REVIEW ARTICLE. AP J Psychological Medicine Vol. 15 (1) January-June 2014

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1 32 REVIEW ARTICLE An approach to the assessment of a patient with erectile dysfunction Pramod KR Mallepalli 1 MD, Dharma Rao Vanamali 2 MD, Raghuram M 3 MD, Sivanaga Reddy B 4, MD 1 Professor of Psychiatry, 3 Assistant Professor, Department of Psychiatry; 2 Professor of Medicine, Department of General Medicine; 4 Professor of DVL, Department of DVL, Mamata Medical College, Khammam, Telangana, India ABSTRACT Background: Erectile dysfunction (ED) is a very distressing condition that not only has a negative impact on the man s sexual ability but also has damaging repercussions on the couple s quality of life. ED leads to depression, anxiety and loss of self-esteem and can contribute to marital breakdowns. Men are reluctant to seek help for fear of not being taken seriously or out of embarrassment and become isolated within their relationship, which may lose all aspects of intimate contact. Objective: In this article, we are reviewing the approach to a patient with ED in the present context. Discussion: All men with ED should undergo a full medical assessment in a stepwise manner. Conclusion: A stepwise approach in the assessment of ED helps clinician to arrive at a proper diagnosis, which in turn may lead to better management. The teatment for ED is readily available and highly effective, yet is underutilized Key words: Erectile dysfunction, neurophysiology, pathophysiology, classification, causes, assessment Date of first submission: 10/3/14 Date of initial decision: 3/4/14 Date of acceptance: 31/5/14 INTRODUCTION ED is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. [1] ED can have a profound negative impact on the quality of life and life satisfaction of the patient (and his partner), resulting in fear, loss of self-image and self confidence, and depression. [1] It was estimated that in 1995, ED affected over 152 million men worldwide. The projection for 2025 is a prevalence of 322 million men worldwide with the largest projected increases in the developing world that is, Africa, Asia, and South America. [2] The stigma associated with ED prevents men from seeking help. Sexual health is an important component of overall wellbeing. Many men with ED have low self esteem and feel isolated because they are unable to discuss this sensitive issue with their physician for fear of embarrassment. Evidence has shown that ED has a significant negative impact on quality of life measures4 and that the successful treatment Address for correspondence: Dr M. Pramod Kumar Reddy. Professor of Psychiatry, Department of Psychiatry, Mamata Medical College, Khammam Telangana, India Phone: dr_mpramod@yahoo.co.in How to cite this article: Mallepalli PKR, Vanamali DR, Raghuram M, Reddy SB. An approach to the assessment of a patient with erectile dysfunction. AP J Psychol Med 2014; 15(1): of ED is associated with significant improvements of overall and emotional wellbeing. [3] Clinicians in India often avoid discussing sexual concerns, even when a problem is suspected because of lack of knowledge and skills in dealing with sexual problems. OBJECTIVE This review article mainly discusses the clinical assessment of a patient with ED. DISCUSSION Anatomy of the penis The internal structure of the penis consists of three cylindrical bodies: dorsally, the two corpora cavernosa communicate with each other for three quarters of their length and ventrally the corpus spongiosum surrounds the penile portion of the urethra. The proximal end of the corpus spongiosum forms a bulb attached to the urogenital diaphragm and at the distal end expands to form the glans penis. The tunica albuginea, which is composed of two layers of elastic and collagen fibres, surrounds the erectile bodies. The erectile tissue in the corpora cavernosa and the corpus spongiosum comprises vascular lacunar spaces, which are surrounded by smooth muscle. The lacunar spaces derive blood from the helicine arteries, which open directly into these sinusoids. Subtunical veins between the inner and outer tunica albuginea form a network and drain blood from the erectile tissue. Neurophysiology of penile erection From a neurophysiological aspect, erection can be classified into three types:

2 Mallepalli, et al: Assessment of erectile dysfunction 33 Reflexogenic erection: It results from tactile stimulation to the genitalia. Impulses reach the spinal erection centre via sacral sensory nerves (S2 4) and thoracic nerves (T10 L2). Some of the impulses follow the ascending tract and culminate in sensory perception, while others reach the autonomic nuclei of the efferent nerves and activate the nuclei and induce the erection process. Psychogenic erection: It results from audiovisual stimuli or fantasy. Impulses descend to the spinal erection centre to activate the erection process. Nocturnal erection: Nocturnal erection occurs mostly during the rapid eye movement stage of sleep. Most men experience three to five erections lasting up to 30 minutes in a