance, but a full erection is not suggested as a prerequisite for a satisfactory sexual performance.
The term erectile dysfunction does not include other sexual dysfunctions such as loss of libido, disorders of ejaculation and disorders of orgasm. Erectile dysfunction constitutes only part of the overall multifaceted process of sexual function, which includes erectile function as a mechanical event plus psychological, behavioural and relational components.
How erectile dysfunction interferes with the sexuality of a couple is greatly influenced by the sexual habits of the couple. Erectile dysfunction which occurs in couples whose sexual habits are characterized by poor or absent foreplay may cause a more relevant impairment of sexuality than in couples for whom foreplay has an important role in sexual intercourse.
Aetiopathogenesis and epidemiology of erectile dysfunction
Erectile dysfunction results from psychogenic, organic (vascular, hormonal, metabolic, neurological), and iatrogenic disorders. Up until the 1960s, psychogenic disorders were considered the most frequent cause of erectile dysfunction; at present this is confirmed only in young men, with psychogenic causes occurring in about 70% of men less than 35 years old (14). To date organic disorders represent about two thirds of the causes of erectile dysfunction (15). According to the Massachusetts Male Aging Study (16), the prevalence of erectile dysfunction is about 50% in men 40–70 years of age. In this study erectile dysfunction correlated positively with age, cigarette smoking, depression, diabetes mellitus, and cardiovascular diseases (16).
Among organic causes, vascular disorders are the most frequent; (17) neurogenic causes occur in 3–10% of the cases (18) and, according to some authors, a hormonal disorder occurs in about 5% of cases of erectile dysfunction (19).
Although erectile dysfunction may be exclusively of psychological origin, a psychological disorder often arises in addition to organic erectile dysfunction; (20) therefore organic and psychogenic erectile dysfunction coexist in many patients.
Furthermore, some diseases can induce erectile dysfunction by more than one pathogenetic mechanism, as is the case of diabetes mellitus, which can simultaneously impair both penile and extrapenile nerves and vessels and, as many chronic diseases, can affect the psychological pattern of a subject, with possible effects on penile erections.
Psychogenic erectile dysfunction
Psychogenic erectile dysfunction is frequently associated with generalized trait anxiety, situational anxiety (e.g. performance anxiety), relationship conflicts, disorders involving sexuality (psychosocial sexual inhibition, sex-preference conflicts, experienced childhood sexual abuse, disorders of sexual orientation), fear of pregnancy, fear of sexually transmitted diseases, fear of failure, and decreased libido. The suggested mechanism in primary psychogenic erectile dysfunction is an activation of the sympathetic nervous system with increased adrenergic and noradrenergic tone (20, 21).
Psychogenic erectile dysfunction can also occur in primary psychiatric diseases, as in depression, and sometimes is worsened by antidepressant drug administration.
Vasculogenic erectile dysfunction
Vasculogenic erectile dysfunction is caused by reduced arterial inflow into the penis or an impaired veno-occlusive mechanism, or both, and its frequency increases with ageing. Arterial insufficiency is a common cause of erectile dysfunction and results from many disorders, including thrombotic and thromboembolic occlusion of the terminal aorta and the iliac, hypogastric, pudendal, and penile arteries. Atherosclerosis is the most common cause of arterial occlusion; therefore arterial penile insufficiency shares the same risk factors of atherosclerosis, which are cigarette smoking, dyslipidaemia, age, diabetes, hypertension, and metabolic syndrome (22). Arterial penile insufficiency may also be due to congenital anomalies, diabetes mellitus, pelvic surgery, and perineal or pelvic trauma (23).
An impairment of the veno-occlusive mechanism of erection may cause erectile dysfunction because of venous leakage with increased venous blood outflow. Failure of the veno-occlusive mechanism may occur at many levels: tunica albuginea, trabecular tissue, endothelial cells, nerve fibres, and veins (23).
Diseases of the tunica albuginea include fibrosis, Peyronie’s disease, penile fracture, diabetes, trauma, and congenital tunical abnormalities (e.g. reduced tunica thickness) (23).
Trabecular compliance is impaired when changes in the smooth muscle/collagen ratio occurs. Morphological and functional changes in cavernous smooth muscle may be due to smooth muscle atrophy with replacement by fibrotic tissue (as in atherosclerosis and diabetes), and to local functional disorders with impaired neurotransmitter release or receptor function (23, 24).
Venous drainage may be impaired by congenital abnormal or ectopic veins and by pathological shunts (traumatic, post-priapism, surgical, or congenital) between the corpus cavernosum and the corpus spongiosum of the glans penis (23).
Endocrine erectile dysfunction
Endocrine disorders are involved in at least 5% of men affected by erectile dysfunction, with primary and secondary hypogonadism as the major endocrine disease causing erectile dysfunction.
Mild hypogonadism may be associated only with loss of libido; severe hypogonadism may also show erectile dysfunction (3). Sleep-related erections are impaired in hypogonadal subjects (3, 4), while erections in response to visual erotic stimulation are only partially androgen-dependent (3). Replacement therapy usually restores a normal libido and normal erectile function (3).
Hyperprolactinaemia with or without hypotestosteronaemia may also be associated with loss of libido and erectile dysfunction, but does not appear to modify sleep-related erections and penile response to visual erotic stimulation, suggesting that hyperprolactinaemic negative effects on libido and sexual behaviour are centrally mediated (25).
Among the other endocrinopathies possibly responsible for erectile dysfunction are adrenal insufficiency, acromegaly, Cushing’s syndrome, hyperthyroidism, and hypothyroidism (19).
Neurological erectile dysfunction
Brain, spinal cord, and nerve diseases can cause neurogenic erectile dysfunction. Lesions in various brain areas may induce erectile and sexual dysfunction (e.g. Parkinson’s disease, cerebrovascular or expansive lesions of either temporal lobes or limbic system).
Congenital (e.g. spina bifida, syringomelia) or acquired (traumas, neoplasia, and inflammatory disorders as multiple sclerosis) spinal cord diseases are the most frequent causes of neurogenic erectile dysfunction (23). Injuries to lower spinal cord segments (lumbar and sacral) often result in complete erectile dysfunction, while lesions of the upper spinal cord segments (cervical and thoracic) do not affect reflexogenic erections (21).
Concerning the peripheral nervous system, erectile dysfunction can result from traumatic (pelvic fracture) or surgical (radical prostatectomy, cystoprostatectomy, proctocolectomy) injuries to the pudendal and cavernous nerves. Peripheral neuropathy can be caused by diabetes mellitus (the most common cause), uraemia, amyloidosis, vitamin deficiency (folic acid, B6 and B12), and alcoholism (23).
Iatrogenic erectile dysfunction
Erectile function can be affected by several drugs (Box 184.108.40.206). Data on drug administration and erectile dysfunction are often collected by uncontrolled studies and/or single observations; therefore a cause–effect relationship is not demonstrated for all the drugs associated with impaired erections.
To varying degrees, erectile dysfunction is a common side effect of antihypertensive drugs (diuretics, β-blockers). Moreover, some drugs affecting the endocrine system (oestrogens, progestins, antiandrogens, both luteinizing hormone-releasing-hormone agonists and antagonists) can impair erectile function by decreasing gonadotropin release. The peripheral bioavailability of androgens is decreased by digitalis, cimetidine, and spironolactone. Hyperprolactinaemia, and the often related low libido and erectile dysfunction, can result from drugs such as reserpine, phenothiazines, and H2-receptor antagonists. Alcohol abuse can cause low testosterone serum levels, peripheral neuropathy, and chronic liver damage (26).
Pelvic surgery, such as radical prostatectomy, cystoprostatectomy, proctocolectomy, is a frequent cause of erectile dysfunction due to pelvic vessel and/or pelvic nerve lesions. Renal transplantation and vascular surgery on the aortoiliac arteries may also cause erectile dysfunction (26).
Pelvic fractures can cause erectile dysfunction if injury to a vessel or to nerves involved in the erectile mechanism occurs (26).
The diagnostic approach to erectile dysfunction has several possible steps whose sequence follows the clinical features and the results of previously performed tests. However, the diagnostic approach may also be influenced by the medical background (psychological, clinical, surgical) of the physician approaching the patient, and by the patient’s choice of therapy, regardless of the aetiology (Fig 220.127.116.11).
General clinical interview
The general clinical interview can detect a medical history that is positive for systemic pathologies or for drugs which can cause erectile dysfunction.
The sexological interview constitutes a main step, because it may indicate either psychogenic or organic erectile dysfunction.
Some information is explicitly concerned with sexual matters, such as sexual orientation, the presence of one, more, or no constant partner, sexual habits, and frequency of sexual intercourse. Other information is not explicitly sexual, but is necessary when approaching the patient, e.g. cultural level, religious beliefs, or profession.