normal night s sleep. Mechanism of nocturnal erection is not fully understood but it is postulated that central impulses descend to the spinal cord (through some unknown mechanism) to activate the erection process. Pathophysiology of penile erection A series of integrated vascular processes results in accumulation of blood under pressure and end-organ rigidity leading to penile erection. This vascular process can be divided into six phases: Flaccidity: In this state, a low flow of blood and low pressure exists in the penis. Both the ischiocavernosus and bulbocavernosus muscles are relaxed. Filling phase: During the initiation of the erectile mechanism, the impulses from efferent segments S2-S4 of the sacral spinal cord reach the penis and cause relaxation of the penile smooth arterial muscles. As a result the cavernosal and helicine arteries dilate and the blood flows into the lacunar spaces. Tumescence: In this process, the venous outflow is reduced by the compression of the Subtunical venules against the tunica albuginea (corporal veno-occlusive mechanism) causing the penis to expand and elongate but with a scant increase in intracavernous pressure. Full erection: In this phase, the intracavernous pressure rapidly increases to produce full penile erection. Rigidity: As intracavernous pressure rises above the diastolic pressure and blood inflow occurs with the systolic phase of the pulse there occurs enabling complete rigidity. At this stage, contraction or reflex contraction of the ischiocavernosus and bulbocavernosus muscles produces changes in the intracavernous pressure. When full rigidity is achieved, no further arterial flow occurs. Detumescence: Contraction of the smooth muscles of the penis and contraction of the penile arteries lead to a decrease of blood in the lacunar spaces and the contraction of the smooth trabecular muscle leads to a collapse of the lacunar spaces and detumescence. The sympathetic nervous system is responsible for detumescence via thoracolumbar segments (T10 12, L1 2) in the spinal cord. In organic erectile dysfunction, the events leading to full erection fail to occur owing to insufficient blood reaching the penis or owing to blood escaping from the penis. Weak pelvic floor muscles compromise penile erection. Role of the pelvic floor muscles The ischiocavernosus and bulbocavernosus muscles are active during penile erection. Contractions of the ischiocavernosus muscles produce an increase in the intracavernous pressure and influence penile rigidity. The middle fibres of the bulbocavernosus muscle assist in erection of the corpus spongiosum penis by compressing the erectile tissue of the bulb of the penis. The anterior fibres spread out over the side of the corpus cavernosum and are attached to the fascia covering the dorsal vessels of the penis and contribute to erection by compressing the deep dorsal vein of the penis thus preventing the outflow of blood from the penis. Classification of erectile dysfunction Erectile dysfunction is divided into two etiologic categories: psychogenic and organic. Most causes of erectile dysfunction were once considered to be psychogenic, but current evidence suggests that up to 80 percent of cases have an organic cause. 3 Organic causes are subdivided into vasculogenic, neurogenic and hormonal etiologies. Vasculogenic etiologies represent the largest group, with arterial or inflow disorders being the most common. Abnormalities of venous outflow (corporeal veno-occlusive mechanism) are much less common. Regardless of the primary etiology, a psychologic component frequently coexists. [4] Vascular causes: If the corpora cavernosa cannot expand and fill with blood, decreased erectile firmness occurs. Although atherosclerotic plaques, or damage by trauma or irradiation, may decrease blood flow to the penis, vascular causes of erectile dysfunction are more often due to a failure of neural, muscular, or chemical factors. Venous leakage occurs when incomplete filling of the corpora, or intracavernosal fibrosis, causes failure of the veins to be pressed shut against the tunica albuginea. Neurological causes: Erectile function can be impaired as a result of a cerebrovascular accident (CVA or stroke), demyelinating diseases, or even seizure disorders. Tumors or trauma to the spinal cord can also be causative factors of erectile dysfunction. Autonomic and peripheral sensory nerves may be damaged by trauma or transurethral resection of the prostate. A common cause of impaired erectile and ejaculatory function is nerve damage attributable to diabetic autonomic neuropathy. Hormonal abnormalities: Most of the hormonal causes leading to ED revolve around dysfunction of the hypothalamic-pituitary-gonadal axis and are associated with either excess prolactin or decreased testosterone levels. Other

3 34 Mallepalli, et al: Assessment of erectile dysfunction endocrine disorders that may be associated with ED include hypothyroidism, hyperthyroidism, adrenal insufficiency, or excessive levels of adrenal corticosteroids. Psychogenic causes: Psychological factors are known to adversely affect a man s sexual functioning, especially in the form of erectile dysfunction. Most of the psychiatric illnesses can cause erectile problems. Assessment of erectile dysfunction General principles The purpose of clinical assessment is to identify and agree to the nature of the individual s/couple s problem(s), why it has occurred, goals for treatment outcome, and whether this may realistically be achieved with biomedical or pysychotherapeutic interventions. Initial assessment of a patient with ED The cornerstone of clinical assessment for all men with ED is the initial evaluation. Although a patient with ED may be referred to a non-physician for psychosexual therapy, the medical (pharmacological) and surgical therapies for ED require the involvement of a physician. In special situations, a multidisciplinary approach may be required. The initial evaluation consists of a comprehensive medical, sexual and psychosocial history, a physical examination and diagnostic testing. Additionally, diagnostic tests are recommended with a proven value in specific patient profiles. Medical history The goal of the medical history is to differentiate between psychogenic and organic ED and to identify risk factors for organic ED. For the first purpose the Leiden Impotence screening Test (LIST) may be helpful. For the latter purpose the medical history should focus on risk factors for organic ED. In this context, it is appropriate to make inquiries into the patient s lifestyle. Does the patient have any high-risk habits such as smoking, excessive alcohol consumption or drug-abuse? Often ED is a first symptom of cardiovascular disease or chronic illness. 16% of patients presenting with ED have previously undiagnosed coronary artery disease 1 or over 35% of all male patients with diabetes mellitus suffer from some degree of ED. [2] The patient s prescription drugs must be carefully identified, because they may be an important causal factor. The most important of these are antihypertensives, antidepressants and tranquillisers. The use of certain drugs can be a contraindication to some forms of ED-treatment (e.g. nitrates in the case of sildenafil). Sexual history The goal of the sexual history is to define the nature of the problem, psychosexual context chronology of the problem, severity of the problem and definition of patient s needs and expectations. Validated sexual-function questionnaires may be used to assist in obtaining the sexual history. They may help the physician to initiate or structure the interview but are not a substitute for the patient - physician dialogue. To date, the international index of erectile function (IIEF), [3] the Erectile dysfunction inventory of treatment satisfaction (EDITS) [4], and the brief male sexual function inventory for urology [ 5] are frequently used for this purpose. To acquire a clear understanding of the various aspects of the patient s sexual activity, the sexological mini-anamnesis may be used. This history, which is based on the sexual response cycle defined by Masters and Johnson, [6] enables the physician to obtain in a simple manner a global picture of the nature and extent of the problem. Psychosocial history A psychosocial assessment is valuable in every patient. The physician also should carefully assess past and present partner relationships. Sexual dysfunction may affect the patient s self-esteem and coping ability, as well as his social and occupational performance. Physical examination Although in general, a physical examination does not identify the cause of ED, a focused physical examination should be performed on every patient with ED. The physical examination should include a general screening for medical risk factors that are associated with ED (co-morbidity) such as, body habitus (secondary sexual characteristics), an assessment of the cardiovascular, neurological and genital system focusing on penile, testicular and rectal exam. Diagnostic Tests A test of proven value in the evaluation of patients with ED but use of which is recommended during initial evaluation. These tests include the following: A fasting glucose or glycosylated haemoglobin (HbA1C) and lipid profile - if not available within the previous 12 months - to rule out diabetes mellitus and hyperlipidemia both of which are significant risk factors for ED. A morning testosterone assay to assess the hypothalamicpituitary-gonadal axis. This is a test of proven value in the evaluation of specific patient profiles, with use left to the clinical judgement of the treating physician. Specialized Evaluation Under certain circumstances further investigation is appropriate and such tests are usually performed in specialist centres. They are indicated when baseline assessment has either suggested a cause that is potentially amenable to specific curative therapy, or has raised the possibility of a serious condition that merits further investigation in its own right, or at the request of the patient himself. The specialized evaluation consists of endocrine, vascular and neurological testing.

4 Mallepalli, et al: Assessment of erectile dysfunction 35 Endocrine evaluation Although endocrinopathy is a rare cause of male erectile dysfunction, ED can be the presenting symptom of several endocrine disorders. Hypogonadism and hyperprolactinemia account for the majority of these cases. In the literature the prevalence of hypogonadism in men with ED ranges from 4.3 to 19.3%. [7] The rate of hyperprolactinemia ranges from 1% to 5%. [8] The prevalence of thyroid disorders is less than 1%. A total testosterone assay to be undertaken routinely in patients with ED, because steroid hormone binding globulin (SHBG) is known to be decreased in hypothyroidism, obesity and acromegaly, and increased in hyperthyroidism and oestrogen therapy, it is necessary to measure the free biologically active testosterone in these conditions, when total testosterone can be misleading. If testosterone is low, a repeat test is advised. If the second test reveals again a low serum testosterone, a full hormonal evaluation consisting of LH, prolactin, FSH, and TSH is recommended. If the patient has a history of decreased libido and/or the physical examination reveals gynaecomastia or testicular atrophy, a full endocrinological evaluation is advised. The blood samples should be taken between 8 and 10 am because of a diurnal peak in the morning. If the prolactin level is raised, a repeat test should be done with the patient completely rested and blood sample taken in the morning after awakening. Secondary causes of hyperprolactinemia should be looked for. Persistent, unexplained hyperprolactinemia should warrant a CT- or a gadolinium enhanced MRI-scan of the head to exclude a pituitary tumour. ED and inhibition of sexual drive also may be associated with thyroid disorder, both hypothyroidism and hyperthyroidism. Evaluation of thyroid should be considered only in a specialised setting. Vascular Evaluation Several tests are available for evaluating the penile vascular inflow and venooclusion. These include pharmacotesting, enhanced pharmacotesting such as in pharmaco penile duplex ultrasonography (PPDU), [9] cavernosometry and selective penile angiography. In the era of effective oral medication, a reason for a pharmacotest in the office is to allow the patient to experience the maximal degree of rigidity he still may get after maximal pharmacological stimulation. This is clinically important because it will allow the patient to compare the responses to the oral agent and the intracavernous injection. Thus, men failing on oral medication who have experienced an effective response to an injection may recall this as a more advantageous therapy and wish to try it at home when oral medication fails. There are several methods to enhance the erectile response to an intracavernous pharmacological challenge: genital self-stimulation, [10] vibratory stimulation, visual erotic stimulation and the application of a penoscrotal tourniquet. In office penile injection pharmacotesting Pharmacotesting is the intracavernous injection of a vasoactive medication and rating of the subsequent erection quality by visual inspection and palpation. [11] The office pharmacotest is the most commonly used diagnostic procedure for erectile dysfunction. It is, despite its lack of specificity, cost-effective, simple, minimally invasive, and performed without special monitoring. A positive response (normal erectile rigidity of sustained duration of at least 20 minutes) implies the patient does not have significant venooclussive or arterial pathology. Recent correlation with PPDU confirms that a positive pharmacological erection test is indicative of normal venoocclusion but may occur with borderline arterial function. [12] There is no consensus as to the best intracavernous agent or dosage for pharmacotesting. The ideal agent offers a maximal erectogenic effect and a minimal chance of prolonged erection. A variety of agents and dosage regimens have been studied: papaverine 60 mg, papaverine 60 mg / phentolamine 1 mg, papaverine 30 mg / phentolamine 1 mg, papaverine 45 /phentolamine 2.5, PGEI 10 ìg, 20 ìg and 30 ìg. [13] To date, a challenge of 10 ìg of PGEI, combined with genital stimulation and/or visual erotic stimulation (VES), is considered to be the best possible initial challenge. [14] In case the best quality erection is not obtained 20 minutes after this challenge, a second and eventually third injection at the same dosage (re-dosing) is advised. Penile pharmaco duplex ultrasound (PPDU) All too often the response to pharmacotesting is suboptimal. This situation leaves the physician questioning: Does my patient have venous leakage, arterial insufficiency, high anxiety or was the pharmacological challenge too low? PPDU provides a more objective, minimally invasive evaluation of penile hemodynamics following a pharmacotest. It should be noted that PPDU merely allows for a qualitative and not for a quantitative assessment of penile blood flow, because blood flow velocities and not blood flow are measured. Parameters to assess the venooclussive function are end diastolic flow velocity (EDV) and resistance index (RI). [15] Clinically, EDV and RI correlate with erectile response, since both are descriptions of penile rigidity/intracavernous pressure. The diagnosis venoocclusive dysfunction should be considered when PSV > 30 cm/s, and EDV > 3-5 cm/sec or RI < 0.9., associated with erectile rigidity rated as inadequate. Dynamic infusion pharmaco-cavernosometry and cavernosography (DICC) Insufficient corporal venoocclusion is implicated in up to 50% of patients complaining of ED who have vascular testing. DICC is invasive requiring two needles to remain in the penis one for heparinized saline / radiographic contrast infusion and one for pressure recording. DICC is reserved for the rare patient who might have a site-specific venous leak, e.g. Peyronie s disease with poor rigidity, history of penile fracture, perineal / pelvic trauma history. DICC is only

5 36 Mallepalli, et al: Assessment of erectile dysfunction performed when vascular surgery is considered a treatment option. [16] Penile arteriography Penile arteriography is the radiographic imaging of the internal pudendal arteries and their outflow tracts. Arteriography provides the best anatomic information about the origin of the common penile arteries, but as a screening test it is too invasive and nonspecific for the assessment cavernosal hemodynamics. It is generally reserved for young men with a history of pelvic / perineal trauma who may be candidates for operative revascularization. CT and MR imaging Computer Tomography and Magnetic Resonance Imageing are sophisticated Imageing techniques, which visualize pelvic and genital anatomy. They may be used in specialized settings of pelvic, perineal or penile trauma or Peyronie s disease. These Imageing techniques provide no insights into cavernosal hemo-dynamics. Nuclear Imageing Radio isotopic penography assesses the rate of washout of a radioisotope from the penis following pharmacotesting or visual erotic stimulation. This test remains experimental without standardization of isotopes or parameters of penile blood flow. It provides dynamic but not anatomic information. Psycho physiological tests These tests are helpful to diagnose ED and to distinguish psychogenic from organic ED. Nocturnal penile tumescence /rigidity testing (NPT) NPT or sleep related erection is a recurring cycle of erections associated with rapid eye movement during sleep. Sleep erections are androgen dependent and thus usually impaired in hypogonadal men. Registration of nocturnal penile tumescence (NPT) is useful for separating psychological and organic cases. Its main advantage is that it is relatively free from psychologically mediated effects. The documented presence of a full erection indicates that the neurovascular axis is functionally intact and that the cause of the ED is most likely psychogenic. Anxiety and depression can at times influence the content of the dream state, negatively affecting spontaneous nocturnal erections. Visual erotic stimulation (VES) A full erectile response to VES makes a psychogenic cause of ED likely. Unlike NPT, response to VES, although possibly closest to normal sexual response, is strongly susceptible to psychological factors, such as erotic excitement inhibition, and maybe normal in states of endocrine abnormality. Degree and latency of erectile responses to VES in eugonadal sexually non-dysfunctional men correlates with endogenous testosterone levels. Moreover, the response to VES is negatively correlated with age, limiting its value in older man. To date, the most important application of VES is to investigate the erectogenic or antierectogenic effect of drugs, in clinical pharmacological studies. [17] Neurological testing Penile erection is elicited by two different neurophysiolocal mechanisms and mediated by somatic and autonomic pathways. Psychogenic erections, initiated in supraspinal centres in response to auditory, visual, olfactory, and imaginative stimuli, are mediated by sympathetic pathways. Reflexogenic erections, elicited by tactile stimulation at the genital level, are mediated by a spinal reflex arc consisting of afferent somatic and efferent parasympathetic nerve fibres. Therefore, the neurological factor in ED may include central and peripheral neural structures. The medical history and physical examination provide the basis for these tests. Test can be classified as those detecting somatic efferent (motor) pathways, afferent (sensory) pathways, reflexes and autonomic responses. In general however, a goal-directed approach to ED does not tend to neurophysiological testing because history and a physical examination alone are likely to reveal clinical signs of neuropathy. Neurophysiological testing is recommended in research protocols or liability procedures after trauma or surgical interventions and it should be specifically tailored for the individual patient No routine work-up should be used. Patients suspected of having CNS lesions should be studied by magnetic stimulation and somatosensory evoked potentials. In patients with a history of neuropathy tests of the peripheral system such as nerve conduction, EMG and thermal testing in the lower limbs are relevant. Patients with a history suggestive of low spine or pelvic disorder should be studied by EMG of the sphincter muscles, bulbocavernosus reflex, dorsal nerve conduction and magnetic stimulation of the genitalia. CONCLUSION The number of patients seeking medical help for ED has greatly increased and the care for these patients has shifted from the dermatologists, psychiatrist and urologist to the primary care physician and other specialists in the field of sexual medicine. Consequently, the basic approach to the management of ED has become multidisciplinary and goaldirected. Key-elements in the initial evaluation are the medical and sexual history and the identification of indications for endocrine, vascular and neurological evaluation and referral to a specialist. Acknowledgements: Nil References 1. Krane RJ, Goldstein I, Saenz de Tejada I. Impotence. N Engl J Med 1989;321:

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