A systematic approach can reveal psychogenic erectile dysfunction when some or even all the following conditions occur: abrupt onset, full morning erections, full erections following visual erotic stimulation, full erections with masturbation, inconstant occurrence, occurrence only with some sort of sexual intercourse, and occurrence with one partner, but not with another.
Conversely, organic erectile dysfunction is often characterized by a progressive loss of erectile function and by an almost constant presence of the problem.
The libido needs to be investigated carefully. When a patient complains of low libido, the physician should try to determine if what is occurring is loss of libido, or unwillingness to face erectile dysfunction. Low libido justifies an evaluation of testosterone and prolactin levels, and consideration of depression, or the use of neuroleptics or antiandrogens.
Sexuality and sexual satisfaction can also be investigated by questionnaires such as the Derogatis Sexual Functioning Index, the Golombock-Rust Inventory of Marital State, and the Sexuality Experience Scales Manual (28). However, the accuracy of these questionnaires in distinguishing between organic and psychogenic erectile dysfunction is doubtful (28).
A psychological evaluation of the patients affected by erectile dysfunction is almost always necessary because of the very frequent involvement of psychological factors, even when the causes are organic. Psychological evaluation should be performed by a psychologist; however, questionnaires, mainly self-filled brief checklists, are available in order to provide a picture of the patient’s personality and anxiety levels, and to indicate depression (20, 29).
Blood glucose should be assayed because of the high occurrence of erectile dysfunction in diabetics. Cholesterol and triglycerides should also be measured in order to detect risk factors for arteriosclerosis.
Erectile dysfunction is associated with almost all severe endocrinological diseases; however, a hormonal assessment is indispensable only when suspicion of an endocrinological pathology is clinically supported (30).
There is no general agreement on whether prolactin, testosterone and luteinizing hormone should be assayed in all patients with erectile dysfunction, regardless of the presence or absence of clinical hypogonadal features. However, even in the absence of such features, prolactin and testosterone should be assayed to detect whether the low libido has an endocrinological or a psychogenic cause.
Visual erotic stimulation
Visual erotic stimulation by movies, slides or magazines provides a cheap test, where the penile response is self-scored by the patient and not by expensive devices. A full erection in response to this stimulation means that both vessels and nerves involved in the erection are not damaged. However, a normal penile erection may not occur because of embarrassment or because the patient is accustomed to visual erotic stimulation. Furthermore, a full erection can occur during visual erotic stimulation in hypogonadal men, which renders the test useless for excluding erectile dysfunction due to low testosterone and/or high prolactin levels (3, 25).
Nocturnal penile tumescence and rigidity monitoring (NPTRM)
NPTRM (31) may help to differentiate between psychogenic (normal NPTRM) and organic (impaired NPTRM) erectile dysfunction. Devices measuring rigidity and tumescence reduce the possibility of false diagnosis of psychogenic erectile dysfunction due to normal increase of tumescence but impaired rigidity.
NPTRM parameters are (1) the number of erections per night, (2) the maximum increase of tumescence, (3) the maximum rigidity. There is no full agreement on the normal ranges of the NPTRM parameters. According to different research groups, the normal increase of tumescence (circumference) ranges between 15 and 30 mm; the maximum rigidity recorded by RigiScan® (a NPTRM device) is normal when it is at least 60% or 70% of the 2.8 N force applied by the loops encircling the penis.
Impaired NPTRM can occur because of hormonal (namely, hypotestosteronaemia) (4), vascular and neurological pathologies, however an impaired test is usually of little help in identifying the specific cause of an organic erectile dysfunction. Furthermore, the usefulness of NPTRM is limited by the possible occurrence of impaired sleep-related erections in men without vascular or neurogenic lesions, but suffering from depression or sleep disturbances.
Intracavernosal injection of vasoactive drugs
Intracavernosal injection of vasoactive drugs (20, 32) promotes penile erection by increasing arterial blood inflow. Although many substances have been used for this test, to date prostaglandin E1 and papaverine hydrochloride are the drugs most frequently used, both alone or added to phentolamine.
A normal penile erection (see NPTRM parameters) in response to the intracavernosal injection test should occur within 10–20 min and indicates a normal veno-occlusive mechanism. It is not an appropriate test to evaluate the arterial penile vessels.
Alternatively, an impaired erection could be due to either an arterial lesion or an impaired veno-occlusive mechanism. Furthermore, the anxiety induced by this test may result in increased vasoconstrictor (catecholamines) input to the penis, with an impaired penile response in men without a vascular lesion; therefore a psychometric test for anxiety should precede the intracavernosal injection (20).
The main acute side effects which can occur are priapism, burning sensation during the injection, haematoma, and pain occurring upon erection.
Penile systolic/brachial systolic blood pressure index
Penile systolic pressure is measured after an intracavernosal injection of a vasoactive drug. An arterial obstruction is suggested by an index of less than 0.6. Anxiety in the patient can influence this measure negatively.
Penile Doppler, duplex scanning, and colour Doppler
Penile Doppler, duplex scanning, and colour Doppler sonography investigate the penile arteries (33). These tests are associated with the intracavernosal injection of a vasoactive drug. After the drug injection, the main parameters are: the cavernosal artery peak blood flow velocity (normal: above 25–30 cm/sec), which reflects the arteries’ function; the cavernosal artery end-diastolic flow velocity (normal: below 5 cm/sec); and the resistance index (peak flow velocity–diastolic flow velocity/peak flow velocity; normal: above 0.9). The latter two parameters provide information on the veno-occlusive mechanism. As in other tests, the patient’s anxiety can influence these measures.
Cavernosometry (33) is usually reserved for patients whose medical history, whose NPTRM, and whose penile examination by both intracavernosal injection of vasoactive drugs and Doppler (or echo-Doppler) suggest a venous lesion.
A needle is placed into one corpus cavernosum and a vasoactive drug is injected. Fifteen minutes later the intracavernosal pressure is measured. A venous leak is suggested by a pressure of less than 30 mmHg.
In a second phase, another needle is inserted in the other corpus cavernosum and heparinized saline is infused into the penis by a pump which records the flow needed for a specific pressure. When the pressure reaches 150 mmHg the saline flow is stopped for 30 s and then the pressure is measured again. Pressure values lower than 105 mmHg confirm a venous leak.
If a venous leak is diagnosed, penile and pelvic radiography is performed after injecting a contrast medium into the corpus cavernosum in an attempt to localize the venous leakage. Cavernosography is not necessary for the diagnosis of venous leakage and should be reserved for subjects eligible for vein ligation. As with other diagnostic measures, cavernosometry may induce anxiety possibly affecting the results of the test.
Contrast arteriography is normally limited to men in whom an arterial lesion has been suggested by Doppler sonography (33).
Neurological instrumental investigation (34) should be reserved for men with erectile dysfunction with positive clinical neurological examination, and/or who are affected by pathologies which can involve impaired erections on a neurological base, such as diabetes mellitus, alcohol abuse, prostatectomy, colorectal exeresis, spinal cord injury, or spinal disc disease.
The list of instrumental neurological tests includes: (1) penile nerve conduction test; (2) penile biothesiometry test, for somatosensory pathways; (3) pudendal sensory threshold test for somatosensory pathways; (4) bulbocavernosus reflex latency test for somatosensory afferents and somatomotor efferents; (5) urethroanal reflex test for autonomic sensory afferents; and (6) corpus cavernosum smooth muscle electromyography for autonomic innervation.
There is no wide agreement on the diagnostic contribution of these tests because of the great overlap between subjects with and without neurological lesions.
Type 5 phosphodiesterase inhibitors (PDE5Is)
Sildenafil, vardenafil, and tadalafil are relatively novel oral active inhibitors of the type 5 cGMP-specific phosphodiesterase (PDE) that induce smooth muscle relaxation by decrease of intracellular Ca2+ (Fig. 18.104.22.168) (8). Some physicians suggest that a PDE5I be prescribed before a clear diagnosis of a patient’s erectile dysfunction is achieved. This does not contribute to an accurate diagnose of erectile dysfunction (35). Rather than providing a diagnostic approach, prescribing PDE5I without prior investigation gives in to the patient’s desire for therapy regardless of the aetiology.
Although the least invasive suitable therapy should be proposed first, the physician should keep in mind what the patient is looking for and consider which therapy is best suited to the patient’s psychological pattern and sexual habits (Fig. 22.214.171.124).
Psychotherapy is normally applied to psychogenic erectile dysfunction; however, it may improve the erection of the man and/or the sexual satisfaction of the couple suffering from organic erectile dysfunction (36).
Oral nonhormonal drugs
Yohimbine is a central and peripheral α-2 adrenoceptor antagonist whose efficacy in organic erectile dysfunction is doubtful. A recent paper reports the efficacy of this drug in about 70% of the tested men, all affected by psychogenic erectile dysfunction (37).
Phentolamine is a direct α-1 and α-2 adrenoceptors antagonist which is used in combination with other drugs for intracavernosal injection. Recently, this drug has been proposed as an oral treatment for men affected by erectile dysfunction (38). However, it is not yet clear for what sort of erectile dysfunction phentolamine is appropriate, its dose possibly being of about 40 mg.
Apomorphine is a direct central D2 receptor agonist with proven efficacy as a central initiator of penile erectile response to erotic stimulation. It is effective in patients with erectile dysfunction with or without other concomitant and potentially erectile dysfunction-inducing diseases (e.g. cardiovascular pathologies and diabetes mellitus). This drug is available as 2 mg and 3 mg sublingual tablets. Apomorphine has a safe cardiovascular side-effect profile and its main side-effect is nausea, which occurs in less than 5% of the tested patients (39). However several studies suggest a poorer efficacy of apomorphine compared to PDE5I in the treatment of erectile dysfunction (40).
Table 126.96.36.199 Pharmacokinetic of PDE5 inhibitors
PDE5, phosphodiesterase 5; Tmax: time required for maximum serum drug concentration to be reached; T1/2: time required for drug serum concentration to be reduced by one-half of its maximum concentration.
These drugs are described as effective for both psychogenic and organic erectile dysfunction. PDE5Is amplify the vasodilator action of nitrates, which can result in death. Therefore, chronic nitrate drug therapy and short-acting nitrate-containing medication are absolute contraindications for sildenafil, vardenafil and tadalafil (41, 42). Retinitis pigmentosa, an inherited disorder of retinal PDE6, is also an absolute contraindication (41).
Their adverse effects include headache, dyspepsia, blue vision and abnormal vision (change in brightness perception), flushing, rhinitis, and pelvic musculoskeletal pain.
Gonadotropins and testosterone should be reserved for patients with documented hypogonadism (3). However, some studies suggest that testosterone may have a positive effect on eugonadal men complaining of low libido (3). Men on testosterone therapy should be advised to have the prostate checked regularly to monitor the trophic influence of this hormone on the prostate.
Low libido and/or erectile dysfunction in hyperprolactinaemic men with or without hypogonadism can be successfully treated with dopaminergic drugs (25).
Intracavernosal self-injection therapy
This therapy is effective in more than 70% of men with psychogenic and neurogenic erectile dysfunction, and is also effective in men with mild to moderate vasculogenic erectile dysfunction (43). The injection is given at the penile base on a lateral side.
The main side effect linked with regular therapeutic use of intracavernosal injections is the development of plaques as in Peyronie’s disease, which are reported to occur in up to 60% of self-injecting men after one year of injections at a rate of once per week.
Transurethral administration of prostaglandin E1 (125–1000 mcg) (44, 45) is less effective than intracavernosal injections; the occurrence of full erection ranges from 10–65% in tested men. However, even though the transurethral absorption of prostaglandin E1 can induce more acute systemic side effects (dizziness, sweating, and hypotension), than intracavernosal injections, the absence of the risk of penile fibrosis is noteworthy.
External vacuum device
Vacuum devices consist of a suction pump connected to a cylinder, which is placed over the penis. The negative pressure causes increased blood flow into the penis. A tension ring is placed at the base of the penis when the erection is reached; the cylinder is then removed. Adverse effects of the vacuum device include pain, blocked and painful ejaculation, haematoma, ecchymosis, petechiae, and ischaemic penile injury (46).
Intracavernosal self-injection, effective oral drugs, and the devices’ cost and invasiveness are causes of the declining use of penile prostheses. There are semi-rigid and inflatable penile prostheses which provide penile rigidity continuously or on demand, respectively. Perioperative infection, poor erection, penile deformity, device failure, and penile glans trauma during sex are included among the complications of penile prostheses.
Vascular surgery is reserved for venous leakage and focal arterial block. The treatment of venous leakage by ligation of the superficial and deep dorsal veins is disappointing with respect to long lasting effectiveness (47). In contrast, arterial surgery—anastomosis of the inferior epigastric artery to the penile dorsal artery or to the deep dorsal vein—is promising (48).
1. Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev, 1995; 75: 191–236.Find this resource:
2. Bancroft J. The biological basis of human sexuality. In: Human Sexuality and its Problems. Singapore: Longman, 1989: 12–145.Find this resource:
3. Christiansen K. Behavioural correlates of testosterone. In: Nieschlag E, Behre HM, ed. Testosterone:Action,Deficiency,Substitution. 2nd edn. Berlin: Springer-Verlag, 1998: 107–42Find this resource:
5. Andersson KE, Holmquist F. The pharmacology of penile smooth muscle. In: Bancroft J, ed. The Pharmacology of Sexual Function and Dysfunction. Amsterdam: Elsevier Science, 1995: 257–69.Find this resource:
6. Raijfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ. Nitric oxide as a mediator of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med, 1992; 326: 90–4.Find this resource:
7. Burnett AL. The role of nitric oxide in the physiology of erection. Biol Reprod, 1995; 52: 485–9.Find this resource:
8. Setter SM, Iltz JL, Fincham JE, Campbell RK, Baker DE. Phosphodiesterase 5 inhibitors for erectile dysfunction. Ann Pharmacother, 2005; 39: 1286–95.Find this resource:
9. Morelli A, Corona G, Filippi S, Ambrosini S, Forti G, Vignozzi L, et al. Which patients with sexual dysfunction are suitable for testosterone replacement therapy? J Endocrinol Invest, 2007; 30: 880–8.Find this resource:
10. Nebra A, Goldstein I, Pabby A, Nugent M, Huang YH, de las Morenas A, et al. Mechanisms of venous lekage: a prospective clinicopathological correlation of corporeal function and structure. J Urol, 1996; 156: 1320–9.Find this resource:
11. Moreland RB. Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the Society for the Study of Impotence. Int J Impot Res 1998; 10: 113–20.Find this resource:
12. National Institute of Health (NIH) Consensus Conference. Impotence. JAMA, 1993; 270: 83–90.Find this resource:
13. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR. 4th edn, Text Revision. American Psychiatric Publishing, Inc. 2000.Find this resource:
14. Slag MF, Morley JE, Elson MK, Trence DL, Nelson CJ, Nelson AE, et al. Impotence in medical clinical outpatients. JAMA, 1983; 249: 1736–40.Find this resource:
15. Benet AE, Melman A. The epidemiology of erectile dysfunction. Urol Clin North Am, 1995; 22: 699–709.Find this resource:
16. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates results of the Massachusetts Male Aging Study. J Urol, 1994; 151: 54–61.Find this resource:
17. Donatucci CF, Lue TF. Erectile dysfunction in men under 40: etiology and treatment choice. Int J Impot Res, 1993; 5: 97–103.Find this resource:
18. Berger RE, Rothman I, Rigaud G. Nonvascular causes of impotence. In: Bennet AH, ed. Impotence-Diagnosis and Management of Erectile Dysfunction. Philadelphia: WB Saunders, 1993: 106–23.Find this resource:
19. Melman A, Gingell JC. The epidemiology and pathophysiology of erectile dysfunction. J Urol, 1999; 161: 5–11.Find this resource:
20. Granata A, Bancroft J, Del Rio G. Stress and the erectile response to intracavernosal prostaglandin E1 in men with erectile dysfunction. Psychosom Med, 1995; 57: 336–44.Find this resource:
21. Carrier S, Brock G, Kour NW. The pathophysiology of erectile dysfunction. Urology, 1993; 42: 468–81.Find this resource:
22. Corona G, Mannucci E, Schulman C, Petrone L, Mansani R, Cilotti A, et al. Psychobiologic correlates of the metabolic syndrome and associated sexual dysfunction. Eur Urol, 2006; 50: 426–7.Find this resource:
23. Carrier S, Zvara P, Lue T. Erectile dysfunction. Endocrinol Metab Clin North Am, 1994; 23: 773–82.Find this resource:
24. Saenz de Tejada I, Goldstein I, Azadzoi K, Krane RJ, Cohen RA. Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N Engl J Med, 1989; 320: 1025–30.Find this resource:
25. Carani C, Granata ARM, Faustini Fustini M, Marrama P. Prolactin and testosterone: their role in male sexual function. Int J Androl, 1996; 19: 48–54.Find this resource:
26. Korenman SG. New insights into erectile dysfunction: a practical approach. Am J Med, 1998; 105: 135–44.Find this resource:
27. Segraves RT. Sexual dysfunction associated with antidepressant therapy. Urol Clin North Am, 2007; 34: 575–9.Find this resource:
28. Gregoire A. Questionnaires and rating scales. In: Gregoire A, Pryon JP, eds. Impotence: An Integrated Approach to Clinical Practice. New York: Churchill Livingstone, 1993; 97–105.Find this resource:
29. Bancroft J. Assessing people with sexual problems. In: Human Sexuality and its Problems. Singapore: Longman Ltd, 1989; 412–55.Find this resource:
30. Johnson AR, Jarrow JP. Is the routine endocrine testing of impotent men necessary? J Urol, 1992; 147: 1542–4.Find this resource:
31. Meisler AW, Carey MP. A critical reevaluation of nocturnal penile tumescence monitoring in the diagnosis of erectile dysfunction. J Nerv Ment Dis, 1990; 178: 78–89.Find this resource:
32. Pescatori E, Hatzichritou DG, Namburi S, Goldstein I. A positive intracavernous injection test implies a normal veno-occlusive but not necessarily normal arterial function: a haemodynamic study. J Urol, 1994; 151: 1209–16.Find this resource:
33. Benet AE, Sharaby JS, Melman A. Male erectile dysfunction–assessment and treatment options. Compr Ther, 1994; 20: 669–73.Find this resource:
34. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: Neurological evaluation of male sexual dysfunction. Neurology, 1995; 45: 2287–92.Find this resource:
35. Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol, 1996; 78: 257–61.Find this resource:
36. De Amicis LA, Goldberg DC, LoPiccolo J, Friedman J, Davies L. Three-year follow-up of couples evaluated for sexual dysfunction. J Sex Marital Ther, 1984; 10: 215–27.Find this resource:
37. Vogt H-J, Brandl P, Kockott G, Schmitz JR, Wiegand MH, Schadrack J, et al. Double-blind, placebo controlled safety and efficacy trial with yohimbine hydrochloride in the treatment of nonorganic erectile dysfunction. Int J Impot Res, 1997; 9: 155–61.Find this resource:
38. Becker AJ, Stief CG, Machtens S, Schultheiss D, Hartmann U, Truss MC, et al. Oral phentolamine as treatment for erectile dysfunction. J Urol, 1998; 159: 1214–16.Find this resource:
39. Heaton JP. Key issues from the clinical trials of apomorphine SL. World J Urol, 2001; 19: 25–31.Find this resource:
40. Giammusso B, Colpi GM, Cormio L, Ludovico G, Soli M, Ponchietti R, et al. An open-label, randomized, flexible-dose, crossover study to assess the comparative efficacy and safety of sildenafil citrate and apomorphine hydrochloride in men with erectile dysfunction. Urologia Internationalis, 2008; 81: 409–15.Find this resource:
41. Seftel AD. Phosphodiesterase type 5 inhibitor differentiation based on selectivity, pharmacokinetic, and efficacy profiles. Clin Cardiol, 2004; 27: 14–19.Find this resource:
42. Herrmann HC, Chang G, Klugherz BD, Mahoney P. Hemodynamic effects of sildenafil in men with severe coronary artery disease. N Engl J Med, 2000; 342: 1622–6.Find this resource:
43. Porst H. The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience. J Urol, 1996; 155: 802–15.Find this resource:
44. Porst H. Transurethral Alprostadil with MUSE™ (medicated urethral system for erection) versus intracavernous Alprostadil–a comparative study in 103 patients with erectile dysfunction. Int J Impot Res, 1997; 9: 187–92.Find this resource:
45. Padma-Nathan H, Hellstrom WJ, Kaiser FE, Labasky RF, Lue TF, Nolten WE, et al. Treatment of men with erectile dysfunction with transurethral alprostadil. N Engl J Med, 1997; 336: 1–7.Find this resource:
46. Katz PG, Haden HT, Mulligan T, Zasler ND. The effect of vacuum devices on penile hemodynamics. J Urol, 1990; 143: 55–6.Find this resource:
47. Lewis RW. Venous surgery for impotence. Urol Clin North Am, 1988; 15: 115–21.Find this resource:
48. Goldstein I, Hatzichristou D, Seftel AD. Arterial reconstruction for impotence. In: Webster GW, ed. Reconstructive Urology. Cambridge: Blackwell, 1993: 935.Find this resource: